Synthesis and Evaluation of Novel Tetrahydronaphthyridine CXCR4 Antagonists with Improved Drug-like Profiles.

Animals Cytochrome P-450 CYP2D6 / metabolism Heterocyclic Compounds Mice Receptors, CXCR4 / metabolism Signal Transduction Structure-Activity Relationship

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
10 03 2022
Historique:
pubmed: 19 2 2022
medline: 7 5 2022
entrez: 18 2 2022
Statut: ppublish

Résumé

Our first-generation CXCR4 antagonist TIQ15 was rationally modified to improve drug-like properties. Introducing a nitrogen atom into the aromatic portion of the tetrahydroisoquinoline ring led to several heterocyclic variants including the 5,6,7,8-tetrahydro-1,6-naphthyridine series, greatly reducing the inhibition of the CYP 2D6 enzyme. Compound

Identifiants

DOI: 10.1021/acs.jmedchem.1c01564 PMID: 35179893
pubmed: 35179893
doi: 10.1021/acs.jmedchem.1c01564
doi:

Substances chimiques

Heterocyclic Compounds 0
Receptors, CXCR4 0
Cytochrome P-450 CYP2D6 EC 1.14.14.1

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

4058-4084

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI128837
Pays : United States

Auteurs

Edgars Jecs (E)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.
ORCID: 0000-0002-2428-3899

Yesim A Tahirovic (YA)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.

Robert J Wilson (RJ)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.
ORCID: 0000-0002-8344-5325

Eric J Miller (EJ)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.
ORCID: 0000-0003-3659-0105

Michelle Kim (M)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.

Valarie Truax (V)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.

Huy H Nguyen (HH)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.

Nicholas S Akins (NS)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.

Manohar Saindane (M)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.

Tao Wang (T)

Bristol-Myers Squibb Research & Development, Princeton, New Jersey 08543, United States.
ORCID: 0000-0002-5866-8148

Chi S Sum (CS)

Bristol-Myers Squibb Research & Development, Princeton, New Jersey 08543, United States.

Mary E Cvijic (ME)

Bristol-Myers Squibb Research & Development, Princeton, New Jersey 08543, United States.

Gretchen M Schroeder (GM)

Bristol-Myers Squibb Research & Development, Princeton, New Jersey 08543, United States.

Samantha L Burton (SL)

Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, United States.
Emory Vaccine Center, Emory University, Atlanta, Georgia 30322, United States.

Cynthia A Derdeyn (CA)

Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, United States.
Emory Vaccine Center, Emory University, Atlanta, Georgia 30322, United States.
Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia 30322, United States.

Lingjie Xu (L)

Hangzhou Junrui Biotechnology, Hangzhou, Zhejiang 310000, China.

Yi Jiang (Y)

Hangzhou Junrui Biotechnology, Hangzhou, Zhejiang 310000, China.

Lawrence J Wilson (LJ)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.
ORCID: 0000-0002-6895-1051

Dennis C Liotta (DC)

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.
ORCID: 0000-0002-7736-7113

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Synthesis and Evaluation of Novel...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Hémoprotéines › Cytochromes › Cytochrome P-450 enzyme system › Famille-2 de cytochromes P450 › Cytochrome P-450 CYP2D6 › Synthesis and Evaluation of Novel...
questionsmedicales.fr › Composés hétérocycliques › Synthesis and Evaluation of Novel...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Synthesis and Evaluation of Novel...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs viraux › Récepteur VIH › Récepteurs CXCR4 › Synthesis and Evaluation of Novel...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Synthesis and Evaluation of Novel...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Synthesis and Evaluation of Novel...