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GB2031427A - N-substituted cyclic amines their preparation and pharmaceutical compositions containing them - Google Patents

N-substituted cyclic amines their preparation and pharmaceutical compositions containing them Download PDF

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Publication number
GB2031427A
GB2031427A GB7934713A GB7934713A GB2031427A GB 2031427 A GB2031427 A GB 2031427A GB 7934713 A GB7934713 A GB 7934713A GB 7934713 A GB7934713 A GB 7934713A GB 2031427 A GB2031427 A GB 2031427A
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carbon atoms
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Sandoz AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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

Abstract

Compounds of formula I (FORMULA) exhibiting vasoconstrictive properties. They can be utilised as pharmaceuticals. They are obtained by cyclisation.

Description

SPECIFICATION N-substituted cyclic amines, their preparation and pharmaceutical compositions containing them The present invention relates to N-substituted cyclic amines, their preparation and pharmaceutical compositions containing them.
In accordance with the invention, there are provided compounds of formula I,
wherein X is an oxygen atom, a sulfur atom or a group NRo, wherein R0 is hydrogen or alkyl of 1 to 4 carbon atoms, A is ethylene, trimethylene or tetramethylene, when X is a group NRo, optionally monosubstituted by alkyl of 1 to 4 carbon atoms, phenyl or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35, R1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 3 to 5 carbon atoms, wherein the double bond is other than in the position a to the nitrogen atom to which R1 is bound, R2 is hydrogen or alkyl of 1 to 4 carbon atoms, R3 and R4 independently are hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, or halogen of atomic number of from 9 to 35 and either m is 0 and n is 1 or 2 or both m and n are 1 with the proviso that, when X is a group NRo, A is unsubstituted, m is 0 and n is 1, then R1 is other than hydrogen.
X preferably is a sulfur atom or a group NRo, especially a sulfur atom. A preferably is ethylene. A preferably is unsubstituted. When it is substituted, it preferably is substituted by alkyl. When it is substituted by phenyl, it preferably is substituted by unsubstituted phenyl.
When phenyl is substituted, it preferably is monosubstituted. The substituent preferably is in the p-position. When phenyl is disubstituted, the substituents preferably are identical. When phenyl is disubstituted, the substituents preferably are in the m-, p-positions. When phenyl is substituted, it preferably is substituted by halogen. R preferably is hydrogen. When it is other than hydrogen, it preferably is alkyl. When it is alkyl of more than 2 carbon atoms, it preferably is straight-chained. R2 preferably is hydrogen. R2 can be bound to any of the methylene groups present in the nitrogen-containing ring. It preferably is attached to a methylene group other than adjacent to the ring nitrogen atom. R3 and/or R4 preferably is hydrogen.When it is not hydrogen, it preferably is bound in a position on the phenyl ring adjacent to the fused nitrogencontaining ring. When R3 and/or R4 are other than hydrogen, they preferably are alkyl, alkoxy or halogen, especially alkyl or halogen. When they are both other than hydrogen, they preferably are identical. m preferably is 0. n preferably is 1.
Alkyl and/or alkoxy and/or alkylthio preferably is of 1 or 2, especially 1 carbon atom(s).
Halogen preferably is chlorine or bromine, especially chlorine. Alkenyl preferably is of 3 carbon atoms.
A group of compounds of formula I is the compounds of formula Ipa
wherein R0, R2, R3, R4 are as defined above Aa is ethylene, trimethylene or tetramethylene and Rpa 1 is alkyl of 1 to 4 carbon atoms or alkenyl of 3 to 5 carbon atoms, wherein the double bond is other than in the position α; to the nitrogen atom to which R1 is bound Another group of compounds of formula I is the compounds of formula lpb
wherein R0 and R1 to R4 are as defined above and Apb is ethylene, timethylene or tetramethylene each monosubstituted by alkyl of 1 to 4 carbon atoms, phenyl or phenyl mono- or independently disubstituted by alkyl of t to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35.
Another group of compounds of formula I is the compounds of formula lpc
wherein Aa and R1 to R4 are as defined above and Xpc is an oxygen or a sulfur atom Another group of compounds of formula I is the compounds of formula Ipd
wherein R0 and R1 to R4 are as defined above and Ab is ethylene, trimethylene or tetramethylene optionally monosubstituted by alkyl of 1 to 4 carbon atoms, phenyl or phenyl mono- or independantly disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35.
Another group of compounds of formula I is the compounds of formula Ipe
wherein Aa and R1 to R4 are as defined above and Xpe is an oxygen or a sulfur atom.
Another group of compounds of formula I is the compounds of formula Ipf
wherein Ab, R0 and R1 to R4 are as defined above.
Another group of compounds of formula I is the compounds of formula Ipg
wherein Aa and R, to R4 are as defined above and XP9 is an oxygen or sulfur atom.
In accordance with the invention, a compound of formula I may be obtained by a process comprising cyclizing a corresponding compound of formula II,
wherein A, R, to R4, m and n are as defined above and either X' is an oxygen or sulfur atom, X" is a leaving group and Rb is hydrogen or X' together with a hydrogen atom is a leaving group, X" is a group Nor6' and one of Ró and Ról is hydrogen and the other is hydrogen or alkyl of 1 to 4 carbon atoms, with the proviso that, when X" is a group NRól, A is unsubstituted, m isO and n is 1, then R1 is other than hydrogen.
The process according to the invention may be effected in a manner analogous to known methods for cyclizing analogous amino derivatives.
When X' together with a hydrogen atom is a leaving group, the reaction is preferably effected in an inert solvent such as methanol or ethanol, or, when the compound of formula VI (see below) is liquid at the reaction temperature, the reaction is conveniently effected in the absence of any additional solvent. The reaction is preferably effected in the presence of a mineral acid such as hydrochloric or hydroiodic acid. The reaction temperature may be from room temperature to about 1 50 C and is preferably at least 50"C, e.g. the boiling temperature of the reaction mixture.
When X' is an oxygen atom, the reaction preferably is effected in water and when X' is a sulfur atom, preferably in an organic solvent such as ether. The reaction temperature may be from room temperature to about 1 00 C, when X' is a sulfur atom it preferably is room temperature.
When X' together with a hydrogen atom is a leaving group, X' is e.g. a group NRa, wherein Ra is alkyl of 1 to 4 carbon atoms, especially methyl, or Ra is hydrogen.
When X" is a leaving group, it is e.g. halogen or a group Rb-SO2-O-, whrein Rb is phenyl, tolyl or lower alkyl, and especially X" is then chlorine or bromine.
The compounds of formula I may be isolated and purified in accordance with known methods.
The compounds of formula I may be present in free base form, in the form of acid addition salts. Acid addition salt forms, for example, the hydrochloride or the hydrogen fumarate or maleate, may be produced from the free base form in known manner, and vice-versa.
The compounds of formula I may also be present in tautomeric form, i.e. with the double bond adjacent to the other nitrogen atom or to the X moiety, insofar this nitrogen atom or X moiety is not fully substituted. It is to be appreciated that such tautomeric forms also fall under the scope of formula I.
The production of the starting materials may be effected in a manner analogous to known methods.
A compound of formula Ila,
wherein R1 to R4, m and n are as defined above, and Xá is an oxygen or a sulfur atom, Xlal is a leaving group and Aa is as defined above, may e.g. be obtained by reacting a corresponding compound of formula Ill,
with a corresponding compound of formula IV,
preferably in a solvent such as ether, e.g. at a temperature of from about 0 to about 50 C, preferably at room temperature.
Xál is identical to X" when this is a leaving group. A compound of formula Ill wherein R1 is other than hydrogen may be obtained by e.g. N-substituting a corresponding compound of formula Ill, wherein R1 is hydrogen.
A compound of formula llb,
wherein Ab, R1 to R4, m and n are as defined above, X'b together with a hydrogen atom is a leaving group and one of Ra'". and Ra"". is hydrogen and the other is hydrogen or alkyl of 1 to 4 carbon atoms, with the proviso that, when Ab is unsubstituted, m is 0 and n is 1, then R1 is other than hydrogen, may e.g. be obtained by reacting a corresponding compound of formula V,
wherein the group S-Y is a leaving group, S being a sulfur atom, with a corresponding compound of formula VI,
The group xb is identical to X' when this together with a hydrogen atom is a leaving group. Y may e.g. be alkyl of 1 to 4 carbon atoms, preferably methyl.
The reaction conditions for the preparation of a compound of formula Ila, particularly when Xá is a sulfur atom, and of formula llb may be chosen such as to be identical with the conditions for cyclization according to the invention. The compounds of formula Ill or V are then advantageously reacted with the compounds of formula IV or VI to give directly the correspondingly compounds of formula I, without intermediate isolation of the corresponding compounds of formula Ila or llb.
A compound of formula Va,
wherein R1, R2, R3, R4, m and n are as defined above and Ya is alkyl of 1 to 4 carbon atoms, may e.g. be obtained from a corresponding compound of formula VII,
by optionally monosubstituting the primary amino moiety with an appropriate group R1 to give a corresponding compound wherein R1 is other than hydrogen, reacting this amine with benzoyl isothiocyanate, hydrolyzing the so obtained product to give a thiourea and S-alkylating the soobtained thiourea.
The above-mentioned considerations on tautomerism may also apply mutatis mutandis to the starting materials described above and such tautomers are therefore also embraced by the formulae herein.
Insofar as the production of any starting material is not particularly described these compounds are known, or may be produced and purified in accordance with known processes, or in a manner analogous to processes described herein, or to known processes.
In the following Examples all temperatures are in degrees Centigrade and are uncorrected.
EXAMPLE 1: N-(4, 5-Dihydrothiazol-2-yl)-2, 3-dihydro-lH-indole- 1-amine 1 8.6 g of 2-bromoethylisothiocyanate diluted with 50 ml of ether are added dropwise under moderate cooling to a solution of 15 g of 1-amino-2,3-dihydro-lH-indole in 60 ml of either. The temperature raises from about 15 to about 21". Stirring is maintained for 2 hours, a crystalline precipitate is formed. After decantation, the precipitate is dissolved in water, the solution is made alkaline with 10% sodium hydroxyde solution and extracted with methylene chloride. The organic phase is dried over magnesium sulfate and the solvent evaporated.The title compound is obtained (M.P. 1 77-178' after recrystallization from methylene chloride/petrol ether; M.P. of the hydrogen maleate 149-150-from methanol/ethyl acetate).
EXAMPLE 2:1 -fN-(2-Imidazolin-2-yI) methylamino]-4-methylindoline 10 g of 1-(4-methylindolin-l-yl)-1,2-dimethylisothiourea hydroiodide are dissolved in 50 ml ethanol. 5-6 ml of ethylene diamine are added and the reaction mixture is heated for 10 hours under reflux. The reaction mixture is concentrated to dryness and then shaken with ethyl acetate and I N aqueous sodium hydroxide solution. The organic phase is dried over magnesium sulfate and then evaporated. The title compound is obtained (M.P. of the hydrochloride 259-260'- from methanol/ether).
The starting material is obtained as follows: The urethane obtained by reacting 1-amino-4-methyl-indoline with chloroformic acid ethyl ester is reduced with lithium aluminium hydride in dioxan to 4-methyl-l-methylaminoindoline (M.P. of the hydrochloride 154-155"--from methanol/ether). Reaction of this product with benzoylisothiocyanate in boiling tetrahydrofuran followed by hydrolysis of the product with dilute sodium hydroxide solution for 30 minutes under reflux yields 1-(4-methylindolin-1-yl)-1methylthiourea (M.P. 152-1 53'-from methanol). This thiourea is reacted with methyl iodide for 1 hour at reflux temperature. 1-(4-methylindolin-1-yl)-1,2-dimethyl-isothiourea hydroiodide (M.P. 193-1 95'--from methynol/ether) is obtained.
EXAMPLE 3: N-(4, 5-Dihydrooxazol-2-yl)-2, 3-dihydro- 1 H-indol- 1-amine The 1-(2-chloroethyl)-3-(2,3-dihydro-1 H-indol-1-yI) urea obtained as described hereunder is suspended in 30 parts v/w of water and the mixture is heated to boiling for 30 minutes. The aqueous solution is then made alkaline with conc. aqueous ammonia solution and extracted with ethyl acetate. After drying of the organic phase over magnesium sulfate and evaporation of the solvent the title compound is obtained (M.P. of the hydrogen maleate 125-127"--from methanol/ethyl acetate).
The starting material is obtained as follows: 1.95 g of 2-chloroethylisocyanate diluted with 1 5 ml ether is added dropwise under stirring to a solution of 2.5 g of 1-amino-2,3-dihydro-1 Hindole in 1 5 mi ether. Temperature rises to about 35 . Stirring is maintained for 2 hours, a precipitate is formed. After decantation and recrystallization from ether, 1-(2-chloroethyl)-3-(2,3 dihydro-l H-indol-l-yl) urea is obtained (M.P. 103-104").
The following compounds of formula I may be obtained in analogous manner: Example Analogous No. to Ex. No. R1 R2 R3 R4 m n A X M.P.
4 2 H H 4-Me H 0 1 methylethylene NH hnl 123-124 5 2 H H H H 0 1 (3,4-dichloro phenyl)ethylene NH hfu 181-183 6 2 H H 5-Cl H 0 1 phenylethylene NH hfu 209-210 7 2 H H H H 0 2 ethylene NH hml 140-142 8 3 H H H H 0 2 ethylene O b 146-147 9 2 H H H H 1 1 ethylene NH hml 134-135 b = in free bas form hfu = in hydrogen fumarate form hml = in hydrogen maleate form The compounds of formula I possess pharmacological activity.
They possess vasoconstricting activity, as indicated by standard tests, e.g. in vivo in rats treated in accordance with the principles of J.S. Gillespie and T.C. Muir, Br. J. Pharmac.
Chemother. (1967), 30, 78-87): a pressor effect is elicited following i.v. administration of from about 0.02 to about 50,ug/kg, particularly of from about 0.02 to about 0.5 jug/kg of the compounds.
The compounds are therefore indicated for use as vasoconstricting agents, e.g. for the prophylaxis and treatment of vascular headaches such as migraine, and of orthostatic disorders such as orthostatic hypotension and its symptoms, such as vertigo. For this use an indicated daily dose is from about 0.02 to about 50 jbg, conveniently given in divided doses 2 to 4 times a day in unit dosage form containing from about 0.0005 to about 0.5 mg, or in sustained release form.
The compounds of formula I may be administered in pharmaceutically acceptable acid addition salt form. Such acid addition salt forms exhibit the same order of activity as the free base forms, and are readily prepared in conventional manner. The present invention also provides a pharmaceutical composition comprising a compound of formula I, in free base form or in pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent. Such compositions may be in the form of, for example, a solution or a tablet.
They can be prepared according to known methods.
The vasoconstricting activity of the compound of Example 1 is especially interesting.

Claims (39)

1. A process for the production of a compound of formula I,
wherein X is an oxygen atom, a sulfur atom or a group NRo, wherein R0 is hydrogen or alkyl of 1 to 4 carbon atoms, A is ethylene, trimethylene or tetramethylene, when X is a group NRo, optionally monosubstituted by alkyl of 1 to 4 carbon atoms, phenyl or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35, R1 is hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 3 to 5 carbon atoms, wherein the double bond is other than in the position a to the nitrogen atom to which R1 is bound, R2 is hydrogen or alkyl of 1 to 4 carbon atoms, R3 and R4 independently are hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35 and either m is 0 and n is 1 or 2 or both m and n are 1 with the proviso that, when X is a group NR,, A is unsubstituted, m is 0 and n is 1, then R1 is other than hydrogen, which comprises cyclizing corresponding a compound of formula II,
wherein A, R1 to R4, m and n are as defined above and either X' is an oxygen or sulfur atom, ) is a leaving group and B0 is hydrogen or X' together with a hydrogen atom is a leaving group, X1' is a group NR"o and one of R'o and R"o is hydrogen and the other is hydrogen or alkyl of 1 to 4 carbon atoms, with the proviso that, when X" is a group NR"o, A is unsubstituted, m is 0 and n is 1, then R1 is other than hydrogen.
2. A process for the production of a compound as defined in claim 1, substantially as hereinbefore described with reference to any one of the Examples.
3. A compound as defined in claim 1, whenever produced by a process according to claim 1.
4. A compound as defined in claim 1.
5. A compound of claim 4, wherein X is a sulfur atom.
6. A compound of claim 4, wherein X is a group NRo as defined in claim 1.
7. A compound of claim 4, wherein A is unsubstituted ethylene.
8. A compound of claim 4, wherein R1 is hydrogen.
9. A compound of claim 4, wherein R2 is hydrogen.
10. A compound of claim 4, wherein R3 and R4 are hydrogen.
11. A compound of claim 4, wherein R3 is halogen and R4 is hydrogen.
12. A compound of claim 4, wherein R3 and R4 are both halogen.
13. A compound of claim 4, wherein R3 is alkyl and R4 is hydrogen.
14. A compound of claim 4, wherein m is 0 and n is 1.
15. A compound of claim 4, wherein m is 0 and n is 2.
16. A compound of claim 4, wherein m and n are 1.
1 7. A compound of claim 4 of formula Ipa,
wherein Rg, and R2 to R4 are as defined in claim 1, Aa is ethylene, trimethylene or tetramethylene and Rpa 1 is alkyl of 1 to 4 carbon atoms or alkenyl of 3 to 5 carbon atoms, wherein the double bond is other than in the position a to the nitrogen atom to which RFa is bound.
18. A compound of claim 4 of formula Ipb,
wherein R0 and R1 to R4 are as defined in claim 1 and Aph is ethylene, trimethylene or tetramethylene each mono-substituted by alkyl of 1 to 4 carbon atoms, phenyl or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35.
1 9. A compound of claim 4 of formula Ipc,
wherein Aa is as defined in claim 17, R, to R4 are as defined in claim 1 and XP" is an oxygen or a sulfur atom.
20. A compound of claim 4 of formula Ipd,
wherein R0 and R, to R4 are as defined in claim 1 and Ab is ethylene, trimethylene or tetramethylene optionally monosubstituted by alkyl of 1 to 4 carbon atoms, phenyl or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35.
21. A compound of claim 4 of formula Ipe,
wherein Aa is as defined in claim 17, R1 to R4 are as defined in claim 1 and Xpe is an oxygen or a sulfur atom.
22. A compound of claim 4 of formula Ipf,
wherein Ab is as defined in claim 20 and R0 and R, and R4 are as defined in claim 1.
23. A compound of claim 4 of formula Ipg,
wherein Aa is as defined in claim 17, R1 to R4 are as defined in claim 1 and XP9 is an oxygen or a sulfur atom.
24. The compound of claim 4, which is N-(4,5-dihydrothiazol-2-yl)-2,3-dihydro-1 H-indole-1amine.
25. The compound of claim 4, which is 1-[N-(2-imidazolin-2-yl)-methylamino]-4-methyl- indoline.
26. A compound of claim 4, wherein R1, R2 and R4 are hydrogen.
27. A compound of claim 26, wherein m is 0 and n is 1.
28. A compound of claim 26, wherein m is 0 and n is 2.
29. A compound of claim 26, wherein m and n are 1.
30. The compound of claim 27, wherein R3, A and X are, respectively, 4-Me, methylethylene and NH.
31. The compound of claim 27, wherein R3, A and X are, respectively, hydrogen, (3,4dichlorophenyl)-ethylene and NH.
32. The compound of claim 27, wherein R3, A and X are, respectively, 5-CI, phenylethylene and NH.
33. The compound of claim 27, wherein R3, A and X are, respectively, hydrogen, ethylene and an oxygen atom.
34. The compound of claim 28, wherein R3, A and X are, respectively, hydrogen, ethylene and NH.
35. The compound of claim 28, wherein R3, A and X are, respectively, hydrogen, ethylene and an oxygen atom.
36. The compound of claim 29, wherein R3, A and X are, respectively, hydrogen, ethylene and NH.
37. A compound according to any one of claims 3 to 36, in free base form.
38. A compound according to any one of claims 3 to 36, in acid addition salt form.
39. A pharmaceutical composition comprising a compound according to any one of claims to 36 in free base form or in pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent.
GB7934713A 1978-10-12 1979-10-05 N-substituted cyclic amines their preparation and pharmaceutical compositions containing them Withdrawn GB2031427A (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
CH1058778 1978-10-12
CH1268178 1978-12-13
CH1268378 1978-12-13
CH1268278 1978-12-13
CH1268478 1978-12-13
CH1268578 1978-12-13
CH1268078 1978-12-13

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DE (1) DE2939998A1 (en)
DK (1) DK415479A (en)
FI (1) FI793063A7 (en)
FR (1) FR2438656A1 (en)
GB (1) GB2031427A (en)
IL (1) IL58429A0 (en)
NL (1) NL7907458A (en)
PT (1) PT70299A (en)
WO (1) WO1980000840A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0275639A1 (en) * 1986-11-27 1988-07-27 Beecham Group Plc N-substituted cyclic amides, their preparation and pharmaceutical compositions containing them

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2905501A1 (en) * 1979-02-14 1980-08-28 Beiersdorf Ag Heterocyclic amine(s) with long lasting antihypertensive activity - e.g. 2-N-amino-iso:indolinyl-imidazoline

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BE642005A (en) * 1963-01-02
CH446337A (en) * 1964-05-29 1967-11-15 Ciba Geigy Process for the preparation of new hydrazinothiazolines
CH495995A (en) * 1966-09-23 1970-09-15 Ciba Geigy Process for the preparation of new hydrazine compounds
US3511851A (en) * 1967-06-12 1970-05-12 Du Pont Heterocyclic amino-oxazolines
SU797580A3 (en) * 1977-11-10 1981-01-15 Рон-Пуленк Эндюстри (Фирма) Method of preparing isoquinoline derivatives, their salts, racemates or optical isomers

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0275639A1 (en) * 1986-11-27 1988-07-27 Beecham Group Plc N-substituted cyclic amides, their preparation and pharmaceutical compositions containing them

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WO1980000840A1 (en) 1980-05-01
FR2438656A1 (en) 1980-05-09
FI793063A7 (en) 1981-01-01
IL58429A0 (en) 1980-01-31
DK415479A (en) 1980-04-13
NL7907458A (en) 1980-04-15
PT70299A (en) 1979-11-01
DE2939998A1 (en) 1980-04-30

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