Compounds useful for inhibition of farnesyl protein transferase

A compound of the formula:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• One of a, b, c and d represents N or NR9 wherein R9 is O−, —CH3 or —(CH2)nCO2H wherein n is 1 to 3, and the remaining a, b, c and d groups represent CR1 or CR2;
• or each of a, b, c, and d are independently selected from CR1 or CR2;
• each R1 and each R2 is independently selected from H, halo, —CF3, —OR10, —COR10, —SR10, —S(O)tR11 (wherein t is 0, 1 or 2), —SCN, —N(R10)2, —NR10R11, —NO2, —OC(O)R10, —CO2R10, —OCO2R11, —CN, —NHC(O)R10, —NHSO2R10, —CONHR10, —CONHCH2CH2OH, —NR10COOR11,
• —SR11C(O)OR11, —SR11N(R75)2 wherein each R75 is independently selected from H and —C(O)OR11, benzotriazol-1-yloxy, tetrazol-5-ylthio, or substituted tetrazol-5-ylthio, alkynyl, alkenyl or alkyl, said alkyl or alkenyl group optionally being substituted with halo, —OR10 or —CO2R10;
• R3 and R4 are the same or different and each independently represents H, any of the substituents of R1 and R2, or R3 and R4 taken together represent a saturated or unsaturated C5-C7 fused ring to the benzene ring (Ring III);
• R5, R6, R7 and R8 each independently represents H, —CF3, —COR10, alkyl or aryl, said alkyl or aryl optionally being substituted with —OR10, —SR10, —S(O)tR11, —NR10COOR11, —N(R10)2, —NO2, —COR10, —OCOR10, —OCO2R11, —CO2R10, OPO3R10, or R5 is combined with R6 to represent ═O or ═S and/or R7 is combined with R8 to represent ═O or ═S;
• R10 represents H, alkyl, aryl, or aralkyl;
• R11 represents alkyl or aryl;
• X represents N and the optional bond (represented by the dotted line) to carbon 11 is absent;
• the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent —R10, halo, —OR11, —OCO2R11 or —OC(O)R10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H2, —(OR11)2;
• H and halo, dihalo, alkyl and H, (alkyl)2, —H and —OC(O)R10, H and —OR10, ═O, aryl and H, ═NOR10 or —O—(CH2)p—O— wherein p is 2, 3 or 4;
• and
• W represents a group selected from the group consisting of:
• wherein:
• R12 is selected from the group consisting of:
• (a) H;
• (b) alkyl;
• (c) aralkyl;
• and (d) heteroarylalkyl;
• R13 and R14 are each independently selected from the group consisting of:
• (a) H;
• (b) —C(O)OR16 wherein R16 represents alkyl, aralkyl, and heteroaralkyl;
• (c) —SO2R17 wherein R17 is selected from the group consisting of:
• NH2, —N(alkyl)2 wherein each alkyl is the same or different, alkyl, aryl, aralkyl, heteroaryl and heteroaralkyl;
• (d) —C(O)R18 wherein R18 is selected from the group consisting of:
• aryl, alkyl, aralkyl, heteroaryl, and heteroaralkyl;
• (e) C1-6 alkyl;
• (f) alkaryl;
• and (g) C3-6 cycloalkyl;
• r is 0, 1 or 2;
• s represents 1, 2, 3, 4, or 5, and each Y for each —CY2— group is independently selected from H or —OH, provided that both Y substituents of each —CY2— group are not —OH, and provided that for the —CY2— group alpha to the nitrogen both Y substituents are H, such that the group
• forms a 3, 4, 5, 6, or 7 membered ring;
• v is 0, 1 or 2;
• R15 is selected from the group consisting of:
• (a) heteroaryl;
• (b) a group selected from:
• (5) —CH(OCH2CH3)2,
• (6) —OH, and
• (7) —CN;
• and
• (c) heterocycloalkyl selected from the group consisting of:
• z is 0, 1, 2, 3, 4, or 5 wherein each —CH2— group is optionally substituted with a —OH group;
• R22 represents a group selected from:
• (5) alkyl,
• (6) —OR23 wherein R23 is selected from the group consisting of:
• alkyl, aryl and H, and
• wherein R24 and R25 are independently selected from the group consisting of:
• —NH2, alkoxy, —OH, —CH2CO2H, —OCH2Ph, —CH(OCH3)CH(CH3)2, alkyl, aryl, H, aralkyl, and heteroaralkyl;
• or R24 and R25 taken together form a carbon chain having 4 or 5 (—CH2—) groups such that R24 and R25 taken together with the nitrogen to which they are bound form a 5 or 6 membered heterocycloalkyl ring.