MX2008002968A - 9-aminocarbonylsubstituted derivatives of glycylcyclines - Google Patents

Abstract

This invention provides compounds of Formula (I) having the structure where R1, R2, R3and A are defined in the specification or a pharmaceutically acceptable salt thereof useful as antibacterial agents. Compounds according to Formula (II):where Q, R4, R5, and R6and A are defined in the specification are useful as chemical intermediates.

Description

DERIVATIVES OF GLICILLYCLINES SUBSTITUTED WITH 9-AMINOCARBONYL This application claims the priority of US Application No. 60 / 713,112 filed on August 31, 2005 whose full disclosure is incorporated herein by reference.

FIELD OF THE INVENTION The present invention relates to 9-aminocarbonyl-substituted glycylcycline derivatives that are useful as antibiotic agents and exhibit antibacterial activity against a broad spectrum of organisms including organisms that are resistant to tetracyclines and other antibiotics.

BACKGROUND OF THE INVENTION Since 1947 a variety of tetracycline antibiotics have been synthesized and described for the treatment of infectious diseases in man and animals. Tetracyclines inhibit the synthesis of the protein by binding to the 30S subunit of the bacterial ribosome preventing the binding of aminoacyl RNA (Chopra, Handbook of Experimental Pharmacology, Vol. 78, 317-392, Springer-Verlag, 1985). Resistance to tetracyclines emerges among many clinically important microorganisms which limit the usefulness of these antibiotics. There are two main mechanisms of bacterial resistance to tetracyclines: a) energy-dependent efflux of the antibiotic mediated by proteins located in the cytoplasmic membrane that prevents the intracellular accumulation of tetracycline (SB Levy, et al., Antimicrob Agents Chemotherapy 33 , 1373-1374 (1989), and b) ribosomal protection mediated by a cytoplasmic protein that interacts with the ribosome so that tetracycline no longer binds or inhibits the synthesis of the protein (AA Salyers, BS Speers and NB Shoemaker, Mol.Microbiol, 4: 151-156, 1990). The mechanism of the efflux of the resistance is coded by resistance determinants designated tetA-tetL. They are common in many Gram-negative bacteria (resistance to Class A and E genes), such as Enterobacteriaceae, Pseudomonas, Haemophilus and Aeromonas, and in Gram-positive bacteria (resistance of the Class K and L genes), such as Staphylococci, Bacillus and Streptococcus. The ribosomal resistance protection mechanism is encoded by resistance determinants TetM, N and O, common in Staphylococcus, Streptococcus, Campylobacter, Gardnerela, Haemofilus and Mycoplasma (AA Salyers, BS Speers and NB Shoemaker, Mol. Microbiol, 4 : 151-156 1990).

A particularly useful tetracycline compound is 7- (dimethylamino) -6-demethyl-6-deoxytetracycline, known as minocycline (see U.S. Patent No. 3,148,212, U.S. Patent No. RE 26,253 and U.S. Patent No. 3,226,436 discussed further ahead). However, the strains that harvest the tetB (efflux in Gram-negative bacteria) as a mechanism, but not the tetK (efflux in Staphylococci) are resistant to the metnocycline. Also, the strains that carry the tetM (ribosomal protection) are resistant to minocycline.

Duggar, U.S. Patent No. 2,482,055, describes the preparation of Aureomycin.RTM. by means of fermentation what has antibacterial activity. Growich et al., U.S. Patent No. 3,007,965, describes improvements in the preparation of the fermentation. Beereboom et al., U.S. Patent No. 3,043,875 describes tetracycline derivatives, Boothe et al., U.S. Patent No. 3,148,212, reissued as U.S. Patent No. RE 26,253, and Petisi et al., U.S. Patent No. 3,226,436, describe U.S. tetracycline which are useful for the treatment of bacterial infections. Blackwood et al., U.S. Patent No. 3,200,149 describes tetracycline derivatives that possess microbiological activity. Petisi et al., U.S. Patent No. 3,338,963 discloses tetracycline compounds having a broad spectrum antibacterial activity. Bitha et al., U.S. Patent No. 3,341, 585 discloses tetracycline compounds having broad spectrum antibacterial activity. Shu, U.S. Patent No. 3,360,557 describes 9-hydroxytetracyclines in which they have been found to possess antibacterial activity. Zambrano, U.S. Patent No. 3,360,561 describes a process for preparing 9-nitrotetracyclines. Martell et al., U.S. Patent No. 3,518,306 discloses tetracyclines which possess antibacterial activity in vivo.

In US Pat. No. 5,021, 407 a method is described for overcoming the resistance of tetracycline resistant bacteria. The method involves using a blocking agent composition in conjunction with a tetracycline-type antibiotic. The patent does not disclose novel tetracycline compounds that themselves have an activity against resistant organisms. Described in U.S. Patent No. 5,494,903 are the 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines which have a broad spectrum antibacterial activity.

In spite of the advances made to overcome the resistance of tetracycline resistant bacteria, there is a need for new and better antibiotics to solve the incremental incidence of resistance. The present invention provides such antibiotics.

In summary, none of the above patents teaches or suggests novel glycylcycline derivatives of this application.

BRIEF DESCRIPTION OF THE INVENTION This invention relates to substituted 9-aminocarbonyl glycylcycline derivatives represented by formula I having antibacterial activity; with methods to treat infectious diseases in humans and other animals when these new compounds are administered; with pharmaceutical preparations containing these compounds; and with novel processes for the production of compounds of the formula I.

In accordance with the present invention, compounds represented by the (i) where: A is a part or is R-, is selected from hydrogen, -OH, amino, -NR7R8, halogen, alkyl of 1 to 12 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amine, cyano , cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl having 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 atoms) carbon) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) - , CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, alkenyl of 2 to 12 atom carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of phenyl, heteroaryl, halogen, amine, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl and aryl of the N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino , alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, and alkynyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group halogen, amino, cyano, alkyl, hydroxyl, and alkoxy; R2 is selected from hydrogen, halogen, alkyl of 1 to 12 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 atoms carbon, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 independently selected substituents halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl , alkenyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of phenyl, heteroaryl, halogen, amino, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 atoms carbon) -aryl, wherein said aryl and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl , haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, and alkynyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the hal group Oxygen, amino, cyano, alkyl, hydroxyl, and alkoxy; R3 is a part of R9, R is selected from hydrogen, alkyl of 1 to 12 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms , phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N - (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen , nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl , alkenyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of phenyl, heteroaryl, halogen, amino, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl and aryl of N- ( alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl -C (O) -, CH 3 -C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, alkynyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the halogen, amino, cyano group, alkyl, hydroxyl, and alkoxy, aryl of 6, 10 or 14 carbon atoms said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, gave alkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, N- (alkyl of 1 to 12 carbon atoms) -aryl, said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, optionally substituted aralkyl of 7 to 16 carbon atoms, optionally substituted aroyl of 7 to 13 carbon atoms, SR3, optionally substituted heteroaryl and optionally substituted heteroarylcarbonyl; R5 is selected from alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl of 6, 10 or 14 atoms of carbon, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl, can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, optionally substituted aralkyl of 7 to 16 carbon atoms, aroyl, -CH2 (CO) OCH2aryl, said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryloxy and phenyl, optionally substituted alternyl of 2 to 12 carbon atoms, optionally substituted heteroaryl, optionally substituted 6, 10 or 14 carbon aryl, optionally substituted alkenyl of 2 to 12 carbon atoms, cycloalkyl of 3 to 6 ring atoms, aryl-CH = CH-, cycloalkyl-alkyl; and adamantyl; R6 is selected from hydrogen, alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N - (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen , nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl , and cycloalkyl of 3 to 6 carbon atoms; R7 and R8 are each independently H or alkyl of 1 to 12 carbon atoms or R7 and R8 when they are optionally taken together with the nitrogen atom to which each is bound form a 3 to 8 membered heterocyclyl ring; R9 is aralkyl of 7 to 16 carbon atoms optionally substituted or alkyl of 1 to 12 carbon atoms; R10 is H or alkyl of 1 to 12 carbon atoms; or a pharmaceutically acceptable salt thereof. One embodiment of this invention provides compounds of Formula I wherein R ^ is -NR7R8, R is hydrogen, R8 is methyl, ethyl, n-propyl, n-butyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl or , 1-dimethylethyl or a pharmaceutically acceptable salt thereof.

Another embodiment of this invention provides compounds of Formula I wherein Ri is -NR7R8, R7 is methyl or ethyl, R8 is methyl, ethyl, n-propyl, 1-methylethyl, n-propyl, 1-methylpropyl, or 2-methylpropyl. or a pharmaceutically acceptable salt thereof.

A further embodiment of this invention provides compounds of Formula I wherein R, is -NR7R8, R7 and R8 are taken together with the nitrogen atom to which each is attached form a 3- to 8-membered heterocyclyl ring or a pharmaceutically salt acceptable of these.

Another embodiment of this invention provides compounds of Formula I wherein R 2 is H or a pharmaceutically acceptable salt thereof.

Another embodiment of this invention supplies compounds of Formula I wherein A is a part Or a pharmaceutically acceptable salt thereof. An additional embodiment of this invention supplies compounds of the Formula 1 wherein A is absent or a pharmaceutically acceptable salt thereof.

An additional embodiment of this invention supplies compounds of Formula I wherein R3 is a part Or a pharmaceutically acceptable salt thereof. An additional embodiment of this invention supplies compounds of the Formula 1 where R3 is a part or a pharmaceutically acceptable salt thereof.

One embodiment of this invention provides compounds of Formula I wherein R3 is a part and R6 and R10 are H or a pharmaceutically acceptable salt thereof.

An additional embodiment of this invention supplies compounds of the Formula wherein R3 is a part and Re and Rio are H or one of these.

A further embodiment of this invention provides compounds of Formula I wherein R3 is R9 or a pharmaceutically acceptable salt thereof.

A further embodiment of this invention provides compounds of Formula I wherein A is a part of, R3 is a part of R5 is aryl of 6 carbon atoms or a pharmaceutically acceptable salt thereof.

An additional embodiment of this invention supplies compounds of Formula I wherein A is a part R3 is a part, R 4 is 1,1-dimethylethyl and R5 is aryl of 6 carbon atoms or a pharmaceutically acceptable salt thereof.

An additional embodiment of this invention supplies compounds of the Formula wherein: A is a part RT is -NR7R8; R2 is hydrogen; R3 is a part of R is selected from alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, and aryloxy wherein said aryl and aryloxy is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryloxy and phenyl; R5 is selected from alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl of 6, 10 or 14 atoms of carbon, and aryloxy wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl, can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl , alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, aralkyl of 7 to 16 carbon atoms optionally substituted carbon, aroyl, -CH2 (CO) OCH2aryl, said aryl is optional is substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryloxy and phenyl, optionally substituted aryl, aryl of 6, 10. or 14 optionally substituted carbon atoms, cycloalkyl of 3 to 6 ring atoms, aryl-CH = CH-, cycloalkyl-alkyl; and adamantyl; R6 is hydrogen; R and R8 are each independently H or alkyl of 1 to 12 carbon atoms; R9 is aralkyl of 7 to 16 carbon atoms optionally substituted or alkyl of 1 to 12 carbon atoms; or a pharmaceutically acceptable salt thereof.

Additional embodiments of the invention are the following specifically preferred compounds of formula I or their pharmaceutically acceptable salts: 2-methylpropanoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11 -tetrahydroxy-10, 12 dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl, 4-methoxybenzoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,8, 10a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 4-methylbenzoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 4-fluorobenzoate of (. { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-b¡s (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5, 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 4-methylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 4-methoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d-methylammon) -1, 8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 4-Fluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, Pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 2-methylpropanoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo phenylacetate -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, phenylacetate of ( { (2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11 -tetrahydroxy-10,12-dioxo-5,5a, 6, 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 4-tert-Butylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 1, 1'-biphenyl-4-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 3,5-dimethylbenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 1, 1 '-biphenyl-4-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 3,5-dimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 4-tert-butylbenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 1 - ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo acetate -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) ethyl, cyclohexanecarboxylate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, cyclohexanecarboxylate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 3,3-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 3,3-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 1 1-tetrahydroxy- 10,12-dioxo-5, 5a, 6, 6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 2, 2-dimethylbutanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10,12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110a, 11-tetrahydroxy-10,12 cyclopentylacetate dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl, adamantan-1-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, Cyclopentylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, adamantan-1-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 3,3-Dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4-tert-Butylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2,2-Dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-methylpropanoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) meth, Cyclopentanecarboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4-methylbenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (diametholamino) -1, 8,10a, 11-tetrahydroxy -10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, and 4-methoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl.

Additional embodiments of the invention are the following specifically preferred compounds of formula I or their pharmaceutically acceptable salts: 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Benzyl-2-oxoethyl (propyl) carbamate, 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amine} Ethyl -2-oxoethyl (propyl) carbamate, and 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Isobutyl-2-oxoethyl (propyl) carbamate.

Additional embodiments of the invention are the following specifically preferred compounds of formula I or their pharmaceutically acceptable salts thiophene-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, thiophene-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, thiophene-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, thiophene-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 2-furoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl, and 2-furoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl.

Additional embodiments of the invention are the following specifically preferred compounds of formula I or their pharmaceutically acceptable salts propionate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110a, 11-tetrahydroxy-10,12 dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahidrotetracen-2-yl] amino.}. -2-oxoethyl) (tert-butyl) am¡no] carbonyl.}. oxy) methyl ciciohexanocarboxilato of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo- 5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 3,5-dimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4-Fluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 3-methylbutanoate ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d¡metilam¡no) -1, 8, 10a, 11 -tetrahidroxi -10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , cyclopentylacetate ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahidroxi-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4- (trifluoromethyl) benzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, cyclopropanecarboxylate ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahidroxi-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, adamantan-1 -carboxylate ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahidroxi-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Butyl-2-oxoethyl (tert-butyl) carbamate, 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10.1 Oa , 12-octahydrotetracen-2-yl] amino} Isobutyl-2-oxoethyl (tert-butyl) carbamate, 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Methyl -2-oxoethyl (tert-butyl) carbamate, pentanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 3-cyclohexylpropanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, (4-fluorophenoxy) acetate ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-cyclohexyl acetate -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2,6-dimethylbenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo- 5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,15a, 11-tetrahydroxy-10, phenylacetate - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d-methylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 1, 1'-biphenyl-4-carboxylate from ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10,12-d-oxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl, 1-naphthoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-naphthoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 2,6-difluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-Fluorobenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10,12 -dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 2- ( trifluoromethyl) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 1, 1 '-biphenyl-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl, 2,4,6-trimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , 4-isopropoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 3,4,5-trimethoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy -10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , 3,5-dimethoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, (2E) -3-phenylprop-2-enoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a , 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl, [3,5- bis (trifluoromethyl) phenyl] acetate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8] 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl, 4- (heptyloxy) benzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl, 2- (2-phenylethyl) benzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11- tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 4- (dodecyloxy) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4- (acetylamino) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, anthracene-9-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4-benzoyl benzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-b¡s (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, and diphenylacetate ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl, yl) oxy) methyl.

Additional embodiments of the invention are the following specifically preferred compounds of formula I or their pharmaceutically acceptable salts 4-Fluorobenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a , 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, 3,5-dimethylbenzoate of [( { [(5aR, 6aSJS, 10aS) -9- ( aminocarbonyl) -4J-bis (dimethylamino) -1,8,8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino. carbonyl) oxy] methyl, pivalate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6 , 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, 3,3-Dimethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-b¡s (d-methylamino) -1,8,8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} carbonyl) oxy] methyl, 2,2-dimethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammono) -1,8,11a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, 2-ethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,11a, 11-tetrahydroxy-10,12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino] carbonyl) oxy] methyl, thiophene-2-carboxylate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,11a, 11-tetrahydroxy-10,12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, Cyclopentylacetate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,11a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6 , 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, and 4-tert-Butylbenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,11a, 11-tetrahydroxy-10,12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl.

Additional embodiments of the invention are the following specifically preferred compounds of formula I or their pharmaceutically acceptable salts 1 H-indole-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11- tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, nicotinate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, isonicotinate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4-pyrrolidin-1-ylbenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , 3-Methyl-1-benzofuran-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a , 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl, 1 - . 1-methyl-1 H-indole-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl, quinolin-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy -10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , 1-Benzofuran-2-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , and ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl-1-methyl-1 H-pyrrole-2-carboxylate.

Additional embodiments of the invention are the following specifically preferred compounds of formula I or their pharmaceutically acceptable salts 2-. { [(7S, 10aR) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6a, 7, 10, 10a, 12-Octahydrotetracen-2-yl] amino} (5-Methyl-2-oxo-1, 3-dioxol-4-yl) methyl -2-oxoethyl (propyl) carbamate, 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12 -octahydrotetracen-2-yl] amino} (5-Methyl-2-oxo-1,3-dioxol-4-yl) methyl-2-oxoethyl (butyl) carbamate, 2-. { [(7R, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12- octahydrotetracen-2-yl] amino} -2-oxoethyl (propyl) carbamate, [5- (4-methoxyphenyl) -2-oxo-1,3-dioxol-4-yl] methyl 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12- octahydrotetracen-2-yl] amino} (2-Oxo-5-phenyl-1,3-dioxol-4-yl) -2-oxoethyl (propyl) carbamate, 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino} 2-Oxo-5-phenyl-1,3-dioxol-4-yl) -2-oxoethyl (butyl) carbamate and 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino} [5- (4-Methoxyphenyl) -2-oxo-1,3-dioxol-4-yl] methyl] -2-oxoethyl (butyl) carbamate.

A further embodiment of this invention are the compounds represented by Formula (II): (II) where: R 4 is selected from hydrogen, alkyl of 1 to 12 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms , phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N - (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen , nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl , alkenyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of phenyl, heteroaryl, halogen, amino, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl and aryl of N- ( alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl -C (O) -, CH 3 -C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, alkynyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the halogen, amino, cyano group, alkyl, hydroxyl, and alkoxy, aryl of 6, 10 or 14 carbon atoms said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, d ialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, N- (alkyl of 1 to 12 carbon atoms) -aryl, said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, optionally substituted aralkyl of 7 to 16 carbon atoms, optionally substituted aroyl of 7 to 13 carbon atoms, SR3, optionally substituted heteroaryl and optionally substituted heteroarylcarbonyl; R5 is selected from alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl of 6, 10 or 14 atoms of carbon, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl, can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, optionally substituted aralkyl of 7 to 16 carbon atoms, aroyl, -CH2 (CO) OCH2aryl, said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryloxy and phenyl, optionally substituted alternyl of 2 to 12 carbon atoms, optionally substituted heteroaryl, optionally substituted aryl of 6, 10 or 14 carbon atoms, optionally substituted alkenyl of 2 to 12 carbon atoms, cycloalkyl of 3 to 6 ring atoms, aryl-CH = CH-, cycloalkyl-alkyl; and adamantyl; R6 is selected from hydrogen, alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, and cycloalkyl of 3 to 6 carbon atoms; R10 is H or alkyl of 1 to 12 carbon atoms; Q is -ORn, Cl, Br or l; Rn is H, benzyl optionally substituted with nitro or a part of the formula R12 is alkyl of 1 to 6 carbon atoms.

The compounds having the Formula II are useful as chemical intermediates for making the compounds having Formula I and their pharmaceutically acceptable salts wherein A: is a part and R3 is a part Where R and R5 are as defined above One embodiment of the invention provides compounds of Formula II wherein R is t-butyl, R5 is alkyl of 1 to 6 carbon atoms, and Rn is benzyl optionally substituted with nitro.

Another embodiment of the invention supplies compounds of Formula II wherein R 4 is alkyl of 1 to 6 carbon atoms, R 5 is optionally substituted phenyl and R n is benzyl optionally substituted with nitro.

One embodiment of the invention provides compounds of Formula II wherein R5 is alkyl of 1 to 6 carbon atoms, R is t-butyl and Rn is H.

A further embodiment of the invention provides compounds of Formula II wherein R5 is alkyl of 1 to 6 carbon atoms, R4 is t-butyl, Q is -ORn, Rn is and R 2 is alkyl of 1 to 6 carbon atoms.

Another embodiment of the invention supplies compounds of Formula II wherein R6 and R10 are H.

Additional embodiments of the invention provide the following specifically preferred compounds of Formula II or their pharmaceutically acceptable salts. 4-Tert-butylbenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 2,2-dimethylbutanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-methylpropanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, Cyclopentanecarboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, 4-methylbenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, heptanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl propionate, cyclohexanecarboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, 3,5-dimethylbenzoate of ( { [[2- (benzyloxy) -2-oxoetyl] (tert-butyl) amino] carbonyl.} Oxy] methyl, 4-Fluorobenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 3-methylbutanoate ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, N- (Tert-butyl) -N- ( { [(Cyclopentylacetyl) oxy] methoxy.} Carbonyl) benzyl glycinate, 4- (Trifluoromethyl) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, Cyclopropanecarboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy] methyl, adamantan-1-carboxylate of ( { [[2- (benzyloxy)] -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, pentanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, Cyclobutanecarboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl 3-cyclohexylpropanoate, N- (Tert-butyl) -N - [( { [(4-fluorophenoxy) acetyl] oxy} methoxy) carbonyl] benzyl glycinate, N- (Tert-butyl) -N- ( { [(Cyclohexylacetyl) oxy] methoxy.} Carbonyl) benzyl glycinate, 2,6-dimethylbenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, N- (Tert-butyl) -N- ( { [(Phenylacetyl) oxy] methoxy.} Carbonyl) benzyl glycinate, ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy] methyl pivalate 1-Benzofuran-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 1 - . 1 - . 1 - . 1-methyl-1H-pyrrole-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 1,1 '-biphenyl -4- ( { [[2- (Benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl carboxylate, 4-methoxybenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 1 H -indole-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, N- (Tert-butyl) -N- ( { [(Diphenylacetyl) oxy] methoxy, carbonyl) benzyl glycinate, 1-naphthoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl}. Oxy) methyl, 2-naphthoate ( { [[2- (benzyloxy) - 2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 1-methyl-1 H-indole-3-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, Quinoline-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, nicotinate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, isonicotinate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, 2,6-difluorobenzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2-Fluorobenzoate 2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2- (Trifluoromethyl) benzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 4- (1 H-pyrrol-1-yl) benzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 1, 1 '-biphenyl-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2,4,6-trimethylbenzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 4-isopropoxybenzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 3,4,5-trimethoxybenzoate of 2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2- (Benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl 3,5-dimethoxybenzoate} oxy) methyl, 3-phenyl-acrylic acid (benzyloxycarbonylmethyl-tert-butyl-carbamoyloxy) -methyl ester, 3-Methyl-1-benzofuran-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, N-. { [( { [3,5-bis (trifluoromethyl) phenyl] acetyl} oxy) methoxy] carbonyl} -N- (tert-butyl) benzyl glycinate, 4- (Hexytyloxy) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2- (2-phenylethyl) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 4- (dodecyloxy) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 4- (Acetylamino) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, anthracene-9-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl and 4-benzoyl benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl.

Additional embodiments of the invention are the following specifically preferred compounds of Formula II or their pharmaceutically acceptable salts.

N- (tert-butyl) -N- ( { [(4-tert-Butylbenzoyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N-. { [(isobutyryloxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N- ( { [(Cyclopentylcarbonyl) oxy] methoxy.} Carbonyl) glycine, N- (Tert-butyl) -N- ( { [(4-methylbenzoyl) oxy] methoxy.} Carboriyl) glycine, N- (tert-butyl) -N-. { [(heptanoyloxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N-. { [(propionyloxy) methoxy] carbonyl} glycine, Nr (tert-butyl) -N- ( { [(Cyclohexylcarbonyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [(3,5-dimethylbenzoyl) oxy] ] methoxy.} carbonyl) glycine, N- (tert-butyl) -N- ( { [(4-fluorobenzoyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [(3-Methylbutanoyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N- ( { [(Cyclopentylacetyl) oxy] methoxy.} Carbonyl) glycine, N- ( Tert-butyl) -N - [( { [4- (trifluoromethyl) benzoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N- ( { [(Cyclopropylcarbonyl) oxy] methoxy} carbonyl) glycine, N- (. {[[(1-adamantylcarbonyl) oxy] methoxy} carbonyl) -N - (tert-butyl) glycine, N- (tert-butyl) -N-. { [(pentanoyloxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N- (. {[[(cyclobutylcarbonyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [(3-cyclohexylpropanoyl) oxy] methoxy.} carbonyl) glycine, N- (Tert-butyl) -N - [( { [(4-fluorophenoxy) acetyl] oxy} methoxy) carbonyl] glycine N- (tert-butyl) -N- ( { [(Cyclohexylacetyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N- ( { [(2,6-dimethylbenzoyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) - N- ( { [[Phenylacetyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N- (. {[[(2,2-dimethylpropanoyl) oxy] methoxy} carbonyl) glycine, N- ( { [(1-Benzofuran-2-ylcarbonyl) oxy] methoxy, carbonyl) -N- (tert-butyl) glycine, N- (Tert-butyl) -N - [( { [(1-methyl-1 H -pyrrol-2-yl) carbonyl] oxy} methoxy) carbonyl] glycine, N- ( { [( 1,1 '-biphenyl-4-ylcarbonyl) oxy] methoxy, carbonyl) -N- (tert-butyl) glycine, N- (tert -butyl) -N- ( { [(4-methoxybenzoyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N- ( { [(1 H-indole -2-ylcarbonyl) oxy] methoxy.} Carbonyl) glycine, N- (Tert-butyl) -N- ( { [(Diphenylacetyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N-. { [(1-naphthoxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N-. { [(2-naphthoxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N - [( { [(1-methyl-1 H-indol-3-yl) carbonyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N- ( { [(Quinolin-2-ylcarbonyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N- ( { [(Pyridin- 3-ylcarbonyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N-. { [(isonicotinoyloxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N- (. {[[(2,6-difluorobenzoyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [( 2-fluorobenzoyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N - [( { [2- (trifluoromethyl) benzoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N- ( { [(4-pyrrolidin-1-ylbenzoyl) oxy] methoxy} carbonyl) glycine, N- ( { [(1,1'-biphenyl-2 -carbonyl) oxy] methoxy, carbonyl) -N- (tert-butyl) glycine, N- (tert-butyl) -N- ( { [(Mesitylcarbonyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [(4-isopropoxybenzoyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N- ( { [(3,4,5-trimethoxybenzoyl) oxy] methoxy.} carbonyl) glycine, N- (Tert-butyl) -N- ( { [(3,5-dimethoxybenzoyl) oxy] methoxy.} Carbonyl) glycine, N- (Tert-butyl) -N - [( { [(2E) -3-phenylprop-2-enoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N - [( { [(3-methyl-1-benzofuran-2-yl) carbonyl] oxy} methoxy) carbonyl] glycine, N-. { [( { [3,5-bis (trifluoromethyl) phenyl] acetyl} oxy) methoxy] carbonyl} -N- (tert-butyl) glycine, N- (Tert-butyl) -N - [( { [4- (heptyloxy) benzoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N - [( { [2- (2-phenylethyl) benzoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N - [( { [4- (dodecyloxy) benzoyl] oxy} methoxy) carbonyl] glycine, N - [( { [4- (acetylamino) benzoyl] oxy} methoxy) carbonyl] -N- (tert-butyl) glycine, N- ( { [(9-anthrylcarbonyl) oxy] methoxy.} Carbonyl) -N- (tert-butyl) glycine and N- ( { [(4-benzoylbenzoyl) oxy] methoxy.} Carbonyl) -N- (tert-butyl) glycine A further embodiment of the invention is the following specifically preferred compound of Formula II or its pharmaceutically acceptable salts.

[Tert-butyl- (2-isobutoxycarbonyloxy-2-oxo-ethyl) -carbamoyloxy) -methyl ester of 3,3-Dimethyl-butyric acid.

DEFINITIONS For the compounds of the invention defined above and referred to herein as amoenes, unless otherwise specified, the following terms are defined: The term "alkyl" means a linear or branched alkyl portion of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 atoms carbon, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 independently selected substituents halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl . In some embodiments of the invention alkyl is a portion of 1 to 6 carbon atoms. In other embodiments of the invention alkyl is a portion of 1 to 3 carbon atoms. In other embodiments of the invention alkyl is 1,1-dimethylethyl also called t-butyl. In some embodiments of the invention when the alkyl is a methyl group wherein the optional substitution is two independent phenyl rings. Non-limiting examples of alkyl are methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl and 1, 1-dimethylethyl.

The term "alkenyl" means a straight or branched carbon chain of 2 to 12 carbon atoms having at least one unsaturation site optionally substituted independently with 1 to 3 substituents selected from the group optionally substituted independently with 1 to 3 substituents selected from the phenyl group , heteroaryl, halogen, amino, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl and aryl of N- (alkyl of 1 to 12 atoms carbon) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) - , CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl. In some embodiments of the invention, alkenyl is a vinyl portion of -CH 2 = CH-.

As used herein the term "alkoxy" refers to alkyl-O- wherein alkyl is as defined above. Non-limiting examples include: methoxy and ethoxy.

As used herein the term "aryl" means an aromatic portion having 6, 10 or 14 carbon atoms preferably 6 to 10 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl , haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH 3 -C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl. In particular, aryl is phenyl or naphthyl optionally substituted with 1 to 3 substituents.

The term aralkyl as used herein of 7 to 16 carbon atoms means an alkyl substituted with an aryl group in which the aryl and alkyl group are as defined above. Non-limiting examples of the aralkyl groups include benzyl and phenethyl and the like.

Perhaloalkyl as used herein means an alkyl portion of 1 to 6 carbon atoms in which each hydrogen atom is replaced with a halogen atom, an illustrative example is trifluoromethyl.

Phenyl as used herein refers to a 6-membered aromatic carbon ring.

As used herein the term "alkynyl" includes both linear chains and branched portions containing 2 to 12 carbon atoms having at least one carbon-to-carbon triple bond optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, amino, cyano, alkyl of 1 to 12 carbon atoms, hydroxyl, and alkoxy of 1 to 12 carbon atoms.

As used herein the term halogen or halo means F, Cl, Br or I.

As used herein, the term "cycloalkyl" means a saturated monocyclic ring having from 3 to 6 carbon atoms. Examples of cycloalkyl rings include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. In one embodiment of the invention cycloalkyl is a portion of 5 or 6 carbon atoms.

The term "aroyl" means an aryl-C (O) - group in which the aryl group is as previously defined. Non-limiting examples include benzoyl and naphthoyl.

The term "heteroaryl" means a monocyclic, heterocyclic aromatic ring of to 6 ring atoms containing 1 to 4 heteroatoms independently selected from O, N and S or bicyclic aromatic rings of 8 to 20 ring atoms containing 1 to 4 heteroatoms independently selected from O, N and S. Heteroaryl rings may be optionally substituted with 1 to 3 substituents independently selected from the group alkyl, halogen, cyano, nitro, hydroxy, amino, alkylamino, dialkylamino, alkoxy, aryloxy, -CH2OCOCH3 and carboxy. Non-limiting heteroaryl moieties optionally substituted include: furanyl, benzofuranyl, benzothienyl, thienyl, pyridinyl, quinolinyl, tetrazolyl, imidazole, thiazolyl and the like.

Where the terms are used in combination, the definition for each individual part of the combination applies unless it is defined otherwise. For example, aralkyl refers to an aryl group, and alkyl refers to the alkyl group as defined above. Also, aryloxy refers to an aryl- group.

The term "heteroarylcarbonyl" means a heteroaryl-C (O) - group in which the heteroaryl group is as previously defined.

The term "heterocyclyl" as used herein represents a saturated ring of 3 to 8 ring atoms containing 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur. In some embodiments of the invention, a saturated ring of 5 or 6 ring atoms is preferred. Representative examples are pyrrolidyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, aziridinyl, tetrahydrofuranyl and the like.

The term "alkylheterocyclyl" means an alkyl-heterocyclyl group in which the alkyl and heterocyclyl group are independently as defined above. Non-limiting examples of alkylheterocyclyl groups include portions of the formulas: Some of the compounds of Formula (I) may also exist in their tautomeric forms. Such forms, although not explicitly indicated in the above formula, are intended to be included within the scope of the present invention. For example, the compounds of Formula (I) that exist as tautomers are represented below: The present invention according to the above provides a pharmaceutical composition comprising a compound of this invention in combination or association with a pharmaceutically acceptable carrier. In particular, the present invention provides a pharmaceutical composition comprising an effective amount of a compound of this invention and a pharmaceutically acceptable carrier.

Proton sponge is [1,8-bis (dimethylamino) naphthalene, N, N, N ', N'-tetramethyl-1,8-naphthalene diamine].

The alkali metal carbonate includes lithium, potassium and sodium carbonate.

DMPU is 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1 H) -pyrimidinone.

N-butyl-glycylcycline (N-bu-glycyl) is N-propyl-glycylcycline (N-prop-glycyl) is DESCRIPTION OF THE PREFERRED MODALITIES The compounds of this invention can be prepared according to the following schemes: (1) from commercially available starting materials or: (2) from known starting materials that can be prepared as described in the literature procedures or : (3) of new intermediates described in the schemes and experimental procedures.

The synthesis of the acyloxy intermediate 8 is shown in scheme 1. The reaction of the amine R 4 NH 2, preferably t-butylamine with the ester 1 supplies the substituted amino ester 2. The preparation of the intermediate 4 is carried out using the proton sponge as a base to effect the acylation of the amino ester 2 substituted with chloromethyl chloroformate 3. The treatment of intermediate 4 with the tetrabutylammonium salt of carboxylic acids gives the benzyl protected by the acyloxy intermediate 6. The benzyl protection group is removed by catalytic removal to give carboxylic acid 7 which is activated to an anhydride mixed with chloroformate CICO2R12 wherein R? 2 is alkyl of 1 to 6 carbon atoms, for example, iso-butyl chloroformate to give the intermediate of acyloxy carbamate 8. In a alternate route, silyl esters can be optionally used in place of the benzyl ester of intermediate 4, treat with the appropriate carboxylic acid This can be activated by the release of the silyl ester with tetrabutylammonium chloride or magnesium bromide to provide carboxylic acid 7. Optionally, the carboxylic acid 7 can be activated by the use of coupling agents not limited to di-t-butyl bicarbonate. (Boc2O); for example, benzotriazol-1-yl-oxy-tris- (dimethylamino) -hexaphluorophosphate phosphonium (also known as asBop); benzothiazol-1-yl-oxy-tris-pyrrolidino-phosphono hexafluorophosphate (also known as PyBop); O-benzotriazole-N.N.N'.N'-tetramethyl-uronium-hexafluoro-phosphate (HBTU); Bromotris-pirolidino-phosphonium hexafluorophosphate; 2-Chloro-N-methylpyridinium iodide (CMPI); dicyclohexylcarbodiimide (DCC); 1,3-diisopropylcarbodiimide (DIC); 1- (3-dimethylaminopropyl) -3-ethyl-carbodiimide hydrochloride (EDC); or Carbonyl diimidazole.

C. H. r. «Or H; • ^ - ° - ... ° - N • .. m. es8- a ce 3-sto- .'CHjU .. O R ^ .r OR CIT.O.R,. 7 Scheme 2 as shown in scheme 2, the reaction of activated acyloxycarbamate intermediate 8 with 7,8-disubstituted-9-aminotetracycline 9 in the presence of triethylamine and DMPU gives acyloxycarbamate 10.

NlCH-ih OH 9 tfíßtllamlna. DMPU tem? ! creature ambiento, 1hr M4CH3) 5 R "or R- 'OM = 0, O O N NH,' 1 '" O O OH O O ^ O 10 Additional acyloxy carbamate compounds can be synthesized by routes shown in Schemes 3 and 4. Treatment of chloromethyl chloroformate 3 with ethanethiol in the presence of triethylamine (TEA) gives carbonothioate 11. Compound 12 is prepared by reacting carbothioate 11 with tetrabutylammonium salt of carboxylic acid 5 in tetrahydrofuran. Chlorination of compound 12 with sulfuryl chloride in the presence of catalytic amount of boron trifluoroetherate provides an intermediate of 13 (using the methods described in M. Folkmann and F.J. Lund, Synthesis, December 1990, 1159-1166).

Scheme 3 12 S02CI2, BF3. Rs ^ < .CI - Y / \ Y Et20 / CH2Cl2 ° Re R10 ° 13 As seen further in Scheme 4, the acyloxycarbamates 16 and 17 wherein R4 is preferably n-butyl or n-propyl are synthesized by the treatment of 14 or 15 wherein R 4 is preferably n-butyl or n-propyl with the intermediate of chlorine 13 to give acyloxycarbamates 16 and 17 respectively.

Scheme 4 H > N, CH * HN. _. i .1 NH, "OH OR OH!" OR 1 R4 = rv? l? J R. O ** W Rs O O N N 16 R, < »N.BuU 17, = rt- DTOBli As shown in scheme 5, the glycylcycline carbamates wherein R is preferably propyl 18 can also be prepared by means of the reaction with the chlorine intermediate 19 in the presence of an alkali metal carbonate preferably sodium carbonate, and DMPU in acetonitrile to provide the preferred compounds (21 and 22). Scheme 5 18 '19 i.Pt 21 22 Scheme 6 9. O O tnailamma DMPU, at room temperature, 1 hr o - s or R «? < "13 2. 3 As shown in scheme 6, the reaction of the intermediate of chlorine 13 with 7,8-disubstituted-9-aminotetracycline 9 in the presence of triethylamine and DMPU gives carbamate 23.

As further shown in Scheme 7, the compounds of Formula I can be generally prepared by removing the benzyl protecting group from the acyl-protected benzylated intermediate 24 to carboxylic acid 25 which is activated to a mixed anhydride. with a CICO2R? 2 chloroformate wherein R12 is alkyl of 1 to 6 carbon atoms, for example isobutyl chloroformate to give the acyloxycarbamate intermediate 26. Additional reaction of 7,8-disubstituted-9-aminotetracycline 9 with acyloxycarbamate mixed with the anhydride intermediate 26 in the presence of triethylamine and DMPU provides compounds of the Formula (I).

Scheme 7 ,, 0 ÍS Cl tnetitamina DMPU. r x T tempertura amD silly, 1 r R. "13 2. 3 The reactions are carried out in a solvent appropriate to the reagents and materials used and suitable for the transformation to take place. It is understood by those versed in the technique of organic synthesis that the various functionalities present in the molecule must be consistent with the proposed chemical transformations. This may require merging to order the synthetic stages, the protection groups and, if required, the conditions of check out. The substituents on the starting materials may be incompatible with some of the reaction conditions. Such restrictions on substituents that are compatible with the reaction conditions will be apparent to those skilled in the art.

Some of the compounds of the schemes described here above have centers of asymmetry. The compounds may, therefore, exist in at least two frequently more stereoisomeric forms. The present invention involves all stereoisomers of the compounds are free of other stereoisomers or mixed with other stereoisomers in any ratio and therefore include, for example, racemic mixture of enantiomers as well as the diastereomeric mixture of isomers. The absolute configuration of any compound can be determined by conventional X-ray crystallography.

The compounds of the invention can be obtained as metal complexes such as aluminum, calcium, iron, magnesium, manganese and complex salts; inorganic and organic salts and corresponding Mannich base adducts using methods known to those skilled in the art (Richard O Larock, Comprehensive Organic Transformations, VCH Publishers, 411-415, 1989). Preferably, the compounds of the invention are obtained as inorganic salts such as hydrochloric, hydrobromic, hydric, phosphoric, nitric or sulfate salts; or organic salts such as acetate, benzoate, citrate, cysteine or other amino acids fumarate, glycolate, maleate, succinate, tartrate alkylsulphonate or arylsulfonate. In all cases, the formation of salts occurs with the group C (4) -dimethylamino. The salts are preferred for oral and parenteral administration.

Standard Pharmacological Test Procedures Methods for antibacterial evaluation in vitro.

Minimum inhibitory concentration (MIC) Antimicrobial susceptibility test. The in vitro activities of the antibiotics are determined by the broth microdilution method as recommended by the National Laboratory Standards Committee (NCCLS) (1). The Mueller-Hinton II (MHBII) broth (BBL Cockeysville, MD) is the medium used in the assay procedures. Microtiter plates containing the serial dilutions of each antimicrobial agent are inoculated with each organism to provide the appropriate density (105 CFU / ml) in a final volume of 100 μl. the plates are incubated for 18 to 22 hours at 75 ° C in ambient air. The minimum inhibitory concentration for all isolates is defined as the lowest concentration of antimicrobial agent that completely inhibits the growth of the organism as detected by the unaided eye.

Methods for Antimicrobial Dilution Susceptibility Tests for Bacteria that grow aerobically; Approved Standards M7-A5, Vol. 20. National Committee for Clinical Laboratory Standards, Wayne, PA.

Standard Pharmacological Test Procedures Tables I to Xlll representative compounds RE.REFLIST of Formula I are presented which were evaluated against a panel of 40 Gram-positive and Gram-negative bacterial strains by pre-incubation in water, mouse serum or human serum. Representative compounds were first incubated in mouse serum for 1 hour prior to the in vitro assay against a panel of selected Gram-positive and Gram-negative bacterial strains. All compounds were also pre-incubated in water for 1 hour before the tests as controls. The representative compounds of Formula I were incubated in human serum before the MIC determination. Representative compounds of Formula I that demonstrated an in vivo activity were additionally subjected to various stability tests. A summary of the in vitro test blocks in representative examples of Formula I are shown in Table 1. The in vitro expanded data of selected examples (87 and 27) are shown in Tables 2 and 5 respectively. The MICs of the representative examples of Formula I are given in Tables III and IV. Table VI shows the in vitro and live activity of representative examples of the compounds of Formula I against Staphilococcus. Aureus Smith in mice. Table 7 shows the in vivo (oral, iv) and in vitro (MIC) activity of representative examples of compounds of Formula I against E. coli in mice. Table 8 shows the in vivo (oral, iv) and in vitro (MIC) activity of representative examples of compounds of Formula I, against Staphylococcus aureus Smith in mice. Table 9 shows the in vitro activity (MIC) of representative examples of the compounds of Formula I against E. Coli in human serum and water and also against Staphylococcus in human serum and water.

Table 10 presents a single in vivo oral dose (SOD) and single intravenous dose (SIV) and its ED50 data for representative examples of compounds of Formula I against Staphylococcus. Smith and E. Coli # 311 in mammals.

TABLE I ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED FROM FORMULA GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Serum Mouse Water Water Water Mouse Water Water Example 1 Example 1 Example 2 Example 2 Example 3 Example 3 Example 4 Example 4 E. coli GC 2236 1 16 4 32 1 > 64 64 10 E. coli GC 2231 1 64 4 64 2 > 64 64 E. coli GC 2235 0.50 16 2 64 1 > 64 64 E. coli GC 2232 0.50 16 2 64 2 > 64 64 E. coli GC 2233 1 16 64 1 > 64 64 E. coli GC 2234 0.50 16 64 1 > 64 64 15 E. coli GC 2270 0.50 16 64 1 > 64 64 E. coli GC 2271 0.50 16 64 1 > 64 0.50 64 E. coli GC 2272 1 16 64 1 > 64 1 64 E. coli GC 4559 1 32 64 2 > 64 2 > 64 E. coli GC 4560 0.50 2 0.25 4 0.50 32 0.25 8 E. coli GC 6465 8 > 64 8 64 8 > 64 4 > 64 E. coli GC 3226 1 32 4 64 2 > 64 2 64 E. coli GC 2203 0.50 16 2 64 1 > 64 1 64 E. coli GC 1073 1 32 4 64 2 > 64 1 > 64 Salmonella spp. GC 235 1 64 8 > 64 2 > 64 2 > 64 TABLE I (Cont) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL REPLACED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum of 10 mouse Water mouse Water mouse Water water Water Example 1 Example 1 Example 2 Example 2 Example 3 Example 3 Example 4 Example 4 Salmonella spp. GC 566 2 64 8 > 64 4 > 64 4 > 64 S. cholerasius GC 1355 8 > 64 > 64 > 64 16 > 64 8 > 64 S. typhimurium GC 2172 4 > 64 > 64 > 64 8 > 64 4 > 64 P. aeruginosa GC 2214 32 > 64 > 64 > 64 32 > 64 32 > 64 twenty S. aureus GC 1131 1 4 2 4 2 4 1 4 S. aureus GC 6466 1 1 1 2 1 4 0.50 2 S. aureus GC 6467 4 4 4 8 4 32 2 8 S. aureus GC 1079 2 4 8 8 2 32 1 4 S. aureus GC 4536 2 4 2 4 2 4 1 4 S. aureus GC 2216 1 4 2 4 1 4 0.50 4 S. aureus GC 6335 2 4 8 8 2 8 1 4 S. aureus GC 6469 2 8 2 4 4 32 2 16 TABLE I (Cont) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL REPLACED OF FORMULA GLICILCLYCINES CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Serum Mouse Water Mouse Water Mouse AgL Example 1 Example 1 Example 2 Example 2 Example 3 Example 3 Example 4 Example S. epidermidis GC 4935 2 8 8 8 4 8 2 4 E. faecalis GC 4555 1 4 2 4 1 8 1 8 E. faecalis GC 2265 1 4 4 8 2 32 2 8 E. faecalis GC 2267 2 8 4 4 2 32 1 8 E. faecalis GC 2242 1 4 4 4 2 16 1 4 E. faecium GC 4556 1 4 4 8 2 16 1 4 E. faecium GC 2243 1 2 1 4 1 4 0.50 2 S. pneumoniae * GC 4465 0.50 0.25 0.50 0.25 0.12 0.25 < 0.06 0.12 S. pneumoniae + GC 4465 2 2 2 4 1 2 2 4 S. pyogenes GC 4563 0.25 0.50 0.25 0.25 0.12 0.25 0.12 0.25 S. agalactiae GC 4564 0.50 1 2 2 2 0.25 0.50 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE II ANTIBACTERIAL ACTIVITY OF DERIVATIVES OF GLICILCICLINES SUBSTITUTED WITH 9-AMINOCHARBONYL OF FORMULA I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum of mouse serum Water mouse Water Serum of mouse Water Serum of mouse Example 5 Example 5 Example 6 Example 6 Example 7 Example 7 Example 8 E. coli GC 2236 2 16 2 8 0.25 2 1 E. coli GC 2231 2 64 2 64 2 16 2 E. coli GC 2235 1 16 1 8 0.50 4 E. coli GC 2232 2 32 2 32 0.50 4 E. coli GC 2233 2 32 2 16 0.50 4 15 E. coli GC 2234 1 32 1 16 1 4 E. coli GC 2270 1 16 1 8 0.50 4 E. coli GC 2271 1 16 1 8 0.50 4 E. coli GC 2272 1 32 1 16 0.50 4 E. coli GC 4559 2 32 2 16 1 8 20 E. coli GC 4560 0.50 4 0.25 2 0.25 0.50 0.50 E. coli GC 6465 8 > 64 4 > 64 16 > 64 8 E. coli GC 3226 2 32 2 16 0.50 8 2 E. coli GC 2203 1 32 2 16 0.50 4 1 E. coli GC 1073 2 32 2 16 0.50 8 1 Salmonella spp. GC 235 2 32 2 16 2 8 4 Salmonella spp. GC 566 4 64 4 64 1 16 4 TABLE II (Contd) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Mouse Water Example 5 Example 5 Example 6 Example 6 Example 7 Example 7 Example 8 Example 8 S. cholerasius GC 1355 16 > 64 16 > 64 16 > 64 32 > 64 S. typhimurium GC 2172 8 > 64 8 > 64 4 > 64 8 > 64 P. aeruginosa GC 2214 32 > 64 32 > 64 16 > 64 32 > 64 S. aureus GC 1131 0.50 1 0.50 1 1 1 1 2 S. aureus GC 6466 0.25 0.50 0.25 1 0.50 0.50 0.50 1 S. aureus GC 6467 2 4 2 4 4 4 4 8 S. aureus GC 1079 2 2 2 4 1 4 2 4 S. aureus GC 4536 1 1 0.50 2 1 1 0.50 2 S. aureus GC 2216 0.50 2 0.50 2 0.50 0.50 0.50 4 S. aureus GC 6335 0.50 1 0.50 2 1 1 1 4 TABLE II (Contd) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULA GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Mouse Water Water Water Water Example 5 Example 5 Example 6 Example 6 Example 7 Example 7 Example 8 Example 8 E. faecalis GC 4555 1 4 1 4 0.50 1 0.50 8 E. faecalis GC 2265 2 4 2 4 1 2 2 8 E. faecalis GC 2267 2 4 1 4 1 2 2 8 E. faecalis GC 2242 1 2 1 2 1 1 1 4 E. faecium GC 4556 1 2 1 2 0.50 1 1 4 E. faecium GC 2243 0.50 1 0.50 2 0.25 0.12 0.25 2 S. pneumoniae * GC 4465 < 0.06 0.12 0.12 0.25 0.25 0.12 < 0.06 0.25 S. pneumoniae + GC 4465 2 4 2 2 4 2 1 4 S. pyogenes GC 4563 0.12 0.25 0.25 0.25 0.25 0.25 0.12 0.50 S. agalactiae GC 4564 0.50 0.50 0.50 0.50 0.25 0.50 0.25 0.50 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE III ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULAR GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum serum of serum of mouse serum Water mouse Water mouse Water water Water Example Example Example Example 9 Example 9 Example 10 10 Example 11 11 Example 12 12 E. coli GC 2236 1 8 0.50 8 0.50 8 1 16 E. coli GC 2231 2 64 2 32 2 64 2 64 E. coli GC 2235 0.50 4 0.25 4 0.25 4 1 16 E. coli GC 2232 1 8 0.50 8 1 16 0.50 32 E. coli GC 2233 0.50 4 0.50 8 0.25 8 1 32 E. coli GC 2234 0.50 8 0.50 8 0.50 16 1 16 E. coli GC 2270 0.50 4 0.50 8 0.50 8 0.50 32 E. coli GC 2271 0.50 8 0.25 8 0.25 4 0.50 16 E. coli GC 2272 0.50 8 0.50 8 0.25 4 1 16 E. coli GC 4559 1 8 0.50 16 0.50 32 1 64 E. coli GC 4560 0.25 1 0.12 0.12 0.12 0.12 0.25 1 E. coli GC 6465 4 > 64 8 > 64 8 > 64 8 > 64 E. coli GC 3226 2 16 0.50 16 0.50 > 64 2 64 E. coli GC 2203 0.50 4 0.50 8 0.25 16 1 32 E. coli GC 1073 1 8 0.50 16 0.50 16 1 64 Salmonella spp. GC 235 1 8 0.50 32 0.50 64 1 64 Salmonella spp. GC 566 2 64 2 > 64 2 > 64 4 > 64 S. cholerasius GC 1355 64 > 64 16 > 64 32 > 64 16 > 64 TABLE III (Contd) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL REPLACED OF FORMULAR GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Mouse Water Example 9 Example 9 Example 10 Example 10 Example 11 Example 11 Example 12 Example 12 S. typhimurium GC 2172 8 > 64 4 > 64 4 > 64 4 > 64 P. aeruginosa GC 2214 16 > 64 16 > 64 16 > 64 32 > 64 S. aureus GC 1131 < 0.06 0.25 0.12 0.12 0.25 0.25 1 2 S. aureus GC 6466 0.12 0.12 0.12 0.12 0.25 0.25 0.50 1 S. aureus GC 6467 1 2 2 2 4 4 4 16 15 S. aureus GC 1079 2 1 0.50 1 2 4 2 8 S. aureus GC 4536 0.50 0.50 0.25 0.50 0.50 0.50 1 2 S. aureus GC 2216 0.25 0.50 0.25 0.50 0.50 0.50 1 4 S. aureus GC 6335 0.25 0.50 0.25 0.50 1 1 1 2 S. aureus GC 6469 1 2 1 2 4 4 4 16 S. epidermidis GC 4935 0.25 1 0.50 1 1 2 4 8 E. faecalis GC 4555 0.50 2 0.50 1 0.50 1 0.50 4 TABLE III (Contd) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM FORMULAR GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Mouse Water Water Water Mouse Water Example Example 9 Example 9 Example 10 Example 10 Example 11 Example 11 Example 12 12 E. faecalis GC 2265 1 2 1 1 2 4 2 8 E. faecalis GC 2267 1 2 1 2 2 2 2 8 E. faecalis GC 2242 0.50 1 0.25 0.50 0.25 0.50 2 4 15 E. faecium GC 4556 0.25 0.50 0.25 0.50 0.25 0.50 1 4 E. faecium GC 2243 0.25 0.50 < 0.06 0.12 0.12 0.25 0.50 4 S. pneumoniae * GC 4465 < 0.06 < 0.06 < 0.06 < 0.06 < 0.06 < 0.06 < 0.06 0.12 S. pneumoniae + GC 4465 2 2 1 1 2 2 4 8 S. pyogenes GC 4563 < 0.06 < 0.06 < 0.06 < 0.06 < 0.06 < 0.06 0.12 0.25 S. agalactiae GC 4564 0.12 0.25 < 0.06 0.12 < 0.06 < 0.06 0.25 0.25 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE IV ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED FROM FORMULA GLICILCLYCINES CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum of mouse serum Water Serum of mouse Water mouse Water Serum of mouse Water Example 13 Example 13 Example 14 Example 14 Example 15 Example 15 Example 16 Example 16 E. coli GC 2236 2 8 > 64 > 64 > 64 64 64 > 64 E. coli GC 2231 2 16 > 64 > 64 > 64 > 64 > 64 > 64 E. coli GC 2235 2 8 32 64 32 32 16 64 E. coli GC 2232 2 8 > 64 > 64 > 64 > 64 > 64 > 64 15 E. coli GC 2233 2 8 > 64 > 64 > 64 > 64 > 64 > 64 E. coli GC 2234 1 8 > 64 > 64 > 64 > 64 > 64 > 64 E. coli GC 2270 1 8 > 64 > 64 64 64 > 64 > 64 E. coli GC 2271 2 8 > 64 > 64 64 64 > 64 > 64 E. coli GC 2272 2 8 > 64 > 64 > 64 > 64 > 64 > 64 20 E. coli GC 4559 4 16 > 64 > 64 > 64 > 64 > 64 > 64 E. coli GC 4560 1 4 4 4 1 1 2 4 E. coli GC 6465 8 > 64 > 64 > 64 > 64 > 64 > 64 > 64 E. coli GC 3226 2 16 > 64 > 64 > 64 > 64 64 > 64 E. coli GC 2203 2 8 32 64 32 64 16 64 E. coli GC 1073 2 16 > 64 > 64 > 64 > 64 > 64 > 64 Salmonella spp. GC 235 2 16 > 64 > 64 > 64 > 64 > 64 > 64 Whey Serum Whey Serum Mouse to Water Water Mouse Ac Water Water Example 13 Example 13 Example 14 Example 14 Example 15 Example 15 Example 16 Example 16 Salmonella spp. GC 566 8 64 > 64 > 64 > 64 > 64 > 64 > 64 S. cholerasius GC 1355 16 > 64 > 64 > 64 > 64 > 64 > 64 > 64 fifteen TABLE IV (Contd) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULA GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Mouse Water Water Water Mouse Water Example Example Example Example 13 Example 13 14 Example 14 15 15 16 Example 16 S. typhimurium GC 2172 8 64 > 64 > 64 > 64 > 64 > 64 > 64 P. aeruginosa GC 2214 32 > 64 > 64 > 64 > 64 > 64 > 64 > 64 S. aureus GC 1131 2 2 1 2 2 4 2 4 S. aureus GC 6466 1 2 2 8 2 4 4 8 S. aureus GC 6467 4 8 2 4 16 16 8 8 S. aureus GC 1079 4 4 1 2 2 4 2 4 S. aureus GC 4536 1 2 2 2 2 4 2 4 S. aureus GC 2216 2 4 2 4 2 4 2 4 S. aureus GC 6335 2 4 1 4 4 4 4 4 S. aureus GC 6469 4 8 2 4 4 8 4 8 S. epidermidis GC 4935 4 8 8 8 16 16 8 8 E. faecalis GC 4555 2 4 2 8 4 8 4 8 TABLE IV (Contd) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED FROM FORMULA GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Mouse Water Water Water Mouse Water Example Example Example Example Example Example Example 13 13 14 14 15 15 16 16 E. faecalis GC 2265 4 8 2 8 8 8 4 8 E. faecalis GC 2267 4 8 2 8 8 8 4 8 E. faecalis GC 2242 4 8 2 8 8 8 8 8 E. faecium GC 4556 2 8 4 8 8 8 4 8 E. faecium GC 2243 2 4 2 4 8 8 4 8 S. pneumoniae * GC 4465 0.50 0.50 S. pneumoniae + GC 4465 8 8 4 4 4 4 8 8 S. pyogenes GC 4563 0.50 1 2 4 2 2 4 8 S. agalactiae GC 4564 1 2 16 16 8 8 16 16 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE V ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Water Water Example 21 Example 21 Example 22 Example 22 Example 23 Example 23 Example 24 Example 24 E. coli GC 2236 1 > 64 2 > 64 2 > 64 1 > 64 E. coli GC 2231 1 > 64 2 > 64 2 > 64 2 > 64 E. coli GC 2235 0.50 > 64 1 > 64 1 > 64 0.50 > 64 E. coli GC 2232 1 > 64 2 > 64 1 > 64 0.50 > 64 E. coli GC 2233 1 > 64 2 > 64 2 > 64 1 > 64 E. coli GC 2234 0.50 > 64 1 > 64 1 > 64 0.50 > 64 E. coli GC 2270 1 > 64 1 > 64 1 > 64 0.50 > 64 E. coli GC 2271 0.50 > 64 1 > 64 1 > 64 0.50 > 64 E. coli GC 2272 1 > 64 1 > 64 1 > 64 1 > 64 E. coli GC 4559 1 > 64 2 > 64 2 > 64 1 > 64 E. coli GC 4560 0.25 > 64 0.50 > 64 0.50 8 0.25 64 E. coli GC 6465 4 > 64 8 > 64 4 > 64 8 > 64 E. coli GC 3226 8 > 64 8 > 64 8 > 64 1 > 64 E. colrGC2203 0.50 > 64 1 > 64 1 > 64 0.50 > 64 E. coli GC 1073 1 > 64 2 > 64 1 > 64 1 > 64 Salmonella spp. GC235 2 > 64 > 64 > 64 > 64 Salmonella spp. GC566 4 > 64 > 64 > 64 > 64 S. cholerasius GC1355 16 > 64 16 > 64 16 > 64 32 > 64 TABLE V (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL REPLACED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Water Water Example 21 Example 21 Example 22 Example 22 Example 23 Example 23 Example 24 Example 24 S. typhimurium GC 2172 4 > 64 8 > 64 4 > 64 8 > 64 P. aeruginosa GC 2214 > 64 > 64 > 64 > 64 > 64 > 64 16 > 64 S. aureus GC 1131 1 64 1 4 1 2 1 2 S. aureus GC 6466 1 64 0.50 2 0.25 0.50 0.25 0.50 S. aureus GC 6467 4 > 64 4 > 64 4 8 4 > 64 twenty S. aureus GC 1079 4 > 64 2 32 2 4 2 64 S. aureus GC 4536 2 32 1 2 1 2 1 4 S. aureus GC 2216 1 64 1 4 1 4 0.50 4 S. aureus GC 6335 2 64 2 8 2 4 2 16 S. aureus GC 6469 4 > 64 4 64 4 4 4 > 64 S. epidermidis GC 4935 2 64 2 16 2 4 2 16 E. faecalis GC 10 4555 1 64 2 64 1 4 1 64 E. faecalis GC 2265 1 64 2 64 1 4 2 32 E. faecalis GC 2267 2 64 4 64 2 8 4 64 E. faecalis GC 2242 2 32 2 32 2 4 2 4 E. faecium GC 4556 2 64 2 64 2 4 1 32 E. faecium GC 20 2243 0.50 8 1 8 0.50 4 0.50 2 S. pneumoniae * GC 4465 0.25 0.50 0.50 1 0.12 0.12 < 0.06 < 0.0 ( TABLE V (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL REPLACED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Mouse Water Water Mouse Water Water Example Example Example Example 21 Example 21 22 Example 22 23 23 Example 24 Example 24 S. pneumoniae + GC 4465 4 4 4 16 4 8 2 1 S. pyogenes GC 4563 0.25 0.12 0.50 1 0.12 0.25 < 0.06 < 0.06 S. agalactiae GC 4564 0.50 8 1 8 0.25 0.25 0.50 8 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 twenty TABLE VI ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM FORMULARY GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum whey serum from mouse Water water Water mouse Water water Water Example 25 Example 25 Example 26 Example 26 Example 27 Example 27 Example 28 Example 28 E. coli GC 2236 2 64 2 > 64 0.50 64 0.50 > 64 E. coli GC 2231 2 > 64 4 > 64 1 > 64 1 > 64 E. coli GC 2235 1 32 1 64 0.50 64 0.50 > 64 E. coli GC 2232 1 > 64 1 > 64 0.50 64 0.50 > 64 E. coli GC 2233 2 32 2 > 64 0.50 64 0.50 > 64 E. coli GC 2234 1 > 64 1 > 64 0.50 64 0.25 > 64 E. coli GC 2270 1 > 64 1 > 64 0.50 64 0.50 > 64 E. coli GC 2271 1 32 1 > 64 0.50 64 0.25 > 64 E. coli GC 2272 2 64 2 64 0.50 32 0.50 > 64 E. coli GC 4559 2 > 64 2 > 64 0.50 > 64 0.50 > 64 E. coli GC 4560 0.50 2 0.50 8 0.25 1 0.25 > 64 E. coli GC 6465 8 > 64 8 > 64 4 > 64 8 > 64 E. coli GC 3226 2 > 64 2 > 64 0.50 > 64 0.50 > 64 E. coli GC 2203 1 > 64 1 > 64 0.50 > 64 0.50 > 64 E. coli GC 1073 2 > 64 2 > 64 0.50 > 64 0.50 > 64 Salmonella spp. GC 235 2 > 64 > 64 > 64 0.50 > 64 Salmonella spp. GC 566 4 > 64 > 64 > 64 > 64 S. cholerasius GC 1355 32 > 64 32 > 64 16 > 64 16 > 64 TABLE VI (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULA GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum whey serum of mouse Water mouse Water mouse Water mouse Water Example Example Example Example Example Example Example 25 25 26 26 27 27 28 28 S. typhimurium GC 2172 8 > 64 16 > 64 4 > 64 8 > 64 P. aeruginosa GC 2214 32 > 64 32 > 64 8 > 64 16 > 64 S. aureus GC 1131 0.50 0.50 0.50 0.50 0.12 0.25 0.50 32 S. aureus GC 6466 0.25 0.25 0.25 0.25 0.12 0.25 0.50 4 S. aureus GC 6467 2 2 1 4 2 2 4 64 S. aureus GC 1079 1 2 1 2 1 2 2 64 S. aureus GC 4536 0.50 0.50 0.25 0.50 0.12 0.12 0.50 32 S. aureus GC 2216 0.50 1 0.50 0.50 0.25 0.25 0.50 32 S. aureus GC 6335 0.50 0.50 0.50 1 0.25 0.50 1 16 S. aureus GC 6469 2 4 1 2 1 2 4 64 S. epidermidis GC 4935 1 2 1 2 0.25 1 1 32 E. faecalis GC 4555 1 2 1 4 0.25 1 0.25 64 E. faecalis GC 2265 2 8 64 E. faecalis GC 2267 2 64 E. faecalis GC 2242 2 0.50 0.50 0.50 E. faecium GC 4556 1 0.50 0.50 32 E. faecium GC 10 2243 0.50 0.12 0.25 0.25 0.25 S. pneumoniae * GC 4465 0.12 0.25 0.25 0.25 < 0.06 < 0.06 < 0.06 < 0.06 fifteen TABLE VI (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Mouse Water Example 25 Example 25 Example 26 Example 26 Example 27 Example 27 Example 28 Example 28 S. pneumoniae + GC 4465 4 4 4 4 1 2 2 0.50 S. pyogenes GC 4563 0.12 0.25 0.25 0.25 < 0.06 < 0.06 < 0.06 < 0.06 S. agalactiae GC 4564 0.50 0.50 1 2 0.12 0.12 0.25 0.50 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE VII ANTIBACTERIAL ACTIVITY OF 9-AMINOCARBONIL DERIVATIVES SUBSTITUTED FROM FORMULA GLICILCLYCINES CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water quarantine water Human mouse Water human mouse Example Example Example 42 Example 42 Example 42 Example 43 Example 43 Example 43 44 Example 44 44 E. coli GC 2236 > 64 4 > 64 > 64 0.50 > 64 > 64 2 > 64 E. coli GC 2231 > 64 4 > 64 > 64 0.50 > 64 > 64 2 > 64 E. coli GC 2235 > 64 4 > 64 > 64 0.25 > 64 > 64 2 > 64 E. coli GC 2232 > 64 4 > 64 > 64 0.50 > 64 > 64 2 > 64 E. coli GC 2233 > 64 4 > 64 > 64 0.50 > 64 > 64 2 > 64 E. coli GC 2234 > 64 4 > 64 > 64 0.25 > 64 > 64 2 > 64 E. coli GC 2270 > 64 4 > 64 > 64 0.25 > 64 > 64 2 > 64 E. coli GC 2271 > 64 4 > 64 > 64 0.25 > 64 > 64 2 > 64 E. coli GC 2272 > 64 4 > 64 > 64 0.50 > 64 > 64 2 > 64 E. coli GC 4559 > 64 8 > 64 > 64 0.50 > 64 > 64 4 > 64 E. coli GC 4560 8 2 8 32 < 0.06 16 4 2 4 E. coli GC 6465 > 64 16 > 64 > 64 2 > 64 > 64 8 > 64 E. coli GC 3226 > 64 16 > 64 > 64 1 > 64 > 64 4 > 64 E. coli GC 2203 > 64 8 > 64 > 64 0.50 > 64 > 64 2 > 64 E. coli GC 1073 > 64 8 > 64 > 64 0.50 > 64 > 64 4 > 64 Salmonella spp. GC 235 > 64 16 > 64 > 64 0.50 > 64 > 64 4 > 64 Salmonella spp. GC 566 > 64 32 > 64 > 64 2 > 64 > 64 8 > 64 TABLE VII (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM GLICILCLYCINES OF FORMULA 1 1 CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Serum Serum Water mouse mouse Water from human mouse Water from mouse Human serum Example Example Example Example Example Example Example Example 42 42 42 43 43 43 44 44 Example 44 S. cholerasius GC 1355 > 64 64 > 64 > 64 4 > 64 > 64 16 > 64 S. typhimurium GC 2172 > 64 64 > 64 > 64 2 > 64 > 64 8 > 64 P. aeruginosa GC 2214 > 64 > 64 > 64 > 64 16 > 64 > 64 > 64 > 64 S. aureus GC 1131 4 2 2 64 1 16 4 2 2 15 S. aureus GC 6466 4 2 4 64 0.50 16 2 2 2 S. aureus GC 6467 8 4 4 > 64 0.50 32 4 2 2 S. aureus GC 1079 4 2 4 64 1 32 4 2 2 S. aureus GC 4536 8 2 4 32 1 16 4 2 2 S. aureus GC 2216 20 4 2 2 64 0.50 32 2 2 2 S aureus GC 6335 4 2 4 64 1 64 4 2 4 S. aureus GC 6469 4 2 4 > 64 1 32 4 2 2 TABLE VII (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULARY GLUCYLLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water mouse mouse Water human mouse Water human mouse Example Example Example Example Example Example 42 42 42 43 43 43 44 Example 44 E Ijemplc S. epidermidis GC 4935 8 4 4 32 2 4 4 2 4 10 E. faecalis GC 4555 4 2 4 32 0.50 8 4 2 4 E. faecalis GC 2265 8 2 4 32 0.50 8 4 2 2 E. faecalis GC 2267 4 2 4 32 0.50 4 4 2 4 E. faecalis GC 2242 8 4 4 16 0.50 4 4 2 4 E. faecium GC 4556 8 2 4 16 0.50 8 4 2 4 15 E. faecium GC 2243 4 2 4 0.25 0.12 0.25 4 2 4 S. pneumoniae * GC 4465 4 2 4 0.50 <; 0.06 1 2 1 2 S. pneumoniae + GC 4465 8 4 8 2 2 2 4 4 4 S. pyogenes GC 4563 4 2 4 < 0.06 < 0.06 < 0.06 2 1 4 S. agalactiae GC 4564 8 2 8 2 < 0.06 2 4 1 4 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE VIII ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED FROM FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water Water Water Human mouse water human mouse human mouse Example Example Example Example Example Example Example Example 4 45 45 45 46 46 46 47 47 E. coli GC 2236 16 1 4 64 0.50 4 > 64 1 32 E. coli GC 2231 32 1 4 64 0.50 4 > 64 1 32 E. coli GC 2235 16 0.50 4 64 0.50 4 > 64 1 16 E. coli GC 2232 16 1 4 64 0.50 4 > 64 1 16 E. coli GC 2233 16 1 4 64 0.50 4 > 64 0.50 16 E. coli GC 2234 16 0.50 4 64 0.50 4 > 64 1 16 E. coli GC 2270 32 0.50 4 > 64 0.50 4 > 64 0.50 16 E. coli GC 2271 16 0.50 4 64 0.50 4 > 64 1 16 E. coli GC 2272 16 1 8 64 1 4 > 64 1 16 E. coli GC 4559 64 1 8 > 64 1 8 > 64 2 64 E. coli GC 4560 2 0.25 0.50 4 0.50 1 16 1 4 E. coli GC 6465 > 64 2 16 > 64 2 16 > 64 2 > 64 E. coli GC 3226 64 1 8 > 64 1 16 > 64 2 32 E. coli GC 2203 32 0.50 4 > 64 0.50 8 > 64 1 32 E. coli GC 1073 64 1 8 > 64 1 8 > 64 2 32 Salmonella spp. GC 235 > 64 1 8 > 64 1 16 > 64 2 64 Salmonella spp. GC 566 > 64 2 32 > 64 2 16 > 64 4 > 6A TABLE VIII (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM FORMULA FORM GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water Human mouse water Human mouse water Human mouse water Example Example Example Example Example Example Example Example Example 45 45 45 46 46 46 47 47 47 S. cholerasius GC 1355 > 64 4 32 > 64 2 32 > 64 4 > 64 S. typhimurium GC 2172 > 64 2 32 > 64 2 32 > 64 4 > 64 P. aeruginosa GC 2214 > 64 16 > 64 > 64 16 > 64 > 64 32 > 64 S. aureus GC 1131 1 0.50 0.50 0.50 0.50 0.50 2 2 S. aureus GC 6466 0.50 0.25 0.25 0.25 0.25 0.25 2 1 S. aureus GC 6467 2 1 1 1 1 0.50 4 2 S. aureus GC 1079 1 0.50 0.12 0.50 0.50 0.50 2 2 S. aureus GC 4536 1 0.50 0.50 0.50 0.50 0.50 4 1 S. aureus GC 2216 1 1 0.50 1 0.50 0.50 2 1 S. aureus GC 6335 2 1 0.50 1 1 0.50 2 2 S. aureus GC 6469 1 1 0.50 1 1 0.50 4 2 S. epidermidis GC 4935 2 1 1 2 1 1 4 2 4 TABLE VIII (CONT) ANTIBACTERIAL ACTIVITY OF Glycylcycline Derivatives Substituted with 9-aminocarbonyl OF FORMULA I CONCENTRATION MINIMUM MIC INHIBITOR (UG / ML) Serum Serum Serum Serum Serum Serum Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example Example 45 45 45 46 46 46 47 Example 47 47 E. faecalis GC 4555 2 1 2 2 0.50 0.50 4 1 4 E. faecalis GC 2265 4 0.50 2 0.50 1 4 1 4 E. faecalis GC 2267 2 0.50 2 0.50 1 4 1 4 E. faecalis GC 2242 2 1 1 0.50 1 4 1 4 E. faecium GC 4556 2 1 1 0.50 1 4 1 4 E. faecium GC 2243 2 0.50 0.50 0.25 0.25 2 0.50 2 S. pneumoniae * GC 4465 0.50 0.25 0.25 0.12 0.12 0.12 0.50 0.25 0.50 S. pneumoniae + GC 4465 4 2 2 1 1 1 4 2 2 S. pyogenes GC 4563 0.50 0.25 0.25 0.25 0.12 0.25 0.25 0.12 0.25 S. agalactiae GC 4564 0.50 0.25 0.50 0.25 0.25 0.25 1 0.50 1 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE IX ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED FROM FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example Example Example 48 48 48 49 49 49 50 50 50 E. col GC 2236 64 0.25 16 16 0.50 4 32 8 E. col GC 2231 64 0.50 16 16 0.50 8 64 8 E. col GC 2235 32 0.25 16 8 0.50 4 32 4 E. col GC 2232 64 0.25 16 16 0.50 4 32 8 E. col GC 2233 64 0.25 16 8 0.25 4 32 8 E. col GC 2234 64 0.50 16 16 0.25 4 64 8 E. col GC 2270 64 0.50 16 16 0.50 4 32 8 E. col GC 2271 32 0.25 8 8 0.25 4 32 4 E. col GC 2272 64 0.25 8 8 0.50 2 32 4 E. col GC 4559 > 64 0.25 32 16 0.50 8 64 2 16 E. col GC 4560 2 0.12 1 1 0.12 0.50 4 0.50 2 E. col GC 6465 > 64 2 > 64 > 64 2 32 > 64 2 16 E. coli GC 3226 > 64 0.50 32 16 0.50 8 32 1 8 E. coli GC 2203 64 0.25 16 8 0.25 4 32 1 8 E. coli GC 1073 64 0.50 32 32 0.50 8 32 2 8 Salmonella spp. GC 235 > 64 0.50 32 32 1 16 > 64 2 32 Salmonella spp. GC 566 > 64 2 > 64 64 2 32 > 64 4 32 S. cholerasius 10 GC 1355 > 64 4 > 64 > 64 4 64 > 64 4 64 TABLE IX (Cont.) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF GLICILCLYCINES OF FORMULA I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Serum Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example Example Example 48 48 48 49 49 49 50 50 50 S. typhimurium GC 2172 > 64 4 > 64 > 64 4 32 > 64 4 32 P. aeruginosa GC 2214 > 64 16 > 64 > 64 32 > 64 > 64 32 > 64 S. aureus GC 1131 0.25 0.25 0.25 0.50 0.50 0.50 1 0.50 0.50 S. aureus GC 6466 0.12 0.12 0.12 0.12 0.12 0.12 0.25 0.25 0.25 S. aureus GC 6467 2 1 0.50 2 1 1 2 0.25 0.25 S. aureus GC 1079 1 0.25 0.25 0.50 0.50 0.50 2 0.50 0.50 S. aureus GC 4536 0.25 0.25 0.25 0.25 0.25 0.25 0.50 0.25 0.25 S. aureus GC 2216 0.50 0.25 0.25 0.50 0.25 0.25 2 1 0.50 S. aureus GC 6335 2 2 2 2 1 1 1 1 1 S. aureus GC 6469 1 0.50 1 1 1 1 2 1 1 S. epidermidis GC 4935 1 0.50 0.50 2 1 1 4 2 2 E. faecalis GC 4555 2 0.12 4 4 0.25 0.50 4 1 2 TABLE IX (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM FORMULA FORMULA GLICILCLYCINS I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water from human mouse Water from human mouse Water from human mouse Example Example Example Example Example Example Example Example 48 48 48 49 49 49 50 50 50 E. faecalis GC 2265 2 0.50 1 2 0.50 1 4 1 2 E. faecalis GC 2267 2 0.50 1 4 0.50 1 4 1 2 E. faecalis GC 2242 1 0.50 1 2 0.50 1 2 1 1 E. faecium GC 4556 1 0.50 1 2 0.50 1 2 1 1 E. faecium GC 2243 0.50 0.25 0.25 0.50 0.25 0.25 0.50 0.25 0.25 S. pneumoniae * GC 4465 0.12 0.12 0.12 0.12 0.12 0.12 < 0.06 < 0.06 < 0.06 S. pneumoniae + GC 4465 0.25 0.25 0.25 1 1 1 0.50 0.50 0.50 S. pyogenes GC 4563 0.12 0.12 0.12 0.12 0.12 0.12 0.25 0.12 0.12 S. agalactiae GC 4564 0.12 0.12 0.12 0.25 0.12 0.12 0.25 0.25 0.25 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE X ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example Example 51 51 51 52 52 52 53 53 Example 53 E. coli GC 2236 > 64 2 32 8 1 8 32 1 16 E. coli GC 2231 > 64 2 32 16 1 8 64 1 16 E. coli GC 2235 > 64 1 32 4 0.50 4 32 0.50 8 E. coli GC 2232 > 64 2 32 8 0.50 4 32 0.50 8 E. coli GC 2233 > 64 2 32 8 0.50 8 32 1 16 E. coli GC 2234 > 64 1 32 8 0.50 4 16 0.50 8 E. coli GC 2270 > 64 1 32 4 0.50 4 32 1 8 E. coli GC 2271 > 64 1 32 4 0.50 4 16 0.50 8 E. coli GC 2272 > 64 2 32 4 0.50 4 16 0.25 8 E. coli GC 4559 > 64 2 32 8 1 8 32 1 16 E. coli GC 4560 32 1 8 2 0.25 2 2 0.50 2 E. coli GC 6465 > 64 4 32 64 2 16 > 64 4 32 E. coli GC 3226 > 64 2 64 16 1 16 32 1 16 E. coli GC 2203 > 64 2 32 8 0.50 8 32 1 16 E. coli GC 1073 > 64 2 64 4 1 8 32 1 16 Salmonella spp. GC 235 > 64 2 64 16 1 16 64 2 64 Salmonella spp. GC 566 > 64 4 64 64 2 32 > 64 2 32 S. cholerasius GC 1355 > 64 8 > 64 > 64 4 > 64 > 64 8 64 S. typhimurium GC 2172 > 64 8 64 64 4 64 > 64 4 64 TABLE X (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example 51 51 51 52 Example 52 52 Example 53 53 53 P. aeruginosa GC 2214 > 64 64 > 64 > 64 64 > 64 > 64 64 > 64 S. aureus GC 1131 1 0.50 0.50 2 0.50 1 1 1 1 S. aureus GC 6466 1 0.25 0.25 2 0.50 1 0.50 0.50 0.50 S. aureus GC 6467 2 0.50 1 4 0.50 4 2 1 1 S. aureus GC 1079 2 0.50 1 2 0.50 1 1 0.50 0.50 S. aureus GC 4536 1 0.50 0.50 2 0.50 0.50 1 0.25 0.50 S. aureus GC 2216 1 0.50 0.50 4 0.50 1 1 0.50 0.50 S. aureus GC 6335 1 0.50 0.50 4 1 2 1 0.50 0.50 S. aureus GC 6469 2 1 1 4 0.50 2 2 1 1 S. epidermidis GC 4935 4 2 2 4 1 4 2 1 2 E. faecalis GC 4555 16 1 8 4 0.50 2 2 0.50 2 E. faecalis GC 2265 8 1 4 4 1 4 4 1 0.50 E. faecalis GC 2267 16 2 4 4 0.50 4 4 0.50 2 TABLE X (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED OF FORMULARY GLICILCLYCINES I MINIMUM MIC INHIBITOR CONCENTRATION (UG / ML) Serum Serum Serum Serum Serum Serum Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example Example Example 51 51 51 52 52 52 53 53 53 E. faecalis GC 2242 8 2 4 4 0.50 4 2 0.50 2 E. faecium GC 4556 8 2 8 4 0.50 2 2 0.50 2 E. faecium GC 2243 4 1 4 1 0.25 1 0.50 0.25 0.25 S. pneumoniae * GC 4465 1 0.50 2 0.12 < 0.06 0.25 0.12 0.12 0.25 S. pneumoniae + GC 20 4465 1 1 2 2 1 4 2 2 1 S. pyogenes GC 4563 2 0.50 2 0.25 0.12 0.25 0.25 0.12 0.25 S. agalactiae GC 4564 2 1 4 0.50 0.12 0.50 0.50 < 0.06 0.50 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE XII ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM FORMULARY GLICILCLYCINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water Water human mouse Water human mouse Water human mouse Example Example 61 Example 61 Example 61 Example 62 Example 62 63 Example 63 Example 63 E. coli GC 2236 16 0.50 4 4 0.50 8 > 64 1 > 64 E. coli GC 2231 32 1 8 8 0.50 4 > 64 1 > 64 E. coli GC 2235 16 0.50 4 4 0.50 2 > 64 0.50 > 64 E. coli GC 2232 16 0 50 4 8 1 2 > 64 1 > 64 E. coli GC 2233 16 1 8 8 2 4 > 64 1 > 64 E. coli GC 2234 16 0.50 8 8 1 2 > 64 1 64 E. coli GC 2270 16 0.50 4 8 0.50 2 > 64 0.50 64 E. coli GC 2271 16 0.50 4 4 1 2 > 64 0.50 > 64 E. coli GC 2272 8 0.50 4 8 1 4 > 64 1 > 64 E. coli GC 4559 64 1 8 16 1 8 > 64 2 > 64 twenty E. coli GC 4560 1 0.25 1 0.50 0.25 0.50 16 0.50 2 E coli GC 6465 > 64 1 32 > 64 2 8 > 64 2 > 64 E coli GC 3226 32 0.50 8 8 1 4 > 64 1 > 64 E coli GC 2203 32 0.50 8 16 1 4 > 64 1 > 64 E coli GC 1073 32 0.50 8 16 0.50 4 > 64 2 > 64 Salmonella spp. GC 235 > 64 1 16 > 64 8 > 64 > 64 Salmonella spp. GC 566 > 64 1 32 > 64 16 > 64 > 64 S. cholerasius GC 1355 > 64 2 64 > 64 32 > 64 > 64 TABLE XII (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED FROM GLICILCLYCINES OF FORMULA I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example Example Example 61 61 61 62 62 62 63 63 63 S typh? Mur? Um GC 2172 > 64 1 64 > 64 2 16 > 64 2 > 64 P aerugmosa GC 2214 > 64 8 > 64 > 64 16 > 64 > 64 32 > 64 S aureus GC 1131 050 050 050 050 050 050 4 1 1 S aureus GC 6466 050 050 050 025 050 050 2 050 1 S aureus GC 6467 1 050 050 050 1 050 16 2 4 S aureus GC 1079 1 025 050 050 1 050 8 2 S aureus GC 4536 050 050 050 050 050 050 4 1 S aureus GC 2216 1 050 050 050 050 050 4 1 S aureus GC 6335 1 050 1 050 1 050 4 1 S aureus GC 6469 2 050 050 1 1 050 16 2 S epidermidis GC 4935 1 050 1 050 050 050 4 2 2 E faecalis GC 4555 2 1 2 1 1 050 4 2 E faecalis GC 2265 2 050 2 1 050 050 8 2 E faecalis GC 2267 2 050 2 1 050 050 16 2 E faeca s GC 2242 2 050 2 050 050 050 1 1 TABLE XII (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCHARBONIL SUBSTITUTED FROM FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Serum Serum Serum Serum Water Water human mouse Water human mouse Water human mouse Example Example Example Example Example Example 61 61 Example 61 62 62 Example 62 63 63 63 E. faecium GC 4556 2 0.50 2 1 1 1 0.50 1 4 E. faecium GC 2243 0.50 0.25 1 0.50 0.50 0.50 0.50 0.25 0.25 S. pneumoniae * GC 4465 0.12 0.12 0.25 0.12 0.12 0.12 0.12 0.12 0.12 S. pneumoniae + GC 4465 0.50 0.50 0.50 0.50 1 0.50 0.50 0.50 0.50 S. pyogenes GC 4563 0.50 0.25 0.25 0.25 0.25 0.12 0.12 0.12 0.12 S. agalactiae GC 20 4564 0.25 0.25 0.50 0.25 0.25 0.12 0.25 0.25 0.25 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 TABLE Xlll ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL REPLACED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Mouse AgL Example Example Example Example Example Example Example 108 108 Example 109 109 109 109 110 11 E. coli GC 2236 0.50 2 0.50 1 0.50 2 1 2 E. coli GC 2231 2 4 0.50 1 1 2 4 8 E. coli GC 2235 0.50 1 0.25 0.50 0.50 1 0.50 1 E. coli GC 2232 1 2 0.50 1 0.50 2 1 2 E. coli GC 2233 0.50 1 0.25 0.50 1 2 0.50 1 E. coli GC 2234 0.50 2 0.12 0.25 0.25 2 1 2 E. coli GC 2270 0.50 1 0.25 0.50 0.25 2 1 1 E. coli GC 2271 0.50 0.50 0.12 0.25 0.25 1 1 2 E. coli GC 2272 0.25 0.50 0.25 0.25 0.50 2 1 1 E. coli GC 4559 0.50 1 0.12 0.25 1 2 2 2 E. coli GC 4560 0.12 0.25 < 0.06 < 0.06 0.25 0.25 0.25 0.50 E. coli GC 6465 8 64 1 4 4 16 64 > 64 E. coli GC 3226 0.50 1 0.50 1 1 4 2 4 E. coli GC 2203 0.50 1 0.50 1 0.50 2 1 4 E. coli GC 1073 0.50 2 0.50 1 1 4 2 8 Salmonella spp. GC 235 1 4 1 2 1 4 4 8 Salmonella spp. GC 566 1 8 2 4 2 4 16 32 S. cholerasius GC 1355 32 64 8 32 8 32 > 64 > 64 TABLE Xlll (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL SUBSTITUTED FROM FORMULA GLICILCLYCINES CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Mouse Water Example Example Example Example 108 Example Expression Example 109 Example 109 Example 109 109 110 110 S. typhimurium GC 2172 4 32 4 16 4 16 64 > 64 P. aeruginosa GC 2214 16 32 16 > 64 32 > 64 > 64 > 64 S. aureus GC 1131 0.25 0.50 1 2 1 4 2 4 S. aureus GC 6466 0.50 1 0.50 1 0.50 4 1 2 S. aureus GC 6467 2 8 2 4 2 8 32 > 64 S. aureus GC 1079 2 4 2 4 2 8 16 16 S. aureus GC 4536 0.50 1 1 2 1 4 4 4 S. aureus GC 2216 0.50 1 1 2 0.50 8 2 4 S. aureus GC 6335 1 2 2 4 1 4 8 8 S. aureus GC 6469 0.25 1 20 1 2 2 8 32 32 S. epidermidis GC 4935 1 2 2 4 2 8 4 8 E. faecalis GC 4555 0.50 0.50 0.50 1 0.50 1 1 2 E. faecalis GC 2265 1 2 1 2 1 4 8 4 TABLE Xlll (CONT) ANTIBACTERIAL ACTIVITY OF DERIVATIVES 9-AMINOCARBONIL REPLACED OF FORMULARY GLICILLICINES I CONCENTRATION MINIMUM MIC INHIBITORY (UG / ML) Serum Whey Serum Mouse Water Water Mouse Water Water Mouse Water Example Example Example Example Example Example 10 108 108 109 109 109 109 110 Example 110 E. faecalis GC 2267 1 2 1 2 1 4 8 4 E. faecalis GC 2242 0.50 1 1 1 1 2 1 1 E. faecium GC 4556 0.50 1 1 2 1 2 1 2 E. faecium GC 2243 0.50 0.50 0.50 0.50 0.50 1 0.50 0.50 S. pneumoniae * GC 4465 0.12 0.12 < 0.06 0.12 < 0.06 0.25 0.25 0.12 S. pneumoniae + GC 4465 1 2 1 1 1 2 4 2 S. pyogenes GC 4563 0.12 0.12 < 0.06 0.12 0.12 0.25 0.12 < 0.06 S. agalactiae GC 4564 0.12 0.12 0.12 0.25 < 0.06 0.25 0.25 0.25 c. albicans GC 3066 > 64 > 64 > 64 > 64 > 64 > 64 > 64 > 64 Table 1. In vitro activity (MIC) a of representative examples of formula I a MIC range (Minimum inhibition concentration) for E. coli and Staph., including MRSA which are selected from these E. coli and Staph., presented in Tables I-XIII.

Table 1 (Cont) .5 1 eleven a MIC range (Minimum inhibition concentration) for E. coli and Staph., including MRSA which are selected from these E. coli and Staph., presented in Tables I-XIII.

Table 1 (Cont) a MIC range (Minimum inhibition concentration) for E. coli and Staph., including MRSA which are selected from these E. coli and Staph., presented in Tables I-XIII. a MIC range (Minimum inhibition concentration) for E. coli and Staph., including MRSA which are selected from these E. coli and Staph., presented in Tables I-XIII.

Table 2. In vitro activity (MIC) of Example 87.

Example 87 water Mouse serum Human serum E. coli, tet (A-D), efflux > 64 0.25-0.5 > 64 E. coli, tet (M, S, O) Tet (M) > 64 0.25-0.5 > 64 E. coli (susceptible) > 64 0.5 > 64 E. coli (IMP) 32 < 0.06 16 S. aureus, tet (M) 64 0.5 16 S. aureus, tet (K), efflux 64 1 32 S. aureus (susceptible) 3 32 1 16 Enterococcus spp. 0.25-32 0.12-0.5 0.25-8 Streptococcus spp. 0.5-2 < 0.06 1-2 O albicans > 64 > 64 > 64 a Strain used for in vivo testing Representative examples of compounds of Formula I are further evaluated for oral efficacy, stability in pH physiology in mouse serum and human plasma.

Table 3. In vitro activity (MIC) 3 of representative examples of compounds of Formula Minimum Inhibition Concentration (MIC), μg / mL Ex. No. E. coli E. coli Staph. Staph. (water) (Serum (water) (mouse serum) mouse) 1 0.5-1 16-64 1-4 1-8 2 1-4 32-64 1-8 2-8 3 1-2 > 64 1-4 4-32 4 0.5-2 64- > 64 0.5-2 2-16 12 0.5-2 16-64 0.5-4 1-16 13 1-4 8-16 1-4 2-8 17 0.5-2 32-64 1-4 2-32 18 0.5-2 4-8 1-4 1-4 20 0.5-2 > 64 1-4 64- > 64 21 0.5-8 > 64 1-4 32- > 64 22 1-8 > 64 0.5-4 2- > 64 23 1-8 > 64 0.25-4 0.5-8 29 0.5-1 > 64 0.25-2 1-4 30 0.5-1 32- > 64 0.25-2 1-8 34 0.5-1 4-16 0.25-4 0.25-4 36 2-8 8-32 2-4 4-16 38 0.5-4 64- > 64 0.5-2 1-8 39 1-4 16-32 1-4 2-16 MIC range (Minimum inhibition concentration) for E. coli and Staph., Including MRSA which are selected from these E. coli and Staph., Presented in Tables I-XIII.

Table 4. In vitro activity (MIC) a of representative examples of compounds of Formula I Minimum inhibition concentration (MIC), μg / mL Ex. No. E. coli E. coli Staph. Staph. (water) (Serum (water) (mouse serum) mouse) 5 1-2 16-64 0.25-2 0.5-4 6 1-2 8-64 0.5-2 1-4 7 0.25-2 2-16 0.5 -4 0.5-4 8 1-2 16- > 54 0.5-4 1-8 9 0.5-2 4-64 0.06-1 0.12-2 10 0.25-2 4-32 0.25-2 0.12-2 11 0.25-2 4- > 64 0.25-4 0.25-4 19. 0.5-2 32- > 64 0.5-4 1-8 24 0.5-2 > 64 0.25-4 0.5- > 64 25 1-2 32- > 64 0.25-2 0.5-4 26 1-4 64- > 64 0.25-1 0.25-4 27 0.5-1 32- > 64 0.12-2 0.12-2 28 0.25-1 > 64 0.5-4 4-64 31 0.5-1 16- > 64 0.25-2 0.5-4 33 0.5-2 32- > 64 0.12-2 0.12-2 35 4-8 8-64 2-4 2-4 40 1-2 16- > 64 0.25-2 0.25-2 41 0.5-4 16-64 0.5-4 1-8 3 MIC range (Minimum inhibition concentration) for E. coli and Staph. including MRSA which are selected from these E. coli and Staph., presented in Tables I-XIII.

Table 5. In vitro activity (MIC) of Example 27 Example 27 Water Whey Serum human mouse E. coli, tet (A-D), efflux 64- > 64 0.5-1 4-16 E. coli, tet (M, S, O) Tet 0.5 0.5 4-8 (M) E. coli (susceptible) 0.5 0.5 16 E. coli (IMP) 0.25 0.25 0.5 S. aureus, tet (M) 0.12 0.12 0.25 S. aureus, tet (K), 1 1 1 S. aureus efflux 0.12 0.12 0.5 (susceptible) 3 Enterococcus spp. 0.12-1 0.12-1 0.5-2 Streptococcus spp. < 0.06-0.12 < 0.06-0.12 0.12-2 O albicans > 64 > 64 > 64 3 Strain used for in vivo testing Representative examples of compounds of Formula I are tested for oral efficacy using S. aureus Smith in mice. In summary of in vivo and in vitro activities of selected compounds are listed in Table 6.

Table 6. Live in vitro activity of the representative examples of compounds of Formula I against Staph. Aureus Smith in mice.

ED50 mg / kg (Staph μg / mL (Staph aureus Smith Smith) Smith) Ex No. SOD6 S? V5 M? C5 42 5.68 1.43 8 44 4 0.75 4 45 5.9 0.66 1 47 14 1.2 4 48 10.1 1.1 0.25 49 16 0.92 0.25 50 16.88 1.65 0.5 52 10.69 1.29 2 53 5.08 0J3 1 54 8.4 0.83 0.5 87 12.82 0.83 32 3 MIC (Minimum inhibition concentration) b SOD (Unit oral dose) c SIV (Unit dose intravenous) Representative examples of compounds of Formula I are tested live against Gram-negative bacteria (E. coli) in mice. The results of the trials (MIC, oral and IV) are listed in Table 7.

Table 7. In vivo (oral, iv) and in vitro (MIC) 3 activity of the representative examples of compounds of Formula I against E. coli in mice.

ED50 I mg / kg (E. g / mL (E. coli) coli) Ex. No. SOD "SIV ° MIC 5> 64 3.17> 64 42 30.3 3.1> 64 44 42.8 2.85> 64 45 64 1.8 64 48 29.8 1.7> 64 49 49 2.2 64 50 29.8 1.7> 64 52 43.7 3J8 8 53 46.88 2.25 32 54 29.2 2.16> 64 87 60.4 3.6 &64 3 MIC (Minimum inhibition concentration) b SOD (Unit oral dose) c SIV (Unit dose intravenous) The results of the in vivo activity assays are shown in Table 8 for representative examples of compounds of Formula I.

Table 8. In vivo (oral, iv) and in vitro (MIC) 3 activity of representative examples of compounds of Formula I against Staph aureus Smith in mice.

ED50 mg / kg (Staph μg / mL (Staph aureus Smith) Smith) Ex. No. SOD "SIV ° MIC 1 4.7 0.6 4 5 8.51 0.5 1 19 8.05 0.31 1 26 8.79 0.43 0.5 27 3.9 0.44 0.12 28 6.61 0.6 32 33 4.91 0.48 0.12 35 3.5 0.43 4 36 5.15 0.84 8 38 5.3 0.6 2 40 4.65 0.39 0.5 3 MIC (Minimum inhibition concentration) b SOD (Unit oral dose) c SIV (Unit dose intravenous) Table 9 Minimum inhibition concentration (MIC), μg / mL Ex. No. E.coli E.coli Staph Staph (Human serum) (Water) (Human serum) (Water) 4 8-32 32- > 64 0.5-4 2-8 19 8-32 16- > 64 0.12-1 0.25-4 27 4-16 64- > 64 0.25-2 0.5-4 42 > 64 > 64 2-4 4-8 43 > 64 > 64 4-64 32- > 64 44 > 64 > 64 2-4 2-4 45 4-16 16- > 64 0.12-1 0.5-2 46 4-16 64- > 64 0.25-1 0.25-2 47 16- > 64 > 64 1-4 2-4 48 8- > 64 32- > 64 0.12-2 0.12-2 49 4-32 8- > 64 0.12-1 0.12-2 50 4-16 32-64 0.25-2 0.25-4 51 32-64 > 64 0.25-2 1-4 52 4-16 4-16 0.5-4 2-4 53 8-16 16-64 0.5-2 0.5-2 54 16-32 > 64 0.5-2 1-4 55 32- > 64 64- > 64 1-4 2-8 56 4-32 8- > 64 0.25-2 1-4 57 > 64 > 64 1-8 4-16 58 > 64 > 64 4 4-8 59 > 64 > 64 2-4 4-8 60 32- > 64 64- > 64 2-8 4-16 61 4-32 8- > 64 0.5-1 0.5-2 62 2-8 4- > 64 0.5 0.25-1 63 64- > 64 > 64 1-4 2-16 102 64- > 64 > 64 105 64 > 64 8- > 64 s > < m or E CN O o_ O < x ro E O O) E CN CM O < x n ra yes E ra O 1- s > ^ ^ ~ O D) • «: > CM E O? "or ü Q UJ UJ Q CM O O O? s) V > - n n co m r ^ CM 00 CM CO n CN lO • f C co uo CM D m h CO or 00 O OO? K ^ o F ÜJ .c o o n ro UJ w o m CM CM c M o co o co CM CO CM O CN CM n CM O 10 o o co o CD CO CD with "co oo o j: O O m o?" CM CO LO n CN CM co lO CD oo cn CN CO O 00 UJ ? r > or CN? CN CO? ^. co O O 1 m - • í or CN | ^ cn CO 00? CO n or CM CN CM CM Table 10 (cont.) ED50 (mg / kg) ED50 mg / kg IV - RAT PO - RAT Staph Smith E. coli # 311 2 mg / kg 20 mg / kg Ex. No. SOD SIV SOD SIV Cmax AUC T1 / 2 Cmax AUC% BA 23 19.01 0.47 24 27 0.59 25 15.71 0.56 26 8.79 0.43 27 3.9 0.44 > 32 > 2 10 28 6.61 0.6 > 32 > 2 29 13.67 0.43 30 15.1 0.41 31 11.11 0.31 32 7.7 0.56 15 33 4.91 0.45 34 12.86 0.71 35 3.5 0.43 36 5.15 0.84 37 4.1 0.55 20 38 5.3 0.6 39 13.3 0.6 40 4.65 0.39 O OO CM -5T CO CN CN LO CM OR THE LO O CO CN - m • - co T-CD co r OO eo - r ^ CM co CO CN - C co t - CN co "-3" OO CM -f o o o o CN CD n CD cn cn co CD "5T CN? CN CO co CO lO CD co oo ^ r 00 r ^ CD oo CN t. CN cn or x ~ O or O or «c- o 00 oo CM co OO LO CM "* - cn" «1-" * CD lO 00 d cb CN O - * m or r- oo cn - ^ r • • < • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Table 10 (cont) ED50 (mg / kg) EDg mg / kg IV - RAT PO - RAT 20 Staph Smith E. coli # 311 2 mg / kg mg / kg Ex. No. SOD SIV SOD SIV Cmax AUC T1 / 2 Cmax AUC% BA 50 16.88 1.65 > 64 2.59 52 10.69 1.29 43.7 3J8 53 5.08 0J3 46.88 2.25 54 > 16 1.17 > 32 3.72 10 55 > 16 1.81 32 4.69 56 > 16 0.79 57 6.36 1.17 58 59 15 60 > 32 > 8 61 > 32 2-4 62 > 32 4-8 63 > 32 4-8 71 > 32 1 > 32 > 4 20 74 > 32 1.08 > 32 > 4 81 16-32 > 4 82 21.97 0.52 Table 10 (cont.) 15 IV - Oral DOG - IV DOG - MONO Oral - MONO 2 mg / kg 10 mg / kg 2 mg / kg 10 mg / kg Ex No Cmax AUC T1 / 2 Cmax AUC% BA Cmax AUC T1 / 2 Cmax AUC% BA 1 10.8 8.3 14.9 0.11 0.67 1.6% 9.1 3.3 17.6 Levels not detected 27 1.9 9.8 10.7 0.018 0.22 0.5% 20 9.3 7.3 0.04 0.21 0.5% 28 0.55 6 7.8 0.09 0J4 2.5% 0J7 3.6 13.2 0.05 0.23 1.3% When the compounds of the invention are used as antibacterials, they can be combined with one or more pharmaceutically acceptable carriers, for example, solvents, diluents, and the like and can be administered orally as in the form of tablets, capsules, dispersible powders, granules, or suspensions containing them, for example, from about 0.05 to 5% of suspending agent, syrups containing for example, about 10 to 50% sugar, and elixirs containing, for example, 20 to 50% ethanol, and similar, or parenterally in the form of sterile injectable solutions or suspensions containing about 0.05 to 5% of suspending agent in an isotonic medium. Such pharmaceutical preparations can contain, for example, from about 25 to about 90% of the active ingredient in combination with the carrier, more usually from about 5% to about 60%; by weight.

An effective amount of the compound of 2.0 mg / kg of body weight at 100.0 mg / kg of body weight can be administered from one to five times per day by any typical route of administration including but not limited to oral, parenteral (including subcutaneous, intravenous, intramuscular, intrasternal injection or infusion techniques), topical or rectal, in unit dose formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles. It is understood, however, that it is specific dose level and the frequency of dosage for any particular patient can be varied and will depend on a variety of factors including the activity of the specific compound employed, age, body weight, health in general, sex, diet, mode and time of administration, rate of excresion, drug combination, the severity of the particular condition, and the therapy that the guest experiences.

These active compounds can be administered orally as well as by intravenous, intramuscular, or subcutaneous routes. Solid carriers include starch, lactose, dicalcium phosphate, microcrystalline cellulose, sucrose and kaolin, liquid carriers include sterile water, polyethylene glycols, nonionic surfactants, edible oils such as corn, peanuts, sesame oils, as appropriate to nature of the active ingredient and the particular form of administration desired. Adjuvants customarily employed in the preparation of pharmaceutical compositions can advantageously be included, such as flavoring agents, coloring agents, preservatives, and antioxidants, for example, vitamin E, ascorbic acid, BHT and BHA.

Preferred pharmaceutical compositions from the standpoint of easy preparation and administration are solid compositions, particularly tablets and capsules filled with liquid or filled with solids. Oral administration of the compounds is preferred.

These active compounds can be administered parenterally or intraperitoneally. Solutions or suspensions of these active compounds can be prepared as a free base or a pharmaceutically acceptable salt in water suitably mixed with a surfactant such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid, polyethylene glycols, and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

Injectable pharmaceutically suitable forms include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid so that there is easy administration with a syringe. It must be stable under manufacturing and storage conditions and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carriers can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils.

The invention will be more fully described in conjunction with the following specific examples which are not construed as limiting the scope of the invention.

The Reference Compound 1 Acid benzyl ester (tert-butyl-chloromethoxycarbonyl-amino) -acidic acid.

To a solution of benzyl ester of tert-butylaminoacetic acid in dichloromethane is added two equivalents of [1,8-bis (dimethylamino) naphthalene, N, N, N ', N'-tetramethyl-1,8-naphthalene diamine] . The reaction mixture is then cooled in an ice bath and one equivalent of chloromethyl chloroformate is added. The reaction is then warmed to room temperature and stirring is continued for 24 hr. This is then washed with water and then with saline.

The Reference Compound 2 3,3-Dimethyl-butyric acid (benzyloxycarbonylmethyl-tert-butyl-carbamoyloxy) -methyl ester Tert-butylacetic acid and 1.0 M tetrabutylammonium hydroxide in methanol are stirred for one hour, the methanol is removed and THF is added. To this solution is then added N- (tert-butyl) -N - [(chloromethoxy) carbonyl] benzyl glycinate and stirred at room temperature for 24 hr. The solvent is removed and the residue is diluted with ether, then washed with water, then with saline. This is dried over magnesium sulfate, filtered and the solvent is removed. MS (ESI) m / z 394.25 Compound of References 3-55 (Table A) Substantially following the method described above in Reference Compound 2 using (Tert-butyl-chloromethoxycarbonyl-amino) -acidic acid benzyl ester of Reference Compound 1 and the appropriate carboxylic acid , the compounds of References 3-55 of this invention that are listed below in Table A are prepared.

Table A 15 20 25 30 10 15 20 25 30 10 15 20 25 15 20 25 10 15 20 25 10 15 20 25 30 10 15 20 25 30 15 20 25 10 15 20 25 Reference Compound 56 (Tert-butyl-carboxymethyl-carbamoyloxy) -methyl ester of 3,3-Dimethyl-butyric acid.

The product of Reference Compound 2, 10% palladium on carbon in ethyl acetate is hydrogenated on a Parr shaker at ca. 40 psi for about an hour. The catalyst is filtered and the solvent is removed to give the corresponding carboxylic acid product of Example MS (ESI) m / z 394.25.

Reference Examples 57-108 (Table B) Substantially following the method described above in Reference Compound 56, Reference compounds 57-108 of this invention listed below in Table B are prepared using the appropriate benzyl esters of Reference Compounds 3-55.

Table B 20 25 30 The Reference Compound 109 Ester of [tert-butyl- (2-isobutoxycarbonyloxy-2-oxo-ethyl) -carbamoyloxy) -methyl 3,3-dimethyl-butyric acid To a solution of Reference Compound 56 in dichloromethane at room temperature is added 1.2 equivalent of [1,8-bis (dimethylamino) naphthalene, N, N, N ', N'-tetramethyl-1,8-naphthalene diamine] and 0.95 equivalent of iso-butylchloroformate. The reaction is stirred for 24 hours, diluted with dichloromethane, washed with dilute HCl, saline, and then with water. It is dried with sodium sulfate. The solvent is removed and the product is used in the next step without further purification.

The Reference Compound 110 3,3-Dimethylbutyric acid ethylsulfanylcarbonyloxymethyl ester To a solution of t-butylacetic acid (0.025 mol, 3 g) in methanol is added tetrabutylammonium hydroxide (1 M / methanol, 25 ml). The mixture is stirred for 1 h and the solvent is removed with a residue. The residue is dissolved in 150 ml of methylene chloride and 150 ml of water and a solution of O-chloromethyl S-ethylcarbonate (0.025 mol, 3.85 f) is added in 50 ml of methylene chloride. The mixture is stirred at room temperature for 24 h. The separated layer of methylene chloride is washed with water, saline and dried over sodium sulfate. The solvent is removed under vacuum and the residue is stirred in 300 ml of ether for 24 h. The resulting white solid is filtered, the solid is discarded and the solvent is removed from the filtrate to give 6 g of a crude oil.

The Reference compound 111 To a stirred solution of this r of ethylsulfanylcarbonyloxymethyl of 3,3-dimethylbutyric acid (Reference Compound 110) (0.025 ml, 6 g) in methylene chloride at -20 ° C (dry ice / carbon tetrachloride) is added sulfuryl (0.025 mol, 3.5 g). After 10 min, 0.1 ml of boron trifluoride ethereate is added. The mixture is stirred at 0 ° C for 1 h, at room temperature for 30 min. The volatiles are removed by distillation to yield 4.9 g of the desired acid chloride.

Following the procedure of Reference Compound 111 the corresponding acid chloride which is used in Examples 112 to 120 is prepared.

The Reference Compound 112 N- (butoxycarbonyl) -N- (tert-butyl) benzyl glycinate The Reference Compound 113 N- (tert-butyl) -N- (isobutoxycarbonyl) benzyl glycinate The Reference Compound 114 N- (tert-butyl) -N- (methoxycarbonyl) benzyl glycinate The Reference Compound 115 N- (butoxycarbonyl) -N- (tert-butyl) glycine The Reference compound 116 25 N- (tert-butyl) -N- (isobutoxycarbonyl) glycine The Reference compound 117 N- (tert-butyl) -N- (methoxycarbonyl) glycine Reference compound 118 isobutoxycarbonyl N- (butoxycarbonyl) -N- (tert-butyl) glycinate Reference compound 119 isobutoxycarbonyl N- (tert-butyl) -N- (isobutoxycarbonyl) glycinate The Reference Compound 120 isobutoxycarbonyl N- (tert-butyl) -N- (methoxycarbonyl) glycinate The Reference Compound 121 4-nitrophenylcarbonate of (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl The product of the Reference example is prepared using the conditions described by R. Sakamoto et al, Chem. Pharm. Bull. 32 (6), 2241-2248 (1984).

The Reference Compound 122 4-Nitrophenyl (2-oxo-5-phenyl-1,3-dioxol-4-yl) methyl carbonate The product of the Reference Example is prepared using the conditions described by R. Sakamoto et al, Chem. Pharm. Bull. 32 (6), 2241-2248 (1984).

Reference compound 123 [5- (4-methoxyphenyl) -2-oxo-1,3-dioxol-4-yl] methyl 4-nitrophenyl carbonate The product of the Reference Example is prepared using the conditions described by R. Sakamoto et al, Chem. Pharm. Bull. 32 (6), 2241-2248 (1984).

Reference Compound 124 (2E) -3-phenylacrylate 4-tert-butyl-10,10-dimethyl-3,6-dioxo-2J-dioxa-4-aza-10-silaundec-1-yl Trans-cinnamic acid (23.1 mmol) and 1.0 M tetrabutylammonium hydroxide (22.2 mmol) in methanol are stirred for one hour, and the methanol is removed. THF is added. To this solution is added 2- (tert-butyl ((chloromethoxy) carbonyl) amino) -acetate of 2- (trimethylsilyl) ethyl (18.5 mmol) and the mixture is stirred at room temperature for 24 hr. The solvent is removed and the residue is diluted with ether. The resulting solution is washed with water and saline. The organic layer is dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 5.01 g (61%) MS (ESI) m / z 436.3.

Using substantially the same procedure as described above for Reference Compound 124 the following Reference compounds are prepared from the appropriate carboxylic acid: The Reference Compound 125 anthracene-9-carboxylate of 4-tert-butyl-10,10-dimethyl-3,6-dioxo-2J-dioxa-4-aza-10-silaundec-1-yl MS (ESI) m / z 510.3 The Reference Compound 126 4-benzoylbenzoate of 4-tert-butyl-10,10-dimethyl-3,6-dioxo-2J-dioxa-4-aza-10-silaundecyl MS (ESI) m / z 536.2 Example 1 2-methylpropanoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,8, 10a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl To a solution of n-Butylglycylcycline in acetonitrile / DMPA (1: 5), sodium carbonate is added. The reaction mixture is stirred for 5 min and 2-methyl - [(chlorocarbonyl) oxy] methyl propanoic acid ester is added and prepared according to the methods described in M. Folkmann and F.J. Lund, Synthesis, December 1990, 1159-1 166. Stirring is continued for about 30 to 45 minutes (or monitored by MS (ES)). Upon completion of the reaction, 0.5 mL of methanol is added and the mixture is poured gently into a mixture of isopropanol and ether. 1.0M HCl in ether is added and the solid filtered. The solid is dissolved in water and extracted with methylene chloride to give the product of the example. MS (ESI) m / z 730.28 (M + H); The following procedure of Example 1, and the corresponding acid chloride are prepared by the methods described in M. Folkmann and F.J. Lund, Synthesis, December 1990, 1159-1166 and N-butylglycylcycline or N-propylglycylcycline in the following Examples 2-41 are prepared Example 2 4-methoxybenzoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1 r8, 10a, 11-tetrahydroxy-10, 12-dioxo- 5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-methoxybenzoate and N-butylglycylcycline to give the product of the example.

Example 3 4-methylbenzoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-methylbenzoate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 778.3 ((M + H) +); Example 4 4-Fluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-fluorobenzoate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 782.3 ((M + H) +); Example 5 4-methylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -xoxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-methylbenzoate and N-propylglycylcycline to give the product of the example. MS (ESI) m / z 764.3 ((M + H) +); Example 6 4-methoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -xoxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-methoxybenzoate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 780.3 ((M + H) +); Example 7 Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl cyclobutanecarboxylate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 728.3 ((M + H) +); Example 8 4-Fluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -xoxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-fluorobenzoate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 768.3 ((M + H) +); Example 9 Pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using propanoic acid, 2,2-dimethyl-, [(chlorocarbonyl) oxy] methyl ester and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 730.3 ((M + H) +); Example 10 2-methylpropanoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -xoxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using propanoic acid, 2-methyl-, [(chlorocarbonyl) oxy] methyl ester and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 716.3 ((M + H) +); emplo 11 Phenylacetate of ( { [(2- { [(5aR, 6aS, 7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using benzeneacetic acid, [(chlorocarbonyl) oxy] methyl ester and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 764.3 ((M + H) + Example 12 Phenylacetate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using benzeneacetic acid, [(chlorocarbonyl) oxy] methyl ester and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 778.3 ((M + H) +) Example 13 Pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using propanoic acid, 2,2-dimethyl-, [(chlorocarbonyl) oxy] methyl ester and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 744.3 ((M + H) +); Example 14 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Benzyl-2-oxoethyl (propyl) carbamate The title compound is prepared by the procedure of Example 1, using benzyl chloroformate and N-propylglycylcycline in the presence of sodium carbonate and DMPU in acetonitrile to give the product of the example.

MS (ESI) m / z 706.3 ((M + H) +); HRMS: calculated for C36H43N5O10 HCl, 741.2777; found (ESI), 706.31133; Example 15 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amine} Ethyl -2-oxoethyl (propyl) carbamate The title compound is prepared by the procedure of Example 1, using ethyl chloroformate and N-propylglycylcycline in the presence of sodium carbonate and DMPU in acetonitrile to give the product of the example.

MS (ESI) m / z 644.3 ((M + H) +); HRMS: calculated for C3? H41N5O? 0 HCl, 679.2620; found (ESI +), 644.29398; Example 16 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Sobutyl-2-oxoethyl (propyl) carbamate The title compound is prepared by the procedure of Example 1, using isobutyl chloroformate and N-propylglycylcycline in the presence of sodium carbonate and DMPU in acetonitrile to give the product of the example.

MS (ESI) m / z 672.3 ((M + H) +); MS (ESI) m / z 336.9 ((M + 2H) 2+); HRMS: calculated for C33H45N5O10 HCl, 707.2933; found (ESI +), 672.32618 Example 17 Heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using heptanoic acid, [(chlorocarbonyl) oxy] methyl ester and N-butylglycylcycline to give the product of the example.

MS (ESI +) m / z 772.2 (M + H); HRMS: calculated for C38H53N5O12 2.00 HCl, 843.3224; found (ESI +), 772.37696; Example 18 Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl cyclobutanecarboxylate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 742.3 ((M + H) +); HRMS: calculated for C36H47N5O12 2.00 HCl, 813.2755; found (ESI +), 742.32898; Example 19 Heptanoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using heptanoic acid, [(chlorocarbonyl) oxy] methyl ester and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 758.4 ((M + H) +); HRMS: calculated for C 37 H 51 N 5 O 2 HCl, 793.3301; found (ESI +), 758.36175; Example 20 4-tert-butylbenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (butl) amino] carbonyl. )methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-tert-butylbenzoate and N-butylglycylcycline to give the product of the example.

MS (ESI +) m / z 820.2 (M + H); HRMS: calculated for C42H53N5O12 HCl, 855.3458; found (ESI +), 820.37684; Example 21 1, 1'-biphenyl-4-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (butyl) amino] carbonyl} oxy) put it The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl biphenyl-4-carboxylate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 840.3 ((M + H) +); HRMS: calculated for C44H49N5O12 HCl, 875.3145; found (ESI +), 840.34337; Example 22 3,5-dimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 3,5-dimethylbenzoate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 792.3 ((M + H) +); HRMS: calculated for C40H49N5O12 2.00 HCl, 863.2911; found (ESI +), 792.34378; Example 23 thiophene-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1, 8,10a, 11-tetrahydroxy -10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The compound of the title is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl thiophene-2-carboxylate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 770.1 ((M + H) +); HRMS: calculated for C36H43N5O12S HCl, 805.2396; found (ESI +), 770.27084; Example 24 1, 1'-btphenyl-4-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl biphenyl-4-carboxylate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 826.4 ((M + H) +); MS (ESI) m / z 414 ((M + 2H) 2+); HRMS: calculated for C43H47N5O? 2 HCl, 861.2988; found (ESI +), 826.32782; Example 25 thiophene-2-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-b¡s (d-methylamino) -1, 8,10a, 11 -tetrahydroxy-10,12-d -oxo-5,5a, 6,6aJ, 10,10a, 12-octahid The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl thiophene-2-carboxylate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 756.3 ((M + H) +); MS (ESI) m / z 378.9 ((M + 2H) 2+); HRMS: calculated for C35H41N5O12S HCl, 791.2239; found (ESI +), 756.2532; Example 26 3,5-dimethylbenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy -10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 3,5-dimethylbenzoate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 778.3 ((M + H) +); HRMS: calculated for C39H47N5O12 HCl, 813.2988; found (ESI +), 778.32984; Example 27 thiophen-3-carboxylic acid ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl thiophene-3-carboxylate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 756.3 ((M + H) +); HRMS: calculated for C35H41N5O12S HCl, 791.2239; found (ESI +), 756.2547; Example 28 4-tert-Butylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 4-tert-butylbenzoate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 806.4 ((M + H) +); MS (ESI) m / z 403.9 ((M + 2H) 2+); HRMS: calculated for C41H5? N5O12 HCl, 841.3301; found (ESI +), 806.36024; Example 29 thiophene-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl] oxy) meth the The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl thiophene-3-carboxylate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 770.3 ((M + H) +); HRMS: calculated for C36H43N5O12S HCl, 805.2396; found (ESI +), 770.27028; Example 30 2-furoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1,8,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl furoate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 752.2 ((M-H) -); HRMS: calculated for C 36 H 43 N 5 O 3 HCl, 789.2624; found (ESI +), 754.29242; Example 31 2-furoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12 -xoxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl furoate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 740.19 (M + H); Example 32 Acetate of 1 - ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1, 8, 10a, 11 • tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) ethyl The title compound is prepared by the procedure of Example 1, using 1 - [(chlorocarbonyl) oxy] ethyl acetate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 716.14 (M + H); HRMS: calculated for C34H45N5O12, 715.3065; found (ESI +), 716.31469; Example 33 Cyclohexanecarboxylate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110,1-tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using cyclohexanecarboxylic acid, [(chlorocarbonyl) oxy] methyl ester and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 756.08 (M + H); HRMS: calculated for C37H49N5O12, 755.3378; found (ESI +), 756.34507; Example 34 Cyclohexanecarboxylate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo- 5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using cyclohexanecarboxylic acid, [(chlorocarbonyl) oxy] methyl ester and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 70.64 (M + H); HRMS: calculated for C38H5? N5O12 HCl, 805.3301; found (ESI +), 770.36093; Example 35 3,3-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using butanoic acid, 3,3-dimethyl-, [(chlorocarbonyl) oxy] methyl ester and N-propylglycylcycline to give the product of the example.

MS m / z 00-304761 LMS; HRMS: calculated for C 36 H 49 N 5 O 2 HCl, 779.3145; found (ESI +), 744.34539; Example 36 3,3-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using butanoic acid, 3, 3-dimethyl-, [(chlorocarbonyl) oxy] methyl ester and N-butylglycylcycline to give the product of the example.

MS m / z 00-304762LMS; HRMS: calculated for C37H51N5O12 HCl, 793.3301; found (ESI +), 758.36071; Example 37 2,2-dimethylbutanoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl 2,2-dimethylbutanoate and N-propylglycylcycline to give the product of the example.

MS m / z 00-304763LMS; HRMS: calculated for C36H49N5O12 HCl, 779.3145; found (ESI +), 744.3452; Example 38 Cyclopentylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl cyclopentylacetate and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 770.7 (M + H); HRMS: calculated for C38H51N5O? 2 HCl, 805.3301; found ESI +), 770.36062; Example 39 adamantan-1-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using adamantan-1-carboxylate [(chlorocarbonyl) oxy] methyl and N-butylglycylcycline to give the product of the example.

MS (ESI) m / z 822.9 (M + H); HRMS: calculated for C42H55N5O? 2 HCl, 857.3614; found ESI +), 822.39184; Example 40 Cyclopentylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-b¡s (dimethylammon) -1,8,110a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl cyclopentylacetate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 754.2 ((M-H) -); HRMS: calculated for C 37 H 49 N 5 O 12 HCl, 791.3145; found (ESI +), 756.34433; Example 41 adamantan-1-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methylo The title compound is prepared by the procedure of Example 1, using [(chlorocarbonyl) oxy] methyl adamantan-1-carboxylate and N-propylglycylcycline to give the product of the example.

MS (ESI) m / z 808.8 (M + H); HRMS: calculated for C41H53N5O12 HCl, 843.3458; found (ESI +), 808.37604; Example 42 3,3-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl.} Oxy) methyl To a solution of 9-amino-minocycline monosulfate (0.0055 mole, 3.135 g, 1 equivalent) in a mixture of 12 ml of acetonitrile and 50 ml of DMPU is added 1.66 g (3 equivalents) of tritytylamine and Reference Compound 109 ( 0.012 mole, 4.88 g), [Tert-butyl- (2-isobutoxycarbonyloxy-2-oxo-ethyl) -carbamoyloxy) -methyl ester of 3,3-Dimethyl-butyric acid. The reaction is stirred at room temperature for 2 hours, 1 mL methanol is added, it is stirred for 5 min. and the mixture is poured into a mixture of 500 ml of ether and 100 ml of isopropanol. The solid is collected and purified by extraction to give 1.5 g of the product of the example.

MS (ESI) m / z 758.55 (M + H); HRMS: calculated for C37H5iN5O12 HCl, 793.3301; found (ESI +), 758.36201; Example 43 Prepared according to Scheme II 4-Tert-butylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 57 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 820.37 (M + H); HRMS: calculated for C42H53N5O12 HCl, 855.3458; found (ESI +), 820.37574; Example 44 2,2-Dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl The title compound is prepared by reacting the reaction product of N- (tert-butyl) -N- (. {[[(2,2-dimethylbutanoyl) oxy] methoxy.} Carbonyl) glycine using the conditions of Reference Compound 109 with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 758.63 (M + H); HRMS: calculated for C 37 H 51 N 5 12 HCl, 793.3301; found (ESI +), 758.36119; Example 45 Prepared according to Scheme 2 2-methylpropanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10,12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} - 2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl Reference Compound 58 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 730.38 (M + H); HRMS: calculated for C35H47N5O12 HCl, 765.2988; found (ESI +), 730.33002; Example 46 Cyclopentanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl] oxy) methylo The Reference compound 59 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 754.09 ((M-H) -); HRMS: calculated for C 37 H 49 N 5 O 12 HCl, 791.3145; found (ESI +), 378.67644; Example 47 4-methylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1,8,110a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methylo Reference Compound 60 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example MS (ESI) m / z 778 34 (M + H), HRMS calculated for C 39 H 47 N 5 O 2, 777 3221, found (ESI +), 778 33065, Example 48 Prepared according to Scheme II heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (am? nocarbon? l) -4J-b? s (d? met? lam? no) -1, 8 , 10a, 11 -tetrah? Drox? -10, 12-d? Oxo-5,5a, 6,6aJ, 10, 10a, 12-octah? Drotetracen-2-? L] am? No.}. oxoet? l) (tert-but? l) am? no] carbon? l.} ox?) met? lo Reference Compound 61 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the example product MS (ESI) m / z 772.45 (M + H); HRMS: calculated for CsßH8NsOu HCl, 807.3458; found (ESI +), 772.37695; Example 49 Prepared according to Scheme II propionate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 62 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 716.3 (M + H); HRMS: calculated for C3 H45N5O12 HCl, 751.2832; found (ESI +), 716.31461; Example 50 cyclohexanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference Compound 63 is it reacts under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 770.36 (M + H); HRMS: calculated for C38H5iN5O12 HCl, 805.3301; found (ESI-), 768.34546; Example 51 Prepared according to Scheme 2 3,5-dimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl Reference Compound 64 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 792.32 (M + H); HRMS: calculated for C o H 49 N 5 O 12 HCl, 827.3145; found (ESI +), 792.34613; Example 52 4-Fluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl Reference Compound 65 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 782.3 (M + H); HRMS: calculated for C38H44FN5O12 HCl, 817.2737; found (ESI +), 782.30406 Example 53 Prepared according to Scheme 2 3-methylbutanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 66 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 744.37 (M + H); HRMS: calculated for C3eH49N5O12 HCl, 779.3145; found (ESI +), 744.34481; Example 54 Cyclopentylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl Reference Compound 67 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 770.4 (M + H); HRMS: calculated for C38H5? N5O12 HCl, 805.3301; found (ESI +), 770.35888; Example 55 Prepared according to Scheme 2 4- (trifluoromethyl) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy- 10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino] -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methylation Reference Compound 68 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 832.2 (M + H); MS (ESI) m / z 416.6 (M + 2H); HRMS: calculated for C39H44F3N5O12 HCl, 867.2705; found (ESI +), 832.30055; Example 56 Cyclopropanecarboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 69 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 728.34 (M + H); HRMS: calculated for C35H45N5O12 HCl, 763.2832; found (ESI +), 728.31289; Example 57 Prepared according to Scheme 2 adamantan-1-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 70 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 822.5 (M + H); HRMS: calculated for C42H55N5O12 HCl, 857.3614; found (ESI +), 822.39237 Example 58 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Butyl-2-oxoethyl (tert-butyl) carbamate The title compound is prepared by the procedure of Example 42, using 1 equivalent of 9-amino-minocycline and 2 equivalents of isobutoxycarbonyl N- (butoxycarbonyl) -N- (tert-butyl) glycinate Reference Example 118 to give the product of example.

MS (ESI) m / z 686.4 (M + H); HRMS: calculated for C34H47N5O10 HCl, 721.3090; found (ESI +), 686.34079; Example 59 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Isobutyl-2-oxoethyl (tert-butyl) carbamate The title compound is prepared by the procedure of Example 42, using 1 equivalent of 9-amino-minocycline and 2 equivalents of isobutoxycarbonyl N- (tert-butyl) -N- (isobutoxycarbonyl) glycinate, Reference Example 119 to give the product of the example.

MS (ESI) m / z 686.3 (M + H); MS (ESI) m / z 1371.7 (2M + H); HRMS: calculated for C34H47N5O10 HCl, 721.3090; found (ESI-), 684.32433; Example 60 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amine} Isobutyl-2-oxoethyl (tert-butyl) carbamate The title compound is prepared by the procedure of Example 42, using 1 equivalent of 9-amino-minocycline and 2 equivalents of isobutoxycarbonyl N- (tert-butyl) -N- (methoxycarbonyl) glycine. Reference Example 120 for give the product of the example.

MS (ESI) m / z 644.3 (M + H); MS (ESI) m / z 322.6 (M + 2H); HRMS: calculated for C3? H41N5O10 HCl, 679.2620; found (ESI-), 642.27736; Example 61 pentanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methylo The Reference compound 71 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 742 (M-H); HRMS: calculated for C36H49N5O12 HCl, 779.3145; found (ESI +), 744.34613; Example 62 Prepared according to Scheme II Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 72 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 742.4 (M + H); Example 63 3-cyclohexylpropanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (diametholamino) -1, 8, 10a, 11 -tetrahydrox -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 73 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 796.4 (M-H); Example 64 (4-fluorophenoxy) acetate ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 74 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 812.4 (M + H); MS (ESI) m / z 406.7 (M + 2H); HRMS: calculated for C39H46FN5O13 HCl, 847.2843; found ESI +), 812.31518; Example 65 ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo cyclohexyl acetate -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 75 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 782.2 (M-H); HRMS: calculated for C39H53N5O12 HCl, 819.3458; found (ESI +), 784.37621; Example 66 2,6-dimethylbenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 76 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 790.4 (M-H); HRMS: calculated for C40H49N5O12 HCl, 827.3145; found (ESI +), 792.34423; Example 67 ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo phenylacetate -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 77 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 778.3 (M + H); HRMS: calculated for C39H47N5O12 HCl, 813.2988; found (ESI +), 778.3299; Example 68 pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 78 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 744.5 (M + H); HRMS: calculated for C36H49N5O12 HCl, 779.3145; found (ESI +), 744.34434; Example 69 Prepared according to Scheme II 1 - . 1-benzofuran-2-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 79 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 804.4 (M + H); MS (ESI) m / z 402.7 (M + 2H); HRMS: calculated for C 0 H 5 N 5 O 3 HCl, 839.2781; found (ESI +), 804.30779; Example 70 1-Benzofuran-2-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydrox -10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl Reference Compound 80 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 767.4 (M + H); HRMS: calculated for C37H46N6O12, 766.3174; found (ESI +), 767.32406; Example 71 1, 1'-biphenyl-4-carboxylate from ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10,12-d-oxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl The Reference compound 81 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 838.2 (M-H); MS (ESI) m / z 113 (TFA-H); HRMS: calculated for C44H49N5O? 2 HCl, 875.3145; found (ESI +), 840.34496; Example 72 4-methoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl] oxy) methylo The Reference compound 82 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 792.3 (M-H); HRMS: calculated for C39H47N5? 13 HCl, 829.2937; found (ESI +), 794.32511; Example 73 Prepared according to Scheme II 1 H -indole-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 1 1 -tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy )methyl The Reference compound 83 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 803.4 (M + H); HRMS: calc'd for C40H46N6O12 HCl, 838.2941; found (ESI +), 803.32375; Example 74 diphenylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1, 8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl The Reference compound 84 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 852.4 (M-H); HRMS: calculated for C45H51N5O? 2 HCl, 889.3301; found (ESI-), 852.3463; Example 75 Prepared according to Scheme 6 thiophene-2-carboxylate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11-tetrahydroxy-10,12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl thiophene-2-carboxylate in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 655.2 (M-H); HRMS: calculated for C3oH32N4OnS HCl, 692.1555; found (ESI +), 657.18613; Example 76 Prepared according to Scheme 6 4-fluorobenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-b¡s (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl 4-fluorobenzoate in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 667.2 (M-H); HRMS: calculated for C 32 H 33 FN 4 OH HCl, 704.1897; found (ESI +), 669.22024; Example 77 Prepared according to Scheme 6 3,5-dimethylbenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl 3,5-dimethylbenzoate in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 679.2 (M + H); HRMS: calculated for C34H38N4On HCl, 714.2304; found (ESI +), 679.26076; Example 78 Prepared according to Scheme 6 pivalate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6 , 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl pivalate in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 631.2 (M + H); HRMS: calculated for C30H38N4On HCl, 666.2304; found (ESI +), 631.26094; Example 79 Prepared according to Scheme 6 3,3-dimethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl 3,3-dimethylbutanoate in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 643.3 (M-H); HRMS: calculated for C31H40N4On HCl, 680.2460; found (ESI +), 645.27632; Example 80 Prepared according to Scheme 6 2,2-dimethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using 2,2-dimethylbutanoate [(chlorocarbonyl) oxy] methyl in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 645.2 (M + H); HRMS: calculated for HCl, 680.2460; found (ESI +), 645.27637; Example 81 1-naphthoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 85 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 812.5 (M-H); HRMS: calculated for C42H47N5O12 HCl, 849.2988; found (ESI +), 814.33029; Example 82 2-naphthoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl Reference Compound 86 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 812.5 (M-H); HRMS: calcd for C42H47N5O12 HCl, 849.2988; found (ESI +), 814.33004; Example 83 1 - . 1-methyl-1 H-indole-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amine] carbonyl} oxy) methyl Reference Compound 87 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 815.5 (M-H); HRMS: calculated for C41H48N6O? 2 HCl, 852.3097; found (ESI-), 815.32484; Example 84 quinolin-2-carboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl Reference Compound 88 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 813.5 (M-H); HRMS: calculated for C4? H46N6O12 HCl, 850.2941; found (ESI +), 815.32509; Example 85 Prepared according to Scheme 6 2-ethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl 2-ethylbutanoate in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 643.4 (M-H); MS (ESI) m / z 1287.7 (2M-H); HRMS: calculated for C31H40N OH HCl, 680.2460; found (ESI +), 645.27618; Example 86 Prepared according to Scheme 6 Cyclopentylacetate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6 , 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl cyclopentylacetate instead of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 655.3 (M-H); MS (ESI) m / z 1311.7 (2M-H); HRMS: calculated for C32H40N4On HCl, 692.2460; found (ESI +), 657.27572; Example 87 Prepared according to Scheme 6 4-tert-Butylbenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl The title compound is prepared by the procedure of Example 42, using [(chlorocarbonyl) oxy] methyl 4-tert-butylbenzoate in place of Reference Compound 109 to give the product of the example.

MS (ESI) m / z 705.1 (M-H); MS (ESI) m / z 1410.9 (2M-H); HRMS: calculated for C36H42N4On HCl, 742.2617; found (ESI +), 707.29336; Example 88 nicotinate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl Reference Compound 89 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 763.5 (M-H); HRMS: calculated for C3 H44N6O? 2 HCl, 800.2784; found (ESI +), 765.30896; Example 89 isonicotinate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,8, 10a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} - Reference Compound 90 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

HRMS: calculated for C 37 H 44 N 6 O 2 HCl, 800.2784; found (ESI +), 765.3117; Example 90 2,6-difluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl Reference Compound 91 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 798.2 (M-H); HRMS: calculated for C38H43F2N5O12 HCl, 835.2643; found (ESI +), 800.29464; Example 91 2-Fluorobenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11 -tetrahydroxy-10, 12 -xoxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl Reference Compound 92 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 780 (M-H); HRMS: calculated for HCl, 817.2737; found (ESI +), 782.30558; Example 92 2- (trifluoromethyl) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl Reference Compound 93 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

HRMS: calculated for C39H44F3N5O12 HCl, 867.2705; found (ESI +), 832.30026; Example 93 4-pyrrolidin-1-ylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy )methyl Reference Compound 94 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 833.4 (M + H); HRMS: calculated for C42H52N6O12 HCl, 868.3410; found (ESI-), 831.3565; Example 94 1, 1'-biphenyl-2-carboxylate from ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) put it Reference Compound 95 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 838.4 (M-H); HRMS: calculated for C4 H49N5O12 HCl, 875.3145; found (ESI +), 840.34553; Example 95 2,4,6-trimethylbenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. )methyl Reference Compound 96 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 804.5 (M-H); HRMS: calculated for C41H5? N5O12 HCl, 841.3301; found (ESI +), 806.36101; Example 96 4-isopropoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 1-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 97 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 820.2 (M-H); HRMS: calculated for C41H51N5O13 HCl, 857.3250; found (ESI-), 820.34117; Example 97 3,4,5-trimethoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11 -tetrahydrox -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl Reference Compound 98 is reacted under the conditions of Reference Compound 109 and the product of said reaction is additionally contacted with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 852.2 (M-H); HRMS: calculated for C41H5? N5O15 HCl, 889.3148; found (ESI +), 854.34728; Example 98 3,5-dimethoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrah Droxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydro-tetracen-2-yl] amino} -2-oxoethyl) (tert-butyl) amino] carbonyl .}. oxy) methyl The Reference compound 99 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 822.1 (M-H); HRMS: calculated for C 0H49N5O14, 824.3349; found (ESI +), 824.3351; Example 99 (2E) -3-phenylprop-2-enoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a , 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl Reference Compound 100 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 788.3 (M-H); HRMS: calculated for C 0H47N5O? 2 HCl, 825.2988; found (ESI +), 790.33068; Example 100 3-Methyl-1-benzofuran-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a , 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbon L.}. Oxy) metllo The Reference compound 101 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 816.5 (M-H); HRMS: calculated for C41H47N5O13 HCl, 853.2937; found (ESI +), 818.3234; Example 101 [3,5- bis (trifluoromethyl) phenyl] acetate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8] 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl Reference Compound 102 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 912 (M-H); HRMS: calculated for C41H45F6N5O12 HCl, 949.2736; found (ESI +), 914.30367; Example 102 4- (heptyloxy) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl The Reference compound 103 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 876.1 (M-H); HRMS: calculated for HCl, 913.3876; found (ESI +), 878.41791; Example 103 2- (2-phenylethyl) benzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11- tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoetyl) (tert-butyl) amino] carbonyl .}. oxi) methyl Reference Compound 104 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 866.5 (M-H); HRMS: calculated for C46H53N5O? 2 HCl, 903.3458; found (ESI), 868.37357; Example 104 4- (dodecyloxy) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl. oxy) methyl Reference Compound 105 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 946.7 (M-H); HRMS: calculated for C5oH69N5Oi3 HCl, 983.4659; found (ESI-), 946.48106; Example 105 4- (acetylamino) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) meth the The Reference compound 106 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 819.1 (M-H); HRMS: calculated for C40H48N6Oi3 HCl, 856.3046; found (ESI-), 819.32051; Example 106 anthracene-9-carboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) meti The Reference compound 107 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 864.3 (M + H); HRMS: calculated for C46H49N5O12 HCl, 899.3145; found (ESI-), 862.32855; Example 107 4-benzoyl benzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl The Reference compound 108 is reacted under the conditions of Reference Compound 109 and the product of said reaction additionally comes in contact with 9-aminominocycline using the conditions of Example 42 to give the product of the example.

MS (ESI) m / z 866.3 (M-H); HRMS: calculated for C 45 H 49 N 5 O 13 HCl, 903.3094; found (ESI-), 866.32405; Example 108 2-. { [(7S, 10aR) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino} (5-Methyl-2-oxo-1,3-dioxol-4-yl) -2-oxoethyl (propyl) carbamate To a solution of 107 mg (0.166 mmol) or N-propyl-glycylcycline (N-prop-glycyl) in DMPU (2 ml) is added 5 equivalents of sodium carbonate (95 mg, 0.9 mmol) followed by 2 equivalents of 4-Nitrophenyl carbonate of (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl (95 mg, 0.33 mmol) the Reference compound 121 and stirred for 2 hr at room temperature. The reaction mixture is filtered through diatomaceous earth and the filtrate is added to a mixture of (1: 4) (20 ml) ether: isopropyl alcohol and HCl (1 M in ether) is added and the solid formed is added. it is filtered, it is redissolved in water, the pH is adjusted to approximately 2 and extracted with methylene chloride to give 15 mg of the exemplified product.

MS (ESI) m / z 728.5 (M + H); MS (ESI) m / z 364.8 (M + 2H); HRMS: calculated for C34H41N5O13, 727.2701; found (ESI +), 728.27606; Example 109 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12 -octahydrotetracen-2-yl] amino} (5-Methyl-2-oxo-1,3-dioxol-4-yl) methyl-2-oxoethyl (butyl) carbamate The title compound is prepared by the procedure of Example 108, using N-butyl-glycylcycline (N-bu-glycyl) and 4-nitrophenyl carbonate (5-methyl-2-oxo-1,3-dioxol-4-yl). ) methyl of Reference Compound 121 to give the product of the example.

MS (ESI) m / z 742.3 ((M + H) +); Example 110 2-. { [(7R, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino} -2-oxoethyl (propyl) carbamate (2-oxo-5-phenyl-1,3-dioxol-4-yl) methyl The title compound is prepared by the procedure of Example 108, using N-propyl-glycylcycline (N-prop-glycyl) and 4-nitrophenyl carbonate (2-oxo-5-phenyl-1,3-dioxol-4-yl). ) methyl of Reference Compound 122 to give the product of the example.

MS (ESI) m / z 790.3 ((M + H) +); HRMS: calculated for C3gH43N5O? 3, 789.2857; found (ESI +), 790.29243; Example 111 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino} [5- (4-methoxyphenyl) -2-oxo-1,3-dioxol-4-yl] -2-oxoethyl (propyl) carbamate The title compound is prepared by the procedure of Example 108, using N-propyl-glycylcycline (N-prop-glycyl) and [5- (4-methoxyphenyl) -2-0X0-1, 3-dioxol 4-nitrophenyl carbonate. -4-yl] methyl of Reference Compound 123 to give the product of the example.

MS (ESI) m / z 820.3 ((M + H) +); Example 112 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino} -2-Oxoethyl (butyl) carbamate of (2-oxo-5-phenyl-1,3-dioxol-4-yl) methylo The title compound is prepared by the procedure of Example 108, using N-butyl-glycylcycline (N-bu-glycyl) and 4-nitrophenyl carbonate (2-oxo-5-phenyl-1,3-dioxol-4-yl). ) enter it from Reference Compound 122 to give the product of the example.

MS (ESI) m / z 804.12 (M + H); MS (ESI) m / z 402.58 (M + 2H); HRMS: calculated for C40H45N5O13, 803.3014; found (ESI +), 804.30946; Example 113 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12 -octahydrotetracen-2-yl] amino} [5- (4-methoxyphenyl) -2-oxo-1,3-dioxol-4-yl] methyl-2-oxoethyl (butyl) carbamate The comp of Example 108, using N-butyl-glycylcycline (N-bu-). glycyl) and [5- (4-methoxy-phenyl) -2-oxo-1,3-dioxol-4-yl] methyl-4-nitrophenyl carbonate of Reference Compound 123 to give the product of the example.

Claims (38)

1. CLAIMS 1. A compound represented by Formula (I); where: (l) A is a part is absent; Ri is selected from hydrogen, -OH, amino, -NR7R8, halogen, alkyl of 1 to 12 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms. carbon, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can optionally be substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) - NH-, aralkyl, aryloxy, heterocyclyl and phenyl, alkenyl having from 2 to 12 carbon atoms optionally their substituted with 1 to 3 substituents independently selected from the group of phenyl, heteroaryl, halogen, amino, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino , carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aryloxy, heterocyclyl and phenyl, and alkynyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the halogen group , amino, cyano, alkyl, hydroxyl, and alkoxy; R2 is selected from hydrogen, halogen, alkyl of 1 to 12 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 atoms carbon, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 independently selected substituents of halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, alkenyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 their independently selected from the group of phenyl, heteroaryl, halogen, amino, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl and aryl of the N- (alkyl of 1 to 12 carbon atoms) -aryl can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, and alkynyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group halogen, amino, cyano, alkyl, hydroxyl, and alkoxy; R3 is a part of R9, R 4 is selected from hydrogen, alkyl of 1 to 12 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amine, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms , phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N - (alkyl of 1 to 12 carbon atoms) -alloy may be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amine, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl , aryl-C (O) -, CH 3 -C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, alkenyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the phenyl group, heteroaryl , halogen, amino, cyano, alkyl, hydroxyl, alkoxy, aryl, alkynyl and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl and aryl of N- (alkyl of 1 to 12 carbon atoms) ) -aryl can be optionally substituted with 1 to 3 substituents independently selected from and halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, alkynyl of 2 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group halogen, amino, cyano, alkyl, hydroxyl, and alkoxy, aryl of 6, 10 or 14 carbon atoms said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxy, alkyl, haloalkyl, alkoxy, amine, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH -, aralkyl, aryloxy, heterocyclyl and phenyl, N- (alkyl of 1 to 12 carbon atoms) -aryl, said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino , dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, aralkyl of 7 to 16 carbon atoms optionally substituted, aroyl of 7 to 13 atoms optionally substituted carbon, SR3, optionally substituted heteroaryl and optionally substituted heteroarylcarbonyl; R5 is selected from alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl of 6, 10 or 14 atoms of carbon, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl, can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, optionally substituted aralkyl of 7 to 16 carbon atoms is, aroyl, -CH2 (CO) OCH2aryl, said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamine, dialkylamino, carboxyl, alkoxycarbonyl, aryloxy and phenyl, optionally substituted alkenyl of 2 to 12 carbon atoms, optionally substituted heteroaryl, optionally substituted aryl of 6, 10 or 14 carbon atoms, optionally substituted alkynyl of 2 to 12 carbon atoms, cycloalkyl of 3 to 6 atoms in ring, aryl-CH = CH-, cycloalkyl-alkyl; and adamantly; R6 is selected from hydrogen, alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, aryloxy and N- (alkyl of 1 to 12 carbon atoms) -aryl, wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl may be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamine, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH 3 -C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, and cycloalkyl of 3 to 6 carbon atoms; R7 and R8 are each independently H or alkyl of 1 to 12 carbon atoms or R7 and R8 when they are optionally taken together with the nitrogen atom to which each is bound form a 3 to 8 membered heterocyclyl ring; R9 is aralkyl of 7 to 16 carbon atoms optionally substituted or alkyl of 1 to 12 carbon atoms; R10 is H or alkyl of 1 to 12 carbon atoms; or a pharmaceutically acceptable salt thereof. A compound according to claim 1, wherein Ri is -NR7R8, R7 is hydrogen, R8 is methyl, ethyl, n-propyl, n-butyl, 1-methylethyl, 1-methylpropyl, 2-methylpropyl or 1, 1- dimethylethyl or a pharmaceutically acceptable salt thereof. 3. A compound according to claim 1, wherein Ri is -NR7R8, R7 is methyl or ethyl, R8 is methyl, ethyl, n-propyl, 1-methylethyl, n-propyl, 1-methylpropyl, or 2-methylpropyl or a pharmaceutically acceptable salt thereof. 4. A compound according to claim 1, wherein Ri is -NR7R8? R7 and R8 are taken together with the nitrogen atom to which each is subject to form a 3- to 8-membered heterocyclyl ring or a pharmaceutically acceptable salt thereof. 5. A compound according to any one of claims 1 to 5, wherein R2 is H or a pharmaceutically acceptable salt thereof. 6. A compound according to any one of claims 1 to 5, wherein A is a part or a pharmaceutically acceptable salt thereof. 7. A compound according to any one of claims 1 to 5, wherein A is absent or a pharmaceutically acceptable salt thereof. 8. A compound according to any one of claims 1 to 7, wherein R3 is a part or a pharmaceutically acceptable salt thereof. 9. A compound according to any one of claims 1 to 7, wherein R3 is a part or a pharmaceutically acceptable salt thereof. 10. A compound according to any one of claims 1 to 7, wherein R3 is a part and Re and Rio are H or a pharmaceutically acceptable salt thereof. 11. A compound according to any one of claims 1 to 7, wherein R3 is a part and Re and Rio are H or a pharmaceutically acceptable salt thereof. 12. A compound according to any one of claims 1 to 7, wherein R3 is R9 or a pharmaceutically acceptable salt thereof. 13. A compound according to claim 1, wherein A is a part of, R3 is a part of R5 is aryl of 6 carbon atoms or a pharmaceutically acceptable salt thereof. 14. A compound according to claim 1, wherein A is a part of R3 is a part of R is 1,1-dimethylethyl and R 5 is aryl of 6 carbon atoms or a pharmaceutically acceptable salt thereof. 15. A compound according to claim 1, wherein A is a part R2 is hydrogen; R3 is a part of R is selected from alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, year, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl, and aryloxy wherein said aryl and aryloxy is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryloxy and phenyl; R5 is selected from alkyl of 1 to 12 carbon atoms optionally substituted with 1 to 3 substituents independently selected from the group of halogen, amino, cyano, cycloalkyl of 3 to 6 carbon atoms, alkyl of 1 to 12 carbon atoms, phenyl, hydroxyl, alkoxy of 1 to 12 carbon atoms, N-alkyl of 1 to 12 carbon atoms, N-cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 3 to 8 ring atoms, aryl of 6, 10 or 14 atoms of carbon, and aryloxy wherein said aryl, aryloxy and aryl of N- (alkyl of 1 to 12 carbon atoms) -aryl, can be optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxyl , alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryl-C (O) -, CH3-C (O) -NH-, aralkyl, aryloxy, heterocyclyl and phenyl, aralkyl of 7 to 16 carbon atoms optionally substituted carbon, aroyl, -CH2 (CO) OCH2aryl, said aryl is optionally substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, alkenyl, hydroxy, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, aryloxy and phenyl, optionally substituted aryl, aryl of 6, 10 or 14 optionally substituted carbon atoms, cycloalkyl of 3 to 6 ring atoms, aryl-CH = CH-, cycloalkyl-alkyl; and adamantyl; R6 is hydrogen; R and R8 are each independently H or alkyl of 1 to 12 carbon atoms; R9 is aralkyl of 7 to 16 optionally substituted carbon atoms or alkyl of 1 to 12 carbon atoms; or a pharmaceutically acceptable salt thereof. 16. A compound according to claim 1, selected from the groups or pharmaceutically acceptable salts thereof: 2-methylpropanoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,11a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl, y) oxy) methyl, 4-methoxybenzoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-b¡s (dimethylamino) -1,8,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl, 4-methylbenzoate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 4-fluorobenzoate of (. { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5.5, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 4-methylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, 4-methoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10,12 -dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, 4-Fluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methylo, Pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl, y) oxy) methyl, 2-methylpropanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10,12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo phenylacetate -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, phenylacetate of ( { (2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6, 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d-methylamino) -1,8,8, 10a, 11-tetrahydroxy-10, 12 -Dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl, Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 4-tert-Butylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butl) amino] carbonyl.} Oxy) methyl, 1, 1 '-biphenyl-4-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (butl) amino] carbon I. oxy) methyl, 3,5-dimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 1, 1 β-biphenyl-4-carboxylate from ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-b¡s (dimethylamino) -1, 8,10a , 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl. oxy) methyl, 3,5-dimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, 4-tert-Butylbenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5, 5a, 6, 6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl , 1 - ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,15,1-tetrahydroxy-10,16 acetate -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) ethyl, cyclohexanecarboxylate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, cyclohexanecarboxylate of ( { [(2- { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (diametholamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) meth, 3,3-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (propyl) amino] carbonyl] oxy) methylo, 3,3-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 2,2 -dimethylbutanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, Cyclopentylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl, y) oxy) methyl, adamantan-1-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl,.} Oxy) methyl, Cyclopentylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11 -tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} oxy) methyl, adamantan-1-carboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl] oxy) methyl , 3,3-dimethylbutanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) meth the, 4-tert-Butylbenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. )methyl, 2,2-dimethylbutanoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1, 8,10a, 11-tetrahydrox -10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl, 2-methylpropanoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy )methyl, Cyclopentanecarboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (tert-butyl) amino] carbonyl] oxy) methylo , 4-methylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, heptanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl, yl) oxy, and 4-methoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl. 17. A compound according to claim 1 selected from the group 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Benzyl-2-oxoethyl (propyl) carbamate, 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a , 12-octahydrotetracen-2-yl] amino} Ethyl -2-oxoethyl (propyl) carbamate, and 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11 -tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetran-2-yl] amine} Isobutyl-2-oxoethyl (propyl) carbamate. or pharmaceutically acceptable salts thereof. 18. A compound according to claim 1 selected from the group thiophene-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) methyl, 2-carboxylate-2-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy -10,12-d-oxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl. )methyl, thiophene-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl, thiophene-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} Oxy) meth, 2-furoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (butyl) amino] carbonyl.} oxy) methyl, and 2-furoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d-methylamino) -1,8,8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5, 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (propyl) amino] carbonyl.} Oxy) methyl. or pharmaceutically acceptable salts thereof. 19. A compound according to claim 1 selected from the propionate group of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl} oxy) methyl, cyclohexanecarboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11 -tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methylo, 3,5-dimethylbenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d-methylamino) -1, 8,10a, 11-tetrahydroxy -10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy )methyl, 4-Fluorobenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1,8,110a, 11 -tetrahydroxy-10, 12 -Dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 3-Methylbutanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10,12 -dixo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, Cyclopentylacetate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 4- (trifluoromethyl) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl] oxy) methyl, Cyclopropanecarboxylate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy-10,12-dioxo -5.5a, 6.6aJ, 10,10a, 12-octahydrotetran-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, adamantan-1-carboxylate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo- 5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d-methylamino) -1,8,10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino} Butyl-2-oxoethyl (tert-butyl) carbamate, 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Isobutyl-2-oxoethyl (tert-butyl) carbamate, 2-. { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-Octahydrotetracen-2-yl] amino} Methyl -2-oxoethyl (tert-butyl) carbamate, pentanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, Cyclobutanecarboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl, yl) oxy) methyl, 3-cyclohexylpropanoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl.} oxy) methylo , (4-fluorophenoxy) acetate ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-cyclohexyl acetate -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amine.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2,6-dimethylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl] oxy) met the, ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo phenylacetate -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, pivalate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11 -tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 1, 1'-biphenyl-4-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl .}. oxy) methyl, 1 - . 1-naphthoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1,8,110a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 2-naphthoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11 -tetrahydroxy-10, 12 - dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 2,6-difluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8, 10a, 11 -tetrahydroxy- 10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-Fluorobenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 2- (trifluoromethyl) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) meti, 1, 1'-biphenyl-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl .}. oxy) methyl, 2,4,6-trimethylbenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. )methyl, 4-isopropoxybenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -xoxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) meth, 3,4,5-trimethoxybenzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1,8,110a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , 3,5-dimethoxybenzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10 , 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, (2E) -3-phenylprop-2-enoate from ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a , 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxi) methyl, [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) [3,5-bis (trifluoromethyl) phenyl] acetate] -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amine.} -2-oxoethyl) (Terc-but L) amino] carbonyl.} Oxy) meth, 4- (heptyloxy) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy -10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl , 2- (2-phenylethyl) benzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11- tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.] oxy) methyl, 4- (dodecyloxy) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamine) -1, 8,10a, 11-tetrahydroxy- 10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino] -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) meti, 4- (acetylamino) benzoate of ( { [(2- {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1, 8, 10a, 11-tetrahydroxy- 10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methyl, anthracene-9-carboxylate of ( { [(2-. {[[(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8,10a, 11-tetrahydroxy- 10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl, 4-benzoyl benzoate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, and diphenylacetate ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl, yl) oxy) methyl. 20. A compound according to claim 1 selected from the group 4-fluorobenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11- tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} carbonyl) oxy] methyl, 3,5-dimethylbenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,110a, 11-tetrahydroxy-10,12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amine.} Carbonyl) oxy] methyl, Pyrlalate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6 , 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, 3,3-dimethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 1 1 -tetrahydroxy-10, 12-dioxo- 5.5a, 6.6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, 2,2-dimethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10,12-dioxo-5 , 5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, 2-ethylbutanoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,10a, 11-tetrahydroxy-10,12-dioxo-5 , 5a, 6,6aJ, 10,10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, thiophene-2-carboxylate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (d.methyllamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, Cyclopentylacetate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6 , 6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} Carbonyl) oxy] methyl, and 4-tert-butylbenzoate of [( { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl ) -4J-bis (dimethylamino) -1,8,8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino. carbonyl) oxy] methyl. or pharmaceutically acceptable salts thereof. 21. A compound according to claim 1 selected from the group 1 H-indole-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J- bis (dimethylamino) -1, 8, 10a, 11- tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12- octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy )methyl, nicotinate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,8, 10a, 11 -tetrahydroxy-10, 12-dioxo -5.5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} - 2-oxoethyl) (tert-butyl) amino] carbonyl.} Oxy) methylo, Spnicotinate of ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) - 1, 8, 10a, 11 -tetrahydroxy-10, 12 -dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} - 2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl, 4-pyrrolidin-1-ylbenzoate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J- bis (dimethylamino) -1, 8, 10a, 1 1-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) methyl, - methyl-1-benzofuran-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J- bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12- octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl. oxy) put it, 1 - . 1-methyl-1 H-indole-3-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J- bis (dimethylamino) -1,8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amine] carbonyl} oxy) methyl, quinoline-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J- bis (dimethylamino) -1, 8,10a , 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12- octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amine] carbonyl .}. oxy) methyl, 5 1-benzofuran-2-carboxylate of ( { [(2- {[[5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J- bis (dimethylamino) -1, 8, 10a, 11- tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12- octahydrotetracen-2-yl] amino.} -2-oxoetyl) (tert-butyl) amino] carbonyl. oxy) methyl, and ( { [(2- { [(5aR, 6aSJS, 10aS) -9- (aminocarbonyl) -4J-bís (dimethylamino) -1, 8, 10a, 11 -10 tetrahydroxy-10, 12- dioxo-5,5a, 6,6aJ, 10, 10a, 12-octahydrotetracen-2-yl] amino.} -2-oxoethyl) (tert-butyl) amino] carbonyl.} oxy) methyl-1-methyl- 1 H-pyrrole-2-carboxylate. or pharmaceutically acceptable salts thereof. E32. A compound according to claim 1 selected from the group 2-. { [(7S, 10aR) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 1 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10,10a, 12-Octahydrotetracen-2-yl] amino} (5-Methyl-2-oxo-1,3-dioxo-4-yl) methyl, -2-oxoethyl (propyl) carbamate. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10, 10a, 12 -octahydrotetracen-2-yl] amino} (5-Methyl-2-oxo-1,3-dioxol-4-yl) methyl-2-oxoethyl (butyl) carbamate, 25 2-. { [(7R, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylammon) -1,8,110a, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12-Octahydrotetracen-2-yl] amino} -2-oxoethyl (propyl) carbamate, [5- (4-methoxyphenyl) -2-oxo-1,3-dioxol-4-yl] methyl 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J- bis (dimethylamino) -1, 8, 10a, 11 -tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12- Octahydrotetracen-2-yl] amine} -2-Oxoethyl (propyl) carbamate (2-oxo-5-phenyl-1,3-dioxol-4-yl) methyl, 2-. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1,8,1 Oa, 11-tetrahydroxy-10,12-dioxo-5,5a, 6,6aJ, 10,10a, 12 -octahydrotetracen-2-yl] amino} 2-Oxo-5-phenyl-1,3-dioxol-4-yl) -2-oxoethyl (butyl) carbamate and -. { [(7S, 10aS) -9- (aminocarbonyl) -4J-bis (dimethylamino) -1, 8, 10a, 11-tetrahydroxy-10, 12-dioxo-5,5a, 6,6aJ, 10, 10a, 12 -octahydrotetracen-2-yl] amino} [5- (4-Methoxyphenyl) -2-oxo-1,3-dioxol-4-yl] methyl] -2-oxoethyl (butyl) carbamate. or pharmaceutically acceptable salts thereof. 23. A pharmaceutical composition comprising a compound according to any one of claims 1 to 22, in association with a pharmaceutically acceptable carrier. 24. A method for the prevention, treatment or control of bacterial infections in warm-blooded animals comprising feeding said hot-blooded animal an effective antibacterial amount according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof. 25. A compound according to any one of claims 1 to 22 for the preparation of a medicament for the treatment of bacterial infections. 26. A compound according to Formula (II): wherein R, R5, R6, and Rio are defined in claim 1, and Q is -ORn, Cl, Br, or I; Rn is H, benzyl optionally substituted with nitro or a part of the formula and R12 is alkyl of 1 to 6 carbon atoms. 27. A compound according to claim 26 wherein R 4 is t-butyl, R 5 is alkyl of 1 to 6 carbon atoms, and R n is benzyl optionally substituted with nitro. 28. A compound according to claim 26 wherein R 4 is alkyl of 1 to 6 carbon atoms, R 5 is optionally substituted phenyl and R n is benzyl optionally substituted with nitro. 29. A compound according to claim 26 wherein R5 is alkyl of 1 to 6 carbon atoms, R4 is t-butyl and R is H. 30. A compound according to claim 26 wherein R5 is alkyl of 1 to 6 carbon atoms, R4 is t-butyl, Q is and R 2 is alkyl of 1 to 6 carbon atoms. 31. A compound according to any of claims 26 to 30 wherein R6 and Rio are H. 32. A compound according to claim 26 selected from the group of (. {[[[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, tert-butyl benzoate, 2,2-dimethylbutanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-methylpropanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy] methyl, Cyclopentanecarboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl] oxy) methyl, 4-methylbenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, heptanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, propionate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy] methion, cyclohexanecarboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, 3,5-dimethylbenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy] methyl, 4-Fluorobenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 3-Methylbutanoate ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy] methyl, N- (Tert-butyl) -N- ( { [(Cyclopentylacetyl) oxy] methoxy.} Carbonyl) benzyl glycinate, 4- (Trifluoromethyl) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, cyclopropanecarboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, adamantan-1-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amine] carbonyl} oxy} methyl, pentanoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methoxy, cyclobutanecarboxylate of ( { [[2- (benzyloxy) -2 -oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl 3-cyclohexylpropanoate, N- (Tert-butyl) -N - [( { [(4-fluorophenoxy) acetyl] oxy} methoxy) carbonyl] benzyl glycinate, N- (tert-butyl) -N- ( { [(Cyclohexyl-acetyl) oxy] methoxy.} Carbonyl) benzyl glycinate, 2,6-dimethylbenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, N- (Tert-butyl) -N- ( { [(Phenylacetyl) oxy] methoxy.} Carbonyl) benzyl glycinate, ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy] methyl pivalate 1 - . 1 - . 1-benzofuran-2-carboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 1-methyl-1 H-pyrrole-2-carboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 1,1 '-biphenyl -4- ( { [[2- (Benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl carboxylate, 4-methoxybenzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 1 H-indole-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amine] carbonyl.} Oxy] methyl, N- (Tert-butyl) -N- ( { [(Diphenylacetyl) oxy] methoxy.} Carbonyl) benzyl glycine, 1-Naphthoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 2-naphthoate ( { [[2- (benzyloxy) -2-oxoetyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 1-methyl-1 H-indole-3-carboxylate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, ( { [[2- (Benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl,} oxy} methyl, carboxylic acid, nicotinate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, isonicotinate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy) methyl, 2,6-Difluorobenzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2-Fluorobenzoate of 2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2- (Trifluoromethyl) benzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 4- (1 H-pyrrol-1-yl) benzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amine] carbonyl} oxy) methyl, 1, 1'-biphenyl-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy] methyl, 2,4,6-trimethylbenzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 4-isopropoxybenzoate of [2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 3,4,5-trimethoxybenzoate of 2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl} oxy) methyl, 2- (Benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl 3,5-dimethoxybenzoate} oxy) methyl, 3-phenyl-acrylic acid (benzyloxycarbonylmethyl-tert-butyl-carbamoxyloxy) -methyl ester, 3-Methyl-1-benzofuran-2-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, N-. { [( { [3,5-bis (trifluoromethyl) pheny] acetyl} oxy] methoxy] carbonyl} -N- (tert-butyl) benzyl glycinate, 4- (heptyloxy) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 2- (2-phenylethyl) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 4- (dodecyloxy) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, 4- (Acetylamino) benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy) methyl, anthracene-9-carboxylic acid ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} oxy} methyl and 4-benzoyl benzoate of ( { [[2- (benzyloxy) -2-oxoethyl] (tert-butyl) amino] carbonyl.} Oxy] methyl. N- (Tert-butyl) -N- ( { [(4-tert-Butylbenzoyl) oxy] methoxy.} Carbonyl) glycine, N- (Tert-butyl N- { [Isobutyryloxy) methoxy] carbonyl} glycine, N- (Tert-butyl-N- ({(cyclopentylcarbonyl) oxy] methoxy, carbonyl) glycine, N- (Tert-butyl N- ( { (4-methylbenzoyl) oxy] methoxy.} Carbonyl) glycine, N- (Tert-butyl-N- { [Heptanoyloxy) methoxy] carbonyl} glycine, N- (Tert-butyl N- { [Propionyloxy) methoxy] carbonyl} glycine, N- (tert-butyl -N- (. {(Cyclohexylcarbonyl) oxy] methoxycarbonyl) glycine, N- (Tert-butyl-N- ({(3,5-dimethylbenzoyl) oxy] methoxy, carbonyl) glycine, N- (Tert-butyl-N- ({(4-fluorobenzoyl) oxy] methoxy, carbonyl) glycine, N- (Tert-butyl-N- (. {(3-methylbutanoyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [(Cyclopentylacetyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N - [( { [4- (trifluoromethyl) benzoyl] oxy]. methoxy) carbonyl] glycine, N- (tert-butyl) -N- ( { [(Cyclopropylcarbonyl) oxy] methoxycarbonyl) glycine, N- (. {[[(1-adamantylcarbonyl) oxy] methoxy} carbonyl ) -N- (tert-butyl) glycine, N- (tert-butyl) -N-. { [(pentanoyloxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N- ( { [(cyclobutylcarbonyl) oxy] methoxy.} carbonyl) glycine, N- (tert-butyl) -N- ( { [( 3-cyclohexylpropanoyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N - [( { [(4-fluorophenoxy) acetyl] oxy} methoxy) carbonyl] glycine N- (tert-butyl) -N- ( { [( cyclohexyl acetal) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N- ( { [(2,6-dimethylbenzoyl) oxy] methoxy, carbonyl) glycine, N- (Tert. -butyl) -N- ( { [(phenylacetyl) oxy] methoxy.} carbonyl) glycine, N: (tert-butyl) -N- ( { [(2,2-dimethylpropanoyl) oxy] methoxy} carbonyl) glycine, N- ( { [(1-benzofuran-2-ylcarbonyl) oxy] methoxy} carbonyl) -N- (tert-butyl) glycine, N- (Tert-butyl) -N - [( { [(1-methyl-1 H -pyrrol-2-yl) carbonyl] oxy} methoxy) carbonyl] glycine, N- ( { [( 1,1 '-biphenyl-4-ylcarbonyl) oxy] methoxy, carbonyl) -N- (tert-butyl) glycine, N- (tert -butyl) -N- ( { [(4-methoxybenzoyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N- ( { [(1 H-indole -2-ylcarbonyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N- (. {[[(Diphenylacetyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- { [(1-naphthoxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N-. { [(2-naphthoxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N - [( { [(1-methyl-1 H-indol-3-yl) carbonyl] oxy} methoxy) carbonyl] glycine, N- (tert-butyl) ) -N- ( { [(Quinolin-2-ylcarbonyl) oxy] methoxy. Carbonyl) glycine, N- (tert-butyl) -N- ( { [(Pyridin-3-ylcarbonyl) oxy] methoxy.} carbonyl) glycine, N- (tert-butyl) -N-. { [(isonicotinoyloxy) methoxy] carbonyl} glycine, N- (tert-butyl) -N- (. {[[(2,6-difluorobenzoyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [( 2-fluorobenzoyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N - [( { [2- (trifluoromethyl) benzoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N- ( { [(4-pyrrolidin-1-ylbenzoyl) oxy] methoxy.} Carbonyl) glycine, Nr ( { [(1,1 '-biphenyl-2-ylcarbonyl) oxy] methoxy.} Carbonyl) -N- (tert-butyl) glycine, N- (tert-butyl) -N- ( { [(Mesitylcarbonyl) oxy] methoxy} carbonyl) glycine, N- (tert-butyl) -N- ( { [(4-isopropoxybenzoyl) oxy] methoxy, carbonyl) glycine, N- (tert-butyl) -N- ( { [(3,4,5-trimethoxybenzoyl) oxy] methoxy.} carbonyl) glycine, N- (Tert-butyl) -N- ( { [(3,5-dimethoxybenzoyl) oxy] methoxy.} Carbonyl) glycine, N- (tert-butyl) -N - [( { [(2E ) -3-phenylprop-2-enoyl] oxy.} Methoxy) carbonyl] glycine, N- (tert-butyl) -N - [( { [(3-methyl-1-benzofuran-2-yl) carbonyl) ] oxy.}. methoxy) carbonyl] glycine, N-. { [( { [3,5-bis (trifluoromethyl) phenyl] acetyl} oxy) methoxy] carbonyl} -N- (tert-butyl) glycine, N- (Tert-butyl) -N - [( { [4- (heptyloxy) benzoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N - [( { [2- (2-phenylethyl) benzoyl] oxy} methoxy) carbonyl] glycine, N- (Tert-butyl) -N - [( { [4- (dodecyloxy) benzoyl] oxy} methoxy) carbonyl] glycine, N - [( { [4- (acetylamino) benzoyl] oxy} methoxy) carbonyl] -N- (tert-butyl) glycine, N- ( { [(9-anthrylcarbonyl) oxy] methoxy.} Carbonyl) -N- (tert-butyl) glycine and N- ( { [(4-benzoylbenzoyl) oxy] methoxy.} Carbonyl) -N- (tert-butyl) glycine 34. A compound according to claim 26 which is [Tert-butyl- (2-isobutoxycarbonyloxy-2-oxo-ethyl) -carbamoyloxy) -methyl ester of 3,3-Dimethyl-butyric acid. 35. A method for the preparation of compounds represented by the Formula Formula (I); (l) where: R3O - A - CO- represents and RL R2, R4, R5, R6, and Rio are defined in claim 1 or a pharmaceutically acceptable salt thereof comprising the step of: to. reacting an activated acyloxycarbamate intermediate of the formula Wherein R, R5, R6, and Rio are defined in claim 1 and R12 is as defined in claim 26 with a 9-aminotetracycline-7,8-disubstituted Formula where R ^ and R2 are defined in claim 1 in the presence of 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1 H) -pyrimidinone and triethylamine to give a compound of Formula (I) and , if desired, b. converting the compound of Formula (I) into a pharmaceutically acceptable salt thereof. 36. A method for the preparation of compounds represented by the Formula (i); (I) where: R3O - A - CO- represents and R1, R2, R4, R5, R6, and R10 are defined in claim 1 or a pharmaceutically acceptable salt thereof comprises: reacting an amine of the formula wherein R1, R2, R, R, R6, and R10 are defined in claim 1 with an intermediate chlorine of the Formula Rs t ° 0? C? 0 R RIO ° in the presence of alkali metal carbonate, 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1 H) -pyrimidinone and acetonitrile to give a compound of the formula or a pharmaceutically acceptable salt thereof and, if desired, converting the compound of Formula (I) to a pharmaceutically acceptable salt thereof. 37. A method for the preparation of compounds represented by the Formula (i); (l) where: R3O - A - CO- represents Ri, R2, R4, R5, R6, and Rio are defined in claim 1 or a pharmaceutically acceptable salt thereof comprising the step of: React a compound of the formula wherein Ri, R2, and R4 are defined in claim 1 with an intermediate chloro of the formula wherein R5 is as defined in claim 1 in the presence of alkali metal carbonate, and 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone in acetonitrile to give a compound of Formula I and, if desired, converting the compound of Formula (I) to a pharmaceutically acceptable salt thereof. 38. A method for the preparation of a compound represented by the Formula (i); (I) where: R3O - A - CO- represents and Ri, R2, R5, R6, and Rio are defined in claim 1 or a pharmaceutically acceptable salt thereof comprising the step of: reacting a 9-aminotetracycline-7,8-disubstituted of the formula with an intermediate chlorine of the formula where Ri, R2, R5, R6, and Rio are defined in the claim in the presence of triethylamine and 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1 H) -pyrimidinone to give a compound of the formula or a pharmaceutically acceptable salt thereof and, if desired, converting the compound of Formula (I) to a pharmaceutically acceptable salt thereof. 38. A method for the preparation of a compound represented by the Formula (i); (I) where: A, Ri, R2, and R3 are defined in claim 1 or a pharmaceutically acceptable salt thereof comprises: reacting a carboxylic acid of the formula OR R > -, XL OH wherein A, and R3 are as defined above with a CICO2R? 2 chloroformate wherein R? 2 is alkyl of 1 to 6 carbon atoms in the presence of 1,8-bis (dimethylamino) naphthalene in methylene chloride to give an anhydride mixture of formula Anhydride mixture and react said anhydride mixture with a 9-aminotetracycline-7,8-di-substituted of the formula where Ri, and R2 are as defined above in the presence of triethylamine and 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1 H) -pyrimidinone to give a compound of Formula (I) (I) or a pharmaceutically acceptable salt thereof and, if desired, converting the compound of Formula (I) to a pharmaceutically acceptable salt thereof.