Patent ID: 6569899
Filing Date: 2003-05-27
Classification: A61P,C07B,C07C,C07F

Abstract:
Aminobutyric acid derivatives of the formula (I): whereinR1 is â€”COOR10, â€”CONHOR10, â€”CONHNHR10, â€”(CH2)nSR50 or â€”Yâ€”PO(OR51)2; R10 is (i) hydrogen, (ii) C1-8 alkyl, (iii) C2-8 alkenyl, (iv) phenyl, (v) C1-8 alkyl substituted by phenyl or C1-8 alkoxy, or (vi) oxycarbonyl substituted by phenyl, benzyl or C1-8 alkyl; n is 0-3; R50 is (i) hydrogen, (ii) C1-8 alkyl, (iii) â€”COR52, in which R52 is C1-8 alkyl or phenyl, (iv) â€”SR53, in which R53 is hydrogen, C1-8 alkyl or phenyl; R51 is hydrogen, C1-8 alkyl or phenyl; Y is a single bond, â€”CH2â€” or â€”Oâ€”; R2, R3, R4, R5, R6 and R7 each, independently, is (1) hydrogen, (2) C1-8 alkyl, (3) C2-8 alkenyl, (4) â€”OR11, (5) â€”SR11, (6) â€”NR12R13, (7) Cyc1, (8) C1-8 alkyl substituted by one or more groups selected from â€”OR11, â€”SR11, â€”NR12R13, â€”COR14, guanidino and Cyc1, (9) C2-8 alkenyl substituted by one or more groups selected from â€”OR11, â€”SR11, â€”NR12R13, â€”COR14, guanidino and Cyc1, (10) C2-8 alkynyl, (11) C1-8 alkyl substituted by one or more groups selected from C3-8 alkenyloxy, with the proviso that a group having a double bond at 1-position is excluded; and C3-8 alkynyloxy, with the proviso that a group having a triple bond at 1-position is excluded; or R3 and R4, taken together is C1-8 alkylene, R5 and R6, taken together is C1-8 alkylene, R3 and R6, taken together is C1-8 alkylene, R2 and R3, taken together is C2-8 alkylene, R4 and R5, taken together is C2-8 alkylene, or R6 and R7, taken together is C2-8 alkylene; in which Cyc1 is carbocyclic ring and carbocyclic ring may be substituted by one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv) guanidino, (v) amidino, (vi) halogen atoms, (vii) cyano (viii) hydroxy, (ix) benzyloxy, (x) â€”NR101R102, in which R101 and R102 each, independently, is hydrogen or C1-8 alkyl, (xi) â€”COOR103, in which R103 is hydrogen or C1-8 alkyl, (xii) trifluoromethyl, (xiii) trifluoromethyloxy, (xiv) phenyl, (xv) phenyl substituted by C1-8 alkyl or C1-8 alkoxy, (xvi) phenyloxy, (xvii) phenylsulfonyl, (xviii) C1-8 alkyl substituted by phenyl or cyano, (xix) heterocyclic ring, (xx) keto, (xxi) C1-8 alkoxy substituted by â€”CONR104R105, in which R104 and R105 each, independently, is hydrogen, C1-8 alkyl or phenyl; R11 is (i) hydrogen, (ii) C1-8 alkyl, (iii) Cyc1, (iv) â€”COR18, (v) C1-8 alkyl substituted by one or more groups selected from â€”OR15, â€”SR15, â€”NR16R17, â€”COR18, guanidino and Cyc1; R15 is hydrogen, C1-8 alkyl, Cyc1 or C1-8 alkyl substituted by Cyc1 or C1-8 alkoxy; R16 is hydrogen or C1-8 alkyl; R17 is hydrogen, C1-8 alkyl or â€”COR19, in which R19 is C1-8 alkyl, Cyc1, C1-8 alkyl substituted by Cyc1; R18 is hydroxy, C1-8 alkyl, C1-8 alkoxy or â€”NR20R21, in which R20 and R21, each independently, is hydrogen, C1-8 alkyl, Cyc1 or C1-8 alkyl substituted by Cyc1; R12 is hydrogen, C1-8 alkyl, Cyc1 or C1-8 alkyl substituted by Cyc1; R13 is hydrogen, C1-8 alkyl, Cyc1, C1-8 alkyl substituted by Cyc1, or â€”COR22, in which R22 is C1-8 alkyl, Cyc1 or C1-8 alkyl substituted by Cyc1; R14 is hydroxy, C1-8 alkyl, C1-8 alkoxy, Cyc1, C1-8 alkyl substituted by Cyc1, or â€”NR23R24, in which R23 and R24, each independently, is (i) hydrogen, (ii) C1-8 alkyl, (iii) Cyc1 or (iv) C1-8 alkyl substituted by Cyc1 or hydroxy; (1) when R8 is 1) hydrogen, 2) C1-8 alkyl, 3) C1-8 alkoxycarbonyl, 4) C1-8 alkyl substituted by one or more groups selected from â€”OR26, â€”SR26, â€”NR27R28 and â€”COR29, or 5) C1-8 alkoxycarbonyl substituted by Cyc2, R9 is (2) when R8 is R9 is 1) C1-8 alkyl, 2) C1-8 alkoxy, 3) C1-8 alkoxy substituted by Cyc2, 4) C1-8 alkyl substituted by one or more groups selected from â€”OR26, â€”SR26, â€”NR27R28, â€”COR29 and Cyc2, or 5) â€ƒin which Cyc2 is carbocyclic ring and carbocyclic ring may be substituted by one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv) guanidino, (v) amidino, (vi) halogen atoms, (vii) cyano, (viii) hydroxy, (ix) benzyloxy, (x) â€”NR201R202, in which R201 and R202 each, independently, is hydrogen or C1-8 alkyl, (xi) â€”COOR203, in which R203 is hydrogen or C1-8 alkyl (xii) trifluoromethyl, (xiii) trifluoromethyloxy, (xiv) phenyl, (xv) phenyl substituted by C1-8 alkyl or C1-8 alkoxy, (xvi) phenyloxy, (xvii) phenylsulfonyl, (xviii) C1-8 alkyl substituted by phenyl or cyano, (xix) heterocyclic ring, (xx) keto, (xxi) C1-8 alkoxy substituted by â€”CONR204 R205, in which R204 and R205 each, independently, is hydrogen, C1-8 alkyl or phenyl; R26 is hydrogen, C1-8 alkyl, Cyc2 or C1-8 alkyl substituted by Cyc2; R27 is hydrogen, C1-8 alkyl, Cyc2 or C1-8 alkyl substituted by Cyc2; R28 is hydrogen, C1-8 alkyl, Cyc2, C1-8 alkyl substituted by Cyc2, or â€”COR30, in which R30 is C1-8 alkyl, Cyc2 or C1-8 alkyl substituted by Cyc2; R29 is hydroxy, C1-8 alkyl, Cyc2, C1-8 alkyl substituted by Cyc2, or â€”NR31R32, in which R31 and R32, each independently, is hydrogen, C1-8 alkyl, Cyc2 or C1-8 alkyl substituted by Cyc2; â€ƒis carbocyclic ring; R25 is â€”Eâ€”G; E is 1) a single bond, 2) â€”CONR33â€”, 3) â€”NR33COâ€”, 4) â€”COâ€”Oâ€”, 5) â€”Oâ€”COâ€”, 6) â€”NR33â€”COâ€”NR34â€”, 7) â€”COâ€”CH2â€”, 8) â€”COâ€”, 9) â€”Oâ€”COâ€”NR33â€”, 10) â€”NR33â€”COâ€”Oâ€”, 11) â€”Oâ€”COâ€”Oâ€”, 12) â€”CSâ€”NR33â€”, 13) â€”NR33â€”CSâ€”, 14) â€”CSâ€”Oâ€”, 15) â€”Oâ€”CSâ€”, 16) â€”NR33â€”CSâ€”NR34â€”, 17) â€”CSâ€”CH2â€”, 18) â€”CSâ€”, 19) â€”Oâ€”CSâ€”NR33â€”, 20) â€”NR33â€”CSâ€”Oâ€”, 21) â€”Oâ€”CSâ€”Oâ€”, 22) â€”CH2â€”CH2â€”, 23) â€”HC&boxH;CHâ€”, 24) â€”Câ‰¡Câ€”, 25) â€”SO2â€”NR33â€”, 26) â€”NR33â€”SO2â€”, 27) â€”SO2â€”CH2â€” or 28) â€”CH2â€”SO2â€”; R33 and R34, each independently, is hydrogen, C1-8 alkyl, Cyc3 or C1-8 alkyl substituted by Cyc3; Cyc3 is carbocyclic ring and carbocyclic ring may be substituted by one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv) guanidino, (v) amidino, (vi) halogen atoms, (vii) cyano, (viii) hydroxy, (ix) benzyloxy, (x) â€”NR301R302, in which R301 and R302 each, independently, is hydrogen or C1-8 alkyl, (xi) â€”COOR303, in which R303 is hydrogen or C1-8 alkyl, (xii) trifluoromethyl, (xiii) trifluoromethyloxy, (xiv) phenyl, (xv) phenyl substituted by C1-8 alkyl or C1-8 alkoxy, (xvi) phenyloxy, (xvii) phenylsulfonyl, (xviii) C1-8 alkyl substituted by phenyl or cyano, (xix) heterocyclic ring, (xx) keto, (xxi) C1-8 alkoxy substituted by â€”CONR304R305, in which R304 and R305 each, independently, is hydrogen, C1-8 alkyl or phenyl; G is 1) hydrogen, 2) C1-8 alkyl, 3) Cyc4, 4) â€”OR35, 5) â€”SR35, 6) halogen atoms, 7) nitro, 8) cyano, 9) â€”NR36R37, 10) â€”COR38, 11) C1-8 alkyl substituted by one or more groups selected from Cyc4, â€”OR35, â€”SR35, halogen atoms, â€”NR36R37 and â€”COR38; in which Cyc4 is carbocyclic ring and carbocyclic ring may be substituted by one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv) guanidino, (v) amidino, (vi) halogen atoms, (vii) cyano, (viii) hydroxy, (ix) benzyloxy, (x) â€”NR401R402, in which R401 and R402 each, independently, is hydrogen or C1-8 alkyl, (xi) â€”COOR403, in which R403 is hydrogen or C1-8 alkyl, (xii) trifluoromethyl, (xiii) trifluoromethyloxy, (xiv) phenyl, (xv) phenyl substituted by C1-8 alkyl or C1-8 alkoxy, (xvi) phenyloxy, (xvii) phenylsulfonyl, (xviii) C1-8 alkyl substituted by phenyl or cyano, (xix) heterocyclic ring, (xx) keto, (xxi) C1-8 alkoxy substituted by â€”CONR404R405, in which R404 and R405 each, independently, is hydrogen, C1-8 alkyl or phenyl; R35 is hydrogen, C1-8 alkyl, C1-8 alkoxy, Cyc4 or C1-8 alkyl substituted by Cyc4; R36 is hydrogen, C1-8 alkyl, Cyc4, C1-8 alkyl substituted by Cyc4; R37 is hydrogen, C1-8 alkyl, Cyc4, C1-8 alkyl substituted by Cyc4, or â€”COR39, in which R39 is C1-8 alkyl, Cyc4 or C1-8 alkyl substituted by Cyc4; R38 is hydroxy, C1-8 alkyl, Cyc4, C1-8 alkyl substituted by Cyc4, or â€”NR40R41, in which R40 and R41, each independently, is hydrogen, C1-8 alkyl, Cyc4 or C1-8 alkyl substituted by Cyc4; or â€”Eâ€”G taken together, is C1-4 alkylidene; p is 1-5; M is C1-8 alkylene; J is a single bond, an oxygen atom, a sulfur atom or â€”NR42â€”, in which R42 is hydrogen or C1-8 alkyl;  is a single bond, or a double bond which prepared by two hydrogens are released, in the case of two of R2, R3, R4, R5, R6 and R7 which do not bond to a same carbon atom but bond to a neighboring carbon, are hydrogens; with the proviso that  is not a double bond, when R3 and R4, taken together is C1-8 alkylene, R5 and R6, taken together is C1-8 alkylene, R3 and R6, taken together is C1-8 alkylene; with the proviso that (1) at least one of R2, R3, R4, R5, R6 and R7 is C2-8 alkynyl, or C1-8 alkyl substituted by one or more groups selected from C3-8 alkenyloxy and C3-8 alkynyloxy, (2) when â€ƒis benzene, and E is a single bond, then G is not hydrogen; (3) the following compound is excluded: the compound wherein R2 is 2-propynyl, and R3, R4, R5, R6 and R7 each, independently, is the above groups (1) to (9) or R3 and R4, taken together is C1-8 alkylene, R5 and R6, taken together is C1-8 alkylene, R3 and R6, taken together is C1-8 alkylene, R4 and R5, taken together is C2-8 alkylene, or R6 and R7, taken together is C2-8 alkylene; non-toxic acid thereof.