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Identification of Substituted 1 H ‐Indazoles as Potent Inhibitors for Immunosuppressive Enzyme Indoleamine 2,3‐Dioxygenase 1
Author(s) -
Pradhan Nirmalya,
Paul Saurav,
Deka Suman Jyoti,
Roy Ashalata,
Trivedi Vishal,
Manna Debasis
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201700906
Subject(s) - indoleamine 2,3 dioxygenase , enzyme , dioxygenase , cytotoxicity , chemistry , stereochemistry , selectivity , tryptophan , pharmacology , biochemistry , medicine , in vitro , catalysis , amino acid
Overexpression of the immunosuppressive enzyme, indoleamine 2,3‐dioxygenase 1 (IDO1) is associated with poor prognosis of patients for a wide range of malignancies. IDO1 is a validated target for the treatment of diseases that are associated with immune suppression, including cancer. In this report, we described the synthesis of a series of C3‐ substituted 1 H ‐indazoles. Activity studies of IDO1 enzyme assisted to the identification of 3‐carbohydrazide derivatives of 1 H ‐indazoles, 5 a and 5 d (IC 50 =720 and 770 nM, respectively) as potent inhibitors with negligible cytotoxicity. Moderate selectivity of these potent compounds for IDO1 enzyme over tryptophan 2,3‐dioxygenase enzyme (17‐25 fold) also suggest that these heterocyclic compounds are attractive molecules for immunotherapeutic applications.