Beta-thiopropionyl-aminoacid derivatives and their use as...

C - Chemistry – Metallurgy – 07 – C

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C07C 323/56 (2006.01) A61K 31/195 (2006.01) A61K 31/215 (2006.01) A61K 31/34 (2006.01) A61K 31/365 (2006.01) A61K 31/38 (2006.01) A61K 31/40 (2006.01) A61K 31/41 (2006.01) A61K 31/47 (2006.01) A61K 45/06 (2006.01) C07C 323/59 (2006.01) C07C 323/60 (2006.01) C07D 209/20 (2006.01) C07D 215/12 (2006.01) C07D 215/14 (2006.01) C07D 231/12 (2006.01) C07D 233/61 (2006.01) C07D 233/96 (2006.01) C07D 277/30 (2006.01) C07D 307/54 (2006.01) C07D 307/89 (2006.01) C07D 317/40 (2006.01) C07D 333/24 (2006.01) C07D 333/60

Patent

CA 2245830

A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a .beta.-lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R1 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C1-6)alkylcarbonyloxy, (C1-6)alkoxycarbonyl, formyl or (C1-6)alkylcarbonyl group, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C2- 6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl(C1-6)alkyl, heterocyclyl or heterocyclyl(C1-6)alkyl; R2 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl; R3 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms, (C3- 7)cycloalkyl, fused aryl(C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2- 6)alkenyl, (C2-6)alkynyl, aryl, aryl-(CHR10)m-X-(CHR11)n, heterocyclyl or heterocyclyl-(CHR10)m-X-(CHR11)n, where m is 0 to 3, n is 1 to 3, each R10 and R11 is independently hydrogen or (C1-4)alkyl and X is O, S(O)x where x is 0-2, or a bond; R4 is hydrogen, or an in vivo hydrolysable acyl group; and R5 and R6 are independently hydrogen and (C1-6)alkyl or together represent (CH2)p where p is 2 to 5. Some compounds are claimed per se.

Procédé de traitement d'infections bactériennes chez l'homme ou chez l'animal, consistant à administrer, combiné à un antibiotique de .beta.-lactame, une quantité efficace sur le plan thérapeutique d'un dérivé d'acide aminé de Formule (I) ou d'un de ses sels, solvates ou esters hydrolysables in vivo, acceptables sur le plan pharmaceutique, formule dans laquelle R représente hydrogène, un cation formant un sel ou un groupe formant un ester hydrolysable in vivo; R¿1? représente hydrogène, alkyle C¿1?-C¿6? éventuellement substitué par trois atomes d'halogène au maximum ou par un groupe mercapto, alcoxy C¿1?-C¿6?,hydroxy, amino, nitro, carboxy, alkylcarbonyloxy C¿1?-C¿6?, alcoxycarbonyle C¿1?-C¿6?, formyle ou alkylcarbonyle C¿1?-C¿6?, cycloalkyle C¿3?-C¿7?, cycloalkyle C¿3?-C¿7? alkyle C¿2?-C¿6?, alkényle C¿2?-C¿6?, alkynyle C¿2?-C¿6?, aryle, arylalkyle C¿1?-C¿6?, hétérocyclyle ou hétérocyclyle alkyle C¿1?-C¿6?; R¿2? représente hydrogène, alkyle C¿1?-C¿6? ou aryle alkyle C¿1?-C¿6?; R¿3? représente hydrogène, alkyle C¿1?-C¿6? éventuellement substitué par trois atomes d'halogène au maximum, cycloalkyle C¿3?-C¿7?, aryl fusionné cycoalkyle C¿3?-C¿7?, cycloalkyle C¿3?-C¿7? alkyle C¿2?-C¿6?, alkényle C¿2?-C¿6?, alkynyle C¿2?-C¿6?, aryle-(CHR¿10?)¿m?-X-(CHR¿11?)¿n?, hétérocyclyle ou hétérocyclyle-(CHR¿10?)¿m?-X (CHR¿11?)¿n? dans laquelle m est 0 à 3, n est 1 à 3, chaque R¿10? et R¿11? représente indépendamment hydrogène ou alkyle C¿1?-C¿4? et X représente 0-2 ou une liaison; R¿4? représente hydrogène ou un groupe acyle hydrolysable in vivo; R¿5? et R¿6? représentent indépendamment hydrogène et alkyle C¿1?-C¿6? ou représentent ensemble (CH¿2?)¿n? dans laquelle p est 2 à 5. On revendique certains composés.

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