Protease inhibitorsThis invention relates to compounds of formula (I) wherein: Y is Ar or NRR; R is R'', R''C(O), R''C(S), R''SO2, R''OC(O), R''R'NC(O), or R''R'NC(S); R is H, C1-6alkyl, C2-6alkenyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R is H, C2-6alkenyl, C2-6alkynyl, Het, Ar or C1-6alkyl optionally substituted by OR', SR', NR'2, N(R')C(O)OR'', CO2R', CO2NR'2, N(C=NH)NH2, Het or Ar; R is H, C1-6alkyl, C2-6alkenyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R is (a), Ar-C0-6alkyl, Het-C0-6alkyl, adamantyl-C(O)-, Ar-C(O)-, Het-C(O)-; R is R'', R''C(O), R''C(S), R''SO2, R''OC(O), R''R'NC(O), R''R'NC(S), or R''OC(O)NR'CH(R*)C(O); R is C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, Ar-C0-6alkoxy, Het-C0-6alkoxy, or C1-6alkyl optionally substituted by OR', SR', NR'2, N(R')C(O)OR'', CO2R', CO2NR'2, N(C=NH)NH2, Het or Ar; R* is H, C1-6alkyl, C2-6alkenyl, C3-6cycloalkyl-C0-6-alkyl, Ar-C0-6alkyl, Het-C0-6alkyl; each R' independently is H, C1-6alkyl, C2-6alkenyl, Ar-C0-6alkyl, or Het-C0-6alkyl; each R'' independently is C1-6alkyl, C3-6cycloalkyl-C0-6-alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R''' is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; Z is C(O) or CH2; and n is 1, 2 or 3; or a pharmaceutically acceptable salt thereof, which are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor.Formula (i) compound or its pharmacy acceptable salt: wherein: y is ar or nr 1r 2r 1be r ', r ' c (o), r ' c (s), r ' so 2, r ' oc (o), r ' r ' nc (o) or r ' r ' nc (s); r 2be h, c 1-6alkyl, c 2-6alkenyl, ar-c 0-6alkyl or het-c 0-6alkyl; r 3be h, c 2-6alkenyl, c 2-6alkynyl, het, ar or by the optional c that replaces of following radicals 1-6alkyl: or ', sr ', nr ' 2, n (r ') c (o) or ', co 2r ', co 2nr ' 2, n (c=nh) nh 2, het or arr 4be h, c 1-6alkyl, c 2-6alkenyl, ar-c 0-6alkyl or het-c 0-6alkyl; r 5for ar-c 0-6alkyl, het-c 0-6alkyl, adamantyl-c (o)-, ar-c (o)-or het-c (o)-r 6be r ', r ' c (o), r ' c (s), r ' so 2, r ' oc (o), r ' r ' nc (o), r ' r ' nc (s) or r ' oc (o) nr ' ch (r *) c (o); r 7be c 3-6cycloalkyl-c 0-6alkyl, ar-c 0-6alkyl, het-c 0-6alkyl, ar-c 0-6alkoxyl group, het-c 0-6alkoxyl group or by the optional c that replaces of following radicals 1-6alkyl: or ', sr ', nr ' 2, n (r ') c (o) or ', co 2r ', co 2nr ' 2, n (c=nh) nh 2, het or ar; r *be h, c 1-6alkyl, c 2-6alkenyl, c 3-6cycloalkyl-c 0-6alkyl, ar-c 0-6alkyl, het-c 0-6alkyl; each r ' is independent to be h, c 1-6alkyl, c 2-6alkenyl, ar-c 0-6alkyl or het-c 0-6alkyl; each r ' be c independently 1-6alkyl, c 3-6cycloalkyl-c 0-6alkyl, ar-c 0-6alkyl or het-c 0-6alkyl; r ' ' be h, c 1-6alkyl, c 3-6cycloalkyl-c 0-6alkyl, ar-c 0-6alkyl or het-c 0-6alkyl; z is c (o) or ch 2and n is 1,2 or 3.
프로테아제 억제제 본 발명은 화학식(I)의 화합물 또는 그의 약제학적으로 허용가능한 염에 관한 것이며, 이들은 시스테인 프로테아제, 특히 카텝신 K의 억제제이고 뼈손실의 억제가 효과적인 질환을 치료하는데 유용하다.〈화학식 1〉상기식에서,Y 는 Ar 또는 NR1R2이고;R1은 R", R"C(O), R"C(S), R"SO2, R"OC(O), R"R'NC(O) 또는 R"R'NC(S)이고;R2는 H, C1-6알킬, C2-6알케닐, Ar-CO-6알킬 또는 Het-CO-6알킬이고;R3는 H, C2-6알케닐, C2-6알키닐, Het, Ar, 또는 OR', SR', NR'2, N(R)C(O)OR", C02R', C02NR'2, N(C=NH)NH2, Het 또는 Ar에 의해서 임의로 치환되는 C1-6알킬이고; R4는 H, C1-6알킬, C2-6알케닐, Ar-CO-6알킬 또는 Het-CO-6알킬이고;R5는 , Ar-C0-6알킬, Het-CO-6알킬, 아다만틸-C(O)-, Ar-C(0)- 또는 Het-C(O)-이고;R6는 R", R"C(O), R"C(S), R"SO2, R"OC(O), R"R'NC(O), R"R'NC(S) 또는 R"OC(O)NR'CH(R*)C(O)이고;R7은 C3-6시클로알킬-CO-6알킬, Ar-CO-6알킬, Het-CO-6알킬, Ar-CO-6알콕시, Het-CO-6알콕시, 또는 OR', SR", NR'2, N(R')C(O)OR", C02R', C0 2NR'2, N(C=NH)NH2, Het 또는 Ar에 의해 임의로 치환되는 C1-6알킬이고;R*는 H, C1-6알킬, C2-6알케닐, C3-6시클로알킬-CO-6-알킬, Ar-CO-6알킬 또는 Het-CO-6알킬이고;R'은 각각 독립적으로 H, C1-6알킬, C2-6알케닐, Ar-CO-6알킬 또는 Het-C O-6알킬이고;R"은 각각 독립적으로 C1-6알킬, C3-6시클로알킬-CO-6-알킬, Ar-C O-6알킬 또는 Het-CO-6알킬이고;R"'은 H, C1-6알킬, C3-6시클로알킬-CO-6알킬, Ar-CO-6알킬 또는 Het-CO-6알킬이고;Z는 C(O) 또는 CH2이고;n은 1, 2 또는 3이다.화학식 (I)의 화합물 또는 그의 약제학적으로 허용가능한 염. 〈화학식 I〉 [이미지] 상기식에서, Y 는 Ar 또는 NR1R2이고; R1은 R", R"C(O), R"C(S), R"SO2, R"OC(O), R"R'NC(O) 또는 R"R'NC(S)이고; R2는 H, C1-6알킬, C2-6알케닐, Ar-CO-6알킬 또는 Het-CO-6알킬이고; R3는 H, C2-6알케닐, C2-6알키닐, Het, Ar, 또는 OR', SR', NR'2, N(R)C(O)OR", C02R', C02NR'2, N(C=NH)NH2, Het 또는 Ar에 의해서 임의로 치환되는 C1-6알킬이고; R4는 H, C1-6알킬, C2-6알케닐, Ar-CO-6알킬 또는 Het-CO-6알킬이고; R5는 [이미지], Ar-C0-6알킬, Het-CO-6알킬, 아다만틸-C(O)-, Ar-C(0)- 또는 Het-C(O)-이고; R6는 R", R"C(O), R"C(S), R"SO2, R"OC(O), R"R'NC(O), R"R'NC(S) 또는 R"OC(O)NR'CH(R*)C(O)이고; R7은 C3-6시클로알킬-CO-6알킬, Ar-CO-6알킬, Het-CO-6알킬, Ar-CO-6알콕시, Het-CO-6알콕시, 또는 OR', SR", NR'2, N(R')C(O)OR", C02R', C0 2NR'2, N(C=NH)NH2, Het 또는 Ar에 의해 임의로 치환되는 C1-6알킬이고; R*는 H, C1-6알킬, C2-6알케닐, C3-6시클로알킬-CO-6-알킬, Ar-CO-6알킬 또는 Het-CO-6알킬이고; R'은 각각 독립적으로 H, C1-6알킬, C2-6알케닐, Ar-CO-6알킬 또는 Het-C O-6알킬이고; R"은 각각 독립적으로 C1-6알킬, C3-6시클로알킬-CO-6-알킬, Ar-C O-6알킬 또는 Het-CO-6알킬이고; R"'은 H, C1-6알킬, C3-6시클로알킬-CO-6알킬, Ar-CO-6알킬 또는 Het-CO-6알킬이고; Z는 C(O) 또는 CH2이고; n은 1, 2 또는 3이다.