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Papers by jeffrey letourneau

L'invention concerne des composes et des methodes concernant les domaines de la chimie et de ... more L'invention concerne des composes et des methodes concernant les domaines de la chimie et de la medecine. Dans certains des modes de realisation decrits, l'invention concerne des composes, des compositions et des methodes mettant en œuvre des amines heterocycliques. Dans d'autres modes de realisation decrits, l'invention concerne des amines heterocycliques utilises pour traiter des troubles inflammatoires.

L'invention concerne des composes N-heterocycliques bloquant la production de cytokines par i... more L'invention concerne des composes N-heterocycliques bloquant la production de cytokines par inhibition de la kinase p38. Dans un mode de realisation, les composes de la presente invention sont representes par la formule (I). L'invention concerne egalement des methodes de production correspondantes, des compositions pharmaceutiques et des methodes de traitement d'etats pathologiques associes a une activite kinase p38 ou une expression TNF-α inappropriee au moyen des composes de la presente invention.

US Patent App. 11/852,762

US 20080090802A1 (19) United States (12) Patent Application Publication GO) Pub. NO.: US 2008/009... more US 20080090802A1 (19) United States (12) Patent Application Publication GO) Pub. NO.: US 2008/0090802 Al Letourneau et al. (43) Pub. Date: Apr. 17,2008 (54) QUINAZOLINONE AND ISOQUINOLINONE ACETAMIDE DERIVATIVES (75) Inventors: ...

1. A 2-(4-oxo-4H-quinazolin-3-yl)acetamide derivative of formula I, wherein R 1 is C 1-6 alkyl, C... more 1. A 2-(4-oxo-4H-quinazolin-3-yl)acetamide derivative of formula I, wherein R 1 is C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-2 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl or benzyl, said C 1-6 alkyl, C 3-6 cycloalkyl and C 3-6 ...

NV ORGANON [NL/NL]; Kloosterstraat 6, NL-5349 AB Oss (NL) (All Except US). PHARMACOPEIA DRUG DISC... more NV ORGANON [NL/NL]; Kloosterstraat 6, NL-5349 AB Oss (NL) (All Except US). PHARMACOPEIA DRUG DISCOVERY, INC. [US/US]; 3000 Eastpark Boulevard, Cranbury, New Jersey 08512 (US) (All Except US). LETOURNEAU, Jeffrey [US/US]; 6 ...

Bioorganic & Medicinal Chemistry Letters, 2018

Synthesis and SAR studies of novel benzodiazepinedione-based inhibitors of Clostridium difficile ... more Synthesis and SAR studies of novel benzodiazepinedione-based inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB), Bioorganic &

Bioorganic & medicinal chemistry letters, Feb 15, 2018

The discovery, synthesis and preliminary structure-activity relationship (SAR) of a novel class o... more The discovery, synthesis and preliminary structure-activity relationship (SAR) of a novel class of inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB) is described. A high throughput screening (HTS) campaign resulted in the identification of moderately active screening hits 1-5 the most potent of which was compound 1 (IC = 0.77 µM). In silico docking of an early analog offered suggestions for structural modification which resulted in the design and synthesis of highly potent analogs 13j(IC = 1 nM) and 13 l(IC = 7 nM) which were chosen as leads for further optimization.

The present invention is by inhibition of p38 kinase, provides a N- heterocyclic compounds that b... more The present invention is by inhibition of p38 kinase, provides a N- heterocyclic compounds that block cytokine production. The present invention is also the formula: [Formula 1] Also provides compounds represented by. The present invention further provides manufacturing methods, compositions and using the compound of the present invention also provides a method of treating diseases associated with inappropriate p38 kinase activity or TNF-alpha expression.

Tetrahedron Letters, 2007

A novel synthesis of 5-aryl-4-bromo-3-carboxyisoxazoles employing a [3+2] cycloaddition of a nitr... more A novel synthesis of 5-aryl-4-bromo-3-carboxyisoxazoles employing a [3+2] cycloaddition of a nitrile N-oxide with 2-aryl-1-bromoalkynes as the key step is described. The utility of these 5-aryl-4-bromo-3-carboxyisoxazoles in the solid-phase synthesis of 4,5-diarylisoxazoles is demonstrated.

Journal of Medicinal Chemistry, 2004

A new structural class of triaminotriazine aniline amides possessing potent p38 enzyme activity h... more A new structural class of triaminotriazine aniline amides possessing potent p38 enzyme activity has been discovered. The initial hit (compound 1a) was identified through screening the Pharmacopeia ECLiPS compound collection. SAR modification led to the identification of a short acting triaminotriazine aniline methoxyamide (compound 1m) possessing in vitro and in vivo oral activity in animal models of acute and chronic inflammatory disease. An X-ray crystal structure of compound 1m in this class, cocrystallized with unactivated p38R protein, indicates that these compounds bind to the ATP binding pocket and possess key H-bonding interactions within a deeper cleft. Hydrogen bonding between one of the triazine nitrogens and the backbone NH of the Met109 residue occurs through a water molecule. The methoxyamide NH and carbonyl oxygen are within H-bonding distance of Glu71 and Asp168.