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Discovery and optimization of pyrazole amides as antagonists of CCR1.

Christian Harcken,Christopher Sarko,Can Mao,John Lord,Brian Raudenbush,Hossein Razavi,Pingrong Liu,Alan Swinamer,Darren Disalvo,Thomas Lee,Siqi Lin,Alison Kukulka,Heather Grbic,Mita Patel,Monica Patel,Kim Fletcher,David Joseph,Della White,Laura Amodeo,Karen Berg,Maryanne Brown,David S Thomson

Bioorganic & Medicinal Chemistry Letters（2019）

Cited 2|Views18
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Abstract
•A HTS screen for CCR1 antagonists afforded a novel hit containing a pyrazole core.•Multi parameter optimization led to advanced candidate compounds.•Candidates show 250-fold improved CCR1 potency compared to initial hit.•Candidates show excellent off-target selectivity, attractive drug-like properties.
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Key words
Chemokine receptors,CCR1,Pyrazole,HTS hit,Development candidate
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