693245-67-9

Upstream product

• 180323-49-3 (1S,3R)-3-amino-cyclopentanecarboxylic acid methyl ester hydrochloride 
• 130931-83-8 (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one 
• 693245-59-9 C₂₃H₂₇NO₂ 
• 624734-28-7 C₂₀H₂₁NO₂ 
• 624734-30-1 (1S,3R)-3-((tert-butoxycarbonyl)amino)-1-isopropylcyclopentane-1-carboxylic acid 
• 624734-29-8 (1S,3R)-methyl-3-[(tert-butoxycarbonyl)amino]-1-isopropylcyclopentanecarboxylate 

Downstream Products

• 1149431-20-8 (1S,3R)-N-(3,5-Bis(trifluoromethyl)benzyl)-1-isopropyl-3-((tetrahydro-2H-pyran-4-yl)amino)cyclopentanecarboxamide 
• 693247-71-1 (1S,3R)-N-(3,5-bis(trifluoromethyl)benzyl)-3-((2,3-dihydro-1H-inden-1-yl)amino)-1-isopropylcyclopentanecarboxamide 
• 693247-56-2 (1S,3R)-N-(3,5-bis(trifluoromethyl)benzyl)-3-(cyclohexylamino)-1-isopropylcyclopentane-1-carboxamide 
• 693247-42-6 (1S,3R)-N-(3,5-bis(trifluoromethyl)benzyl)-1-isopropyl-3-((tetrahydro-2H-thiopyran-4-yl)amino)cyclopentane-1-carboxamide 

Relevant academic research and scientific papers

Structure-kinetic relationships - An overlooked parameter in hit-to-lead optimization: A case of cyclopentylamines as chemokine receptor 2 antagonists

Preclinical models of inflammatory diseases (e.g., neuropathic pain, rheumatoid arthritis, and multiple sclerosis) have pointed to a critical role of the chemokine receptor 2 (CCR2) and chemokine ligand 2 (CCL2). However, one of the biggest problems of high-affinity inhibitors of CCR2 is their lack of efficacy in clinical trials. We report a new approach for the design of high-affinity and long-residence-time CCR2 antagonists. We developed a new competition association assay for CCR2, which allows us to investigate the relation of the structure of the ligand and its receptor residence time [i.e., structure-kinetic relationship (SKR)] next to a traditional structure-affinity relationship (SAR). By applying combined knowledge of SAR and SKR, we were able to re-evaluate the hit-to-lead process of cyclopentylamines as CCR2 antagonists. Affinity-based optimization yielded compound 1 with good binding (Ki = 6.8 nM) but very short residence time (2.4 min). However, when the optimization was also based on residence time, the hit-to-lead process yielded compound 22a, a new high-affinity CCR2 antagonist (3.6 nM), with a residence time of 135 min.

ALKYLAMINO, ARYLAMINO, AND SULFONAMIDO CYCLOPENTYL AMIDE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

Compounds of the formula (I) which are modulators of chemokine receptor activity useful in the prevention or treatment of certain inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis, and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which chemokine receptors are involved.