232275-50-2

Upstream product

• 67-56-1 methanol 
• 22509-50-8 2,6-dichloro-4-nitrobenzoic acid 
• 88135-16-4 2,6-dichloro-4-nitrobenzoyl chloride 
• 7149-69-1 1,3-dichloro-2-methyl-5-nitrobenzene 
• 99-99-0 1-methyl-4-nitrobenzene 
• 74-88-4 methyl iodide 

Downstream Products

• 232275-49-9 methyl 4-amino-2,6-dichlorobenzoate 
• 1098619-73-8 2,6-dichloro-4-iodo-benzoic acid methyl ester 
• 1613730-12-3 methyl 4-amino-2,6-dichloro-3-((trimethylsilyl)ethynyl)benzoate 
• 1613730-11-2 methyl 4-amino-2,6-dichloro-3-iodobenzoate 
• 232275-55-7 2,6-dichloro-4-fluorobenzoic acid 
• 232275-51-3 4-bromo-2,6-dichloro-benzoic acid 
• 4641-38-7 2,6-Dichloro-4-hydroxybenzoic acid 
• 232275-53-5 methyl 4-bromo-2,6-dichlorobenzoate 
• 232275-56-8 methyl 2,6-dichloro-4-fluorobenzoate 

Relevant academic research and scientific papers

A convenient synthesis of a lymphocyte function-associated antigen-1 (LFA-1) antagonist of 'Compound 4'

The lymphocyte function-associated antigen-1 (LFA-1) antagonist of 'Compound 4' was synthesised by a convenient route using cheap, commercially available starting materials and catalysts under mild reaction conditions and by easily handled reactions. The total yield in the preparation of 'Compound 4' was more than 38% via Sonogashira coupling of an iodide and an alkyne, reduction of the alkyne catalysed by Raney nickel and later steps involving hydrolysis of an ester, condensation of an acid and an amine and a final hydrolysis of an ester.

Preparation of fluorous Yamaguchi reagents and evaluation of their reactivity in esterification

Fluorous Yamaguchi (FY) reagents bearing a perfluoroalkyl chain were prepared and employed in esterification reactions; the yields were similar to those obtained with the traditional Yamaguchi (TY) reagent. Fluorous benzoic acids derived from the FY reagents were separated easily after the reaction. GC analysis revealed that the initial rates of reaction with the FY reagents were higher than those with the TY reagent. The acidities of benzoic acids produced from the FY and TY reagents were predicted by DFT to be similar (1.20 and 0.96, respectively).

INDOLE CARBOXAMIDE DERIVATIVES AS P2X7 RECEPTOR ANTAGONISTS

The invention relates to indole carboxamide derivatives of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and n are as defined in the description, their preparation and their use as pharmaceutically active compounds.

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.