191611-56-0

Upstream product

• 64-17-5 ethanol 
• 201230-82-2 carbon monoxide 
• 897921-78-7 2,2-dimethyl-7-(trifluoromethylsulfonyloxy)chromanone 
• 934388-20-2 ethyl 4-acetyl-3-hydroxybenzoate 
• 67-64-1 acetone 
• 102297-62-1 3-hydroxy-4-(1-oxo-ethane)benzoic acid 
• 6304-89-8 3-acetoxybenzoic acid 
• 17771-33-4 7-hydroxy-2,2-dimethyl-chroman-4-one 

Downstream Products

• 1393844-52-4 N-(2-aminophenyl)-2-(2-chloro-6-fluorophenyl)-4,4-dimethyl-1,4-dihydrochromeno[3,4-d]imidazole-7-carboxamide 
• 1393843-93-0 ethyl 2-(2-chloro-6-fluorophenyl)-4,4-dimethyl-1,4-dihydrochromeno[3,4-d]imidazole-7-carboxylate 
• 1393843-91-8 2-(2-chloro-6-fluorophenyl)-4,4-dimethyl-1,4-dihydrochromeno[3,4-d]imidazole-7-carboxylic acid 
• 1393843-05-4 2-(2-chloro-6-fluorophenyl)-4,4-dimethyl-N-[4-(trifluoromethyl)phenyl]-1,4-dihydrochromeno[3,4-d]imidazole-7-carboxamide 
• 1393843-20-3 2-(2-chloro-6-fluorophenyl)-4,4-dimethyl-N-(4-methylthiazol-2-yl)-1,4-dihydrochromeno[3,4-d]imidazole-7-carboxamide 
• 1393843-04-3 7-(1H-benzo[d]imidazol-2-yl)-2-(2-chloro-6-fluorophenyl)-4,4-dimethyl-1,4-dihydrochromeno[3,4-d]imidazole 
• 1393843-02-1 2-(2-chloro-6-fluorophenyl)-7-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4,4-dimethyl-1,4-dihydro-chromeno[3,4-d]imidazole 

Relevant academic research and scientific papers

Synthesis and biological activity of cyclic analogues of MPPG and MCPG as metabotropic glutamate receptor antagonists

The synthesis of two rigidified phenylglycine analogues is disclosed. The cyclic analogue 1 of (R,S)-α-methyl-4-phosphonophenylglycine (MPPG) is shown to be a particularly interesting pharmacological tool, for it is a group II selective mGluR antagonist that possesses an inverse agonist-like action.

Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors: SAR and in vivo efficacy in hyperalgesia pain model

A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE2 release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F?=?33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model.

TRICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS

The present invention relates to tricyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. (I)