Back to Search
Start Over
Discovery and evaluation of non-basic small molecule modulators of the atypical chemokine receptor CXCR7.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Oct 15; Vol. 50, pp. 128320. Date of Electronic Publication: 2021 Aug 14. - Publication Year :
- 2021
-
Abstract
- The atypical chemokine receptor C-X-C chemokine receptor type 7 (CXCR7) is an attractive therapeutic target for a variety of cardiac and immunological diseases. As a strategy to mitigate known risks associated with the development of higher molecular weight, basic compounds, a series of pyrrolidinyl-azolopyrazines were identified as promising small-molecule CXCR7 modulators. Using a highly enabled parallel medicinal chemistry strategy, structure-activity relationship studies geared towards a reduction in lipophilicity and incorporation of saturated heterocycles led to the identification of representative tool compound 20. Notably, compound 20 maintained good potency against CXCR7 with a suitable balance of physicochemical properties to support in vivo pharmacokinetic studies.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Drug Delivery Systems
Drug Design
Immunologic Factors pharmacokinetics
Male
Mice
Mice, Inbred C57BL
Models, Molecular
Molecular Structure
Signal Transduction
Structure-Activity Relationship
Drug Discovery
Immunologic Factors chemical synthesis
Immunologic Factors pharmacology
Receptors, CXCR antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 50
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 34400299
- Full Text :
- https://doi.org/10.1016/j.bmcl.2021.128320