N′-[2-(2-thiophene)ethyl]-N′-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of nni-resistant and multidrug-resistant human immunodeficiency virus-1

Bioorganic & Medicinal Chemistry Letters
1999.0

Abstract

The thiophene-ethyl thiourea (TET) compound N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea (compound HI-443) was five times more potent than trovirdine, 1250 times more potent than nevirapine, 100 times more potent than delavirdine, 75 times more potent than MKC-442, and 50 times more potent than AZT against the multidrug resistant HIV-1 strain RT-MDR with a V106A mutation. HI-443 was almost as potent against the NNI-resistant HIV-1 strain A17 with a Y181C mutation as it was against HTLV(IIIB). The activity of HI-443 against A17 was ten times more potent than that of trovirdine, 2083 times more potent than that of nevirapine, and 1042 times more potent than that of delavirdine. HI-443 inhibited the replication of the NNI-resistant HIV-1 strain A17 variant with Y181C plus K103N mutations in RT with an IC50 value of 3.3 microM, whereas the IC50 values of trovirdine, nevirapine, and delavirdine were all >100 microM. These findings establish the novel thiophene containing thiourea compound HI-443 as a novel NNI with potent antiviral activity against NNI-sensitive, NNI-resistant and multidrug-resistant strains of HIV-1.

DOI： 10.1016/s0960-894x(99)00624-1

Knowledge Graph

Similar Paper

N′-[2-(2-thiophene)ethyl]-N′-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of nni-resistant and multidrug-resistant human immunodeficiency virus-1
Bioorganic & Medicinal Chemistry Letters 1999.0
N-[2-(1-cyclohexenyl)ethyl]-N′-[2-(5-bromopyridyl)]-thiourea and N′-[2-(1-cyclohexenyl)ethyl]-N′-[2-(5-chloropyridyl)]- thiourea as potent inhibitors of multidrug-resistant human immunodeficiency virus-1
Bioorganic & Medicinal Chemistry Letters 1999.0
Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus
Bioorganic & Medicinal Chemistry Letters 1999.0
Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase
Bioorganic & Medicinal Chemistry Letters 2000.0
Anti-HIV activity of aromatic and heterocyclic Thiazolyl Thiourea compounds
Bioorganic & Medicinal Chemistry Letters 2001.0
Structure-based design of N-[2-(1-piperidinylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea and N-[2-(1-piperazinylethyl)]-N′-[2-(5-bromopyridyl)]-thiourea as potent non-nucleoside inhibitors of HIV-1 reverse transcriptase
Bioorganic & Medicinal Chemistry Letters 1998.0
Phenethylthiazolylthiourea (PETT) Compounds as a New Class of HIV-1 Reverse Transcriptase Inhibitors. 2. Synthesis and Further Structure−Activity Relationship Studies of PETT Analogs
Journal of Medicinal Chemistry 1996.0
Phenethylthiazolethiourea (PETT) Compounds, a New Class of HIV-1 Reverse Transcriptase Inhibitors. 1. Synthesis and Basic Structure-Activity Relationship Studies of PETT Analogs
Journal of Medicinal Chemistry 1995.0
Structure-Based Optimization of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with Improved Potency against Resistance-Associated Variants
Journal of Medicinal Chemistry 2017.0
Antioxidant function of phenethyl-5-bromo-pyridyl thiourea compounds with potent anti-HIV activity
Bioorganic & Medicinal Chemistry Letters 2000.0