1024603-85-7

Upstream product

• 16234-14-3 2,4-dichlorothieno[3,2-d]pyrimidine 
• 4198-90-7 3,5-dimethyl-4-hydroxybenzonitrile 

Downstream Products

• 1024603-75-5 4-(2-(4-cyanophenylamino)thieno[3,2-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile 

Relevant academic research and scientific papers

Design, synthesis, and antiviral evaluation of novel hydrazone-substituted thiophene[3,2-d]pyrimidine derivatives as potent human immunodeficiency virus-1 inhibitors

In the previous studies of our laboratory, the thiophene[3,2-d]pyrimidine was identified as a promising scaffold for seeking highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we designed, synthesized, and biologi

Discovery of potent HIV-1 non-nucleoside reverse transcriptase inhibitors by exploring the structure–activity relationship of solvent-exposed regions I

Two novel series of human immunodeficiency virus-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) bearing a thiophene[3,2-d]pyrimidine scaffold and sulfonamide linker in the right wing have been identified, which demonstrated activity against the wild-type (WT) HIV-1 strain in MT-4 cells with inhibitory concentrations ranging from micromolar to submicromolar. Especially, against the mutant strains K103N and E138K, most compounds exhibited more potent activity than against WT HIV-1. Compound 7 (EC50?=?0.014, 0.031?μM) achieved the most potent activity against the two mutants, being more effective than that of nevirapine (NVP, EC50?=?7.572, 0.190?μM) and comparable to that of etravirine (ETV, EC50?=?0.004, 0.014?μM). Molecular docking experiments on the novel analogs have also suggested that the extensive network of main chain hydrogen bonds are important in the binding mode, which may provide valuable insights for further optimization.

Discovery of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the Tolerant Region i of NNIBP

Our previous studies led us to conclude that thiophene[3,2-d]pyrimidine is a promising scaffold for diarylpyrimidine (DAPY)-type anti-HIV agents with potent activity against resistance-associated human immunodeficiency virus (HIV) variants (J. Med. Chem. 2016, 59, 7991-8007; J. Med. Chem. 2017, 60, 4424-4443). In the present study, we designed and synthesized a series of thiophenepyrimidine derivatives with various substituents in the right wing region of the structure with the aim of developing new interactions with the tolerant region I of the binding pocket of the HIV-1 non-nucleoside reverse transcriptase (NNRTI), and we evaluated their activity against a panel of mutant HIV-1 strains. All the derivatives exhibited moderate to excellent potency against wild-type (WT) HIV-1 in MT-4 cells. Among them, sulfonamide compounds 9b and 9d were single-figure-nanomolar inhibitors with EC50 values of 9.2 and 7.1 nM, respectively. Indeed, 9a and 9d were effective against the whole viral panel except RES056. Notably, both compounds showed potent antiviral activity against K103N (EC50 = 0.032 and 0.070 μM) and E138K (EC50 = 0.035 and 0.045 μM, respectively). Furthermore, 9a and 9d exhibited high affinity for WT HIV-1 RT (IC50 = 1.041 and 1.138 μM, respectively) and acted as classical NNRT inhibitors (NNRTIs). These results are expected to be helpful in the design of thiophenepyrimidine-based NNRTIs with more potent activity against HIV strains with RT mutations.

Boronic acid-containing diarylpyrimidine derivatives as novel HIV-1 NNRTIs: Design, synthesis and biological evaluation

Drug resistance remains to be a serious problem with type I human immunodeficiency virus (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs). A series of novel boronic acid-containing diarylpyrimidine (DAPY) derivatives were designed via bioisosterism and scaffold-hopping strategies, taking advantage of the ability of a boronic acid group to form multiple hydrogen bonds. The target compounds were synthesized and evaluated for their anti-HIV activities and cytotoxicity in MT-4 cells. Compound 10j yielded the most potent activity and turned out to be a single-digit nanomolar inhibitor towards the HIV-1 IIIB [wild-type (WT) strain], L100I and K103N strains, with 50% effective concentration (EC50) values of 7.19–9.85 nmol/L. Moreover, 10j inhibited the double-mutant strain RES056 with an EC50 value of 77.9 nmol/L, which was 3.3-more potent than that of EFV (EC50 = 260 nmol/L) and comparable to that of ETR (EC50 = 32.2 nmol/L). 10j acted like classical NNRTIs with high affinity for WT HIV-1 reverse transcriptase (RT) with 50% inhibition concentration (IC50) value of 0.1837 μmol/L. Furthermore, molecular dynamics simulation indicated that 10j was proposed as a promising molecule for fighting against HIV-1 infection through inhibiting RT activity. Overall, the results demonstrated that 10j could serve as a lead molecule for further modification to address virus-drug resistance.

Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility

To address the intractable issues of drug resistance and poor solubility, a novel series of morpholine-substituted diarylpyrimidines targeting the tolerant region I and tolerant region II of NNIBP were rationally designed by utilizing the available crystallography studies. The biological evaluation results showed that four most promising compounds (14e1, 14g1, 14g2 and 14j2) displayed excellent potency against WT HIV-1 strain with EC50 values ranging from 58 to 87 nM, being far more potent than NVP and comparable to ETV. Besides, some derivatives exhibited moderate activity in inhibiting the mutant HIV-1 strains. More encouragingly, 14d2 (RF = 0.4) possessed higher antiresistance profile than ETV (RF = 6.3) and K-5a2 (RF = 3.0) toward the double mutant strain F227L + V106A. The HIV-1 RT inhibition assay confirmed their binding target. The molecular docking studies were conducted and discussed in detail to rationalize the preliminary SARs. Further test indicated that morpholine could indeed promote the improvement of water solubility. Additionally, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability were investigated to evaluate their drug-like features.

Diaryl thienopyrimidine HIV-1 (human immunodeficiency virus type 1) reverse transcriptase inhibitors as well as preparation method and application thereof

The invention relates to diaryl thienopyrimidine HIV-1 (human immunodeficiency virus type 1) reverse transcriptase inhibitors as well as a preparation method and an application thereof. The compoundshave the structure shown in a formula I. The invention also relates to pharmaceutical composition containing the compounds with the structure shown in the formula I and also provides the compounds andthe application of composition of one or more compounds in preparation of drugs for treating and preventing HIV.

Triazole-ring-containing diaryl pyrimidine HIV-1 inhibitor as well as preparation method and application of triazole-ring-containing diaryl pyrimidine HIV-1 inhibitor

The invention relates to a triazole-ring-containing diaryl pyrimidine HIV-1 inhibitor as well as a preparation method and application of the triazole-ring-containing diaryl pyrimidine HIV-1 inhibitor.The compound has a structure as shown in a formula I. T

Diaryl thienopyrimidine HIV-1 reverse transcriptase inhibitor and preparation method and application thereof

The invention relates to a diaryl thienopyrimidine HIV-1 reverse transcriptase inhibitor and a preparation method and application thereof. The diaryl thienopyrimidine HIV-1 reverse transcriptase inhibitor has a structure shown in the formula I. The invention also relates to a pharmaceutical composition containing the compound shown in the formula I. The invention also provides a use of the compound and a compound composition containing the same type of one or more compounds in preparation of drugs for treating and preventing human immunodeficiency viruses (HIV).

Thieno [3,2-d] miazines HIV-1 reverse transcriptase inhibitor, and preparation method and application thereof

The invention relates to a thieno [3,2-d] miazines HIV-1 reverse transcriptase inhibitor, and a preparation method and application thereof. The compound has a structure as shown as formula I. The invention also relates to a drug compound containing the compound with the structure as shown as formula I. The invention also provides the compound and the application of the composition containing one or more compounds in preparing the drug for treating and preventing human immunodeficiency virus (HIV).

A thieno [3, 2 - d] pyrimidine derivative and its preparation method and application

The invention relates to a thieno [3, 2-d] pyrimidine derivative and a preparation method and application thereof. The compound has the structure as shown in formula I in the specification. The invention further relates to a medical composition containing