title: Spirocyclic compounds, potent CCR1 antagonists.
abstract: Conformationally constrained spirocycles (17-23) and (31-36) were synthesised. In vitro data revealed that these compounds are CCR1 antagonists with sub-nanomolar potency. In a functional assay 22, 23 and 36 inhibited CCR1 mediated chemotaxis with an IC50 value of 2, 2.6 and 68nM, respectively.
authors: Department of Medicinal Chemistry, R&I Innovative Medicines, AstraZeneca R&D, Pepparedsleden 1, Mölndal 431 83, Sweden. Nafizal.Hossain@astrazeneca.com
authors: Nafizal
authors: N
authors: Hossain
authors: Svetlana
authors: S
authors: Ivanova
authors: Jonas
authors: J
authors: Bergare
authors: Tomas
authors: T
authors: Eriksson
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D010880:Piperidines; D054389:Receptors, CCR1; D013141:Spiro Compounds; C032727:piperidine