Category: 89793-12-4

Khamrai, Jagadish; Ghosh, Indrajit; Savateev, Aleksandr; Antonietti, Markus; Koenig, Burkhard published the artcile< Photo-Ni-Dual-Catalytic C(sp2)-C(sp3) Cross-Coupling Reactions with Mesoporous Graphitic Carbon Nitride as a Heterogeneous Organic Semiconductor Photocatalyst>, Related Products of 89793-12-4, the main research area is cross coupling reaction photocatalyst organic semiconductor nickel carbon nitride.

The synergistic combination of a heterogeneous organic semiconductor mesoporous graphitic carbon nitride (mpg-CN) and a homogeneous nickel catalyst with visible-light irradiation at room temperature affords the C(sp2)-C(sp3) cross-coupling of aryl halides and potassium alkyl trifluoroborates by single electron transmetallation. Like the homogeneously catalyzed protocol, the reaction is compatible with a variety of functional groups including electron-donating and electron-withdrawing aryl and heteroaryl moieties. Moreover, this protocol allows the installation of allyl groups onto (hetero)arenes, enlarging the scope of the method. The heterogeneous mpg-CN photocatalyst is easily recovered from the reaction mixture and reused several times, paving the way for larger-scale industrial applications of this type of photocatalytic bond-forming reactions.

ACS Catalysis published new progress about Cross-coupling reaction catalysts. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Related Products of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yoon, Hyung; Galls, Alexandra; Rozema, Soren D.; Miller, Scott J. published the artcile< Atroposelective Desymmetrization of Resorcinol-Bearing Quinazolinones via Cu-Catalyzed C-O Bond Formation>, Formula: C7H7ClN2O2, the main research area is resorcinol quinazolinone preparation enantioselective; quinazolinone aryl bromide Ullmann coupling atroposelective desymmetrization copper catalyst.

Enantioselective Cu-catalyzed C-O cross coupling reactions yielding atropisomeric resorcinol-bearing quinazolinones have been developed. By utilizing a new guanidinylated dimeric peptidic ligand, products I (R = H, Br, R1 = H, NO2, CF3, R2 = Me, Et, R3 = H, Me, OMe, R4 = H, OMe, X = CH; R = R1 = R3 = R4 = H, R2 = Me, X = N) were generated in good yields with excellent stereocontrol. The transformation was readily scalable and a range of product derivatizations were performed.

Organic Letters published new progress about Aryl bromides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Formula: C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chen, Yong; Wang, Xiaoyan; Xiang, Wei; He, Lin; Tang, Minghai; Wang, Fang; Wang, Taijin; Yang, Zhuang; Yi, Yuyao; Wang, Hairong; Niu, Ting; Zheng, Li; Lei, Lei; Li, Xiaobin; Song, Hang; Chen, Lijuan published the artcile< Development of Purine-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities>, HPLC of Formula: 89793-12-4, the main research area is purine hydroxamic acid derivative preparation histone deacetylase inhibitor cancer.

In the present study, a series of novel histone deacetylase (HDAC) inhibitors using the morpholinopurine as the capping group were designed and synthesized. Several compounds demonstrated significant HDAC inhibitory activities and antiproliferative effects against diverse human tumor cell lines. Among them, compound 10o was identified as a potent class I and class IIb HDAC inhibitor with good pharmaceutical profile and druglike properties. Western blot anal. further confirmed that 10o more effectively increased acetylated histone H3 than panobinostat (LBH-589) and vorinostat (SAHA) at the same concentration in vitro. In in vivo efficacy evaluations of HCT116, MV4-11, Ramos, and MM1S xenograft models, 10o showed higher efficacy than SAHA or LBH-589 without causing significant loss of body weight and toxicity. All the results indicated that 10o could be a suitable candidate for treatment of both solid and hematol. cancer.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, HPLC of Formula: 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Casimiro-Garcia, Agustin; Allais, Christophe; Brennan, Agnes; Choi, Chulho; Dower, Gabriela; Farley, Kathleen A.; Fleming, Margaret; Flick, Andrew; Frisbie, Richard K.; Hall, Justin; Hepworth, David; Jones, Hannah; Knafels, John D.; Kortum, Steve; Lovering, Frank E.; Mathias, John P.; Mohan, Sashi; Morgan, Paul M.; Parng, Chuenlei; Parris, Kevin; Pullen, Nick; Schlerman, Franklin; Stansfield, John; Strohbach, Joseph W.; Vajdos, Felix F.; Vincent, Fabien; Wang, Hong; Wang, Xiaolun; Webster, Robert; Wright, Stephen W. published the artcile< Discovery of a Series of Pyrimidine Carboxamides as Inhibitors of Vanin-1>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is pyrimidine carboxamide vanin inhibitor pharmacokinetic ADME.

A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe 2 that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophys. and crystallog. methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochem. and ADME properties, and guided by co-crystal structures with vanin-1, 3 was identified with a suitable profile for advancement into preclin. development.

Journal of Medicinal Chemistry published new progress about Crystal structure. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Prier, Christopher K.; MacMillan, David W. C. published the artcile< Amine α-heteroarylation via photoredox catalysis: a homolytic aromatic substitution pathway>, Related Products of 89793-12-4, the main research area is alpha heteroaryl amine regioselective preparation photoredox; tertiary amine heteroarene heteroarylation iridium.

The direct α-heteroarylation of tertiary amines has been accomplished via photoredox catalysis to generate valuable benzylic amine pharmacophores. A variety of five- and six-membered chloroheteroarenes are shown to function as viable coupling partners for the α-arylation of a diverse range of cyclic and acyclic amines. Evidence is provided for a homolytic aromatic substitution mechanism, in which a catalytically-generated α-amino radical undergoes direct addition to an electrophilic chloroarene.

Chemical Science published new progress about Aromatic heterocyclic amines Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (α-). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Related Products of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kickinger, Stefanie; Al-Khawaja, Anas; Haugaard, Anne Staehr; Lie, Maria E. K.; Bavo, Francesco; Loeffler, Rebekka; Damgaard, Maria; Ecker, Gerhard F.; Froelund, Bente; Wellendorph, Petrine published the artcile< Exploring the molecular determinants for subtype-selectivity of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid analogs as betaine/GABA transporter 1 (BGT1) substrate-inhibitors>, Application of C7H7ClN2O2, the main research area is amino tetrahydropyrimidine carboxylic acid betaine GABA transporter substrate inhibitor.

We have previously identified 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA) as the most potent substrate-inhibitor of the betaine/GABA transporter 1 (BGT1) (IC50 2.5 μM) reported to date. Herein, we characterize the binding mode of 20 novel analogs and propose the mol. determinants driving BGT1-selectivity. A series of N1-, exocyclic-N-, and C4-substituted analogs was synthesized and pharmacol. characterized in radioligand-based uptake assays at the four human GABA transporters (hGATs) recombinantly expressed in mammalian cells. Overall, the analogs retained subtype-selectivity for hBGT1, though with lower inhibitory activities (mid to high micromolar IC50 values) compared to ATPCA. Further characterization of five of these BGT1-active analogs in a fluorescence-based FMP assay revealed that the compounds are substrates for hBGT1, suggesting they interact with the orthosteric site of the transporter. In silico-guided mutagenesis experiments showed that the non-conserved residues Q299 and E52 in hBGT1 as well as the conformational flexibility of the compounds potentially contribute to the subtype-selectivity of ATPCA and its analogs. Overall, this study provides new insights into the mol. interactions governing the subtype-selectivity of BGT1 substrate-inhibitors. The findings may guide the rational design of BGT1-selective pharmacol. tool compounds for future drug discovery.

Scientific Reports published new progress about Aminopyrimidines Role: PAC (Pharmacological Activity), PRP (Properties), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Application of C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Xu, Hongtao; Gu, Yuang; Zhang, Shuning; Xiong, Huan; Ma, Fei; Lu, Fengping; Ji, Qun; Liu, Lili; Ma, Peixiang; Hou, Wei; Yang, Guang; Lerner, Richard A. published the artcile< A Chemistry for Incorporation of Selenium into DNA-Encoded Libraries>, COA of Formula: C7H7ClN2O2, the main research area is selenium DNA encoded library preparation; C−H activation; DNA-encoded library; benzoselenazolone; rhodium; selenylation.

Conventional direct C-H selenylation suffers from simple selenation with limited atom economy and complicated reaction system. The authors designed benzoselenazolone as a novel bifunctional selenide reagent for both off- and on-DNA C-H selenylation under rhodium(III) catalysis. Using benzoselenazolone gave a series of selenylation products containing an adjacent aminoacyl group in a fast and efficient way, with high atom economy. The synthetic application of this method was demonstrated by taking advantage of the amide functionality as a nucleophile, directing group, and amide coupling partner. This work shows great potential in facilitating rapid construction of selenium-containing DNA-encoded chem. libraries (SeDELs), and lays the foundation for the development of selenium-containing drugs.

Angewandte Chemie, International Edition published new progress about Azoles Role: RCT (Reactant), RACT (Reactant or Reagent) (benzoselenazolones). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, COA of Formula: C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Thakur, Ashish; Tawa, Gregory J.; Henderson, Mark J.; Danchik, Carina; Liu, Suiyang; Shah, Pranav; Wang, Amy Q.; Dunn, Garrett; Kabir, Md.; Padilha, Elias C.; Xu, Xin; Simeonov, Anton; Kharbanda, Surender; Stone, Richard; Grewal, Gurmit published the artcile< Design, Synthesis, and Biological Evaluation of Quinazolin-4-one-Based Hydroxamic Acids as Dual PI3K/HDAC Inhibitors>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is quinazolinone hydroxamic acid dual PI3K HDAC inhibitor anticancer.

A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3Kγ, δ and HDAC6 enzymes and exhibited good antiproliferative activity against multiple cancer cell lines. The lead compound 48c, induced necrosis in several mutant and FLT3-resistant AML cell lines and primary blasts from AML patients, while showing no cytotoxicity against normal PBMCs, NIH3T3, and HEK293 cells. Target engagement of PI3Kδ and HDAC6 by 48c was demonstrated in MV411 cells using the cellular thermal shift assay (CETSA). Compound 48c showed good pharmacokinetics properties in mice via i.p. administration and provides a means to examine the biol. effects of inhibiting these two important enzymes with a single mol., either in vitro or in vivo. Journal of Medicinal Chemistry published new progress about Antitumor agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Safety of Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Takamatsu, Kayo; Takano, Atsushi; Yakushiji, Nobumasa; Morohashi, Kazunori; Morishita, Kenichi; Matsuura, Nobuyasu; Makishima, Makoto; Tai, Akihiro; Sasaki, Kenji; Kakuta, Hiroki published the artcile< The first potent subtype-selective retinoid X receptor (RXR) agonist possessing a 3-isopropoxy-4-isopropylphenylamino moiety, NEt-3IP (RXRα/β-dual agonist)>, Related Products of 89793-12-4, the main research area is isopropoxy isopropylphenylamino derivative preparation structure retinoid X receptor agonist.

Retinoid X receptor (RXR) agonists (rexinoids) are attracting much attention for their use in treatment of cancers, including tamoxifen-resistant breast cancer and taxol-resistant lung cancer, and metabolic disease. However, known RXR agonists have a highly lipophilic character. In addition, no subtype-selective RXR agonists have been found. The authors previously reported an RXRα-preferential agonist 4-[N-methanesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl) amino]benzoic acid. The RXR agonistic activity is much less than that of well-known RXR agonists. To develop potent, less-lipophilic, and subtype-selective RXR agonists, the authors created new RXR agonists possessing alkoxy and iso-Pr groups as a lipophilic domain of the common structure of well-known RXR agonists. As a result, compounds possessing branched alkoxy groups (I) and (II), showed RXR agonistic activity as potent as, or more potent than, the activities of representative RXR agonists. Moreover, I was the first RXRα/β-selective (or RXRα/β-dual) agonist. Being potent, less lipophilic, and having RXR subtype-selective activity, NEt-3IP I is expected to become a new drug candidate and to be a useful biol. tool for clarifying each RXR subtype function.

ChemMedChem published new progress about Retinoid X receptor α Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Related Products of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Xu, Ana; He, Feng; Zhang, Xiangna; Li, Xiaoyang; Ran, Yingying; Wei, Chao; James Chou, C.; Zhang, Rui; Wu, Jingde published the artcile< Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is tacrine hydroxamate derivative preparation anti Alzheimer; structure activity tacrine hydroxamate cholinesterase inhibitor; Alzheimer’s disease; Antioxidant; Cholinesterase inhibitor; Metal chelator; Multitarget-directed ligands.

In order to develop multitarget-directed ligands as potential treatments for Alzheimer’s disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biol. evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, I showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, I exhibited inhibitory activity on Aβ1-42 self-aggregation as well as disaggregation activity on pre-formed Aβ fibrils. Furthermore, I exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that I is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It was shown that I is a BBB penetrant by online prediction. Taken together, the results indicate that I can serve as a lead compound to develop promising candidate analogs as AD therapeutics.

Bioorganic Chemistry published new progress about Alzheimer disease. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia