Design and Synthesis of P1-P3 Macrocyclic Tertiary-Alcohol-Comprising HIV-1 Protease Inhibitors
(2013) In Journal of Medicinal Chemistry 56(22). p.8999-9007- Abstract
- To study P1-P3 macrocyclizations of previously reported tertiary-alcohol-comprising HIV-1 protease inhibitors (PIs), three new 14- and 15-member macrocyclic PIs were designed, synthesized by ring-closing metathesis, and evaluated alongside with 10 novel linear PIs. Cocrystallized complexes of the macrocyclic PIs and the HIV-1 protease are presented, analyzed, and discussed. The macrocyclic structures exhibited higher activities than the linear precursors with K-i and EC50 values down to 3.1 nM and 0.37 mu M, respectively.
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4272923
- author
- Joshi, Advait ; Veron, Jean-Baptiste ; Unge, Johan LU ; Rosenquist, Asa ; Wallberg, Hans ; Samuelsson, Bertil ; Hallberg, Anders and Larhed, Mats
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Medicinal Chemistry
- volume
- 56
- issue
- 22
- pages
- 8999 - 9007
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000327812600004
- scopus:84889261380
- pmid:24160253
- ISSN
- 1520-4804
- DOI
- 10.1021/jm400811d
- language
- English
- LU publication?
- yes
- id
- 737fcf4f-7588-45cb-9d20-75c6960b8959 (old id 4272923)
- date added to LUP
- 2016-04-01 10:02:22
- date last changed
- 2022-03-19 08:48:50
@article{737fcf4f-7588-45cb-9d20-75c6960b8959, abstract = {{To study P1-P3 macrocyclizations of previously reported tertiary-alcohol-comprising HIV-1 protease inhibitors (PIs), three new 14- and 15-member macrocyclic PIs were designed, synthesized by ring-closing metathesis, and evaluated alongside with 10 novel linear PIs. Cocrystallized complexes of the macrocyclic PIs and the HIV-1 protease are presented, analyzed, and discussed. The macrocyclic structures exhibited higher activities than the linear precursors with K-i and EC50 values down to 3.1 nM and 0.37 mu M, respectively.}}, author = {{Joshi, Advait and Veron, Jean-Baptiste and Unge, Johan and Rosenquist, Asa and Wallberg, Hans and Samuelsson, Bertil and Hallberg, Anders and Larhed, Mats}}, issn = {{1520-4804}}, language = {{eng}}, number = {{22}}, pages = {{8999--9007}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Journal of Medicinal Chemistry}}, title = {{Design and Synthesis of P1-P3 Macrocyclic Tertiary-Alcohol-Comprising HIV-1 Protease Inhibitors}}, url = {{http://dx.doi.org/10.1021/jm400811d}}, doi = {{10.1021/jm400811d}}, volume = {{56}}, year = {{2013}}, }