164463-34-7

Upstream product

• 699-98-9 Pyridine-2,3-dicarboxylic anhydride 
• 150356-67-5 1-bromo-4-methoxy-2-(phenylmethoxy)benzene 
• 100-39-0 benzyl bromide 
• 63604-94-4 2-bromo-5-methoxyphenol 

Downstream Products

• 496047-44-0 2-(2-benzyloxy-4-methoxybenzoyl)-3-[(1-imidazolyl)carbonyl]pyridine 
• 169745-61-3 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(3,4-methylenedioxyphenyl)-5-hydroxycyclopenta-1,3-dieno[2,1-b]pyridine 
• 496047-50-8 5-benzo[1,3]dioxol-5-yl-7-(2-benzyloxy-4-methoxy-phenyl)-5H-[1]pyrindine-6-carboxylic acid tert-butyl ester 
• 496047-45-1 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-7-hydroxy-5-oxocyclopenteno[1,2-b]pyridine 
• 496047-46-2 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-oxocyclopenta-1,3-dieno[2,1-b]pyridine 

Relevant academic research and scientific papers

A convenient synthetic method of a 5,7-diarylcyclopenteno-[1,2-b]pyridine-6-carboxylate: A key intermediate for potent endothelin receptor antagonists

A convenient synthetic method of 4, a key intermediate for a new class of endothelin receptor antagonists, was developed. Racemic 4 was synthesized from quinolinic anhydride in 13.4% overall yield without chromatographic purification.

6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives: a novel class of endothelin receptor antagonists.

Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC(50) value of 2.4 nM against (125)I-labeled ET-1 binding to human ET(A) receptors and a 170-fold selectivity for ET(A) over ET(B) receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound 1 in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization on substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ET(A) selective antagonist 2p with an IC(50) value of 0.87 nM for ET(A) receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model.

ENDOTHELIN ANTAGONISTIC HETEROAROMATIC RING-FUSED CYCLOPENTENE DERIVATIVES

A heteroaromatic ring-fused cyclopentene derivative of the formula: STR1 wherein the variables are as defined in the specification; or a pharmaceutically acceptable salt thereof.

ENDOTHELIN ANTAGONISTIC HETEROAROMATIC RING-FUSED CYCLOPENTENE DERIVATIVES

A heteroaromatic ring-fused cyclopentene derivative of the formula: STR1 wherein the variables are as defined in the specification; or a pharmaceutically acceptable salt thereof.