Prenyl Transferase Inhibitors

A compound of formula I,

• wherein
• n1 is 0 or 1;
• X is, independently for each occurrence, (CHR11)n3(CH2)n4Z(CH2)n5;
• Z is O, N(R12), S, or a bond;
• n3 is, independently for each occurrence, 0 or 1;
• n4 and n5 each is, independently for each occurrence, 0, 1, 2, or 3;
• Y is, independently for each occurrence, CO, CH2, CS, or a bond;
• R1 is
• or N(R24R25);
• R2, R11, and R12 each is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl and aryl, wherein said optionally substituted moiety is optionally substituted with one or more of R8 or R30;
• R3 is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-6)alkyl, (C5-7)cycloalkenyl, (C5-7)Cycloalkenyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, heterocyclyl, and heterocyclyl(C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more R30;
• R4 and R5 each is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C3-6)cycloalkyl, aryl, and heterocyclyl, wherein said optionally substituted moiety is optionally substituted with one or more R30, wherein each said substituent is independently selected, or R4 and R5 can be taken together with the carbons to which they are attached to form aryl;
• R6 is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-6)alkyl, (C5-7)cycloalkenyl, (C1-7)cycloalkenyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, heterocyclyl, and heterocyclyl(C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more substituents each independently selected from the group consisting of OH, (C1-6)alkyl, (C1-6)alkoxy, —N(R8R9), —COOH, —CON(R8R9), and halo,
• where R8 and R9 each is, independently for each occurrence, H, (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, or aryl(C1-6)alkyl;
• R7 is, independently for each occurrence, H, ═O, ═S, or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-6)alkyl, (C5-7)cycloalkenyl, (C1-7)cycloalkenyl(C1-6)alkyl, aryl, aryl(C1-6)alkyl, heterocyclyl, and heterocyclyl(C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more substituents each independently selected from the group consisting of OH, (C1-6)alkyl, (C1-6)alkoxy, —N(R8R9), —COOH, —CON(R8R9), and halo;
• R10 is C;
• or when n1=0, R6 and R7 can be taken together with the carbon atoms to which they are attached to form aryl or cyclohexyl;
• R21 is, independently for each occurrence, H or an optionally substituted moiety selected from the group consisting of (C1-6)alkyl and aryl(C1-6)alkyl, wherein said optionally substituted moiety is optionally substituted with one or more substituents each independently selected from the group consisting of R8 and R30;
• R22 is H, (C1-6)alkylthio, (C3-6)cycloalkylthio, R8—CO—, or a substituent according to the formula
• R24 and R25 each is, independently for each occurrence, H, (C1-6)alkyl, or aryl(C1-6)alkyl;
• R30 is, independently for each occurrence, (C1-6)alkyl, —O—R8, —S(O)n6R8, —S(O)n7N(R8R9),
• —N(R8R9), —CN, —NO2, —CO2R8, —CON(R8R9), —NCO—R8, or halogen;
• n6 and n7 each is, independently for each occurrence, 0, 1, or 2;
• wherein said heterocyclyl is azepinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, cinnolinyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothio-pyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isothiazolidinyl, morpholinyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, piperidyl, piperazinyl, pyridyl, pyridyl N-oxide, quinoxalinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydro-quinolinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, or thienyl;
• and
• wherein said aryl is phenyl or naphthyl;
• provided that:
• when n1=1, R10 is C and R6 is H, then R10 and R7 can be taken together to form
• or when n1=1, R10 is C, and R7 is ═O, —H, or ═S, then R10 and R6 can be taken together to form
• wherein X1, X2, and X3 each is, independently, H, halogen, —NO2, —NCO—R8, —CO2R8, —CN, or —CON(R8R9);
• and
• when R1 is N(R24R25), then n3 is 1, n4 and n5 each is 0, Z is a bond, and R3 and R11
• can be taken together to form
• wherein n2 is 1-6, and X4 and X1 each is, independently, H, (C1-6)alkyl, or
• aryl, or X4 and X1 can be taken together to form (C3-6)cycloalkyl;
• or a pharmaceutically acceptable salt thereof.