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WO1999020274A1 - Derives de triterpene tetracyclique ayant une activite immunosuppressive - Google Patents

Derives de triterpene tetracyclique ayant une activite immunosuppressive Download PDF

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Publication number
WO1999020274A1
WO1999020274A1 PCT/US1998/021605 US9821605W WO9920274A1 WO 1999020274 A1 WO1999020274 A1 WO 1999020274A1 US 9821605 W US9821605 W US 9821605W WO 9920274 A1 WO9920274 A1 WO 9920274A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
lla
hydroxy
llb
aryl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1998/021605
Other languages
English (en)
Inventor
Robert K. Baker
Frank Kayser
Jianming Bao
Shouwu Miao
William H. Parsons
Kathleen M. Rupprecht
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9807388.5A external-priority patent/GB9807388D0/en
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Priority to AU10829/99A priority Critical patent/AU1082999A/en
Publication of WO1999020274A1 publication Critical patent/WO1999020274A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02—Seven-membered rings
    • C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems

Definitions

  • Rl i is:
  • R 6 is:
  • X is O or H and RiO
  • R 3 is:
  • salts include, but are not limited to salts of inorganic acids such as hydrochloride, sulfate, phosphate, diphosphate, hydrobromide, and nitrate or salts of an organic acid such as malate, maleate, fumarate, tartrate, succinate, citrate, acetate, lactate, methanesulfonate, p-toluenesulfonate or palmoate, salicylate and stearate.
  • inorganic acids such as hydrochloride, sulfate, phosphate, diphosphate, hydrobromide, and nitrate or salts of an organic acid such as malate, maleate, fumarate, tartrate, succinate, citrate, acetate, lactate, methanesulfonate, p-toluenesulfonate or palmoate, salicylate and stearate.
  • C4 ether derivatives can also be prepared.
  • the best procedure involves reacting an alcohol with trifluoromethanesulfonic anhydride (Tf2 ⁇ , triflic anhydride) to obtain the preformed triflate in dichloromethane at reduced temperature, preferably -78°C.
  • Tf2 ⁇ trifluoromethanesulfonic anhydride
  • Ethers may also be prepared by heating a mixture of triterpene C4 alcohol, the appropriate alkylhalide and an excess of silver oxide (Ag2 ⁇ ) in an aprotic invert solvent such as THF.
  • a large number of tablets are prepared by conventional procedures so that the dosage unit is 100 milligrams of active ingredient, 0.2 milligrams of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose. Appropriate coatings may be applied to increase palatability or delay absorption.
  • INJECTABLE A parenteral composition suitable for administration by injection is prepared by stirring 1.5% by weight of active ingredient in 10% by volume propylene glycol. The solution is made to volume with water for injection and sterilized.
  • aqueous suspension is prepared for oral administration so that each 5 milliliters contain 100 milligrams of finely divided active ingredient, 100 milligrams of sodium carboxymethyl cellulose, 5 milligrams of sodium benzoate, 1.0 grams of sorbitol solution, U.S. P., and 0.025 milliliters of vanillin.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Les composés de la formule (I) conviennent comme agents immunosuppresseurs.
PCT/US1998/021605 1997-10-17 1998-10-13 Derives de triterpene tetracyclique ayant une activite immunosuppressive Ceased WO1999020274A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU10829/99A AU1082999A (en) 1997-10-17 1998-10-13 Tetracyclic triterpene derivatives with immunosuppressant activity

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US6193397P 1997-10-17 1997-10-17
US60/061,933 1997-10-17
GB9807388.5 1998-04-06
GBGB9807388.5A GB9807388D0 (en) 1998-04-06 1998-04-06 Teracyclic triterpene derivatives with immunosuppressant activity

Publications (1)

Publication Number Publication Date
WO1999020274A1 true WO1999020274A1 (fr) 1999-04-29

Family

ID=26313442

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/021605 Ceased WO1999020274A1 (fr) 1997-10-17 1998-10-13 Derives de triterpene tetracyclique ayant une activite immunosuppressive

Country Status (2)

Country Link
AU (1) AU1082999A (fr)
WO (1) WO1999020274A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2583678A2 (fr) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Immunopotentiateurs de petites molécules et dosages pour leur détection

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5010104A (en) * 1987-10-14 1991-04-23 Kyowa Hakko Kogyo Co., Ltd. Tricyclic compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5010104A (en) * 1987-10-14 1991-04-23 Kyowa Hakko Kogyo Co., Ltd. Tricyclic compounds

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2583678A2 (fr) 2004-06-24 2013-04-24 Novartis Vaccines and Diagnostics, Inc. Immunopotentiateurs de petites molécules et dosages pour leur détection

Also Published As

Publication number Publication date
AU1082999A (en) 1999-05-10

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