232275-99-9

Upstream product

• 23112-96-1 (2,6-dimethoxyphenyl)boronic acid 
• 232277-15-5 N-(2,6-dichlorobenzoyl)-4-bromo-L-phenylalanine methyl ester 
• 99359-32-7 (S)-2-amino-3-(4-bromophenyl)propionic acid methyl ester hydrochloride 
• 24250-84-8 H-p-BrPhe-OH 
• 151-10-0 1,3-Dimethoxybenzene 
• 4659-45-4 2,6-Dichlorobenzoyl chloride 

Downstream Products

• 232271-19-1 [14C]-TR-14035 
• 232277-05-3 N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxy-3-nitrophenyl)-L-phenylalanine methyl ester 
• 232277-06-4 N-(2,6-dichlorobenzoyl)-4-(3-amino-2,6-dimethoxyphenyl)-L-phenylalanine methyl ester 
• 232276-53-8 N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxy-3-fluorophenyl)-L-phenylalanine methyl ester 
• 232276-83-4 N-(2,6-dichlorothiobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine methyl ester 

Relevant academic research and scientific papers

Inhibitors of α4 mediated cell adhesion

The present invention relates to a pharmaceutical composition comprising as an active ingredient a compound of formula (I), wherein Ring A is an aromatic or a heterocyclic ring; Q is a bond, carbonyl, lower alkylene, lower alkenylene, —O-(lower alkylene)-, etc.; n is 0, 1 or 2; Z is oxygen or sulfur, W is oxygen, sulfur, —CH═CH—, —NH— or —N═CH—; R1, R2and R3are the same or different and are hydrogen, halogen, hydroxyl, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkoxy group, a substituted or unsubstituted amino group, etc.; R4is tetrazolyl, carboxyl group, amide or ester; R5is hydrogen, nitro, amino, hydroxyl, lower alkanoyl, lower alkyl etc.; R6is selected from (a) a substituted or unsubstituted phenyl group, (b) a substituted or unsubstituted pyridyl group, (c) a substituted or unsubstituted thienyl group, (d) a substituted or unsubstituted benzofuranyl group, etc.; or a pharmaceutically acceptable salt thereof.

Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: Discovery of TR-14035, a dual α4β7/α4β1 integrin antagonist

α4β1 and α4β7 integrins are key regulators of physiologic and pathologic responses in inflammation and autoimmune disease. The effectiveness of anti-integrin antibodies to attenuate a number of inflammatory/immune conditions provides a strong rationale to target integrins for drug development. Important advances have been made in identifying potent and selective candidates, peptides and peptidomimetics, for further development. Herein, we report the discovery of a series of novel N-benzoyl-L-biphenylalanine derivatives that are potent inhibitors of α4 integrins. The potency of the initial lead compound (1: IC50 α4β7/α4β1 =5/33 μM) was optimized via sequential manipulation of substituents to generate low nM, orally bioavailable dual α4β1/α4β7 antagonists. The SAR also led to the identification of several subnanomolar antagonists (134, 142, and 143). Compound 81 (TR-14035; IC50 α4β7/α4β1 =7/87 nM) has completed Phase I studies in Europe. The synthesis, SAR and biological evaluation of these compounds are described.