IE46269B1 - Isoxazole derivatives,process for their manufacture and preparations containing these compounds - Google Patents
Isoxazole derivatives,process for their manufacture and preparations containing these compoundsInfo
- Publication number
- IE46269B1 IE46269B1 IE245277A IE245277A IE46269B1 IE 46269 B1 IE46269 B1 IE 46269B1 IE 245277 A IE245277 A IE 245277A IE 245277 A IE245277 A IE 245277A IE 46269 B1 IE46269 B1 IE 46269B1
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- IE
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- Prior art keywords
- compound
- formula
- radical
- unsubstituted
- general formula
- Prior art date
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Classifications
-
- 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
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
Abstract
Novel 5-methylisoxazole-4-carboxamides of the formula I are prepared in which R denotes a mono-, di- or trinuclear, unsaturated heterocyclic radical having 3 to 13 carbon atoms and one, two, three or four hetero atoms from the group comprising oxygen, sulphur and nitrogen, where at most one of the hetero atoms is other than nitrogen, in the ring system, which radical is unsubstituted or ring-substituted one, two or three times by C1-C3-alkyl, C1-C3-alkoxy, halogen, nitro, hydroxyl, carboxyl, carbamoyl or oxo, and their physiologically tolerable acid addition salts, by reaction of corresponding carboxylic acid derivatives, namely the corresponding acid halides, esters or anhydrides, with amines of the formula H2N-R. The compounds of the formula I are distinguished in particular by anti-inflammatory, antipyretic and analgesic properties combined with low toxicity and good gastric tolerability.
Description
This invention relates to isoxazole derivatives and is an improvement in, or modification of, the invention of Patent Specification No. 43136.
Patent Specification No. 43136 describes and claims 5 5 - methyl - isoxazole - 4 - carboxylic acid anilides of the general formula
2 in which R and R , which may be identical or different, each represents a hydrogen atom; an alkyl group of 1, 2 or
3 carbon atoms, an alkoxy group of 1, 2 or 3 carbon atoms, an alkylthio group of 1, 2 or 3 carbon atoms, the alkyl groups of which may be substituted partly or totally by identical or different halogen atoms, for example, fluorine, chlorine, bromine or iodine atoms, or represents a halogen atom, for example, a fluorine, chlorine, bromine or iodine atom, or represents a nitro or cyano group or an alkoxycarbonyl group having 1, 2 or 3 carbon atoms in the alkyl moiety.
R represents an alkyl group of 1, 2 or 3 carbon atoms, an alkoxy group of 1, 2 or 3 carbon atoms, an alkylthio group of 1, 2 or 3 carbon atoms, the alkyl groups of which may be substituted partly or totally by identical or different halogen atoms, for example, fluorine, chlorine, bromine or iodine atoms, or represents a halogen atom, for example, a fluorine, chlorine, bromine or iodine atom, or represents a nitro or cyano group or an alkoxycarbonyl group having 1, or 3 carbon atoms in the alkyl moiety; or represents a phenyl group which may carry one or two substituents selected from fluorine, chlorine, bromine and iodine atoms, alkyl groups of 1, 2 or 3 carbon atoms and alkoxy groups of 1, 2 or 3 carbon atoms, or a phenoxy group which may carry one or two substituents selected from fluorine, chlorine, bromine and iodine atoms, alkyl groups of 1, 2 or 3 carbon atoms and alkoxy groups of 1, 2 or 3 carbon atoms;
2 3 or in which R stands for a hydrogen atom, and R and R together represent a methylenedioxy group or, together with the phenyl ring, to which they are linked, represent 3 a naphthalene ring; with the proviso that R does not repre1 2 sent a methyl group when R and R both represent hydrogen atoms.
We have now found that pharmacological properties are also shown by 5 - methylisoxazole - 4 - carboxylic acid amides of the general formula
O c'
(I) in which R represents a mononuclear, binuclear or trinuclear, unsaturated heterocyclic radical having in the ring system
- 4 3 to 13 carbon atoms and one, two, three or four hetero atoms selected from oxygen, sulphur and nitrogen, one of which at most is other than nitrogen, which ring system is unsubstituted or substituted by one or more substituents, preferably by one, two or three substituents selected from alkyl and alkoxy radicals each having one, two or three carbon atoms, by halogen atoms, i.e. fluorine, chlorine, bromine and iodine atoms, nitro, hydroxy and carboxy groups, unsubstituted and substituted carbamoyl radicals and oxo groups. Preferably, if there is more than one substituent, the substituents are the same.
The present invention also provides a salt, especially a physiologically tolerable acid addition salt, of a compound of the general formula I.
The ring system may include a carbocyclic ring or rings, provided it contains at least one heterocyclic ring. The rings may be aromatic or non-aromatic and usually all are unsaturated.
Suitable radicals represented by R are, for example, thienyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, irnidazolyl, thiazolyl, thiazolinyl, oxazolyl, thiadiazolyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolyl, pyrazolyl, acridinyl and tetrazolyl radicals, each of which may be unsubstituted or substituted as specified.
Preferred compounds are those of the general formula I in which R represents a pyridyl radical which is unsubstituted or substituted by one, two or three of the same or different halogen atoms, i.e. fluorine, chlorine, bromine and iodine atoms, or represents a pyrimidinyl radical which is unsubstituted or substituted once, twice or three times by a (C^—C^)-alkyl radical and/or by the oxo group, or a thiazolyl radical which is unsubstituted or substituted by a nitro group.
The present invention also provides a process for the 5 preparation of a compound of the general formula I or a salt thereof, which comprises reacting a 5 - methylisoxazole - 4carboxylic acid derivative of the general formula
in which X represents
a) a halogen atom, preferably a chlorine or bromine atom;
b) a YO-group, in which Y represents (i) a phenyl radical which is unsubstituted or substituted by one, two or three substituents selected 15 from fluorine, chlorine, bromine and iodine atoms, and methyl, ethyl, methoxy, ethoxy or trifluoromethyl, nitro and cyano groups, or (ii) the acyl radical corresponding to the formula (II) that is
(II1) ^46269
- 6 or
c) a ZO—CO—O-group in which Z represents a (C^—c^)alkyl radical, a benzyl radical or a phenyl radical; or another reactive functional derivative of the carboxylic acid corresponding to the general formula II, with an unsaturated heterocyclic amine of the general formula
H2N~r (III) in which R has the meaning given above, or with a salt thereof.
Preferably, a substituted phenyl radical Y contains one substituent or two or three of the same substituents.
The reaction is advantageously carried out in a dispersing agent or a solvent that is inert towards the reactants. Suitable polar solvents that may be used are, for example, nitriles, e.g. acetonitrile; ethers, e.g. diethyl ether, tetrahydrofuran or dioxan; and alcohols, e.g. methanol, ethanol, propanol or isopropanol. Non-polar solvents, e.g. benzene, toluene and cyclohexane, may also be used.
Preferably the compound of the general formula II is the carboxylic acid chloride. It is advantageous in this case for the reaction to be carried out in the presence of an acid-binding agent, e.g. potassium or sodium carbonate, an alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal alcoholate or alkaline earth metal alcoholate, an organic base, for example triethylamine, pyridine, picoline or quinoline or the amine reactant used in excess, at temperatures of from 0 to 160°C', preferably from 20 to 80°C. The reaction time may be from a few minutes to two hours.
A 5- methylisoxazole - 4 - carboxylic acid derivative of the general formula II required as starting material may
- 7 be obtained in accordance with the method described in German Patent No. 634 286. In this method ethoxymethylideneacetoacetic ester is reacted with hydroxylamine to form the 5methylisoxazole - 4 - carboxylic acid ester, the ester is hydrolysed under acid conditions, preferably with a mixture of glacial acetic, acid and concentrated hydrochloric acid in the ratio 1:1, and the 5- methylisoxazole - 4 - carboxylic acid formed is converted according to a customary method into a carboscylic acid halide, ester or mixed anhydride.
The following are examples of carboxylic acid derivatives of the general formula II:
- methylisoxazole - 4 - carboxylic acid phenyl esters, especially the 2,4 - dichlorophenyl ester of the 2,4 6-trichlorophenyl ester; and
- methylisoxazole - 4 - carboxylic acid anhydrides, especially those in which X represents the methoxycarbonyloxy radical, the ethoxycarbonyloxy radical, the phenoxycarbonyloxy radical or the benzyloxycarbonyloxy radical.
The compounds according to the invention of the general formula I are generally substances that are readily crystallisable. They may be converted into acid addition salts, preferably physiologically tolerable acid addition salts, for example with strong acids, e.g. hydrohalic acids, especially hydrochloric acid, sulphuric acid, phosphoric acid, p-toluene25 sulphonic acid, methanesulphonic acid or cyclohexylamidosulphonic acid.
The 5 - methylisoxazole - 4 - carboxylic acid amides of the general formula I and their physiologically tolerable salts have useful pharmacological properties. In particular they exhibit antiphlogistic, antipyretic and analgesic
- 8 46^69 properties. Their toxicity is low, and their compatibility with the stomach is good.
Accordingly, the present invention provides a pharmaceutical preparation, which comprises a compound of the general formula I or a physiologically tolerable salt thereof, in admixture or conjunction with a pharmaceutically suitable carrier. Preferably the preparation is in dosage unit form.
The following Examples illustrate the invention.
1. N - (5 - bromo - 2 - pyridyl) 5 - methylisoxazole - 4carboxamide of the general formula I.
a) A solution of 0.05 mole of 5 - methylisoxazole - 4carboxylic acid chloride of the formula (II) (7.3 g) in 20 ml of tetrahydrofuran is added dropwise at room temperature, while stirring, to 0.1 mole of 2-amino-5-bromopyridine of the formula (III) (17.3 g) dissolved in 200 ml of tetrahydrofuran. After stirring for a further 10 minutes, the precipitate formed is filtered off and the filtrate is evaporated to dryness under reduced pressure. 13.6 g (96% of the theoretical yield) of a colourless crystalline product are obtained; melting point from ethanol: 168—169°C.
b) 0.1 mole of 2-amino-5-bromopyridine of the formula (III) (17.3 g) and 0.1 mole of 2,4-dichlorophenyl 5 .- methylisoxazole - 4 - carboxylate of the formula (II) (27.2 g) dissolved in 150 ml of tetrahydrofuran are refluxed for 75 minutes. The solution is then brought to dryness under reduced pressure and the oily residue is digested with cyclohexane.
After decanting, the residue is dissolved in 300 ml of chloroform and shaken with 200 ml of 2N hydrochloric acid.
- 9 The chloroform phase is washed with water until neutral, dried, and brought to dryness under reduced pressure. 21.4 g (76% of the theoretical yield) of a crystalline product are obtained; melting point after recrystallisation from ethanol:
168 to 169°C.
c) 0.1 mole of 2-amino-5-bromopyridine of the formula (II) (17.3 g) and 0.1 mole of benzyloxycarbonyl 5 - methylisoxazole - 4 - carboxylate of the formula II (26.1 g), dissolved in 200 ml of tetrahydrofuran, are refluxed for 90 minutes. The mixture is brought to dryness under reduced pressure and the residue is digested with cyclohexane. After decanting, the residue is dissolved in 300 ml of chloroform and shaken with 200 ml of 2N hydrochloric acid. The chloroform phase is washed with water until neutral, dried and brought to dryness under reduced pressure. In this manner 20.6 g (73% of the theoretical yield) of a crystalline product are obtained; melting point after recrystallisation from ethanol; 168 to 169°C.
In accordance with the process described above:
N-(3-pyridyl) 5 - methylisoxazole - 4 - carboxamide hydrochloride of the formula (I) is obtained by reacting 5methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 3-aminopyridine of the formula (III).
N-(4-methyl-2-thiazolyl) 5 - methylisoxazole - 425 carboxamide hydrochloride of the formula (I) is obtained by reacting 5 - methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 2 - amino - 4 - methylthiazole of the formula (III).
N-(4-pyridyl) 5 - methylisoxazole - 4 - carboxamide hydrochloride of the formula (I) is obtained by reacting
2,4-dichlorophenyl 5 - methylisoxazole - 4 - carboxylate
- 10 of the formula (II) with 2 - amino - 4 - pyridine of the formula (III),
N - (4 - chloro - 2 - benzothiazolyl) 5 - methylisoxazole - 4 - carboxamide of the formula I is obtained by reacting 2,4-dichlorophenyl 5 - methylisoxazole - 4 carboxylate of the formula (II) with 2 - amino - 4 - chlorobenzothiazole of the formula (III),
N-(2-pyridyl) 5 - methylisoxazole - 4 - carboxamide hydrochloride of the formula (I) is obtained by reacting
2,4-dichlorophenyl 5 - methylisoxazole - 4 - carboxylate of the formula II. with 2-aminopyridine of the formula (III),
11-(5- bromo - 2 - pyridyl) 5 - methylisoxazole - 4carboxamide of the formula (I) is obtained by reacting 5methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 2 - amino - 5 - bromopyridine of the formula (III) ,
N - (1,3 - dimethyl - 2,4 - dioxo - 1,2,3,4 - tetrahydro - 6 - pyrimidinyl) 5 - methylisoxazole - 4 - carboxamide of the formula (I) is obtained by reacting 5 - methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 6 - amino - 1,3 - dimethyl - 2,4 - dioxo - 1,2,3,4tetrahydropyrimidirie of the formula (III),
N - (5 - nitro - 2 - thiazolyl) - 5 - methylisoxazole4 - carboxamide hydrochloride of the formula (I) is obtained by reacting 5 - methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 2 - amino - 5 - nitrothiazole of the formula (III),
11-(2- thiazolin - 2 - yl) 5 - methylisoxazole - 4carboxamide hydrochloride of the formula (I) is obtained by reacting 2,4-dichlorophenyl 5 - methylisoxazole - 4carboxylate of the formula (II) with 2 - amino - 2 - thiazo46269
- 11 line of the formula (III),
N-(2-benzothiazolyl) 5 - methylisoxazole - 4 - carboxamide hydrochloride of the formula (I) is obtained by reacting benzyloxycarbonyl 5 - methylisoxazole - 4 - carboxylate of the formula (II) with 2 - aminobenzothiazole of the formula (III),
N - (2 - benzimidazolyl) - 5 - methylisoxazole - 4carboxamide hydrochloride of the formula (I) is obtained by reacting 2,4 - dichlorophenyl 5 - methylisoxazole - 410 carboxylate of the formula (II) with 2 - amino - benzimidazole of the formula (III),
11-(5- chloro - 2 - benzoxazolyl) 5 - methylisoxazole4 - carboxamide of the formula (I) is obtained by reacting benzyloxycarbonyl 5 - methylisoxazole - 4 - carboxylate of the formula (II) with 2 - amino - 5 - chlorobenzoxazole of the formula (III),
N - (5 - nitro - 2 - pyridyl) 5· - methylisoxazole - 4carboxamide of the formula (I) is obtained by reacting 2,4dichlorophenyl 5 - methylisoxazole - 4 - carboxylate of the formula (II) with 2 - amino - 5 - nitropyridine of the formula (III),
N - (3,5 - dibromo - 2 - pyridyl) 5 - methylisoxazole4 - carboxamide of the formula (I) is obtained by reacting benzyloxycarbonyl 5 - methylisoxazole - 4 - carboxylate of the formula (II) with 2 - amino - 3,5 - dibromopyridine of the formula (III),
N - (5 - chloro - 2 - pyridyl) 5 - methylisoxazole4 - carboxamide of the formula (I) is obtained by reacting
- methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 2 - amino - 5 - chloropyridine of the
- 12 formula (III),
N - (2 - chloro - 3 - pyridyl) 5 - methylisoxazole - 4carboxamide of the formula (I) is obtained by reacting 5methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 3 - amino - 2 - chloropyridine of the formula (III),
N - (4 - methyl - 3 - thienyl) 5 - methylisoxazole - 4carboxamide of the formula (I) is obtained by reacting 5methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 3 - amino - 4 - methylthiophene of the formula (III),
N - (6 - methoxy - 2 - benzothiazolyl) 5 - methylisoxazole - 4 - carboxamide of the formula (I) is obtained by reacting 2,4-dichlorophenyl 5-methylisoxazole - 4 - carboxylate of the formula (II) with 2 - amino - 6 - methoxybenzothiazole of the formula (III),
N - (5 - chloro - 2 - thiazolyl) - 5 - methylisoxazole4 - carboxamide of the formula (I) is obtained by reacting
2,4-dichlorophenyl 5 - methylisoxazole - 4 - carboxylate of the formula (II) with 2 - amino - 5 - chlorothiazole of the formula (III),
N - (2 - methoxy - 5 - pyridyl) 5 - methylisoxazole - 4carboxamide of the formula (I) is obtained by reacting 5methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 5 - amino - 2 - msthoxypyridine of the formula (III),
11-(6- ethoxy - 2 - benzothiazolyl) 5 - methylisoxa25 zole - 4 - carboxamide of the formula (I) is obtained by reacting benzyloxycarbonyl 5 - methylisoxazole - 4 - carboxylate of the formula (II) with 6 - ethoxy - 2 - aminobenzothiazole of the formula (III),
N - (5 - bromo - 2 - thiazolyl) 5 - methylisoxazole30 4 - carboxamide of the formula (I) is obtained by reacting
- 13 5 - methylisoxazole - 4 - carboxylic acid chloride of the formula (II) with 2 - amino - 5 - bromothiazole of the formula (III).
TABLE I:
-Methylisoxazole-4-carboxylic acid amides of the formula I
No. R Melting point °C
250-252 (with decomposition)
221-223
4
210-215 (with decomposition)
218-220 . HCl
239-242
- 14 >46369
TABLE 1 continued
No.
Melting point °C
260-265
234-237
230-235 (with decomposition) (with decomposition) (with decomposition)
- 15 TABLE I continued
112-114 (with decomposition)
Cl
113-115
- 16 >4-6 20 9
TABLE I continued
203-211 (with decompos ition)
Claims (16)
1. CLAIMS:1. A compound of the general formula in which R represents a mononuclear, binuclear or trinuclear, 5 unsaturated heterocyclic radical having in the ring system 3 to 13 carbon atoms and one, two, three or four hetero atoms selected from oxygen, sulphur and nitrogen, one of which at most is other than nitrogen, which ring system is unsubstituted or substituted by one or more substituents selected from 10 alkyl and alkoxy radicals each having one, two or three carbon atoms, halogen atoms, nitro, hydroxy and carboxy groups, unsubstituted and substituted carbamoyl radicals and oxo groups.
2. A compound as claimed in claim 1, wherein the ring 15 system is unsubstituted or contains up to 3 substituents.
3. A compound as claimed in claim 2, wherein R represents a pyridyl radical which is unsubstituted or substituted by 1 to 3 of the same or different halogen atoms; a pyrimidinyl radical which is unsubstituted or substituted by 1 to 3 of 20 the same or different substituents selected from (C^“nc 3 )alkyl radicals and oxo groups; or a thiazolyl radical which is unsubstituted or substituted by a nitro group.
4. A salt of a compound as claimed in any one of claims 1 to 3.
5. A physiologically tolerable salt of a compound as claimed in any one of claims 1 to 3.
6. A compound as claimed in claim 1, which is listed in any of the Examples and Table herein. 5
7. A process for the preparation of a compound as claimed in claim 1 or a salt thereof, which comprises reacting a compound of the general formula z c \ X (II) H 3 in which X represents 10 a) a halogen atom; b) a YO-group, in which Y represents (i) a phenyl radical which is unsubstituted or substituted by one, two or three of the same or different substituents selected from fluorine, 15 chlorine, bromine and iodine atoms, and methyl, ethyl, methoxy, ethoxy, trifluoromethyl, nitro and cyano groups, or (ii) the acyl radical corresponding to the formula II; or 20 c) a ZO—CO—O-group in which Z represents a (C^— C 4^“ alkyl radical, a benzyl radical or a phenyl radical; or another reactive functional derivative of the carboxylic acid corresponding to the general formula II with an unsaturated heterocyclic amine of the general formula - 19 HgN—~R (III) in which R has the meaning given in claim 1 or with a salt thereof, and, if desired, converting a compound of the general formula I formed into a salt.
8. A process as claimed in claim 7, wherein the compound of the general formula II is the chloride and the reaction is carried out in the presence of an acid-binding agent.
9. A process as claimed in claim 8, wherein the reaction is carried out at a temperature in the range of from 20 to 80°C.
10. A process as claimed in claim 7, wherein the compound of the general formula II is the 2,4-dichlorophenyl ester, the 2,4,6-trichlorophenyl ester or an anhydride in which X represents the methoxycarbonyloxy, ethoxycarbonyloxy, phenoxycarbonyloxy or benzyloxycarbonyloxy radical.
11. A process as claimed in claim 7, carried out substantially as described in any one of the Examples herein.
12. A compound as claimed in claim 1, whenever prepared by a process as claimed in any one of claims 7 to 11.
13. A salt of a compound as claimed in claim 1, whenever prepared by a process as claimed in any one of claims 7 to 11.
14. A physiologically tolerable salt of a compound as claimed in claim 1, whenever prepared by a process as claimed in any one of claims 7 to 11.
15. A pharmaceutical preparation which comprises a compound as claimed in any one of claims 1 to 3, 5, 6, 12 and 14, in admixture or conjunction with a pharmaceutically suitable carrier. 4 6 2 6 9 - 20
16. A pharmaceutical preparation as claimed in claim 15, which is in dosage unit form.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19762655009 DE2655009A1 (en) | 1976-12-04 | 1976-12-04 | ISOXAZOLE DERIVATIVES, THE PROCESS FOR THEIR MANUFACTURING AND MEANS CONTAINING THESE COMPOUNDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE46269L IE46269L (en) | 1978-06-04 |
| IE46269B1 true IE46269B1 (en) | 1983-04-20 |
Family
ID=5994666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE245277A IE46269B1 (en) | 1976-12-04 | 1977-12-02 | Isoxazole derivatives,process for their manufacture and preparations containing these compounds |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS5371070A (en) |
| AT (1) | AT362366B (en) |
| BE (1) | BE861503R (en) |
| CA (1) | CA1102341A (en) |
| CH (1) | CH608498A5 (en) |
| DE (1) | DE2655009A1 (en) |
| DK (1) | DK538677A (en) |
| FR (1) | FR2372830A2 (en) |
| GB (1) | GB1596383A (en) |
| IE (1) | IE46269B1 (en) |
| IT (1) | IT1126219B (en) |
| LU (1) | LU78628A1 (en) |
| NL (1) | NL7713151A (en) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55500866A (en) * | 1978-11-03 | 1980-10-30 | ||
| EP0035285A3 (en) * | 1979-08-17 | 1981-10-14 | American Cyanamid Company | Novel isoxazole carboxylic acid phenyl esters, pharmaceutical compositions containing certain of said esters, and process for preparing said esters |
| DE2854438A1 (en) * | 1978-12-16 | 1980-07-03 | Hoechst Ag | ISOXAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, MEANS CONTAINING THESE COMPOUNDS AND THEIR USE |
| DE3247454A1 (en) * | 1982-12-22 | 1984-06-28 | Laboratorios Bago S.A., Buenos Aires | Substituted 3-phenyl-5-methylisoxazole-4-carboxanilides, process for their preparation and pharmaceutical compositions containing these compounds |
| GB8619432D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
| GB8619433D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
| US4935434A (en) * | 1988-01-26 | 1990-06-19 | Bristol-Myers Company | Antiarthritic isoxazole-4-carboxamides |
| IT1228288B (en) * | 1989-01-09 | 1991-06-07 | Zambon Spa | COMPOUNDS WITH ANTI-SEROTONIN ACTIVITY |
| US5001124A (en) * | 1990-02-02 | 1991-03-19 | Syntex (U.S.A.) Inc. | 4-isoxazolecarboxamide derivatives |
| JP2995086B2 (en) * | 1990-05-18 | 1999-12-27 | ヘキスト・アクチエンゲゼルシヤフト | Preparation containing isoxazole-4-carboxamides and hydroxyalkylidene cyanoacetamides |
| ZA913762B (en) | 1990-05-18 | 1992-01-29 | Hoechst Ag | Isoxazole-4-carboxamides and hydroxyalkylidenecyanoacetamides,pharmaceuticals containing these compounds and their use |
| US7338956B2 (en) * | 2002-08-07 | 2008-03-04 | Sanofi-Aventis Deutschland Gmbh | Acylamino-substituted heteroaromatic compounds and their use as pharmaceuticals |
| CN103772376B (en) * | 2012-10-24 | 2017-01-11 | 中国医学科学院医药生物技术研究所 | Substituted benzo-1,3-miscellaneous azole compound and preparation method and application thereof |
| US20170088545A1 (en) * | 2014-05-14 | 2017-03-30 | Novartis Ag | Carboxamide inhibitors |
| TWI714528B (en) * | 2014-05-14 | 2021-01-01 | 瑞士商諾華公司 | Carboxamide derivatives |
-
1976
- 1976-12-04 DE DE19762655009 patent/DE2655009A1/en active Granted
-
1977
- 1977-11-15 CH CH1393477A patent/CH608498A5/en not_active IP Right Cessation
- 1977-11-29 NL NL7713151A patent/NL7713151A/en not_active Application Discontinuation
- 1977-12-02 AT AT866377A patent/AT362366B/en not_active IP Right Cessation
- 1977-12-02 DK DK538677A patent/DK538677A/en unknown
- 1977-12-02 GB GB5034777A patent/GB1596383A/en not_active Expired
- 1977-12-02 IE IE245277A patent/IE46269B1/en unknown
- 1977-12-02 CA CA292,302A patent/CA1102341A/en not_active Expired
- 1977-12-02 IT IT3035277A patent/IT1126219B/en active
- 1977-12-02 LU LU78628A patent/LU78628A1/xx unknown
- 1977-12-03 JP JP14562277A patent/JPS5371070A/en active Pending
- 1977-12-05 BE BE183170A patent/BE861503R/en not_active IP Right Cessation
- 1977-12-05 FR FR7736547A patent/FR2372830A2/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| DE2655009C2 (en) | 1990-03-29 |
| CA1102341A (en) | 1981-06-02 |
| IT1126219B (en) | 1986-05-14 |
| BE861503R (en) | 1978-06-05 |
| LU78628A1 (en) | 1978-07-11 |
| NL7713151A (en) | 1978-06-06 |
| IE46269L (en) | 1978-06-04 |
| FR2372830B2 (en) | 1980-06-20 |
| DE2655009A1 (en) | 1978-06-15 |
| GB1596383A (en) | 1981-08-26 |
| CH608498A5 (en) | 1979-01-15 |
| DK538677A (en) | 1978-06-05 |
| AT362366B (en) | 1981-05-11 |
| ATA866377A (en) | 1980-10-15 |
| FR2372830A2 (en) | 1978-06-30 |
| JPS5371070A (en) | 1978-06-24 |
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