Design, synthesis and biological evaluation of 3-substituted 2,5-dimethyl-N-(3-(1H-tetrazol-5-yl)phenyl)pyrroles as novel potential HIV-1 gp41 inhibitors

He, Xiaoyang; Zou, Peng; Qiu, Jiayin; Hou, Ling; Jiang, Shibo; Liu, Shuwen; Xie, Linghai

doi:10.1016/j.bmc.2011.09.047

Cited by 52 publications

(24 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly to the preparation of 7g , methylation of 8h afforded methoxymethyl compound 8i . A tetrazolyl ring (R 3 ) was formed 11 from the cyano group in 8j by treatment with sodium azide and triethylamine hydrochloride in refluxing toluene to afford 8k . However, this reaction did not go to completion, and ca .…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and biological evaluation of N-alkyl-N-(4-methoxyphenyl)pyridin-2-amines as a new class of tubulin polymerization inhibitors

Wang¹,

Ohkoshi

Wang³

et al. 2013

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Based on our prior antitumor hits, 32 novel N-alkyl-N-substituted phenylpyridin-2-amine derivatives were designed, synthesized and evaluated for cytotoxic activity against A549, KB, KBVIN, and DU145 human tumor cell lines (HTCL). Subsequently, three new leads (6a, 7g, and 8c) with submicromolar GI50 values of 0.19 to 0.41 μM in the cellular assays were discovered, and these compounds also significantly inhibited tubulin assembly (IC50 1.4–1.7 μM) and competitively inhibited colchicine binding to tubulin with effects similar to those of the clinical candidate CA-4 in the same assays. These promising results indicate that these tertiary diarylamine derivatives represent a novel class of tubulin polymerization inhibitors targeting the colchicine binding site and showing significant anti-proliferative activity.

show abstract

Section: Chemistrymentioning

confidence: 99%

Synthesis and biological evaluation of N-alkyl-N-(4-methoxyphenyl)pyridin-2-amines as a new class of tubulin polymerization inhibitors

Wang¹,

Ohkoshi

Wang³

et al. 2013

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…16. The inhibition values for 2e and 2k as the most potent compounds in 2a -2l series revealed that 4-chlorophenyl substituent at C(4) position of 1,2,3,4-tetrahydropyrimidine (2e) was more favorable for HIV-1 inhibitory activity than 4methylphenyl group (2k).…”

Section: Biological Assaymentioning

confidence: 97%

“…[16] We have previously reported the moderate anti-HIV-1 activity of some Biginelli-type tetrahydropyrimidines (THPM, 4aryl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate esters). It is reported that the elimination of the COOH group will decrease the anti-HIV-1 potency of the compound.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Anti‐HIV‐1 Evaluation of a Novel Series of 1,2,3,4‐Tetrahydropyrimidine‐5‐Carboxylic Acid Derivatives

Sepehri

Soleymani

Zabihollahi

et al. 2018

Chemistry & Biodiversity

View full text Add to dashboard Cite

A series of tetrahydropyrimidine derivatives (2a - 2l) were designed, synthesized, and screened for anti-HIV-1 properties based on the structures of HIV-1 gp41 binding site inhibitors, NB-2 and NB-64. A computational study was performed to predict the pharmacodynamics, pharmacokinetics, and drug-likeness features of the studied molecules. Docking studies revealed that the carboxylic acid group in the molecules forms salt bridges with either Lys574 or Arg579. Physiochemical properties (e.g., molecular weight, number of hydrogen bond donors, number of hydrogen bond acceptors, and number of rotatable bonds) of the synthesized compounds confirmed and exhibited that these compounds were within the range set by Lipinski's rule of five. Compounds 2e and 2k with 4-chlorophenyl substituent and 4-methylphenyl group at C(4) position of the tetrahydropyrimidine ring was the most potent one among the tested compounds. This suggests that these compounds may serve as leads for development of novel small-molecule HIV-1 inhibitors.

show abstract

“…In addition to peptide-based inhibitors, there is a major effort to design small molecule inhibitors of fusion [61,62,63,64,65,66,67,68,69,70,71]. Much of the focus has been in designing inhibitors that bind in the deep pocket [55].…”

Section: Virus-cell Fusion and Structural Biology Of Hivgp41mentioning

confidence: 99%

Computer-Aided Approaches for Targeting HIVgp41

Allen

Rizzo

2012

Biology

View full text Add to dashboard Cite

Virus-cell fusion is the primary means by which the human immunodeficiency virus-1 (HIV) delivers its genetic material into the human T-cell host. Fusion is mediated in large part by the viral glycoprotein 41 (gp41) which advances through four distinct conformational states: (i) native, (ii) pre-hairpin intermediate, (iii) fusion active (fusogenic), and (iv) post-fusion. The pre-hairpin intermediate is a particularly attractive step for therapeutic intervention given that gp41 N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) domains are transiently exposed prior to the formation of a six-helix bundle required for fusion. Most peptide-based inhibitors, including the FDA-approved drug T20, target the intermediate and there are significant efforts to develop small molecule alternatives. Here, we review current approaches to studying interactions of inhibitors with gp41 with an emphasis on atomic-level computer modeling methods including molecular dynamics, free energy analysis, and docking. Atomistic modeling yields a unique level of structural and energetic detail, complementary to experimental approaches, which will be important for the design of improved next generation anti-HIV drugs.

show abstract

Design, synthesis and biological evaluation of 3-substituted 2,5-dimethyl-N-(3-(1H-tetrazol-5-yl)phenyl)pyrroles as novel potential HIV-1 gp41 inhibitors

Cited by 52 publications

References 28 publications

Synthesis and biological evaluation of N-alkyl-N-(4-methoxyphenyl)pyridin-2-amines as a new class of tubulin polymerization inhibitors

Synthesis and biological evaluation of N-alkyl-N-(4-methoxyphenyl)pyridin-2-amines as a new class of tubulin polymerization inhibitors

Design, Synthesis, and Anti‐HIV‐1 Evaluation of a Novel Series of 1,2,3,4‐Tetrahydropyrimidine‐5‐Carboxylic Acid Derivatives

Computer-Aided Approaches for Targeting HIVgp41

Contact Info

Product

Resources

About