Discovery and development of a novel N-(3-bromophenyl)-{[(phenylcarbamoyl)amino]methyl}-N-hydroxythiophene-2-carboximidamide indoleamine 2,3-dioxygenase inhibitor using knowledge-based drug design
Copyright © 2021 Elsevier Masson SAS. All rights reserved..
Indoleamine 2,3-dioxygenase-1 (IDO1) is a potential target for the next generation of cancer immunotherapies. We describe the development of two series of IDO1 inhibitors incorporating a N-hydroxy-thiophene-carboximidamide core generated by knowledge-based drug design. Structural modifications to improve the cellular activity and pharmacokinetic (PK) properties of the compounds synthesized, including extension of the side chain of the N-hydroxythiophene-2-carboximidamide core, resulted in compound 27a, a potent IDO1 inhibitor which demonstrated significant (51%) in vivo target inhibition on IDO1 in a human SK-OV-3 ovarian xenograft tumor mouse model. This strategy is expected to be applicable to the discovery of additional IDO1 inhibitors for the treatment of other diseases susceptible to modulation of IDO1.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:229 |
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| Enthalten in: |
European journal of medicinal chemistry - 229(2022) vom: 05. Feb., Seite 114043 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yeh, Teng-Kuang [VerfasserIn] |
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| Links: |
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| Themen: |
Amides |
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| Anmerkungen: |
Date Completed 07.02.2022 Date Revised 07.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2021.114043 |
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| funding: |
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| PPN (Katalog-ID): |
NLM334656192 |
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| 245 | 1 | 0 | |a Discovery and development of a novel N-(3-bromophenyl)-{[(phenylcarbamoyl)amino]methyl}-N-hydroxythiophene-2-carboximidamide indoleamine 2,3-dioxygenase inhibitor using knowledge-based drug design |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Indoleamine 2,3-dioxygenase-1 (IDO1) is a potential target for the next generation of cancer immunotherapies. We describe the development of two series of IDO1 inhibitors incorporating a N-hydroxy-thiophene-carboximidamide core generated by knowledge-based drug design. Structural modifications to improve the cellular activity and pharmacokinetic (PK) properties of the compounds synthesized, including extension of the side chain of the N-hydroxythiophene-2-carboximidamide core, resulted in compound 27a, a potent IDO1 inhibitor which demonstrated significant (51%) in vivo target inhibition on IDO1 in a human SK-OV-3 ovarian xenograft tumor mouse model. This strategy is expected to be applicable to the discovery of additional IDO1 inhibitors for the treatment of other diseases susceptible to modulation of IDO1 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cancer immunotherapy | |
| 650 | 4 | |a Indoleamine 2,3-dioxygenase | |
| 650 | 4 | |a Knowledge-based drug design | |
| 650 | 7 | |a Amides |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Indoleamine-Pyrrole 2,3,-Dioxygenase |2 NLM | |
| 650 | 7 | |a Thiophenes |2 NLM | |
| 700 | 1 | |a Song, Jen-Shin |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Po-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jin-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Chia-Hwa |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Fang-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Tien, Ya-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Kuppusamy, Ramajayam |e verfasserin |4 aut | |
| 700 | 1 | |a Li, An-Siou |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chi-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chieh-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Li-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Hsin-Huei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chih-Hsiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Jau-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Mine-Hsine |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Yi-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Hsueh, Ching-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Hsiao, Wen-Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Pei-Husan |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Chin-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Hsieh, Su-Huei |e verfasserin |4 aut | |
| 700 | 1 | |a Shih, Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Ming-Shiu |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Su-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Kuo, Ching-Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ueng, Shau-Hua |e verfasserin |4 aut | |
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