Cinolin - 3 - carboxamide Derivatives, Methods for their preparation, Pharmaceutical compositions containing them and their use in the manufacture of medicaments for the treatment of diseases mediated by the Modulation of Gabaa receptor

摘要

These compounds are used to treat or prevent anxiety disorders, disorders, and / or mental disorders. They are also used in pharmaceutical synthesis and in the manufacture of GABA based drugs. In addition, a comprehensive approach is provided. Item 1: a formula compound (1)or one of its pharmaceutically acceptable salts, tautomers, atropisomers or in vivo hydrolyzable precursors, where R1 is C1-6 alkyl, C1-6 haloalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, with 1, 2, 3, 4 or 5 R7; R2 is H, C (= O) Rb, C (= O) NRcRd, C (O) ORa, S (O) 2Rb, C1-6 alkyl, C1-6 haloalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, where each of C 1-6 alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl,cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4 or 5 R8; R3, R4 and R5 are each, independently, H, halo, Si (C1-10 alkyl) 3, CN, NO2, ORa, SRa, OC (= O) Ra, OC (= O) ORb, OC ( = O) NRcRCd, C (= O) Ra, C (= O) ORb, C (= O) NRcRd, NRcRd, NRcC (= O) Ra, N RcC (O) ORb, NRcS (O) 2Rb, S ( = O) Ra, S (= O) NRcRd, S (= O) 2Ra, S (= O) 2NRcRd, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, where C1-6alkyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl,One, two or three R9 can be selected to replace the heteromorphic tequila, ring clathra or non ring methyltequila; R6 is arilo, ring methylquinolo, heteromorphic or isopropyllu, and one, two, three, four or five A1 can be selected to replace each; R7, R8 and R9 are halogenated, C1-4 tar, C1-4 halotar, arilo and ring methylquinoi respectively, Straight, straight, straightMadam,This is my life.C (3DO) NRc Rdit is life.OC (3DO) RbOC (3DO) NRc RdNRC'RD',NRc C (3DO) RbNRc C (3DO) ORaNRc S (3DO) 2RbYes, that's it.S (3DO) NRc RdS (3DO) 2Rb o S (3DO) 2NRc Rd { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { { C1-4, amino acid, c1-4-amino acid, diaquil c2-4-amino, C1-6, alquenilo c2-6, c12-6, acquinio c2-6, arilalquilo, cyclo clalquilo, Non-n-propyl, non-n-propyltequila, arillo, cyclopropyl, non-n-propyl or non-n-propyl coagulation, in which each type of C1-6, alquenilo c2-6, tar layer c2-6, arilalquilo, cyclopropyllong, isopropyllong, arillo, cyclopropyllu, non cyclopropyllong, isopropyltequila, heterogeneous or non cyclopentadienedienediallyoxybenzene is replaced.4 or 5. Independently selected halogenated, C1-6 tar, c2-6 alquenilo c2-6, c2-6 tar, C1-4 halogenated, arilo, cyclopentanediol, isopropene, isoacrylonitrile, isopropyl propylene, CN, NO2, ora substitutes,Madam,This is my life.C (3DO) NRc Rdit is life.OC (3DO) RbOC (3DO) NRc RdNRC'RD',NRc C (3DO) RbNRc C (3DO) ORaNRc S (3DO) RbNRc S (3DO) 2RbYes, that's it.S (O) NRc RdS (3DO) 2Rb o S (3DO) 2Rc RdRA and RA's are h, C1-6, C1-6, C1-6, c12-6, alquenilo c2-6, c12-6, acrylonitrile, isopropyl, isopropyl, isopropyl propyl, arilalquilo, isoacrylonitrile, cyclopentadiene, cyclopentadienediallyl methanol or isopropyl propyl methanol, respectively, of which C1-6, C1-6 halo-6, alquenilo c2-6, c2-6, C2 Isopropylene, isopropenylpropene, isopropenylpropene, cyclopropene or isopropenylpropenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propenyl propylpropylpropylpropylpropylpropyl propenyl propenyl propenyl propenyl propylpropylpropylpropylC1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, where C1-6 alkyl, C2-6alkenyl, C2-6alkenyl, -6, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6alkyl, haloC1-6alkyl, aryl, arylalkyl, heteroaryl, , cycloalkyl or heterocycloalkyl; Rc and Rd are each independently H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl,Right angle, ring armour, non ring armour, non ring armour, arilachilo, alien, ring armour, ring armour carat or non ring armour carat Cyclomequilol or non cyclomequilol can be replaced by Oh, amino, halo, C1-6 asphalt, C1-6 halo tar, C1-6 halo tar, arilo, arilalquilo, heterosexual, heterosexual, cyclomequilol or non cyclomequilol; or RC and RD can form a non cyclomequilol compound with N atoms, 6 or 7 members; RC 'and RD's are independent members, h,C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, where C 1-10 alkyl, C 1-6 haloalkyl, -6, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C1-6alkyl, haloalkyl, aryl, heteroaryl, heteroaryl, , cycloalkyl or heterocycloalkyl; or Rc 'and Rd' together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group;The condition is that when R2, R3, R4 and R5 are h, R6 is different from the unmodified phenyl or the unmodified cyclopentyl.