Category: 18740-39-1

Wang, Zhao; Kang, Dongwei; Feng, Da; Cherukupalli, Srinivasulu; Jiang, Xiangyi; Fu, Zhipeng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published the artcile< Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility>, Formula: C6H2Cl2N2S, the main research area is morpholine diarylpyrimidine synthesis antiHIV NNRTI HIV1 CYP450; HIV-1; Morpholine; NNRTIs; SARs; Tolerant region I; Tolerant region II.

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 crystallog. studies. The biol. 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 mol. 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 Addnl., the in silico prediction of physicochem. properties and CYP enzymic inhibitory ability were investigated to evaluate their drug-like features.

European Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Formula: C6H2Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wu, Tianxiao; Qin, Qiaohua; Liu, Nian; Zhang, Chu; Lv, Ruicheng; Yin, Wenbo; Sun, Yin; Sun, Yixiang; Wang, Ruifeng; Zhao, Dongmei; Cheng, Maosheng published the artcile< Rational drug design to explore the structure-activity relationship (SAR) of TRK inhibitors with 2,4-diaminopyrimidine scaffold>, SDS of cas: 18740-39-1, the main research area is diaminopyrimidine preparation tropomyosin receptor kinase inhibitor SAR mol docking; Anticancer; NTRK gene fusion; Pharmacophore model; TRK inhibitors.

Tropomyosin receptor kinase (TRK) is an ideal target for treating cancers caused by the NTRK gene fusion. In this study, more than 60 2,4-diaminopyrimidine derivatives were prepared to understand the structure-activity relationship and confirm the rationality of the pharmacophore model reported previously. Among them, compound I was found to be a potent pan-TRK inhibitor that inhibits the proliferation of Km-12 cell lines. Addnl., compound I induced the apoptosis of Km-12 cells in a concentration-dependent manner. Western blot anal. revealed that compound I inhibited the phosphorylation of TRK to block downstream pathways. Compound I also possessed outstanding plasma stability and liver microsomal stability in vitro, with half-lives greater than 289.1 min and 145 min, resp. Pharmacokinetic studies indicated that the oral bioavailability of compound I is 17.4%. These results demonstrate that compound I could serve as a novel lead compound for overcoming NTRK-fusion cancers.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, SDS of cas: 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhang, Liandi; Xin, Minhang; Shen, Han; Wen, Jun; Tang, Feng; Tu, Chongxing; Zhao, Xinge; Wei, Ping published the artcile< Five-membered heteroaromatic ring fused-pyrimidine derivatives: Design, synthesis, and hedgehog signaling pathway inhibition study>, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is purine pyrrolopyrimidine thienopyrimidine furopyrimidine benzamide preparation hedgehog signaling inhibition; Five-membered heteroaromatic ring fused-pyrimidine; Hedgehog signaling pathway; Inhibitors; Synthesis.

A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives I [X = N, Y = NH, NMe; X = CH, Y = NH, NMe, S; R1 = Me, R2 = H; R1 = H, R2 = 4-morpholinylmethyl, 4-methyl-1-piperazinylmethyl, 2-(4-morpholinyl)ethoxy] and II (Z = NH, NMe, O, S; the same R1 and R2), including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines, have been prepared and identified to be potent inhibitors of hedgehog signaling pathway. Among this new series of hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for hedgehog signaling pathway inhibitors, deserving more exploration and further investigation.

Bioorganic & Medicinal Chemistry Letters published new progress about Hedgehog protein Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kang, Dongwei; Ruiz, F. Xavier; Feng, Da; Pilch, Alyssa; Zhao, Tong; Wei, Fenju; Wang, Zhao; Sun, Yanying; Fang, Zengjun; De Clercq, Erik; Pannecouque, Christophe; Arnold, Eddy; Liu, Xinyong; Zhan, Peng published the artcile< Discovery and Characterization of Fluorine-Substituted Diarylpyrimidine Derivatives as Novel HIV-1 NNRTIs with Highly Improved Resistance Profiles and Low Activity for the hERG Ion Channel>, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is HIV1 NNRTIs hERG inhibition half life hybridization bioisosterism cytotoxicity.

Our previous efforts have led to the development of two potent NNRTIs, K-5a2 and 25a, exhibiting effective anti-HIV-1 potency and resistance profiles compared with etravirine. However, both inhibitors suffered from potent hERG inhibition and short half-life. In this article, with K-5a2 and etravirine as leads, series of novel fluorine-substituted diarylpyrimidine derivatives were designed via mol. hybridization and bioisosterism strategies. The results indicated 24b was the most active inhibitor, exhibiting broad-spectrum activity (EC50 = 3.60-21.5 nM) against resistant strains, significantly lower cytotoxicity (CC50= 155μM), and reduced hERG inhibition (IC50 > 30μM). Crystallog. studies confirmed the binding of 24b and the role of the fluorine atom, as well as optimal contacts of a nitrile group with the main-chain carbonyl group of H235. Furthermore, 24b showed longer half-life and favorable safety properties. All the results demonstrated that 24b has significant promise in circumventing drug resistance as an anti-HIV-1 candidate.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents (anti-HIV-1 agents). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Prabhakar, Virupakshi; Kondra, Sudhakar Babu; Maddula, Srinivasula Reddy; Parandhama, G.; Latha, J. published the artcile< Synthesis, structural elucidation of novel thieno [2,3-d] pyrimidine core unit containing 1,2,4-triazoles and thiophenes as potent antimicrobial activity>, Application In Synthesis of 18740-39-1, the main research area is aryl thiophenyl thienotriazolopyrimidine preparation antibacterial antifungal activity SAR.

Several new thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines I [R = Ph, 4-MeC6H4, 4-MeOC6H4, etc.] were synthesized starting from thieno[2,3-d]pyrimidine-2,4-diol. The characterization of the newly synthesized compounds was established by IR, 1H NMR, 13C NMR and mass spectral anal. The final compounds I were screened for their antibacterial activity against Bacillus subtilis and Staphylococcus aureus from Gram pos. group of bacteria and Escherichia coli and Klebsiella pneumonia from Gram neg. group of bacteria and antifungal activity against Candida albicans and Aspergillus flavus. Antibacterial and antifungal activities were evaluated and compared with the standard drugs. From antibacterial and antifungal activities screening results, it was observed that compounds I [R = pyridin-3-yl, 1H-indol-2-yl, 4-F3CC6H4] possessed good activity.

Organic Chemistry: Current Research published new progress about Antibacterial agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Application In Synthesis of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Goto, Taiji; Shiina, Akiko; Yoshino, Toshiharu; Mizukami, Kiyoshi; Hirahara, Kazuki; Suzuki, Osamu; Sogawa, Yoshitaka; Takahashi, Tomoko; Mikkaichi, Tsuyoshi; Nakao, Naoki; Takahashi, Mizuki; Hasegawa, Masashi; Sasaki, Shigeki published the artcile< Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors>, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is fused bicyclic aminophenylpyrimidine preparation PDE4 inhibitor SAR; anti inflammatory activity lung inflammation bicyclic aminophenylpyrimidine.

2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d]pyrimidine derivative I was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivative II showed potent PDE4B inhibitory activity (IC50 = 25 nM). Finally, N-propylacetamide derivative III (R = n-Pr) was determined to be a potent inhibitor for both PDE4B (IC50 = 7.5 nM) and TNF-α production in mouse splenocytes (IC50 = 9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18 mg/kg). The binding mode of the new inhibitor III (R = t-Bu) in the catalytic site of PDE4B is presented based on an x-ray crystal structure of the ligand-enzyme complex.

Bioorganic & Medicinal Chemistry Letters published new progress about Anti-inflammatory agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yu, Lide; Wang, Qinqin; Wang, Caolin; Zhang, Binliang; Yang, Zunhua; Fang, Yuanying; Zhu, Wufu; Zheng, Pengwu published the artcile< Design, Synthesis and biological evaluation of novel thienopyrimidine derivatives as PI3Kα inhibitors>, Electric Literature of 18740-39-1, the main research area is morpholinyl diphenyldihydropyrazolyl thienopyrimidine preparation; diphenyldihydropyrazolyl morpholinyl tetrahydrobenzothienopyrimidine preparation; antitumor activity mTOR PI3Ka kinase inhibition SAR mol docking; PI3Kα inhibitor; Pyrazole; Thienopyrimidine.

Three series of novel thienopyrimidine derivatives I [R1 = H, 4-F, 4-Br, 3,4-di-Cl; R2 = H, 4-Me, 4-Br, etc.], II and III [R3 = H, 4-F, 4-Br, 3,4-di-Cl; R4 = H, 4-Me, 4-Br, etc.] were synthesized and their IC50 values against four cancer cell lines HepG-2, A549, PC-3 and MCF-7 were evaluated. Most compounds showed moderate cytotoxicity against the tested cancer cell lines. The most promising compound I [R1 = R2 = H (IV)] showed moderate activity with IC50 values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32 and 9.80 ± 0.93μM, resp. The inhibitory activities of compounds IV and II [R1 = R2 = H (V)] against PI3Kα and mTOR kinase were further evaluated. Compound IV exhibited PI3Kα kinase inhibitory activity with IC50 of 9.47 ± 0.63μM. In addition, docking studies of compounds IV and V were also investigated.

Molecules published new progress about Acetophenones Role: RCT (Reactant), RACT (Reactant or Reagent). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Electric Literature of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Feng, Da; Wei, Fenju; Sun, Yanying; Sharma, Prem Prakash; Zhang, Tao; Lin, Hao; Rathi, Brijesh; De Clercq, Erik; Pannecouque, Christophe; Kang, Dongwei; Zhan, Peng; Liu, Xinyong published the artcile< Boronic acid-containing diarylpyrimidine derivatives as novel HIV-1 NNRTIs: Design, synthesis and biological evaluation>, HPLC of Formula: 18740-39-1, the main research area is boronic acid diarylpyrimidine preparation human immunodeficiency virus 1 inhibitor; acid boronic diarylpyrimidine preparation HIV1 nonnucleoside reverse transcriptase inhibitor; mol dynamics simulation boronic acid diarylpyrimidine HIV 1 inhibitor.

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 0.1837μmol/L. Furthermore, mol. dynamics simulation indicated that 10j was proposed as a promising mol. for fighting against HIV-1 infection through inhibiting RT activity. Overall, the results demonstrated that 10j could serve as a lead mol. for further modification to address virus-drug resistance.

Chinese Chemical Letters published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, HPLC of Formula: 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Prabhakar, Virupakshi; Kondra, Sudhakar Babu; Maddula, Srinivasula Reddy; Parandhama, G.; Latha, J. published the artcile< Synthesis, structural elucidation of novel thieno [2,3-d] pyrimidine core unit containing 1,2,4-triazoles and thiophenes as potent antimicrobial activity>, Name: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is thiophenylboronic acid chloro arylthienotriazolopyrimidine Suzuki coupling; thiophenyl arylthienotriazolopyrimidine preparation antibacterial antifungal activity SAR.

Several new thieno[2,3-d]pyrimidine derivatives 3-substituted phenyl-5-(thiophen-2-yl)thieno[3,2-e] [1,2,4]triazolo[4,3-c]pyrimidines I [R = Ph, 3-pyridyl, 1H-indol-2-yl, etc.] were synthesized starting from thieno[2,3-d]pyrimidine-2,4-diol. The characterization of the newly synthesized compounds I was established by IR, 1H NMR, 13C NMR and mass spectral anal. The final compounds I were screened for their antibacterial activity against Bacillus subtilis and Staphylococcus aureus from Gram pos. group of bacteria and Escherichia coli and Klebsiella pneumonia from Gram neg. group of bacteria and antifungal activity against Candida albicans and Aspergillus flavus. Antibacterial and antifungal activities were evaluated and compared with the standard drugs. From antibacterial and antifungal activity screening results, it was observed that compounds I [R = 3-pyridyl, 1H-indol-2-yl, 4-F3CC6H5] possessed good activity.

Organic Chemistry: Current Research published new progress about Antibacterial agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Name: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Liu, Zhiqing; Ai, Jing; Peng, Xia; Song, Zilan; Wu, Kui; Zhang, Jing; Yao, Qizheng; Chen, Yi; Ji, Yinchun; Yang, Yanhong; Geng, Meiyu; Zhang, Ao published the artcile< Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities>, Formula: C6H2Cl2N2S, the main research area is arylaminopyrimidine preparation SAR cMet ALK multikinase inhibitor antitumor; 2,4-diarylaminopyrimidine analogues; C1-Substituted-N3-benzazepine; c-Met/ALK dual inhibitor; structure repurposing.

By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogs (DAAPalogues) were developed. Two compounds were identified possessing high potency against both c-Met and ALK kinases. Compound (I) displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Formula: C6H2Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia