EP0456835B1
Expired / Lapsed
EP
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Quinazoline-3-alkanoic acid derivative, salt thereof, and production thereof
Assignee: Kyorin Pharmaceutical Co Ltd
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Filing: 1990-12-10
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Granted: 1996-05-15
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Expires: 2010-12-10
Abstract
Abstract A quinazoline-3-alkanoic acid derivative of general formula (I), which has both of platelet agglutination inhibition and aldose reductase inhibition activities, salts thereof, process for producing the same, and a medicine containing the same, wherein R represents hydrogen or a protective group of the carboxyl group; R' represents lower alkyl, alkenyl, alkynyl, lower alkoxy, lower alkylthio, halogen, phenyl (which may be substituted with 1 to 3 substituents selected from among lower alkyl, lower alkoxy, halogen, trifluoromethyl, carboxyethylene, and ethoxy-carbonylethylene groups), naphthyl, heterocycle (which may be substituted with 1 to 3 lower alkyl groups), cycloalkyl, or benzoyl (which may be substituted with lower alkyl or halogen); R?2 and R3¿ may be the same or different from each other and each represents hydrogen, halogen, lower alkyl, lower alkoxy, optionally substituted aralkyl, nitro, imidazolyl, imidazolylmethyl, or -NR4R5 wherein R?4 and R5¿ may be the same or different from each other and each represents hydrogen or lower alkyl, or they are combined with each other to form a 5- or 6-membered heterocycle which may contain other heteroatom(s); X represents carbonyl, thiocarbonyl or methylene (which may be substituted with lower alkyl); A represents lower alkylene or lower alkenylene; and n is an integer of 1 to 3.
Inventors
- 👤 Shizuyoshi Fujimori
- 👤 Michiro Ohnota
- 👤 Yoshihiro Hirata
- 👤 Koji Murakami
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-01 21:43
CPC Classifications
C; C07; C07D; C07D231/00; C07D231/02; C07D231/10; C07D231/12; A; A61; A61P; A61P3/00; A61P3/08; A61P3/10; A61P43/00; A61P7/00; A61P7/02; C07D233/00; C07D233/54; C07D233/56; C07D239/00; C07D239/70; C07D239/72; C07D239/78; C07D239/80; C07D239/95; C07D239/96; C07D249/00; C07D249/02; C07D249/08; C07D401/00; C07D401/02; C07D401/06; C07D403/00; C07D403/02; C07D403/04; C07D405/00; C07D405/02; C07D405/06; C07D409/00; C07D409/02; C07D409/06; C07D413/00; C07D413/02; C07D413/06; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
181 words
Quinazoline-3-alkanoic acid derivatives represented by the general formula (I) wherein R is hydrogen or a protecting group for the carboxyl group, R¹ is a phenyl group which may be substituted by one to three of lower alkyl group having 1 to 6 carbon atoms, lower alkoxy group having 1 to 3 carbon atoms, halogen, trifluoromethyl group, carboxyethylene group or ethoxycarbonylethylene group, R and R³ which are identical or different from each other, each represents hydrogen, halogen, lower alkyl group having 1 to 6 carbon atoms, lower alkoxy group having 1 to 3 carbon atoms, aralkyl group, nitro group, imidazolyl group, imidazolylmethyl group or (R⁴ and R⁵ which are identical or different from each other, each represents hydrogen or lower alkyl group having 1 to 6 carbon atoms, or are connected with each other to form a five- or six-membered heterocyclic group which may contain other hetero atoms), X is a carbonyl or thiocarbonyl group, and n indicates an integer of 1 to 3, or their salts and the compounds: Ethyl 6-(2,4-dichlorobenzyloxy)-1-(2,4-dichlorophenyl)methyl-1,4-dihydro-2,4-dioxo-3(2H) quinazoline acetate and 6-(2,4-dichlorobenzyloxy)-1-(2,4-dichlorophenyl)methyl-1,4-dihydro-2,4-dioxo-3(2H) quinazoline acetic acid or their salts.
Claim 2
Dependent Claim
149 words
A process for preparing the quinazoline-3-alkanoic acid derivatives or their salts according to claim 1, characterized in that (a) compounds represented by the general formula (II) wherein R, R, R³, X and n are as defined in claim 1, or their salts are reacted with compounds represented by the general formula (III) R¹-CH₂-Z [III] wherein Z is an eliminating group and R¹ is as defined in claim 1, or (b) compounds represented by the general formula (IV) wherein R¹, R, R³ and X are as defined in claim 1, or their salts are reacted with compounds represented by the general formula (V) Z-(CH₂)n-COOR [V] wherein Z is an eliminating group and Rand n are as defined in claim 1, or (c) compounds represented by the general formula (VI) wherein R, R¹, R, R⁴, X and n are as defined in claim 1, or their salts are reacted with N,N'-carbonyldiimidazole.
Claim 3
Dependent Claim
56 words
A process for preparing the quinazoline-3-alkanoic acid derivatives or their salts according to claim 1, wherein R is a hydrogen atom, characterized in that compounds represented by the general formula (VII) wherein R' is a protecting group for the carboxyl group and R¹, R, R³, X and n are as defined in claim 1, are hydrolyzed.
Claim 4
Dependent Claim
48 words
A process for preparing the quinazoline-3-alkanoic acid derivatives or their salts according to claim 1, wherein X is a thiocarbonyl group, characterized in that compounds represented by the general formula (IX) wherein R, R¹, R, R³ and n are as defined in claim 1, are reacted with sulfide.
Claim 5
Dependent Claim
112 words
A process for preparing the quinazoline-3-alkanoic acid derivatives or their salts according to claim 1, wherein R is a protecting group for the carboxyl group, characterized in that compounds represented by the general formula (X) wherein R¹, R, R³, X and n are as defined in claim 1, are reacted with compounds represented by the general formula (XI) R'-Z [XI] wherein R' is a protecting group for the carboxyl group and Z is an eliminating group, in the presence of a suitable base, or, after produced reactive derivatives of carboxylic acid once, then they are reacted with compounds represented by the general formula (XII) R'-OH [XII] wherein R' is as described above.
Claim 6
Dependent Claim
161 words
A process for preparing the quinazoline-3-alkanoic acid derivatives or their salts according to claim 1, wherein R is an imidazolylmethyl group, R³ is hydrogen, halogen or lower alkoxy group having 1 to 3 carbon atoms and X is a carbonyl group, characterized in that with quinazoline-3-alkanoic acid derivatives represented by the general formula (XIV) wherein R 1' is a phenyl group (this phenyl group may be substituted by one to three of lower alkyl group having 1 to 6 carbon atoms, lower alkoxy group having 1 to 3 carbon atoms, halogen, trifluoromethyl group, carboxyethylene group or ethoxycarbonylethylene group), R 3' is hydrogen, halogen or lower alkoxy group having 1 to 3 carbon atoms, and R and n are as defined in claim 1, a halogenating agent is reacted to obtain compounds represented by the general formula (XV) wherein Hal is halogen and R, R 1' , R 3' and n are as described above, and then they are reacted with imidazole.
Claim 7
Dependent Claim
155 words
A process for preparing the quinazoline-3-alkanoic acid derivatives or their salts according to claim 1, wherein R is an imidazolyl group, R³ is hydrogen, halogen, lower alkyl group having 1 to 6 carbon atoms, lower alkoxy group having 1 to 3 carbon atoms, aralkyl group or nitro group, and X is a carbonyl group, characterized in that compounds represented by the general formula (XVII) wherein R 3" is hydrogen, halogen, lower alkyl group having 1 to 6 carbon atoms, lower alkoxy group having 1 to 3 carbon atoms, aralkyl group or nitro group and R and n are as defined in claim 1, are treated with N,N'-carbonyldiimidazole to obtain compounds represented by the general formula (XVIII) wherein R, R 3" and n are as described above, and then they are reacted with compounds represented by the general formula (III) R¹-CH₂-Z [III] wherein Z is an eliminating group and R¹ is as defined in claim 1.
Claim 8
Dependent Claim
32 words
An inhibitor of platelet aggregation consisting of at least one kind of quinazoline-3-alkanoic acid derivatives represented by the general formula (I) or their salts, as defined in claim 1 as effective ingredient(s).
Claim 9
Dependent Claim
33 words
An inhibitory agent on aldose reductase consisting of at least one kind of quinazoline-3-alkanoic acid derivatives represented by the general formula (I) or their salts as defined in claim 1 as effective ingredient(s).
References Cited (Backward Citations)
JPS5795966A
Cited
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