183500-36-9

Upstream product

• 17201-43-3 4-cyanobenzyl bromide 
• 10406-25-4 4-aminobenzyl cyanide 
• 96-26-4 dihydroxyacetone 
• 198648-98-5 [3-(4-cyanobenzyl)-3H-imidazol-4-yl]methyl acetate 
• 252882-62-5 1-(4-cyanobenzyl)-2-mercapto-5-hydroxymethylimidazole 

Downstream Products

• 183500-37-0 4-[(5-formyl-1H-imidazol-1-yl)methyl]benzonitrile 
• 833490-42-9 2-(benzoyl-{1-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethyl]-piperidin-4-yl}-amino)-4-methylsulfanyl-butyric acid methyl ester 
• 833490-43-0 2-(benzoyl-{1-[3-(4-cyano-benzyl)-3H-imidazol-4-ylmethyl]-piperidin-4-yl}-amino)-3-phenyl-propionic acid methyl ester 

Relevant academic research and scientific papers

Design and synthesis of piperidine farnesyltransferase inhibitors with reduced glucuronidation potential

The design and synthesis of a novel piperidine series of farnesyltransferase (FTase) inhibitors with reduced potential for metabolic glucuronidation are described. The various substitution and exchange of the phenyl group at the C-2 position of the previously described 2-(4-hydroxy)phenyl-3-nitropiperidine 1a (FTase IC50 = 5.4 nM) resulted in metabolically stable compounds with potent FTase inhibition (14a IC50 = 4.3 nM, 20a IC50 = 3.0 nM, and 50a IC50 = 16 nM). Molecular modeling studies of these compounds complexed with FTase and farnesyl pyrophosphate are also described.

Novel N-(4-piperidinyl)benzamide antimalarials with mammalian protein farnesyltransferase inhibitory activity

Protein farnesyltransferase of Plasmodium falciparum is a potential target in the treatment of malaria for which increased drug resistance is observed. The design, synthesis and evaluation of a series of N-(4-piperidinyl)benzamides is reported. The most potent compounds showed in vitro activity against the parasite at submicromolar concentrations.

Method of treating cancer

The present invention relates to methods of treating cancer using a combination of a compound which is an antineoplastic agent and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either s

Potent and selective farnesyl transferase inhibitors

We recently described a novel series of CA1A2X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A1A 2 residue. Extensive exploration of structure-activity relationships revealed that replacement of cysteine by substituted benzylimidazoles provided nanomolar FTIs with in vitro activities (18e, IC50 = 4.60 nM on isolated enzyme, EC50 = 20.0 nM for growth inhibition on a tumor cell line). The molecular docking of 18e and 19e in the active site of the enzyme provided details of key interactions with the protein and showed that the methionine or phenylalanine residue fits into the aryl binding site.

Synthesis and activity of 1-aryl-1′-imidazolyl methyl ethers as non-thiol farnesyltransferase inhibitors

A series of imidazole-containing methyl ethers (4-5) have been designed and synthesized as potent and selective farnesyltransferase inhibitors (FTIs) by transposition of the D-ring to the methyl group on the imidazole of the previously reported FTIs 3. Several compounds such as 4h and 5b demonstrate superior enzymatic activity to the current benchmark compound tipifarnib (1) with IC50 values in the lower subnanomolar range, while maintaining excellent cellular activity comparable to tipifarnib. The compounds are characterized as being simple, easier to make, and possess no chiral center involved.

ORGANIC COMPOUNDS AS AGENTS FOR THE TREATMENT OF ALDOSTERONE MEDIATED CONDITIONS

Compounds of formula (I), provide pharmacological agents which are inhibitors of the P450 enzyme, aldosterone synthase, and thus may be employed for the treatment of aldosterone mediated conditions. Accordingly, the compounds of formula (I) may be employe

Method of treating cancer

The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.

Parallel liquid synthesis of N,N′-disubstituted 3-amino azepin-2-ones as potent and specific farnesyl transferase inhibitors

A rapid structure-activity study was performed by parallel liquid synthesis on N,N′-disubstitution of 3-amino azepin-2-one to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities. The activities of the selected compounds were validated in vivo, and compounds 41a and 44a presented significant antitumour activity.

Preparation of a clinically investigated ras farnesyl transferase inhibitor

The synthesis of ras farnesyl-protein transferase inhibitor 1 is described on a multi-kilogram scale. Retrosynthetic analysis reveals chloromethylimidazole 2 and a piperazinone 3 as viable precursors. The 1,5-disubstituted imidazole system was regioselectively assembled via an improved Marckwald imidazole synthesis. A new imidazole dethionation procedure has been developed to convert the Marckwald mercaptoimidazole product to the desired imidazole. This methodology was found to be tolerant of a variety of functional groups providing good to excellent yields of 1,5-disubstituted imidazoles. A new Mitsunobu cyclization strategy was developed to prepare the arylpiperazinone fragment 3.

Cycloheptene compounds

Compound of formula (I): wherein: X represents a bond or alkylene, CO, S(O)n, —S(O)n—A1—, —CO—A1—, —A—S(O)n—A′1— or —A1—CO—A′1—, Y represents aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted, R1, R2, R3 and R4 each independently of the others represent hydrogen or aryl, heteroaryl, cycloalkyl or heterocycloalkyl, each unsubstituted or substituted, ?or R1, R2, R3 and R4, taken in pairs, together form a bond, or form a fused benzene ring or a fused aromatic or partially unsaturated heterocycle, T represents —CH(R5)—, —N(R5)— or —N(R5)CO—, V represents hydrogen or unsubstituted or substituted aryl or heteroaryl, A2 represents [C(R6)(R′6)]p, R7 and R8 are as defined in the description, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base and medicinal products containing the same are useful as farnesyl transferase inhibitors.