| US 7,517,899 B2 | ||
| Phenylaminopropanol derivatives and methods of their use | ||
| Callain Younghee Kim, Collegeville, Pa. (US); Paige Erin Mahaney, Pottstown, Pa. (US); Eugene John Trybulski, Huntingdon Valley, Pa. (US); Puwen Zhang, Audobon, Pa. (US); Eugene Anthony Terefenko, Center Valley, Pa. (US); Casey McComas, Phoenixville, Pa. (US); Michael Anthony Marella, Limerick, Pa. (US); Richard Dale Coghlan, Phoenixville, Pa. (US); Gavin David Heffernan, Florence, N.J. (US); Stephen Todd Cohn, Reading, Pa. (US); An Thien Vu, Pottstown, Pa. (US); Joseph Peter Sabatucci, Collegeville, Pa. (US); and Fei Ye, Audubon, Pa. (US) | ||
| Assigned to Wyeth, Madison, N.J. (US) | ||
| Filed on Mar. 28, 2005, as Appl. No. 11/91,885. | ||
| Claims priority of provisional application 60/569863, filed on May 11, 2004. | ||
| Claims priority of provisional application 60/557651, filed on Mar. 30, 2004. | ||
| Prior Publication US 2005/0222148 A1, Oct. 06, 2005 | ||
| Int. Cl. A61K 31/40 (2006.01); A61K 31/415 (2006.01); C07D 235/00 (2006.01); C07D 209/04 (2006.01) | ||
| U.S. Cl. 514—394 [514/418; 548/304.4; 548/491] | 28 Claims |
1. A compound of formula I:
 or a pharmaceutically acceptable salt thereof
wherein:
the dotted line between Y and Z represents an optional double bond;
the dotted line between the two R4 groups represents an optional heterocyclic ring of 4 to 6 ring atoms that may be formed between the two R4 groups, together with the nitrogen through which they are attached;
Y is CR6, or C═O;
Z is N, NR7, CR5, or C(R5)2;
R1 is, independently at each occurrence, alkyl, alkoxy, halo, CF3, OCF3, arylalkyloxy substituted with 0-3 R11, aryloxy substituted with 0-3 R11, aryl substituted with 0-3 R11, heteroaryl substituted with 0-3 R11, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, phenylsulfoxide substituted with 0-3 R11, alkylsulfone, phenylsulfone substituted with 0-3 R11, alkylsulfonamide, phenylsulfonamide substituted with 0-3 R11, heteroaryloxy substituted with 0-3 R11, heteroarylmethyloxy substituted with 0-3 R11, alkylamido, or arylamido substituted with 0-3 R11; or two adjacent R1 also represent methylenedioxy;
R2 is aryl substituted with 0-3 R1 or heteroaryl substituted with 0-3 R1;
R3 is H or C1-C4 alkyl;
R4 is, independently at each occurrence, H, C1-C4 alkyl, arylalkyl, heteroarylmethyl, cycloheptylmethyl, cyclohexylmethyl, cyclopentylmethyl, or cyclobutylmethyl, or
both R4 groups, together with the nitrogen through which they are attached, form a heterocyclic ring of 4 to 6 ring atoms, where one
carbon may be optionally replaced with N, O, S, or SO2, and where any carbon ring atom or additional N atom may be optionally substituted with C1-C4 alkyl, F, or CF3;
R5 is, independently at each occurrence, H, C1-C4 alkyl, aryl substituted with 0-3 R1, or cyano; or when two R5 are present, they form a carbocyclic ring of 3-7 carbons;
R6 is H, C1-C4 alkyl, or cyano;
R7 is H, C1-C6 alkyl, C3-C6 cycloalkyl, or aryl substituted with 0-3 R1;
R8 is H, or C1-C4 alkyl;
R9 is H, or C1-C4 alkyl;
R10 is, independently at each occurrence, H, or C1-C4 alkyl; or R10 and R4 together with the nitrogen to which R4 is attached form a nitrogen-containing ring containing 3-6 carbon atoms;
n is an integer from 0 to 4;
x is an integer from 1 to 2; and
R11 is alkyl, alkoxy, halo, CF3, OCF3, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; or
two adjacent R11 also represent methylenedioxy;
wherein 1-3 carbon atoms in ring A may optionally be replaced with N.
|