- 4-PHENYL-N-(PHENYL)THIAZOL-2-AMINE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS
-
4-phenyl-N-(phenyl)thiazol-2-amine and 4-(pyridin-3-yl)-N-( phenyl) thiazol-2-amine derivatives and the corresponding thiadiazole, thiophene, oxazole, oxadiazole, imidazole and triazole derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders.
- -
-
Paragraph 00221; 00286
(2021/06/26)
-
- Identification of potent RORβ modulators: Scaffold variation
-
We sought to develop RORβ-selective probe molecules in order to investigate the function of the receptor in vitro and in vivo and its role in the pathophysiology of disease. To accomplish this, we modified a potent dual RORβ/RORγ inverse agonist from the primary literature with the goal of improving selectivity for RORβ vs RORγ. Truncation of the Western portion of the molecule ablated activity at RORγ and led to a potent series of RORβ modulators. Continued exploration of this series investigated alternate replacement cores for the aminothiazole ring. Numerous suitable replacements were found during the course of our SAR investigations and are reported herein.
- Doebelin, Christelle,Patouret, Rémi,Garcia-Ordonez, Ruben D.,Chang, Mi Ra,Dharmarajan, Venkatasubramanian,Novick, Scott,Ciesla, Anthony,Campbell, Sean,Solt, Laura A.,Griffin, Patrick R.,Kamenecka, Theodore M.
-
supporting information
p. 3210 - 3215
(2018/08/24)
-
- Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors
-
The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.
- Green, Jeremy,Cao, Jingrong,Bandarage, Upul K.,Gao, Huai,Court, John,Marhefka, Craig,Jacobs, Marc,Taslimi, Paul,Newsome, David,Nakayama, Tomoko,Shah, Sundeep,Rodems, Steve
-
p. 5028 - 5037
(2015/07/02)
-
- INHIBITORS OF Akt ACTIVITY
-
Invented are novel thiophene compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
- -
-
Page/Page column 65
(2010/11/27)
-
- Selective inhibitors of rock protein kinase and uses thereof
-
Described herein are compounds that are useful as ROCK inhibitors. These compounds, and pharmaceutically acceptable compositions thereof, are useful for treating or lessening the severity of a variety of disorders, including cardiovascular, inflammatory,
- -
-
Page/Page column 36
(2008/06/13)
-
- AZAINDOLES USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES
-
The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
- -
-
Page/Page column 183-184
(2008/06/13)
-