申请人:H. LUNDBECK A/S
公开号:EP0939077A2
公开(公告)日:1999-09-01
3-substituted 1-arylindole compound having general Formula I
wherein Ar is an optionally substituted aryl group;
X represents a bond, a divalent hydrocarbon group or methyleneoxy or -thioxo; R1_R4 are hydrogen or substituents; R5 is hydrogen, hydroxy, alkoxy, halogen, trifluoromethyl, alkyl or alkenyl; R6 and R7 are hydrogen, alkyl or alkenyl;
R8 is alkyl or alkenyl a group of Formula 1a or 1b :
wherein; W is O or S; U is N or CH ; Z is (CH2)m, 1,2-phenylene, CH=CH, COCH2 or CSCH2-; V is O, S, CH2, or NR10, wherein R10 is hydrogen or alkyl; U1 is O, S, CH2 or NR11, wherein R11 is as R10; and V1 is NR12R13, OR14, SR15 or CR16R17R18, where each of R12-R18 are as the R10-substituents;
R9 is hydrogen or alkyl; or R9 is linked to R7 to form a ring; or
R8 and R9 together form a morpholinyl or piperidinyl ring, the latter optionally substituted by alkyl or a group of Formula 1a or 1b, or a carbamoyl group,
show central antiserotonergic activity and possibly also antidopaminergic activity and are, accordingly, useful in the treatment of central nervous system (CNS) disorders. The compounds are prepared by methodt known pr. se.
通式 I 的 3-取代 1-芳基吲哚化合物
其中 Ar 是任选取代的芳基;
R1_R4 是氢或取代基;R5 是氢、羟基、烷氧基、卤素、三氟甲基、烷基或烯基; R6 和 R7 是氢、烷基或烯基;
R8 是式 1a 或 1b 的烷基或烯基:
其中;W 是 O 或 S;U 是 N 或 CH;Z 是 (CH2)m、1,2-亚苯基、CH=CH、COCH2 或 CSCH2-;V 是 O、S、CH2 或 NR10,其中 R10 是氢或烷基;U1 是 O、S、CH2 或 NR11,其中 R11 与 R10 相同;以及 V1 是 NR12R13、OR14、SR15 或 CR16R17R18,其中每个 R12-R18 与 R10 取代基相同;
R9 是氢或烷基;或 R9 与 R7 连接形成一个环;或
R8 和 R9 共同形成吗啉基或哌啶基环,后者可选择被烷基或式 1a 或 1b 基团或氨基甲酰基取代、
显示出中枢抗iserotonergic活性,也可能显示出抗多巴胺能活性,因此可用于治疗中枢神经系统(CNS)疾病。这些化合物是通过已知的方法制备的。