166169-82-0

Upstream product

• 166169-81-9 (S)-1,2,3,4-tetrahydro-2-<3-methyl-N-<(phenylmethoxy)-carbonyl>-L-valyl>-3-isoquinolinecarboxylic acetic acid, methyl ester 
• 62965-10-0 (S)-N-carbobenzoxy-tert-butylleucine 

Downstream Products

• 166169-85-3 (R^*)-N²-<<1,2,3,4-tetrahydro-2-<3-methyl-N-<(phenylmethoxy)-carbonyl>-L-valyl>-3-isoquinolinyl>carbonyl>-L-glutamine, 1,1-dimethylethyl ester 
• 1027187-22-9 (S)-2-{[(S)-2-((S)-2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl]-amino}-4-methoxy-butyric acid tert-butyl ester 
• 1055033-46-9 (S)-2-{[(S)-2-((S)-2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl]-amino}-4-dimethylcarbamoyl-butyric acid tert-butyl ester 
• 1027306-43-9 (S)-2-({(S)-2-[(S)-2-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propylamino)-3,3-dimethyl-butyryl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-4-methoxy-butyric acid tert-butyl ester 
• 166169-87-5 (R*,S*)-N-<<2-amino>-3-<(triphenylmethyl)thio>propyl>-3-methyl-L-valyl>-1,2,3,4-tetrahydro-3-isoquinolinyl>carbonyl>-L-glutamine tert-butyl ester 
• 1027505-27-6 (S)-2-({(S)-2-[(S)-2-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propylamino)-3,3-dimethyl-butyryl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-4-methanesulfonyl-butyric acid tert-butyl ester 
• 1054652-15-1 (S)-2-({(S)-2-[(S)-2-((R)-2-tert-Butoxycarbonylamino-3-tritylsulfanyl-propylamino)-3,3-dimethyl-butyryl]-1,2,3,4-tetrahydro-isoquinoline-3-carbonyl}-amino)-4-dimethylcarbamoyl-butyric acid tert-butyl ester 

Relevant academic research and scientific papers

Development of highly potent inhibitors of Ras farnesyltransferase possessing cellular and in vivo activity

Analogs of CVFM (a known nonsubstrate farnesyltransferase (FT) inhibitor derived from a CA2A2X sequence where C is cysteine, A is an aliphatic residue, and X is any residue) were prepared where phenylalanine was replaced by (Z)-dehyd

Potent, cell active, non-thiol tetrapeptide inhibitors of farnesyltransferase.

All previously reported CAAX-based farnesyltransferase inhibitors contain a thiol functionality. We report that attachment of the 4-imidazolyl group, via 1-, 2-, or 3-carbon alkyl or alkanoyl spacers, to Val-Tic-Met or tLeu-Tic-Gln provides potent FT inhibitors. (R*)-N-[[1,2,3,4-Tetrahydro-2-[N-[2-(1H-imidazol-4-yl)ethyl] -L-valyl]-3-isoquinolinyl]carbonyl]-L-methionine ([imidazol- 4-yl-ethyl]-Val-Tic-Met), with FT IC50 = 0.79 nM, displayed potent cell activity in the absence of prodrug formation (SAG EC50 = 3.8 muM).

Inhibitors of farnesyl protein transferase

Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formula their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs, and solvates, wherein:, ???G is ???when G is it is optionally substituted, at any available position or positions, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, or a combination of these groups;, ???G1is optionally substituted, at any of the available position or positions on the ring, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, aryl, aralkyl, hydroxy, alkanoyl, alkanoyloxy, amino, alkylamino, dialkylamino, alkanoylamino, thiol, alkylthio, alkylthiono, alkylsulfonyl, sulfonamido, nitro, cyano, carboxy, carbamyl, N-hydroxycarbamyl, N-alkylcarbamyl, N-dialkylcarbamyl, alkoxycarbonyl, phenyl, substituted phenyl, or a combination of these groups;, ???G2is or -NR6-CH(Q1)-;, ???J, K and L are each, independently, N, NR7, O, S or CR6with the provisos that only one of the groups J, K and L can be O or S, and at least one of the groups J or L must be N, NR7, O or S to form a fused five-membered heteroring; the bond between J and K or K and L may also form one side of a phenyl ring fused to the fused five-membered heteroring;, ???Q is is alkyl, cycloalkyl, substituted alkyl, aryl, pyrrolyl, furyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, pyrrolidyl or pyridyl;, ???Q1, A1and A2are each, independently, H, alkyl, substituted alkyl, phenyl or substituted phenyl;, ???G3is R8, -C(O)OR8, -C(O)NR8R9, -C(O)N(R10)OR8, -C(O)NHSO2R11or -CH2OR8;, ???X is -SH, -OH or -NHR12;, ???X1is -NR13-, -CH2- or -CH(NHR14)-;, ???Y and Z are each, independently, -CH2- or -C(O)-;, ???R1- R14are each, independently, H or alkyl having 1 to 20 carbon atoms;, ???R3may also be substituted alkyl or cycloalkyl; R4, R5and R11may also be aryl or aralkyl; R7, R8, R9and R10may also be aralkyl; and R12, R13and R14may also be substituted alkyl or aralkyl;, ???m is 0 or an integer from 1 to 2;, ???q is 0 or an integer from 1 to 3;, ???t is an integer from 1 to 2; and, ???the dotted line represents an optional double bond.

Imidazole-containing inhibitors of farnesyl protein transferase

Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formula their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs, and solvates, wherein:, G is G1 is G2 is or -NR10-CH(Q1)-;, J, K and L are each, independently, N, NR9, O, S or CR10 with the provisos that only one of the groups J, K and L can be O or S, and at least one of the groups J or L must be N, NR9, O or S to form a fused five-membered heteroring; the bond between J and K or K and L may also form one side of a phenyl ring fused to the fused five-membered heteroring;, Q is aryl;, Q1, A1 and A2 are each, independently, H, alkyl, substituted alkyl, phenyl or substituted phenyl;, G3 is R11, -C(O)OR11, -C(O)NR11R12, 5-tetrazolyl, -C(O)N(R13)OR11, -C(O)NHSO2R14 or -CH2OR11;, G4 is attached at the 1, 2, 4 or 5 position and optionally substituted, at any of the available position or positions on the ring, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, aryl, aralkyl, hydroxy, alkanoyl, alkanoyloxy, amino, alkylamino, dialkylamino, alkanoylamino, thiol, alkylthio, alkylthiono, alkylsulfonyl, sulfonamido, nitro, cyano, carboxy, carbamyl, N-hydroxycarbamyl, N-alkylcarbamyl, N-dialkylcarbamyl, alkoxycarbonyl, phenyl, substituted phenyl, or a combinaton of these groups;, Y and Z are each, independently, -CH2- or -C(O)-;, R1 - R14 are each, independently, H or alkyl having 1 to 20 carbon atoms;, R7, R8 and R14 may also be aryl or aralkyl, and R3, R9, R11, R12 and R13 may also be aralkyl;, m, n and p are each, independently, 0 or an integer from 1 to 2;, q is 0 or an integer from 1 to 4; and, the dotted line represents an optional double bond.

Heterocyclic inhibitors of farnesyl protein transferase

Inhibition of farnesyl protein transferase is effected by compounds of the formula its enantiomers, diastereomers, pharmaceutically acceptable salts, prodrugs or solvates thereof, wherein:, A1 and A2 are each independently H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, phenyl or substituted phenyl;, G1 is S or O;, G2 is H, -C(O)OH, -C(O)NH2, 5-tetrazolyl, -C(O)N(R7)OH or -CH2OH;, X is O or R8N;, Y and Z are each independently -CH2- or -C(O)-;, R1, R2, R3, R4, R5, R6 and R7 are each independently H or alkyl;, R1 may also be alkanoyl, R1 and A1 taken together may be -(CH2)m;, R8 is H, alkyl, phenyl, phenylalkyl, substituted phenyl, (substituted phenyl)alkyl or -C(O)R9;, R9 is H, alkyl, phenyl, phenylalkyl, substituted phenyl or (substituted phenyl)alkyl;, m is 3 or 4;, n is 0, 1 or 2;, p is 0, 1 or 2; and, q is 0 or 1, with the proviso that when p is 0, then q is also 0.