75322-09-7Relevant academic research and scientific papers
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.
CARBAMATE DERIVATIVES OF LACTAM BASED N-ACYLETHANOLAMINE ACID AMIDASE (NAAA) INHIBITORS
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Paragraph 0639; 0640, (2014/09/29)
Described herein are compounds and pharmaceutical compositions which inhibit N-acylethanolamine acid amidase (NAAA). Described herein are methods for synthesizing the compounds set forth herein and methods for formulating these compounds as pharmaceutical compositions which include these compounds. Also described herein are methods of inhibiting NAAA in order to sustain the levels of palmitoylethanolamide (PEA) and other N-acylethanolamines (NAE) that are substrates for NAAA, in conditions characterized by reduced concentrations of NAE. Also, described here are methods of treating and ameliorating pain, inflammation, inflammatory diseases, and other disorders in which modulation of fatty acid ethanolamides is clinically or therapeutically relevant or in which decreased levels of NAE are associated with the disorder.
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] .
AMINO ALCOHOL DERIVATIVES
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, (2008/06/13)
The present invention relates to compounds of formula (I) which exhibit excellent immune suppression activity, pharmacologically acceptable salts thereof, esters thereof or other derivatives: wherein R1 and R2 are a hydrogen atom, an amino protecting group; R3 is a hydrogen atom, a hydroxy protecting group; R4 is a lower alkyl group; n is an integer from 1 to 6; X is an ethylene group; Y is a C1-C10 alkylene group, a C1-C10 alkylene group substituted with 1 to 3 substituents selected from substituent group a and b; R5 is an aryl group; R6 and R7 are a hydrogen atom, a group selected from substituent group a; with the proviso when R5 is a hydrogen atom, Y is not 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.
A novel nonpeptide HIV-1 protease inhibitor: Elucidation of the binding mode and its application in the design of related analogs
Lunney,Hagen,Domagala,Humblet,Kosinski,Tait,Warmus,Wilson,Ferguson,Hupe,Tummino,Baldwin,Bhat,Liu,Erickson
, p. 2664 - 2677 (2007/10/02)
HIV-1 protease has been identified as a significant target enzyme in AIDS research. While numerous peptide-derived inhibitors have been described, the identification of a nonpeptide inhibitor remains an important goal. Using an HIV-1 protease mass screening technique, 4-hydroxy-3-(3-phenoxypropyl)-2H-1- benzopyran-2-one (1) was identified as a nonpeptide competitive inhibitor of the enzyme. Employing a Monte Carlo-based docking procedure, the coumarin was docked in the active site of the enzyme, revealing a binding mode that was later confirmed by the X-ray crystal analysis. Several analogs were prepared to test the binding interactions and improve the overall binding affinity. The most active compound in the study was 4,7-dihydroxy-3-[4-(2- methoxyphenyl)butyl]-2H-1-benzopyran-2-one (31).
Regio- and Diastereo-Chemically Controlled Photocycloaddition of an Arene and an Alkene Linked by a Chiral Auxiliary
Sugimura, Takashi,Nishiyama, Norio,Tai, Akira,Hakushi, Tadao
, p. 1163 - 1166 (2007/10/02)
Intramolecular meta-arene alkene photocycloaddition of 1b, the substrate having a chiral auxiliary as a linking bridge between the arene and the alkene, resulted in high diastereofacial differentiation of the alkene at the addition step and sufficient regiocontrol of the subsequent ring closure step to give a single diastereomer 4.
REDUCTIVE CLEAVAGE OF CYCLIC KETALS WITH ZrCl4-LiAlH4
Shaozu, Wu,Tianhui, Ren,Yulan, Zhang
, p. 357 - 358 (2007/10/02)
Both aliphatic and aromatic cyclic ketals were selectively reduced to the corresponding glycol monoethers in high yield with ZrCl4-LiAlH4 at 30 deg C in Et2O for 12 hr.
REDUCTION OF ACETALS WITH CpTiCl3-LiAlH4
Shaozu, Wu,Yin, Chen,Yulan, Zhang
, p. 421 - 424 (2007/10/02)
The reduction of cyclic acetals and ketals derived from aromatic or aliphatic aldehydes and ketones with CpTiCl3-LiAlH4 system in diethyl ether at 30 deg C affords the corresponding hydroxyethyl ethers and the corresponding alkyl benzene or aliphatic hydrocarbons.
The 9-Decalyl and Related Cations. VII Solvolysis of 3-(Cyclohex-1'-enyloxy)propyl p-Nitrobenzenesulfonate
Ferber, Peter H.,Gream, George E.,Stoneman, Terry I.
, p. 699 - 711 (2007/10/02)
The solvolysis of 3-(cyclohex-1'-enyloxy)propyl p-nitrobenzenesulfonate (5) in ethanol buffered separately with sodium ethoxide and triethylzmine and 2,2,2-trifluoroethanol buffered with triethylamine has been investigated.Kinetic determinations and product studies have been carried out.In ethanol buffered with sodium ethoxide, ?-bond participation in the above ester occurs to the extent of 30percent; this is raised to 84percent when triethylamine is used as the buffering agent.With buffered trifluoroethanol as solvent, ?-bond participation in the ester is complete; kunsat/ksat = 920 and a quantitative yield of cyclized products is obtained.Kinetic evidence indicates a lack of significant involvement of a lone pair on oxygen (enol ether system) in the solvolysis of the sulfonate ester; in trifluoroethanol, the compound solvolyses only 1.15 times more rapidly than does 4-(cyclohex-1'-enyl)butyl p-nitrobenzenesulfonate (2), its carbon analogue.
