Difluoromethylbenzoxazole Pyrimidine Thioether Derivatives: A Novel Class of Potent Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors
(2011) In Journal of Medicinal Chemistry 54(23). p.7974-7985- Abstract
- This paper reports the synthesis and antiviral properties of new difluoromethylbenzoxazole (DFMB) pyrimidine thioether derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors. By use of a combination of structural biology study and traditional medicinal chemistry, several members of this novel class were synthesized using a single electron transfer chain process (radical nucleophilic substitution, Si) and were found to be potent against wild-type HIV-1 reverse transcriptase, with low cytotoxicity but with moderate activity against drug-resistant strains. The most promising compound 2,4 showed a significant EC(50) value close to 6.4 nM against HIV-1 IIIB, a moderate EC(50) value close to 54 mu M against an NNRTI resistant... (More)
- This paper reports the synthesis and antiviral properties of new difluoromethylbenzoxazole (DFMB) pyrimidine thioether derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors. By use of a combination of structural biology study and traditional medicinal chemistry, several members of this novel class were synthesized using a single electron transfer chain process (radical nucleophilic substitution, Si) and were found to be potent against wild-type HIV-1 reverse transcriptase, with low cytotoxicity but with moderate activity against drug-resistant strains. The most promising compound 2,4 showed a significant EC(50) value close to 6.4 nM against HIV-1 IIIB, a moderate EC(50) value close to 54 mu M against an NNRTI resistant double mutant (K103N + Y181C), but an excellent selectivity index >15477 (CC(50) > 100 mu M). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2320759
- author
- Boyer, Jeremie ; Arnoult, Eric ; Medebielle, Maurice ; Guillemont, Jerome ; Unge, Johan LU and Jochmans, Dirk
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Medicinal Chemistry
- volume
- 54
- issue
- 23
- pages
- 7974 - 7985
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000297445400003
- scopus:82555187418
- ISSN
- 1520-4804
- DOI
- 10.1021/jm200766b
- language
- English
- LU publication?
- yes
- id
- 8f9705d0-97f0-43e8-964a-a7c3facd2985 (old id 2320759)
- date added to LUP
- 2016-04-01 10:04:43
- date last changed
- 2022-04-27 18:08:30
@article{8f9705d0-97f0-43e8-964a-a7c3facd2985, abstract = {{This paper reports the synthesis and antiviral properties of new difluoromethylbenzoxazole (DFMB) pyrimidine thioether derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors. By use of a combination of structural biology study and traditional medicinal chemistry, several members of this novel class were synthesized using a single electron transfer chain process (radical nucleophilic substitution, Si) and were found to be potent against wild-type HIV-1 reverse transcriptase, with low cytotoxicity but with moderate activity against drug-resistant strains. The most promising compound 2,4 showed a significant EC(50) value close to 6.4 nM against HIV-1 IIIB, a moderate EC(50) value close to 54 mu M against an NNRTI resistant double mutant (K103N + Y181C), but an excellent selectivity index >15477 (CC(50) > 100 mu M).}}, author = {{Boyer, Jeremie and Arnoult, Eric and Medebielle, Maurice and Guillemont, Jerome and Unge, Johan and Jochmans, Dirk}}, issn = {{1520-4804}}, language = {{eng}}, number = {{23}}, pages = {{7974--7985}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Journal of Medicinal Chemistry}}, title = {{Difluoromethylbenzoxazole Pyrimidine Thioether Derivatives: A Novel Class of Potent Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors}}, url = {{http://dx.doi.org/10.1021/jm200766b}}, doi = {{10.1021/jm200766b}}, volume = {{54}}, year = {{2011}}, }