Inhibitors of protein isoprenyl transferases

Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2-, and (i) heterocyclic -L2-; R2 is selected from formula, (b) -C(O)NH-CH(R14)-C(O)OR15, (c) formula, (d...

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Bibliographische Detailangaben
Hauptverfasser: DONNER, BERNARD G, BARR, KENNETH J, HAMIL TON, ANDREW D, SEBTI, SAID M, AUGERT, DAVID J.
Format: Patent
Sprache:eng
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Zusammenfassung:Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2-, and (i) heterocyclic -L2-; R2 is selected from formula, (b) -C(O)NH-CH(R14)-C(O)OR15, (c) formula, (d) -C(O)NH-CH(R14)-C(O)NHSO2R16, (e) -C(O)NH-CH(R14)-tetrazolyl, (f) -C(O)NH-heterocyclic, and (g) -C(O)NH-CH(R14)-C(O)NR17R18; R3 is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, and -P(W)RR3RR3; R4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) -L4-N(R5)-L5-, (b) -L4-O-L5-, (c) -L4-S(O)n-L5-, (d) -L4-L6C(W)-N(R5)-L5, (e) -L4-L6-S(O)m-N(R5)-L5-, (f) -L4-N(R5)-C(W)-L7-L5-, (g) -L4-N(R5)-S(O)p-L7-L5, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) formula, and (m) formula are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.