Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides

Naoyuki Masuda; Osamu Yamamoto; Masahiro Fujii; Tetsuro Ohgami; Jiro Fujiyasu; Toru Kontani; Ayako Moritomo; Masaya Orita; Hiroyuki Kurihara; Hironobu Koga; Hideaki Nakahara; Shunji Kageyama; Mitsuaki Ohta; Hiroshi Inoue; Toshifumi Hatta; Hiroshi Suzuki; Kenji Sudo; Yasuaki Shimizu; Eiichi Kodama; Masao Matsuoka; Masatoshi Fujiwara; Tomoyuki Yokota; Shiro Shigeta; Masanori Baba

doi:10.1016/j.bmc.2004.08.050

Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides

Naoyuki Masuda, Osamu Yamamoto, Masahiro Fujii, Tetsuro Ohgami, Jiro Fujiyasu, Toru Kontani, Ayako Moritomo, Masaya Orita, Hiroyuki Kurihara, Hironobu Koga, Hideaki Nakahara, Shunji Kageyama, Mitsuaki Ohta, Hiroshi Inoue, Toshifumi Hatta, Hiroshi Suzuki, Kenji Sudo, Yasuaki Shimizu, Eiichi Kodama, Masao MatsuokaMasatoshi Fujiwara, Tomoyuki Yokota, Shiro Shigeta, Masanori Baba

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

A series of thiazolidenebenzenesulfonamides have been discovered as nonnucleoside reverse transcriptase inhibitors. Compound 17a exhibited the most potent inhibitory activity against the Y181C mutant reverse transcriptase (RT). The introduction of the 4-chloro-5-isopropyl moiety (17k) markedly increased the activity against the wild type RT. Both 17a and 17k strongly inhibited HIV-1 replication. A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1 _IIIB-R. The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.

Original language	English
Pages (from-to)	6171-6182
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry
Volume	12
Issue number	23
DOIs	https://doi.org/10.1016/j.bmc.2004.08.050
Publication status	Published - 2004 Dec 1
Externally published	Yes

Keywords

Benzenesulfonamide
Nonnucleoside HIV-1 reverse transcriptase inhibitor
Thiazolidene

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmc.2004.08.050

Cite this

Masuda, N., Yamamoto, O., Fujii, M., Ohgami, T., Fujiyasu, J., Kontani, T., Moritomo, A., Orita, M., Kurihara, H., Koga, H., Nakahara, H., Kageyama, S., Ohta, M., Inoue, H., Hatta, T., Suzuki, H., Sudo, K., Shimizu, Y., Kodama, E., ... Baba, M. (2004). Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides. Bioorganic and Medicinal Chemistry, 12(23), 6171-6182. https://doi.org/10.1016/j.bmc.2004.08.050

Masuda, N, Yamamoto, O, Fujii, M, Ohgami, T, Fujiyasu, J, Kontani, T, Moritomo, A, Orita, M, Kurihara, H, Koga, H, Nakahara, H, Kageyama, S, Ohta, M, Inoue, H, Hatta, T, Suzuki, H, Sudo, K, Shimizu, Y, Kodama, E, Matsuoka, M, Fujiwara, M, Yokota, T, Shigeta, S & Baba, M 2004, 'Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides', Bioorganic and Medicinal Chemistry, vol. 12, no. 23, pp. 6171-6182. https://doi.org/10.1016/j.bmc.2004.08.050

@article{49ed4002093d4d02892ffe5864e5268d,

title = "Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides",

abstract = "A series of thiazolidenebenzenesulfonamides have been discovered as nonnucleoside reverse transcriptase inhibitors. Compound 17a exhibited the most potent inhibitory activity against the Y181C mutant reverse transcriptase (RT). The introduction of the 4-chloro-5-isopropyl moiety (17k) markedly increased the activity against the wild type RT. Both 17a and 17k strongly inhibited HIV-1 replication. A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1 IIIB-R. The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.",

keywords = "Benzenesulfonamide, Nonnucleoside HIV-1 reverse transcriptase inhibitor, Thiazolidene",

author = "Naoyuki Masuda and Osamu Yamamoto and Masahiro Fujii and Tetsuro Ohgami and Jiro Fujiyasu and Toru Kontani and Ayako Moritomo and Masaya Orita and Hiroyuki Kurihara and Hironobu Koga and Hideaki Nakahara and Shunji Kageyama and Mitsuaki Ohta and Hiroshi Inoue and Toshifumi Hatta and Hiroshi Suzuki and Kenji Sudo and Yasuaki Shimizu and Eiichi Kodama and Masao Matsuoka and Masatoshi Fujiwara and Tomoyuki Yokota and Shiro Shigeta and Masanori Baba",

year = "2004",

month = dec,

day = "1",

doi = "10.1016/j.bmc.2004.08.050",

language = "English",

volume = "12",

pages = "6171--6182",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "23",

}

TY - JOUR

T1 - Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1

T2 - Design and synthesis of thiazolidenebenzenesulfonamides

AU - Masuda, Naoyuki

AU - Yamamoto, Osamu

AU - Fujii, Masahiro

AU - Ohgami, Tetsuro

AU - Fujiyasu, Jiro

AU - Kontani, Toru

AU - Moritomo, Ayako

AU - Orita, Masaya

AU - Kurihara, Hiroyuki

AU - Koga, Hironobu

AU - Nakahara, Hideaki

AU - Kageyama, Shunji

AU - Ohta, Mitsuaki

AU - Inoue, Hiroshi

AU - Hatta, Toshifumi

AU - Suzuki, Hiroshi

AU - Sudo, Kenji

AU - Shimizu, Yasuaki

AU - Kodama, Eiichi

AU - Matsuoka, Masao

AU - Fujiwara, Masatoshi

AU - Yokota, Tomoyuki

AU - Shigeta, Shiro

AU - Baba, Masanori

PY - 2004/12/1

Y1 - 2004/12/1

N2 - A series of thiazolidenebenzenesulfonamides have been discovered as nonnucleoside reverse transcriptase inhibitors. Compound 17a exhibited the most potent inhibitory activity against the Y181C mutant reverse transcriptase (RT). The introduction of the 4-chloro-5-isopropyl moiety (17k) markedly increased the activity against the wild type RT. Both 17a and 17k strongly inhibited HIV-1 replication. A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1 IIIB-R. The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.

AB - A series of thiazolidenebenzenesulfonamides have been discovered as nonnucleoside reverse transcriptase inhibitors. Compound 17a exhibited the most potent inhibitory activity against the Y181C mutant reverse transcriptase (RT). The introduction of the 4-chloro-5-isopropyl moiety (17k) markedly increased the activity against the wild type RT. Both 17a and 17k strongly inhibited HIV-1 replication. A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1 IIIB-R. The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.

KW - Benzenesulfonamide

KW - Nonnucleoside HIV-1 reverse transcriptase inhibitor

KW - Thiazolidene

UR - http://www.scopus.com/inward/record.url?scp=7444224177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7444224177&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2004.08.050

DO - 10.1016/j.bmc.2004.08.050

M3 - Article

C2 - 15519161

AN - SCOPUS:7444224177

VL - 12

SP - 6171

EP - 6182

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 23

ER -

Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this