Inhibitors of protein isoprenyl transferases

Details Inhibitors of protein isoprenyl transferases Inhibitors of protein isoprenyl transferases

C - Chemistry, Metallurgy

07

D

C07D 213/63 (2006.01) A61K 31/41 (2006.01) A61K 31/435 (2006.01) A61K 31/495 (2006.01) A61K 31/535 (2006.01) A61K 31/54 (2006.01) A61K 31/55 (2006.01) A61K 31/695 (2006.01) C07D 213/56 (2006.01) C07D 213/71 (2006.01) C07D 213/82 (2006.01) C07D 213/89 (2006.01) C07D 233/64 (2006.01) C07D 405/04 (2006.01) C07D 405/12 (2006.01) C07D 409/12 (2006.01) C07D 413/12 (2006.01) C07D 417/12 (2006.01) C07D 471/08 (2006.01) C07D 493/08 (2006.01) C07F 7/10 (2006.01)

Patent

CA 2235986

Compounds having formula (I) or a pharmaceutically acceptable salt thereof wherein R1 is selected from: (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halogen, (g) haloalkyl, (h) aryl- L2 - and (i) heterocyclic - L3; R2 is selected from the group consisting of: (a) formula (II), (b) -C(O)NH-CH(R14)-C(O)OR15, (c) formula (III), (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 pyridyl, substituted pyridyl, imidazolyl, or substituted imidazolyl; R4 is selected from hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, and (heterocyclic)alkyl; and L1 is absent or is selected from (a) -L4-N(R4)-L5-, (b) -L4-O-L5-, (c) -L4- S(O)n-L5-, (d) -L4-L6-C(W)-N(R5)-L5-, (e) -L4-L6-S(O)m-N(R7)-L5-, (f) -L4-N(R7)-C(W)-L7-L5-, (g) -L4-N(R7)-S(O)p-L7-L5-, (h) C2-C4-alkylene optionally substituted with 1 or 2 hydroxy groups, (i) C2-to-C4-alkenylene, and (j) C2-to-C4-alkynylene, are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

L'invention concerne des composés représentés par la formule (I) ou un sel pharmaceutiquement acceptable de ces composés. Dans ladite formule R1 est choisi parmi: (a) hydrogène, (b) alkyle inférieur, (c) alcenyl, (d) alcoxy, (e) thioalcoxy, (f) halogène, (g) haloalkyle, (h) aryle-L2- et (i) hétérocyclique-L3-; R2 est choisi dans le groupe qui comprend: (a) la formule (II), (b) -C(O)NH-CH(R14)-C(O)OR15, (c) la formule (III), (d) -C(O)NH-CH(R14)-C(O)NHSO2R16, (e) -C(O)NH-CH(R14)-tétrayolyle, (f) -C(O)NH-hétérocyclique, et (g) -C(O)NH-CH(R14)-C(O)NR17R18; R3 est pyridile, pyridile substitué, imidazolyle ou imidazolyle substitué; R4 est choisi hydrogène, alkyle inférieur, haloalkyle, halogène, aryle, arylalkyle, hétérocyclique et alkyle(hétérocyclique); et L1 est absent ou choisi parmi (a) -L4-N(R4)-L5-, (b) -L4-O-L5-, (c) -L4-S(O)n-L5-, (d)-L4-L6-C(W)-N(R5)-L5-, (e) -L4-L6-S(O)m-N(R7)-L5-, (f) -L4-N(R7)-C(W)-L7-L5-, (g) -L4-N(R7)-S(O)p-L7-L5-, (h) alkylène C2-C4 éventuellement substitué par un ou deux groupes hydroxy, (i) alcénylène C2-C4, et (j) alcynylène C2-C4. Ces produits sont des inhibiteurs de protéine-isoprényle-transférase. On décrit par ailleurs des compositions et un procédé qui inhibent la protéine-isoprényle-transférase.

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