1361413-95-7

Upstream product

• 2393-23-9 4-methoxy-benzylamine 
• 17061-62-0 N,N-bis(p-methoxybenzyl)amine 
• 1711-11-1 3-cyanobenzoyl chloride 
• 123-11-5 4-methoxy-benzaldehyde 
• 1147550-11-5 ammonium thiocyanate 

Downstream Products

• 1361413-99-1 3-[2-amino-5-(phenylcarbonyl)-1,3-thiazol-4-yl]benzonitrile 
• 1361413-97-9 3-{2-amino-5-[(2-chlorophenyl)carbonyl]-1,3-thiazol-4-yl}benzonitrile 
• 1361413-28-6 N-[5-[(2-chlorophenyl)carbonyl]-4-(3-cyanophenyl)-1,3-thiazol-2-yl]-2-[4-(ethylsulfonyl)phenyl] acetamide 
• 1361413-29-7 N-(5-benzoyl-4-(3-cyanophenyl)thiazol-2-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide 
• 1361413-38-8 N-[5-[(2-chlorophenyl)carbonyl]-4-(3-cyanophenyl)-1,3-thiazol-2-yl]-2-{4-[(2,2,2-trifluoroethyl)sulfonyl]phenyl}acetamide 
• 1361413-43-5 N-(4-(3-cyanophenyl)-5-{[4-(2-hydroxyethyl)phenyl]carbonyl}-1,3-thiazol-2-yl)-2-[4-(ethylsulfonyl)phenyl] acetamide 
• 1361414-41-6 2-(4-{[2-amino-4-(3-cyanophenyl)-1,3-thiazol-5-yl]carbonyl}phenyl)ethyl acetate 
• 1552267-70-5 C₃₃H₂₇N₃O₃S 

Relevant academic research and scientific papers

Identification of an aminothiazole series of RORβ modulators

Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fig. 1). To our knowledge, this is one of only two small molecule RORβ inverse agonists identified in the primary literature from a tractable chemical series and represents an ideal starting point from which to design RORβ-selective modulators. Herein we describe our SAR optimization efforts that led to a series of potent neutral antagonists of RORβ.

Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors

Novel series of N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitors. SAR studies of the RORγt HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration.

NOVEL COMPOUNDS

Disclosed are retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.