Design and synthesis of novel spirocyclic carboxylic acids as potent and orally bioavailable DGAT1 inhibitors and their biological evaluation.

Animals Carboxylic Acids / pharmacology Diacylglycerol O-Acyltransferase / antagonists & inhibitors Disease Models, Animal Drug Design Enzyme Inhibitors / pharmacology Mice Oxadiazoles / pharmacology Triglycerides
Azaspiro DGAT1 Diabetes Pharmacophore Spirocyclic Triglycerides

Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 04 2022
Historique:
received: 08 12 2021
revised: 15 02 2022
accepted: 16 02 2022
pubmed: 22 2 2022
medline: 3 5 2022
entrez: 21 2 2022
Statut: ppublish

Résumé

A series of novel spirocyclic DGAT1 inhibitors containing the oxadiazole motif were designed and synthesized for biological evaluation. Several compounds exhibited potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activity. Optimization of the series led to the identification of five lead compounds 8, 9, 10, 11 and 12 that showed excellent in-vitro activity with IC

Identifiants

DOI: 10.1016/j.bmcl.2022.128632 PMID: 35189320
pubmed: 35189320
pii: S0960-894X(22)00108-1
doi: 10.1016/j.bmcl.2022.128632
pii:
doi:

Substances chimiques

Carboxylic Acids 0
Enzyme Inhibitors 0
Oxadiazoles 0
Triglycerides 0
Dgat1 protein, mouse EC 2.3.1.20
Diacylglycerol O-Acyltransferase EC 2.3.1.20

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

128632

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Auteurs

Summon Koul (S)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India; School of Consciousness, Dr.Vishwanath Karad MIT World Peace University, Pune, Maharashtra 411038, India. Electronic address: summon.koul@mitwpu.edu.in.

Suresh Kurhade (S)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Sandeep Bhosale (S)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Keshav Naik (K)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Videsh Salunkhe (V)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Sudhir Ravula (S)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Prasad Punde (P)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Ravikumar Velayutham (R)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Atul Tiwari (A)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Daniela Ahl (D)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Srividya Malkapuram (S)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Vamsi Mudagala (V)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Amol Raje (A)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Dhananjay Umrani (D)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Suhas Tambe (S)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Poonam Patil (P)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Umesh Singh (U)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Debnath Bhuniya (D)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Narayanan Hariharan (N)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

Kasim Mookhtiar (K)

Department of Discovery Chemistry, Discovery Biology and DMPK, Advinus Therapeutics. Ltd., Hinjewadi, Pune 411 057, India.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Acyltransferases › Diacylglycerol O-acyltransferase › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Conception de médicament › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Oxazoles › Oxadiazoles › Design and synthesis of novel spirocyclic...
questionsmedicales.fr › Lipides › Glycérides › Triglycéride › Design and synthesis of novel spirocyclic...