ARYL SUBSTITUTED CYCLIC AMINES AS SELECTIVE DOPAMINE D3 LIGANDS

摘要

Compounds and their pharmaceutically acceptable salts suitable for treating central nervous system disorders associated with the dopamine D3 receptor activity of structural Formula (I) where X and Y are at the 5, 6, or 7 position wherein i) n is 1 then X is (CH2)mCONR4R5, (CH2)mSO2R3, (CH2)mSO2NR4R5, (CH2)mNR4CONHR5, (CH2)mNHSO2R3, (CH2)mNHCOR3, or C(O)R4 (where m is 0 or 1, except that where m is 0, the Y is not hydrogen or halogen); and Y is R4, (CH2)pCONR4R5, (CH2)pCN, (CH2)pSO2NR4R5, OR6, (CH2)pSO2R3, (CH2)pNHSO2R3, halogen or (CH2)pNHCOR3 (where p is 0 or 1); ii) n is 0 or 1 then X and Y are in ortho-positions relative to each other and are jointly: a) -C(O)NR10C(O)-, b) -C(O)NR4(CH2)xNR10C(O)- (where x is 0 or 1), c) -CH2NR10C(O)-, d) -(CH2)2NR10C(O)-, e) -CH2C(O)NR10-, f) -N(R3)-C(O)-N(R3)-, g) -N(R3)-C(O)-O-, h) -N=C(R7)-N(R3)-, or j) -CH2N(R8)CH2-; or iii) n is 0 and Y is OR9 then X is (CH2)mCONR4R5, (CH2)mSO2NR4R5, (CH2)mNR4CONHR5, (CH2)mSO2R3, (CH2)mNHSO2R3 or (CH2)mNHCOR3, C(O)R4 (where m is 0 or 1). A compound of structural Formula (II) or its pharmaceutically acceptable salts where one of A, B, C, or D is nitrogen and remaining positions are CH; n is 1 or 2; X and Y are: i) substituted at positions A, B, C, or D wherein X is (CH2)mCONR4R5, (CH2)mCN, (CH2)mSO2NR4R5, OSO2R3, (CH2)mNR4CONHR5, (CH2)mSO2R3, (CH2)mNHSO2R3 or (CH2)mNHCOR3, C(O)R4 (where m is 0 or 1, except that where m is 0, Y is not hydrogen or halogen); and Y is R4, (CH2)pCONR4R5, (CH2)pCN, (CH2)pSO2NR4R5, OR6, OSO2R3, (CH2)pSO2R3, (CH2)pNHSO2R3, halogen or (CH2)pNHCOR3 (where p is 0 or 1); or ii) jointly in an ortho-positions relative to each other and are: -C(O)NR4C(O)-, -CH2NR4C(O)-, -CH2C(O)NR4- or -CH2N(R4)CH2-. A compound of structural Formula (III) or its pharmaceutically acceptable salts wherein one of E or F is N and the other is S; n is 1 or 2. The R1-10 groups for structural Formula (I), (II) and (III) are as defined above.