| US 7,557,125 B2 | ||
| Fab I inhibitors | ||
| William H. Miller, Collegeville, Pa. (US); Kenneth A. Newlander, West Chester, Pa. (US); Mark A. Seefeld, Collegeville, Pa. (US); Irene N. Uzinskas, Villanova, Pa. (US); Walter E. DeWolf, Glenmoore, Pa. (US); and Dalia R. Jakas, Norristown, Pa. (US) | ||
| Assigned to Affinium Pharmaceuticals, Inc., Toronto, Ontario (Canada) | ||
| Filed on Dec. 09, 2004, as Appl. No. 11/7,927. | ||
| Application 11/007927 is a continuation of application No. 10/089755, granted, now 6,846,819, previously published as PCT/US00/27844, filed on Oct. 06, 2000. | ||
| Claims priority of provisional application 60/158704, filed on Oct. 08, 1999. | ||
| Prior Publication US 2005/0250810 A1, Nov. 10, 2005 | ||
| Int. Cl. A61K 31/473 (2006.01); C07D 215/14 (2006.01) | ||
| U.S. Cl. 514—314 [546/165] | 5 Claims |
| 1. A method for screening for an inhibitor of Fab I or Fab K which comprises:
(i) providing a reaction mixture comprising Fab I or Fab K, crotonyl-ACP and NAPDH or NADH;
(ii) contacting a candidate compound to said reaction mixture; and
(iii) detecting inhibition of Fab I or Fab K
wherein said candidate compound is represented by formula (I):
  R1 is H or C1-4alkyl;
R2 is H, C1-4alkyl or C3-6cycloalkyl;
 R4 is H or C1-4alkyl;
 indicates that one of the two designated bonds is a double bond and the other is a single bond;
R5 is CH2 when the bond to which it is attached is a double bond; or R5 is H or C1-4alkyl when the bond to which it is attached is a single bond;
R6 is H or C1-4alkyl;
R7 is H, C1-6alkyl or —C0-6alkyl-Ar;
Y is H, C1-4alkyl, N(R′)2, NHC(O)R′, NHCH2C(O)R′ or NHC(O)CH═CHR′;
each X independently is H, C1-4alkyl, CH2OH, OR′, SR′, CN, N(R′)2, CH2N(R′)2, NO2, CF3, CO2R′, CON(R′)2, COR′, NR′C(O)R′, F, Cl, Br, I or —S(O)rCF3;
W is S or O;
Q is H or C1-4alkyl;
M is CH2 or O;
L is CH2 or C(O);
E is O or NR′;
each R′ independently is H, C1-6alkyl or —C0-6alkyl-Ar; and
r is 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.
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