Patent Number: 6,310,095

Title: Inhibitors of protein isoprenyl transferases

Abstract: Compounds having the formula ##STR1## or a pharmaceutically acceptable salt thereof wherein R.sub.1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L.sub.2 --, and (i) heterocyclic-L.sub.2 --; R.sub.2 is selected from (a) ##STR2## (b) --C(O)NH--CH(R.sub.14)--C(O)OR.sub.15, ##STR3## (d) --C(O)NH--CH(R.sub.14)--C(O)NHSO.sub.2 R.sub.16, (e) --C(O)NH--CH(R.sub.14)-tetrazolyl, (f) --C(O)NH-heterocyclic, and (g) --C(O)NH--CH(R.sub.14)--C(O)NR.sub.17 R.sub.18 ; R.sub.3 is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, ##STR4## and --P(W)R.sup.R3 R.sup.R3' ; R.sub.4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L.sub.1 is absent or is selected from (a) --L.sub.4 --N(R.sub.5)--L.sub.5 --, (b) --L.sub.4 --O--L.sub.5 --, (c) --L.sub.4 --S(O).sub.n --L.sub.5 -- (d) --L.sub.4 --L.sub.6 --C(W)--N(R.sub.5)--L.sub.5 --, (e) --L.sub.4 --L.sub.6 --S(O).sub.m --N(R.sub.5)--L.sub.5 --, (f) --L.sub.4 --N(R.sub.5)--C(W)--L.sub.7 --L.sub.5 --, (g) --L.sub.4 --N(R.sub.5)--S(O).sub.p --L.sub.7 --L.sub.5 --, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) ##STR5## and (m) ##STR6## are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

Inventors: Sebti; Said M. (Tampa, FL), Hamilton; Andrew D. (Guilford, CT), Augeri; David J. (Kenosha, WI), Barr; Kenneth J. (Chicago, IL), Fakhoury; Stephen A. (Mundelein, IL), Janowick; David A. (Beach Park, IL), Kalvin; Douglas M. (Buffalo Grove, IL), O'Connor; Stephen J. (Wilmette, IL), Rosenberg; Saul H. (Grayslake, IL), Shen; Wang (Gurnee, IL), Swenson; Rolf E. (Grayslake, IL), Sorenson; Bryan K. (Waukegan, IL), Sullivan; Gerard M. (Round Lake Beach, IL), Tasker; Andrew S. (Simi Valley, CA), Wasicak; James T. (Waterford, WI), Nelson; Lissa T. J. (Highland Park, IL), Henry; Kenneth J. (Fishers, IN), Wang; Le (Mundelein, IL)

Assignee: University of Pittsburgh

International Classification: C07C 323/59 (20060101); C07C 327/00 (20060101); C07C 239/20 (20060101); C07C 323/00 (20060101); C07C 323/60 (20060101); C07C 317/00 (20060101); C07C 271/00 (20060101); C07C 317/50 (20060101); C07C 237/36 (20060101); C07C 239/00 (20060101); C07D 209/48 (20060101); C07D 295/155 (20060101); C07D 211/42 (20060101); C07D 211/00 (20060101); C07D 207/26 (20060101); C07D 405/04 (20060101); C07D 205/00 (20060101); C07D 207/08 (20060101); C07D 207/267 (20060101); C07D 207/12 (20060101); C07C 327/42 (20060101); C07D 207/00 (20060101); C07C 237/00 (20060101); C07C 271/22 (20060101); C07D 207/09 (20060101); C07D 207/10 (20060101); C07D 317/60 (20060101); C07D 213/32 (20060101); C07D 239/42 (20060101); C07D 241/04 (20060101); C07D 213/38 (20060101); C07D 307/54 (20060101); C07D 213/30 (20060101); C07D 213/00 (20060101); C07D 307/00 (20060101); C07D 409/00 (20060101); C07D 241/18 (20060101); C07D 235/06 (20060101); C07D 209/00 (20060101); C07D 211/58 (20060101); C07D 237/14 (20060101); C07D 295/185 (20060101); C07D 235/00 (20060101); C07D 213/34 (20060101); C07D 241/12 (20060101); C07D 213/36 (20060101); C07D 233/54 (20060101); C07D 233/90 (20060101); C07D 233/00 (20060101); C07D 241/00 (20060101); C07D 405/00 (20060101); C07D 405/12 (20060101); C07D 211/52 (20060101); C07D 237/00 (20060101); C07D 239/26 (20060101); C07D 211/14 (20060101); C07D 307/81 (20060101); C07D 205/04 (20060101); C07D 409/12 (20060101); C07D 521/00 (20060101); C07D 213/64 (20060101); C07D 277/48 (20060101); C07D 213/68 (20060101); C07D 333/00 (20060101); C07D 277/36 (20060101); C07D 265/30 (20060101); C07D 277/20 (20060101); C07D 253/00 (20060101); C07D 261/02 (20060101); C07D 213/65 (20060101); C07D 263/00 (20060101); C07D 277/30 (20060101); C07D 257/00 (20060101); C07D 257/04 (20060101); C07D 263/32 (20060101); C07D 261/00 (20060101); C07D 213/56 (20060101); C07D 213/89 (20060101); C07D 317/00 (20060101); C07D 263/22 (20060101); C07D 213/75 (20060101); C07D 213/70 (20060101); C07D 239/00 (20060101); C07D 213/71 (20060101); C07D 253/06 (20060101); C07D 213/76 (20060101); C07D 213/74 (20060101); C07D 317/30 (20060101); C07D 213/82 (20060101); C07D 333/20 (20060101); C07D 333/24 (20060101); C07D 295/00 (20060101); C07D 279/12 (20060101); C07D 333/18 (20060101); C07D 277/50 (20060101); C07D 277/00 (20060101); C07D 295/084 (20060101); C07D 265/00 (20060101); C07D 295/13 (20060101); C07D 417/00 (20060101); C07D 401/12 (20060101); C07D 279/00 (20060101); C07D 401/00 (20060101); C07F 9/00 (20060101); C07F 9/53 (20060101); C07D 487/08 (20060101); C07D 487/00 (20060101); C07D 417/12 (20060101); A61K 031/192 (); C07C 053/134 ()

Expiration Date: 10/30/2018