204972-82-7

Upstream product

• 2457-76-3 4-amino-2-chlorobenzoic acid 
• 232275-73-9 4-(tert-butoxycarbonylamino)-2-chlorobenzoic acid 
• 232275-74-0 2-chloro-4-[N-methyl-N-(tert-butoxycarbonyl)amino]benzoic acid methyl ester 

Relevant academic research and scientific papers

THERAPEUTIC AGENT FOR RESPIRATORY DISEASE CONTAINING 4-HYDROXYPIPERIDINE DERIVATIVE AS ACTIVE INGREDIENT

An agent for preventing/treating respiratory diseases contains, as an active ingredient, a compound represented by following Formula (I): wherein A is a group represented by L-W [wherein L is a bond or CH2; and W is O, SOn (wherein n is 0 to 2), or -NR7-(wherein R7 is hydrogen or lower alkyl)]; each of G1 and G2 is (CH2)r (wherein r is 0 to 2), provided that when n is 1, G1 and G2 may be bridged by lower alkylene; Y is a lower alkylene or (substituted) benzylidene; Z is a bond or O, provided that when Z is a bond, Y may form a 5- or 6-membered ring with carbon on the benzene ring; R1 is, for example, NO2, a lower alkoxycarbonyl, (substituted) carbamoyl, (protected) hydroxyl group, (protected) carboxyl, or (protected) N-hydroxycarbamoyl; each of R2and R3 is hydrogen, halogen, (halogenated) lower alkyl, (halogenated) lower alkoxy or NO2; each of R4 and R5 is, for example, hydrogen, halogen, (halogenated) lower alkyl, (halogenated) lower alkoxy, CN, or lower alkylsulfonyl; and R6 is hydrogen or lower alkyl, a salt thereof or a solvate of them. It has excellent antitussive activity when used as an agent for preventing/treating respiratory diseases such as lung cancer, common cold syndrome, pulmonary tuberculosis, pneumonia, acute bronchitis or chronic bronchitis.

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.

Pyrrolidinyl and pyrrolinyl ethylamine compounds as kappa agonists

A compound of the following formula: and the salts thereof wherein A is hydrogen, halo, or hydroxy, broken line represents an optional double bond with proviso that if the broken line is a double bond, then A is absent; Ar1is optionally substituted phenyl; Ar2is aryl or heteroaryl selected from phenyl, napththyl, or pyridyl, the aryl or heteroaryl being optionally substituted; R1is hydrogen, hydroxy, or C1-C4alkyl; and R2and R3are independently selected from optionally substituted C1-C7alkyl, C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, or R2and R3, together with the nitrogen atom to which they are attached, form an optionally substituted pyrrolidine. These compounds are useful as kappa agonists.