Vitronectin receptor antagonists

Details Vitronectin receptor antagonists Vitronectin receptor antagonists

C - Chemistry, Metallurgy

07

D

C07D 213/74 (2006.01) A61K 31/33 (2006.01) A61K 31/44 (2006.01) A61K 31/445 (2006.01) A61K 31/47 (2006.01) A61K 31/495 (2006.01) A61K 31/535 (2006.01) A61K 31/55 (2006.01) C07D 237/20 (2006.01) C07D 239/42 (2006.01) C07D 401/12 (2006.01) C07D 403/12 (2006.01) C07D 405/12 (2006.01) C07D 409/12 (2006.01) C07D 413/12 (2006.01) C07D 417/12 (2006.01) C07D 487/04 (2006.01) C07D 495/04 (2006.01)

Patent

CA 2241755

Compounds of formula (I) are disclosed, wherein: A is a fibrinogen antagonist template; W is a linking moiety of the form -(CHRg)a-U-(CHRg)b-V-; Q1, Q2, Q3 and Q4 are independently N or C-Ry, provided that no more than one of Q1, Q2, Q3 and Q4 is N; R' is H or C1-6alkyl, C3-7cycloalkyl-C0-6alkyl or Ar-C0- 6alkyl; Rg is H or C1-6alkyl, Het-C0-6alkyl, C3-7cycloalkyl-C0-6alkyl or Ar-C0- 6alkyl; Rk is Rg, -C(O)Rg or -C(O)ORg Ri is H, C1-6alkyl, Het-C0-6alkyl, C3- 7cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl-U'-C1-6alkyl, C3- 7cycloalkyl-C0-6alkyl-U'-C1-6alkyl or Ar-C0-6alkyl-U'-C1-6alkyl; Ry is H, halo, -ORg, -SRg, -CN, -NRgRk, -NO2, -CF3, CF3S(O)r-, -CO2Rg, -CORg or - CONRg2, or C1-6alkyl optionally substituted by halo, -ORg, -SRg, -CN, -NRgR'', -NO2, -CF3, R'S(O)3-, -CO2Rg, -CORg or -CONRg2; U and V are absent or CO, CRg2, C(=CRg2), S(O)c, O, NRg, CRgORg, CRg(ORk)CRg2, CRg2CRg(ORk), C(O)CRg2, CRg2C(O), CONRi, NRiCO, OC(O), C(O)O, C(S)O, OC(S), C(S)NRg, NRgC(S), S(O)2NRg, NRgS(O)2N=N, NRgNRg, NRgCRg2, NRgCRg2, CRg2O, OCRg2, CRg=CRg, CC, Ar or Het; a is 0, 1, 2 or 3; b is 0, 1 or 2; c is 0, 1 or 2; r is 0, 1 or 2; and u is 0 or 1; or pharmaceutically acceptable salts thereof, which are vitronectin receptor antagonists useful in the treatment of osteoporosis.

La présente invention concerne des composés de la formule (I), dans laquelle A est une matrice d'antagoniste fibrinogène; W est un fragment de liaison dont la forme est -(CHR?g¿)¿a?-U-(CHR?g¿)¿b?-V-; Q?1¿, Q?2¿, Q?3¿ et Q?4¿ sont, de manière indépendante, N (au maximum l'un d'entre eux) ou C-R?y¿; R' est H ou alkyle C¿1-6?, cycloalkyle C¿3-7?-alkyle C¿0-6? ou Ar-alkyle C¿0-6?, R?g¿ est H ou alkyle C¿1-6?, Het-alkyle C¿0-6?, cycloalkyle C¿3-7?-alkyle C¿0-6? ou Ar-alkyle C¿0-6?; R?k¿ est R?g¿, -C(O)R?g¿ ou -C(O)OR?g¿, R?i¿ est H, alkyle C¿1-6?, Het-alkyle C¿0-6?, cycloalkyle C¿3-7?-alkyle C¿0-6?, Ar-alkyle C¿0-6?, Het-alkyle C¿0-6?-U'-alkyle C¿1-6?, cycloalkyle C¿3-7?-alkyle C¿0-6?-U'-alkyle C¿1-6? ou Ar-alkyle C¿0-6?-U'-alkyle C¿1-6?; R?y¿ est H, halo, -OR?g¿, -SR?g¿, -CN, -NR?g¿R?k¿, -NO¿2?, -CF¿3?, CF¿3?S(O)¿r?-, -CO¿2?R?g¿, -COR?g¿ ou -CONR?g¿¿2?, ou alkyle C¿1-6? facultativement substitué par halo, -OR?g¿, -SR?g¿, -CN, -NR?g¿R'', -NO¿2?, -CF¿3?, R'S(O)¿3?-, -CO¿2?R?g¿ ou -CONR?g¿¿2?; U and V sont absents ou CO, CR?g¿¿2?, C(=CR?g¿¿2?), S(O)¿c?, O, NR?g¿, CR?g¿OR?g¿, CR?g¿(OR?k¿)CR?g¿¿2?, CR?g¿¿2?CR?g¿(OR?k¿), C(O)CR?g¿¿2?, CR?g¿¿2?C(O), CONR?i¿, NR?i¿CO, OC(O), C(O)O, C(S)O, OC(S), C(S)NR?g¿, NR?g¿C(S), S(O)¿2?NR?g¿, NR?g¿S(O)¿2?N=N, NR?g¿NR?g¿, NR?g¿CR?g¿¿2?, NR?g¿CR?g¿¿2?, CR?g¿¿2?O, OCR?g¿¿2?, CR?g¿=CR?g¿, C?C, Ar ou Het; a vaut 0, 1, 2 ou 3; b vaut 0, 1 ou 2; c vaut 0, 1 ou 2; r vaut 0, 1 ou 2; et u est 0 ou 1. L'invention concerne aussi des sels de ces composés acceptables sur le plan pharmacologique qui sont des antagonistes de récepteurs de la vitronectine utiles dans le traitement de l'ostéoporose.

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