478908-69-9

Upstream product

• 2491-18-1 (S)-methyl 2-amino-4-(methylthio)butanoate hydrochloride 
• 478908-68-8 4-(N-benzyl-N-pyridin-3-ylaminomethyl)-2-(2-methylphenyl)benzoic acid 
• 462-08-8 pyridin-3-ylamine 
• 247236-38-0 methyl 4-(N-benzyl-N-3-pyridylaminomethyl)-2-(2-methylphenyl)benzoate 
• 32258-83-6 1-phenyl-N-(pyridine-3-yl)methaneimine 
• 100-52-7 benzaldehyde 
• 114081-08-2 N-(3-pyridine)benzylamine 

Relevant academic research and scientific papers

Inhibitors of protein isoprenyl transferases

Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2 is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (c) (d) —C(O)NH—CH(R14)—C(O)NHSO2R16 (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4-L6—C(W)—N(R5)—L5—, (e) —L4-L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7-L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core awl ring resulted in inhibitors of equator less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor- derived cell line.