75322-09-7Relevant articles and documents
Potent α-amino-β-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure-activity relationship (SAR) studies
Nuzzi, Andrea,Fiasella, Annalisa,Ortega, Jose Antonio,Pagliuca, Chiara,Ponzano, Stefano,Pizzirani, Daniela,Bertozzi, Sine Mandrup,Ottonello, Giuliana,Tarozzo, Glauco,Reggiani, Angelo,Bandiera, Tiziano,Bertozzi, Fabio,Piomelli, Daniele
supporting information, p. 138 - 159 (2016/02/18)
4-Cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate (3b) is a potent, selective and systemically active inhibitor of intracellular NAAA activity, which produces profound anti-inflammatory effects in animal models. In the present work, we describe structure-activity relationship (SAR) studies on 3-aminoazetidin-2-one derivatives, which have led to the identification of 3b, and expand these studies to elucidate the principal structural and stereochemical features needed to achieve effective NAAA inhibition. Investigations on the influence of the substitution at the β-position of the 2-oxo-3-azetidinyl ring as well as on the effect of size and shape of the carbamic acid ester side chain led to the discovery of 3ak, a novel inhibitor of human NAAA that shows an improved physicochemical and drug-like profile relative to 3b. This favourable profile, along with the structural diversity of the carbamic acid chain of 3b, identify this compound as a promising new tool to investigate the potential of NAAA inhibitors as therapeutic agents for the treatment of pain and inflammation.
AMINO ALCOHOL DERIVATIVE OR PHOSPHONIC ACID DERIVATIVE AND MEDICINAL COMPOSITION CONTAINING THESE
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Page 308, (2008/06/13)
The present invention relates to amino alcohol derivatives or phosphonic acid derivatives having excellent immunosuppressive activity, pharmacologically acceptable salts thereof or pharmacologically acceptable esters thereof, and to pharmaceutical compositions comprising said compounds as an active ingredient: [wherein, ???R1 and R2 each represent a hydrogen atom, or a protecting group of the amino group; ???R3 represents a hydrogen atom, or a protecting group of the hydroxyl group; ???R4 represents a lower alkyl group; ???n represents an integer of from 1 to 6; ???X represents an oxygen atom or a nitrogen atom unsubstituted or substituted with a lower alkyl group or the like; ???Y represents an ethylene group; ???Z represents a C1-C10 alkylene group; ???R5 represents an aryl group, or an aryl group substituted with substituents; ???R6 and R7 each represents a hydrogen atom; provided that when R5 represents a hydrogen atom, then Z represents a group other than a single bond or a straight chain C1-C10 alkylene group] .
Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 3. Synthesis and biological activities of oxazolecarboxamide-substituted ω-phenyl-ω-(3-pyridyl)alkenoic acid derivatives and related compounds
Takeuchi, Kumiko,Kohn, Todd J.,True, Timothy A.,Mais, Dale E.,Wikel, James H.,Utterback, Barbara G.,Wyss, Virginia L.,Jakubowski, Joseph A.
, p. 5362 - 5374 (2007/10/03)
A novel series of oxazolecarboxamide-substituted ω-phenyl-ω-(3- pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA2 receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4- [4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept- 6-enoic acid (14) with K(d) = 9.9 ± 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 ± 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, 'shunt' effect to elevate PGI2 level, and absence of agonist activity.
