Inhibitors of farnesyl protein transferase

US6455523B1 · kind B1 · utility

Assignee

• Bristol-Myers Squibb Company · US

Inventors

• Charles Z. Ding · San Mateo, US
• Soong-Hoon Kim · Titusville, US
• John T. Hunt · Princeton, US
• Toomas Mitt · Plainsboro, US
• Rajeev S. Bhide · Princeton Junction, US
• Katerina Leftheris · Skillman, US

Key dates

• Filing date: Aug 13, 1999
• Grant date: Sep 24, 2002
• Expiry date: Aug 13, 2019

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D495/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Inhibition of farnesyl transferase, which is an enzyme involved in ras ocogene expression, is effected by compounds of the formulas their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs and solvates thereof inhibit farnesyl protein transferase which is an enzyme involved in ras oncogene expression. In formulas I-IV and throughout their specification, the above symbols are defined as follows:m, n, r, s and t are 0 or 1; p is 0, 1 or 2; V, W and X are selected from the group consisting of oxygen, hydrogen, R1, R2 or R3;Z and Y are selected from the group consisting of CHR9, SO2, SO3, CO, CO2, O, NR10, So2NR11, CONR12, or Z may be absent;R6, R7, R9, R10, R11, R12 R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R24, R25, R26, R27, R28, R29, R30, R31, R32,R33, R34, R35, R36, R37, and R38 are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl;R4, R5 are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R23;U is selected from the group consisting of sulfur, oxygen, NR24, CO, SO, SO2, CO2, NR25CO2, NR26CONR27, NR28SO2, NR29SO2NR30, SO2NR31, NR32CO, CONR33, PO2R34 and PO3R35 or U is ab…