Tag: M.W=200-250

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

Dolsak, Ana; Mrgole, Kristjan; Sova, Matej published the artcile< Microwave-assisted regioselective suzuki coupling of 2,4-dichloropyrimidines with aryl and heteroaryl boronic acids>, Application of C4H2Br2N2, the main research area is dihalopyrimidine boronic acid palladium regioselective Suzuki coupling microwave irradiation; halo arylpyrimidine preparation.

The Suzuki coupling of 2,4-dihalopyrimidines with aryl and heteroaryl boronic acids was investigated. A thorough screening of reaction conditions and the use of microwave irradiation leded to a very efficient and straightforward synthetic procedure provided arylpyrimidines in good to excellent yields. Short reaction time (15 min) and extremely low catalyst loading (0.5 mol%) were the main advantages of our tetrakis(triphenylphosphine)palladium(0) catalyzed microwave-assisted procedure, which could be used for quick and low-cost regioselective preparation of pyrimidine rings.

Catalysts published new progress about Arylboronic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Application of C4H2Br2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mosrin, Marc; Knochel, Paul published the artcile< Regio- and Chemoselective Multiple Functionalization of Pyrimidine Derivatives by Selective Magnesiations using TMPMgCl·LiCl>, Product Details of C4H2Br2N2, the main research area is chlorotetramethylpiperidinylmagnesium lithium chloride magnesiation pyrimidine reaction electrophile.

Successive regio- and chemoselective magnesiations of pyrimidines using TMPMgCl·LiCl furnish, after trapping with various electrophiles, highly functionalized derivatives, e.g. I, in good to excellent yields. Applications to the synthesis of antiviral and anti-inflammatory agents such as p38 and sPLA2 kinase inhibitors are reported.

Organic Letters published new progress about Chemoselectivity. 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Product Details of C4H2Br2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gronowitz, S.; Hoernfeldt, A. B.; Kristjansson, V.; Musil, T. published the artcile< On the synthesis of various thienyl- and selenienylpyrimidines>, Computed Properties of 3921-01-5, the main research area is halopyrimidine coupling thiopheneboronic acid; selenopheneboronic acid coupling halopyrimdine; pyrimidineboronic acid coupling bromothiophene; bromoselenophene coupling pyrimidineboronic acid; palladium coupling catalyst halopyrimidine; thienylpyrimidine; selenienylpyrimidine.

Various thienyl- and selenienylpyrimidines, including 5-substituted uracils, were prepared by the Pd(0)-catalyzed coupling between halopyrimidines I (R = H, Cl, Br, Me3CO, PhCH2O; R1 = Br, H) and thiopheneboronic acids and selenopheneboronic acids II [R2 = B(OH)2; X = S, Se, resp.]. 5-Bromouracil had to be protected as the tert-butoxy or benzyloxy derivative in order to achieve successful coupling. The compounds could also be obtained in a reversed manner, when pyrimidineboronic acids I [R = H, Me3CO; R1 = B(OH)2] were coupled with halothiophenes and haloselenophenes II (R2 = Br; X = S, Se).

Chemica Scripta published new progress about Coupling reaction. 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Computed Properties of 3921-01-5.

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

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

Schweizer, Stefan A.; Bach, Thorsten published the artcile< Regioselective Pd(0)-catalyzed Hiyama cross-coupling reactions at dihalo-substituted heterocycles>, Product Details of C4H2Br2N2, the main research area is haloheterocycle regioselective Hiyama cross coupling alkyl fluorosilane palladium catalyst.

The regioselectivity of the Hiyama cross-coupling reaction at various dihalo-substituted heterocycles was studied. Me 2,3-dibromo-5-furancarboxylate and n-octyltrifluorosilane were employed to find optimum reaction conditions [CsF; Pd2dba3/P(2-furyl)3 as catalyst, 80-150 °C in toluene or benzene] for the desired transformation. Subsequent experiments with the title compounds and with different primary alkyltrifluorosilanes illustrate the generality of this regiochem. process.

Synlett published new progress about Haloalkyl silanes, fluoroalkyl Role: RCT (Reactant), RACT (Reactant or Reagent). 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Product Details of C4H2Br2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia