| 主权项 |
1. A compound having the absolute stereochemistry according to formula (I)wherein
R1 is hydrogen, C1-6alkyl, C2-6alkenyl or —(C(R5aR5b))m—(C3-6cycloalkyl); wherein said alkyl, alkenyl or cycloalkyl moieties may independently be optionally substituted with one to three R6; R2 is halogen, hydrogen, C1-6alkyl, C2-6alkenyl or —(C(R5aR5b))m—(C3-6cycloalkyl); wherein said alkyl, alkenyl or cycloalkyl moieties may independently be optionally substituted with one to three R6; R3a is hydrogen, C1-6alkyl, C2-6alkenyl, —(C(R5aR5b))m—(C3-6cycloalkyl), —(C(R5aR5b))m-(4- to 10-membered heterocycloalkyl), —(C(R5aR5b))m—(C6-10aryl), —(C(R5aR5b))m-(5- to 10-membered heteroaryl), —(C(R5aR5b))m—OR7, —C(O)N(R8)2, —(C(R5aR5b))n—NHC(O)R8 or —(C(R5aR5b))n—N(R8)2; wherein said alkyl, alkenyl, cycloalkyl or heterocycloalkyl moieties may independently be optionally substituted with one to three R10; and wherein the aryl or heteroaryl moieties may independently be optionally substituted with one to five R10; R3b is hydrogen, C1-3alkyl, —(C(R5aR5b))m—(C3-5cycloalkyl), —(C(R5aR5b))m-(4- to 5-membered heterocycloalkyl) or —(C(R5aR5b))m—OR7; wherein said alkyl, cycloalkyl or heterocycloalkyl moieties may independently be optionally substituted with one to three R10; R4a and R4e are independently halogen, hydrogen, C1-6alkyl, —CN or —OR9; wherein said alkyl is optionally substituted by one to three fluoro; R4b and R4d are independently fluoro, chloro, hydrogen, C1-6alkyl, —CN or —OR12; wherein said alkyl is optionally substituted by one to three fluoro; or R4c and R4d, together with the carbons to which they are bonded, form a 5- to 6-membered cycloalkyl or a 6-membered aryl, wherein said cycloalkyl or aryl is optionally substituted with one to three —CF3, fluoro, C1-6alkyl, —OC1-6alkyl, —OH, —NH2 or —NH—C1-6alkyl; R4c is halogen, hydrogen, C1-6alkyl, —CN or —OR12; wherein said alkyl is optionally substituted by one to three fluoro; or R4b and R4c, together with the carbons to which they are bonded, form a 5- to 6-membered cycloalkyl or a 6-membered aryl, wherein said cycloalkyl or aryl is optionally substituted with one to three —CF3, fluoro, C1-6alkyl, —OC1-6alkyl, —OH, —NH2 or —NH—C1-6alkyl; R5a and R5b are each independently fluoro, hydrogen or C1-6alkyl; R6 is independently fluoro, —CN, C1-6alkyl or OR9; R7 is independently hydrogen, C1-6alkyl, —(C(R5aR5b))t—(C3-6cycloalkyl), —(C(R5aR5b))t-(4- to 10-membered heterocycloalkyl), —(C(R5aR5b))t—(C6-10aryl), —(C(R5aR5b))t-(5- to 10-membered heteroaryl) or —C(O)R11; wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one to three R10; R8 is independently hydrogen, C1-6alkyl, —(C(R5aR5b))t—(C3-6cycloalkyl), —(C(R5aR5b))t-(4- to 10-membered heterocycloalkyl), —(C(R5aR5b))t—(C6-10aryl) or —(C(R5aR5b))t-(5- to 10-membered heteroaryl), wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one to three fluoro; R9 is independently hydrogen, C1-6alkyl or C3-6alkenyl, optionally substituted with one to three fluoro; R10 is independently halogen, —OH, —CN, wherein said alkyl groups are optionally substituted with one to three fluoro; R11 is independently C6-10aryl, C1-6alkyl or —NR13aR13b; R12 is hydrogen or C1-6alkyl optionally substituted with one to three fluoro; R13a and R13b are each independently hydrogen, C1-6alkyl, wherein said alkyl is optionally substituted with one to three fluoro; or R13a and R13b taken together with the nitrogen to which they are bonded form a 4- to 6-membered heterocycloalkyl ring, which may optionally include one oxygen to form a morpholine moiety; m is 0, 1 or 2; n is 1 or 2; and t is 0 or 1; provided that,
if one of R4a or R4e is fluoro, while the other is hydrogen, and R1, R2, R4b, R4c and R4d are hydrogen, and one of R3a or R3b is hydrogen, methyl, —CH2OCH3, —CH2OCH2-phenyl or —CH2OH, then the other (R3a or R3b) cannot be hydrogen;(ii) if one of R4a or R4e is fluoro, while the other is hydrogen, and R3a, R3b, R4b, R4c and R4d is hydrogen, and R2 is fluoro, —CH3 or —OCH3, R1 cannot be hydrogen; and(iii) if one of R4a or R4e is fluoro, while the other is hydrogen, and if R2, R3a, R3b, R4b, R4c and R4d are hydrogen, R1 cannot be methyl; and(iv) if one of R4a or R4e is —OR9, wherein R9 is —CF3, while the other is hydrogen, and if R4b, R4c, and R4d are hydrogen, then at least one of R1, R2 or R3a, R3b, cannot be hydrogen.or a pharmaceutically acceptable salt thereof. |
