C - Chemistry – Metallurgy – 07 – D
Patent
C - Chemistry, Metallurgy
07
D
C07D 243/14 (2006.01) A61K 31/5513 (2006.01) A61P 35/00 (2006.01) A61P 37/02 (2006.01) C07D 401/04 (2006.01) C07D 401/06 (2006.01) C07D 403/04 (2006.01) C07D 403/10 (2006.01) C07D 405/04 (2006.01) C07D 407/04 (2006.01) C07D 409/04 (2006.01)
Patent
CA 2466055
The present invention is directed to novel 1,4-benzodiazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have formula (I) or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein: X and Y are independently - C(O)-, CH2- or -C(S)-; R1, R2, R3, R4, R7, R8, Rb, Rc, Rd and M are defined herein, R5 is hydrogen, alkyl cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaryl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonylalkyl, alkylaminocarbonyl or alkylaminocarbonylalkyl; R6 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; R9 is cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkyl(alkyl), aralkyl or heteroarylalkyl, each of which is optionally substituted; and R10 is -(CH2)n- CO2Rb, -(CH2)m-CO2M, -(CH2)i-OH or -(CH2)j-CONRcRd n is 0-8, m is 0-8, i is 1- 8 and j is 0-8.
L'invention concerne des nouvelles 1,4-benzodiazépines, des compositions pharmaceutiques les contenant, et leur utilisation en tant qu'inhibiteurs d'interactions de HDM2-p53. Les composés de l'invention sont représentés par la formule (I) ou un solvate, un hydrate ou un sel pharmaceutiquement acceptable de ceux-ci, dans laquelle: X et Y sont indépendamment -C(O)-, CH¿2?- ou -C(S)-; R?1¿, R?2¿, R¿3?, R?4¿, R¿7?, R¿8?, R?b¿, R?c¿, R?d ¿et M ont la signification indiquée dans la description; R?5 ¿est hydrogène, alkyle, cycloalkyle, aryle éventuellement substitué, hétéroaryle éventuellement substitué, aralkyle éventuellement substitué, hétéroaralkyle éventuellement substitué, carboxyalkyle, alcoxycarbonyle, alcoxycarbonylalkyle, aminocarbonyle, aminocarbonylalkyle, alkylaminocarbonyle ou alkylaminocarbonylalkyle; R?6 ¿est cycloalkyle, aryle, hétéroaryle, cycloalkylalkyle, aralkyle, hétéroarylalkyle, ou un hétérocycle saturé ou partiellement insaturé, chacun étant éventuellement substitué; R?9 ¿est cycloalkyle, aryle, hétéroaryle, un hétérocycle saturé ou partiellement insaturé, cycloalkyle(alkyle), aralkyle ou hétéroarylalkyle, chacun étant éventuellement substitué; et R?10 ¿est -(CH¿2?)¿n?-CO¿2?R?b¿, -(CH¿2?)¿m?-CO¿2?M, -(CH¿2?)¿i?-OH ou -(CH¿2?)¿j?-CONR?c¿R?d¿; n vaut 0-8, m vaut 0-8, i vaut 1-8 et j vaut 0-8.
Calvo Raul R.
Carver Theodore E. Jr.
Cummings Maxwell David
Grasberger Bruce L.
Kim Alexander J.
3-Dimensional Pharmaceuticals Inc.
Mbm Intellectual Property Law Llp
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