发明名称 1-(CYCLOALKYL-CARBONYL)PROLINE DERIVATIVE
摘要 A compound represented by formula (1) (in the formula: ring-D represents a three- to eight-membered hydrocarbon ring; Ra represents an optionally substituted amino C1-6 alkyl group or the like; Rb1 and Rb2 each independently represent a hydrogen atom, a halogen atom, or the like; Rc represents an optionally substituted C6-10 aryl group or the like; Rd represents a hydrogen atom or the like; and ring-Q represents a (hetero)aryl group or the like which may be substituted with a carboxyl group or the like) or a pharmaceutically acceptable salt thereof exhibits an excellent FXIa inhibitory activity, and is useful as a therapeutic agent against thrombosis or the like.;
申请公布号 US2015210640(A1) 申请公布日期 2015.07.30
申请号 US201314414838 申请日期 2013.07.18
申请人 SUMITOMO DAINIPPON PHARMA CO., LTD. 发明人 Ikuma Yohei;Fukuda Nobuhisa;Iwata Masato;Kimura Hidenori;Suzuki Kuniko
分类号 C07D207/16;C07D401/12;C07D413/12;C07D417/14;C07D409/12;C07D471/04;C07D417/12;C07D403/12;C07D405/12 主分类号 C07D207/16
代理机构 代理人
主权项 1. A compound represented by formula (1) or a pharmaceutically acceptable salt thereof: wherein ring D represents a 3- to 8-membered hydrocarbon ring; Ra represents an optionally substituted amino group, an optionally substituted amidino group, an optionally substituted guanidino group, an optionally substituted aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted C1-6 alkoxycarbonylamino group, an optionally substituted amino C1-6 alkyl group, an optionally substituted amidino C1-6 alkyl group, an optionally substituted imino C1-6 alkyl group, an optionally substituted amino C3-10 cycloalkyl group, an optionally substituted amidino C3-10 cycloalkyl group, an optionally substituted imino C3-10 cycloalkyl group, an optionally substituted C1-6 alkoxy C1-6 alkyl group, an optionally substituted C1-6 alkylthio C1-6 alkyl group, an optionally substituted mercapto C1-6 alkyl group, an optionally substituted hydroxy C1-6 alkyl group, an optionally substituted carboxyl C1-6 alkyl group, an optionally substituted alkoxycarbonylamino C1-6 alkyl group or a carboxyl group; Rb1 and Rb2 each independently represent a hydrogen atom, a halogen atom, a hydroxy group, an optionally substituted C1-6 alkyl group or an optionally substituted C1-6 alkoxy group; Rc represents a halogen atom, a cyano group, a carboxyl group, a hydroxy group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C3-10 cycloalkoxy group, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkoxycarbonyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 4- to 10-membered saturated heterocyclic group, an optionally substituted C6-10 aryloxy group, an optionally substituted 5- to 10-membered heteroaryloxy group, an optionally substituted 4- to 10-membered saturated heterocyclic oxy group, an optionally substituted amino group, an optionally substituted 4- to 10-membered cyclic amino group, an optionally substituted C1-6 alkylcarbonylamino group, an optionally substituted C3-10 cycloalkylcarbonylamino group, an optionally substituted C6-10 arylcarbonylamino group, an optionally substituted 5- to 10-membered heteroarylcarbonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic carbonylamino group, an optionally substituted C1-6 alkylsulfonylamino group, an optionally substituted C3-10 cycloalkylsulfonylamino group, an optionally substituted C6-10 arylsulfonylamino group, an optionally substituted 5- to 10-membered heteroarylsulfonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic sulfonylamino group, an optionally substituted aminocarbonyl group, an optionally substituted C1-6 alkoxycarbonylamino group, an optionally substituted C3-10 cycloalkoxycarbonylamino group, an optionally substituted C6-10 aryloxycarbonylamino group, an optionally substituted 5- to 10-membered heteroaryloxycarbonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic oxycarbonylamino group or an optionally substituted 4- to 10-membered cyclic aminocarbonyl group; Rd represents a hydrogen atom, an optionally substituted C1-6 alkyl group, or an optionally substituted C3-10 cycloalkyl group; and ring Q is a group represented by any one of formulae (2a) to (2d): wherein X1, X2, and X3 each independently represent N or CR1; X4 and X5 each independently represent CR2, O, S, N or NR3; A1 and A2 each independently represent N or C; wherein X1, X2, X3, X4, X5, A1, and A2 are selected in such a manner that a ring containing these can form a bicyclic aromatic heterocyclic group; X6 and X9 each independently represent N or CR4; X7 and X8 each independently represent N or CRf; X10 and X11 each independently represent N or CR5; X12 represents O, S or NR3; R1 represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-10 cycloalkyl group wherein when two or three R1 are present in the formula, these R1 groups represent groups identical to or different from each other; R2 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted amino group, an optionally substituted 4- to 10-membered cyclic amino group, an optionally substituted C1-6 alkylcarbonyl group, an optionally substituted aminocarbonyl group, an optionally substituted 4- to 10-membered cyclic aminocarbonyl group, an optionally substituted C1-6 alkylsulfonylamino group, an optionally substituted C1-6 alkylcarbonylamino group, an optionally substituted C1-6 alkoxycarbonylamino group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 4- to 10-membered saturated heterocyclic group, an optionally substituted C1-6 alkoxycarbonyl group, an optionally substituted 4- to 10-membered saturated heterocyclic oxycarbonyl group, an optionally substituted C1-6 alkoxy group or a carboxyl group wherein when two R2 are present in the formula, these R2 groups represent groups identical to or different from each other; R3 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 4- to 10-membered saturated heterocyclic group, an optionally substituted C1-6 alkylcarbonyl group, an optionally substituted C3-10 cycloalkylcarbonyl group, an optionally substituted C1-6 alkoxycarbonyl group, an optionally substituted aminocarbonyl group, an optionally substituted 4- to 10-membered cyclic aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted 4- to 10-membered cyclic aminosulfonyl group, an optionally substituted C3-10 cycloalkylsulfonyl group or an optionally substituted C1-6 alkylsulfonyl group; R4 represents a hydrogen atom, a halogen atom, a cyano group, a carboxyl group, a 4- to 10-membered saturated heterocyclic oxycarbonyl group, a C1-6 alkoxycarbonyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted amino group, an optionally substituted 4- to 10-membered cyclic amino group, an optionally substituted aminocarbonyl group, an optionally substituted 4- to 10-membered cyclic aminocarbonyl group or an optionally substituted C1-6 alkoxy group, wherein when two R4 are present in the formula, these R4 groups represent groups identical to or different from each other; R5 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted amino group, an optionally substituted 4- to 10-membered cyclic amino group, an optionally substituted C1-6 alkylcarbonyl group, an optionally substituted aminocarbonyl group, an optionally substituted 4- to 10-membered cyclic aminocarbonyl group, an optionally substituted C1-6 alkylsulfonylamino group, an optionally substituted C1-6 alkylcarbonylamino group, an optionally substituted C1-6 alkoxycarbonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic group, an optionally substituted C1-6 alkoxycarbonyl group, an optionally substituted 4- to 10-membered saturated heterocyclic oxycarbonyl group or a carboxyl group wherein when two R5 are present in the formula, these R5 groups represent groups identical to or different from each other; Re and Rf each independently represent a hydrogen atom, a halogen atom, a cyano group, a carboxyl group, a hydroxy group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-10 cycloalkoxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted 5- to 10-membered heteroaryloxy group, an optionally substituted 4- to 10-membered saturated heterocyclic oxy group, an optionally substituted C1-6 alkylthio group, an optionally substituted C3-10 cycloalkylthio group, an optionally substituted C6-10 arylthio group, an optionally substituted 5- to 10-membered heteroarylthio group, an optionally substituted 4- to 10-membered saturated heterocyclic thio group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted 4- to 10-membered cyclic amino group, an optionally substituted 4- to 10-membered cyclic aminocarbonyl group, an optionally substituted 4- to 10-membered cyclic aminosulfonyl group, an optionally substituted C1-6 alkoxycarbonylamino group, an optionally substituted C3-10 cycloalkoxycarbonylamino group, an optionally substituted C6-10 aryloxycarbonylamino group, an optionally substituted 5- to 10-membered heteroaryloxycarbonylamino group, an optionally substituted 4- to 10-membered heterocyclic oxycarbonylamino group, an optionally substituted C1-6 alkylcarbonylamino group, an optionally substituted C3-10 cycloalkylcarbonylamino group, an optionally substituted C6-10 arylcarbonylamino group, an optionally substituted 5- to 10-membered heteroarylcarbonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic carbonylamino group, an optionally substituted C1-6 alkylsulfonylamino group, an optionally substituted C3-10 cycloalkylsulfonylamino group, an optionally substituted C6-10 arylsulfonylamino group, an optionally substituted 5- to 10-membered heteroarylsulfonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic sulfonylamino group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C3-10 cycloalkylsulfonyl group, an optionally substituted C6-10 arylsulfonyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 4- to 10-membered saturated heterocyclic group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkylsulfonylaminocarbonyl group, an optionally substituted C3-10 cycloalkylsulfonylaminocarbonyl group, an optionally substituted C6-10 arylsulfonylaminocarbonyl group, an optionally substituted 4- to 10-membered saturated heterocyclic sulfonylaminocarbonyl group, an optionally substituted 5- to 10-membered heteroarylsulfonylaminocarbonyl group, an optionally substituted aminosulfonylaminocarbonyl group, an optionally substituted 4- to 7-membered cyclic aminosulfonylaminocarbonyl group, an optionally substituted C4-7 cycloalkoxycarbonyl group, an optionally substituted 4- to 10-membered saturated heterocyclic oxycarbonyl group or an optionally substituted C1-6 alkoxycarbonyl group wherein when two Rf are present in the formula, these Rf groups represent groups identical to or different from each other; and Rg represents a hydrogen atom, a halogen atom, a cyano group, a carboxyl group, a hydroxy group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-10 cycloalkoxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted 4- to 10-membered heteroaryloxy group, an optionally substituted 4- to 10-membered saturated heterocyclic oxy group, an optionally substituted C1-6 alkylthio group, an optionally substituted C3-10 cycloalkylthio group, an optionally substituted 5- to 10-membered heteroarylthio group, an optionally substituted 4- to 10-membered saturated heterocyclic thio group, an optionally substituted C6-10 arylthio group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted 4- to 10-membered cyclic amino group, an optionally substituted 4- to 10-membered cyclic aminocarbonyl group, an optionally substituted 4- to 10-membered cyclic aminosulfonyl group, an optionally substituted C1-6 alkoxycarbonylamino group, an optionally substituted C3-10 cycloalkoxycarbonylamino group, an optionally substituted C6-10 aryloxycarbonylamino group, an optionally substituted 5- to 10-membered heteroaryloxycarbonylamino group, an optionally substituted 4- to 10-membered heterocyclic oxycarbonylamino group, an optionally substituted C1-6 alkylcarbonylamino group, an optionally substituted C6-10 arylcarbonylamino group, an optionally substituted 5- to 10-membered heteroarylcarbonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic carbonylamino group, an optionally substituted C1-6 alkylsulfonylamino group, an optionally substituted C3-10 cycloalkylsulfonylamino group, an optionally substituted C6-10 arylsulfonylamino group, an optionally substituted 5- to 10-membered heteroarylsulfonylamino group, an optionally substituted 4- to 10-membered saturated heterocyclic sulfonylamino group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C3-10 cycloalkylsulfonyl group, an optionally substituted C6-10 arylsulfonyl group, an optionally substituted 4- to 10-membered saturated heterocyclic group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkylsulfonylaminocarbonyl group, an optionally substituted C3-10 cycloalkylsulfonylaminocarbonyl group, an optionally substituted C6-10 arylsulfonylaminocarbonyl group, an optionally substituted 5- to 10-membered heteroarylsulfonylaminocarbonyl group, an optionally substituted 4- to 10-membered saturated heterocyclic sulfonylaminocarbonyl group, an optionally substituted aminosulfonylaminocarbonyl group, an optionally substituted 4- to 7-membered cyclic aminosulfonylaminocarbonyl group, an optionally substituted C4-7 cycloalkoxycarbonyl group, an optionally substituted saturated heterocyclic oxycarbonyl group or an optionally substituted C1-6 alkoxycarbonyl group.
地址 Osaka-shi, Osaka JP