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    • 73. 发明申请
    • CYCLIC AMIDES AND IMIDES HAVING SELECTIVE ANTAGONIST ACTIVITY AT ALPHA-1D ADRENERGIC RECEPTOR
    • 在ALPHA-1D ADRENERGIC受体中具有选择性拮抗剂活性的循环氨基酸和咪唑
    • WO01005765A1
    • 2001-01-25
    • PCT/EP2000/006738
    • 2000-07-14
    • A61K31/438A61K31/4545A61K31/496A61K31/55A61P9/08A61P9/10A61P13/10A61P43/00C07D207/40C07D207/404C07D207/408C07D209/54C07D211/88C07D221/20C07D223/14C07D401/06A61K31/4015A61K31/403
    • C07D207/404C07D209/54C07D211/88C07D221/20C07D401/06
    • Compounds (I) R and R1 independently = H or C1-C4 alkyl or together = (CH2)2-6, n=0 or 1, ...... is a single or a double bond, A=CO or CH2, A1 represents a CO or CH2 or CH, each R3 independently = H or C1-C4 alkyl, B is B1 or B2 (B2); Y=N or CH, R2 = halogen, C1-C4 alkyl or CN, R5 = halogen, C1-C4 alkyl, polyfluoroalkyl or NO2, R6 = H or halogen, m is 1 to 3, Z = O, S, NH or NMe) interact selectively with the alpha 1D subtype of the alpha 1 adrenergic receptor. This selectively makes these compounds useful agents in tissues particularly rich in alpha 1D adrenergic receptors, thus useful in reducing contractility of an unstable urinary bladder, in the treatment and prevention of atherosclerosis as they are inhibitors of noradrenaline-mediated cell proliferation in smooth muscles, and in reducing vascular adrenergic tone. The preparation of these compounds, their enantiomers, diastereoisomers, N-oxides and pharmaceutically acceptable salts, and pharmaceutical compositions containing them are also claimed.
    • 化合物(I)R和R 1独立地为H或C 1 -C 4烷基或一起=(CH 2)2-6,n = 0或1,...是单或双 键,A = CO或CH 2,A 1表示CO或CH 2或CH,每个R 3独立地为H或C 1 -C 4烷基,B为B 1或B 2(B 2); Y = N或CH,R2 =卤素,C1-C4烷基或CN,R5 =卤素,C1-C4烷基,多氟烷基或NO2,R6 = H或卤素,m为1至3,Z = O,S,NH或 NMe)与α1肾上腺素能受体的α1D亚型选择性相互作用。 这选择性地使这些化合物在特别富含α1D肾上腺素能受体的组织中有用,因此可用于降低不稳定膀胱的收缩性,在治疗和预防动脉粥样硬化中,因为它们是平滑肌中去甲肾上腺素介导的细胞增殖的抑制剂,以及 在减少血管肾上腺素能力。 还要求保护这些化合物,它们的对映异构体,非对映异构体,N-氧化物和药学上可接受的盐以及含有它们的药物组合物的制备。