90433-20-8Relevant articles and documents
Discovery of selective, orally bioavailable pyrazolopyridine inhibitors of protein kinase cθ (pkcθ) that ameliorate symptoms of experimental autoimmune encephalomyelitis
Collier, Philip N.,Twin, Heather C.,Knegtel, Ronald M. A.,Boyall, Dean,Brenchley, Guy,Davis, Christopher J.,Keily, Shazia,Mak, Chau,Miller, Andrew,Pierard, Fran?oise,Settimo, Luca,Bolton, Clare M.,Chiu, Peter,Curnock, Adam,Doyle, Elisabeth,Tanner, Adam J.,Jimenez, Juan-Miguel
supporting information, p. 1134 - 1139 (2019/08/27)
PKCθ plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKCθ inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKCθ. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.
MODULATORS OF ROR-GAMMA
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Paragraph 00212; 00213; 00214, (2017/06/12)
Provided are novel compounds of Formula I: pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORy. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
ISOPROPYL TRIAZOLO PYRIDINE COMPOUNDS
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Paragraph 0069-0071, (2016/12/01)
The present invention provides a compound of the Formula (I) below: Wherein R1 is selected from the group consisting of H, CH3, CN, CH2CN, C(CH3)2CN, and F; R2 is selected from the group consisting of H, O(C1-C3alkyl)R5, CH2CN, and CN; R3 is selected from the group consisting of H, OCH3, CN, C(CH3)2CN, and CH2CN; R4 is selected from the group consisting of H and CH3; R5 is selected from the group consisting of H, CN, C(CH3)2CN, OCH3, S(O)2CH3, and C(CH3)2OH; provided that at least one selected from the group consisting of R1, R2, R3 and R4 is H; or a pharmaceutically acceptable salt thereof, methods of treating diabetes using the compound and a process for preparing the compound.
