Category: 89793-12-4

Suwal, Sujit; Rahman, Mahmuda; O’Brien, Gregory; Karambizi, Victoire G.; Wrotny, Matthew; Scott Goodman, M. published the artcile< Chemo-selective syntheses of N-t-boc-protected amino ester analogs through Buchwald-Hartwig amination>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is amino ester preparation chemoselective; heterocyclic halo ester amine Buchwald Hartwig amination.

Synthesis of N-protected amino esters, e.g., I is achieved via a chemo-selective Buchwald Hartwig cross-coupling reaction using PEPPSI-IPr Pd-catalyst. Nearly two dozen functionally and structurally diverse mols. are created by individually cross-coupling eight II (R = Me, Et; Y = CH, N; X = Cl, Br) and three different secondary amines, e.g., tert-Bu piperazine-1-carboxylate. It was the observed that product formation is more facile in those heterocyclic esters II where nitrogen is present ortho to the halo substituent in the heteroaromatic ring. Based on this observation, a possible intermediate step in the cross-coupling cycle is proposed, where the nitrogen electron lone pair in the heterocycle may play an important role leading to a higher reaction yield.

New Journal of Chemistry published new progress about Amino esters Role: SPN (Synthetic Preparation), PREP (Preparation). 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

Park, Tae-Hong; Cychosz, Katie A.; Wong-Foy, Antek G.; Dailly, Anne; Matzger, Adam J. published the artcile< Gas and liquid phase adsorption in isostructural Cu3[biaryltricarboxylate]2 microporous coordination polymers>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is gas liquid adsorption copper isostructural biaryltricarboxylate microporous polymer; crystal structure copper carboxypyrimidinyl carboxypyridinyl isophthalate microporous coordination polymer; copper biaryltricarboxylate microporous polymer preparation gas liquid adsorption.

N-Heteroarene substitution in biphenyl-based linkers enhances the uptake of electron-rich organosulfur mols. in microporous coordination polymers (MCP). Three isostructural MCPs are prepared (Cu3L2) possessing nearly uniform surface areas from homologous biaryl tricarboxylate linkers containing Ph (biphenyltricarboxylate UMCM-150), pyrimidine (carboxypyrimidinyl-isophthalate UMCM-150N2), and pyridine (carboxypyridinyl-isophthalate UMCM-150N1) units, building the ideal system to probe linker influence upon guest adsorption. The almost identical isotherms of H2 and CO2 in these MCPs imply that the N-heteroaryl linkers in the UMCM-150 analogs do not considerably affect the gas phase adsorption behavior. The electronic nature and contact interactions with the aromatic linker play an important role to enhance interactions between the host MCP framework and the large guest organic mols. in the liquid phase.

Chemical Communications (Cambridge, United Kingdom) published new progress about Adsorption (isotherm). 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

Amano, Yohei; Noguchi, Masayuki; Shudo, Koichi published the artcile< Diarylamines incorporating hexahydrophenalene or octahydrobenzoheptalene as retinoid X receptor (RXR)-specific agonists>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is arylamino hexahydro phenalene preparation retinoid X receptor agonist; octahydro benzoheptalene arylamino preparation retinoid X receptor agonist.

A series of diarylamines I (X = CH2, R1 = H, Me; X = CH2CH2, R1 = H; Z = CH, N; R2 = H, Me, Et, cyclopropylmethyl, i-Bu, PhCH2) incorporating hexahydrophenalene or octahydrobenzoheptalene as a hydrophobic moiety was synthesized and examined for their activities towards retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Most of these compounds showed agonistic activity towards RXRs, but were inactive towards RARs. These RXR-specific ligands showed synergistic activity in RARα,β ligand-induced terminal differentiation of leukemia cell line HL-60.

Chemical & Pharmaceutical Bulletin published new progress about Aromatic amines Role: PAC (Pharmacological Activity), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 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

Law, Robert P.; Ukuser, Sabri; Tape, Daniel T.; Talbot, Eric P. A. published the artcile< Regioselective Synthesis of 3-Aminoimidazo[1,2-a]pyrimidines with Triflic Anhydride>, Electric Literature of 89793-12-4, the main research area is regioselective synthesis aminoimidazopyrimidine cyclization pyrimidine amide triflic anhydride pyridine.

The regioselective synthesis of 3-aminoimidazo[1,2- a]pyrimidines via triflic anhydride mediated amide activation and intramol. cyclization is reported. The nature of the added pyridine base allows access to both regioisomers from a simple common precursor [e.g., treatment of pyrimidine amide I with Tf2O and pyridine bases yielded II + III (yield ratios 8:45 % using 2,6-difluoropyridine and 83:9 % using 2-fluoropyridine)]. The method tolerates a range of functional groups and provides access to novel heterocyclic scaffolds.

Synthesis published new progress about Cyclization catalysts (regioselective). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Electric Literature of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rabal, Obdulia; Sanchez-Arias, Juan A.; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Garcia-Barroso, Carolina; Ugarte, Ana; Estella-Hermoso de Mendoza, Ander; Saez, Elena; Espelosin, Maria; Ursua, Susana; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease>, Application In Synthesis of 89793-12-4, the main research area is histone deacetylase HDAC phosphodiesterase PDE5 inhibitor antialzheimer Alzheimer.

Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer’s Disease (AD). To further extend this concept, the authors designed and synthesized the first chem. series of dual acting PDE5 and HDAC inhibitors, and the authors validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate the hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into mols. with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit) and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Application In Synthesis of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Tsuno, Naoki; Yukimasa, Akira; Yoshida, Osamu; Suzuki, Shinji; Nakai, Hiromi; Ogawa, Tomoyuki; Fujiu, Motohiro; Takaya, Kenji; Nozu, Azusa; Yamaguchi, Hiroki; Matsuda, Hidetoshi; Funaki, Satoko; Yamanada, Natsue; Tanimura, Miki; Nagamatsu, Daiki; Asaki, Toshiyuki; Horita, Narumi; Yamamoto, Miyuki; Hinata, Mikie; Soga, Masahiko; Imai, Masayuki; Morioka, Yasuhide; Kanemasa, Toshiyuki; Sakaguchi, Gaku; Iso, Yasuyoshi published the artcile< Pharmacological evaluation of novel (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives as TRPV4 antagonists for the treatment of pain>, Application In Synthesis of 89793-12-4, the main research area is TRPV4 antagonist analgesic pain; Ion channel; Pain; TRPV4 antagonist; Transient receptor potential vanilloid 4; Vanilloid receptor.

A novel series of (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives were identified as selective transient receptor potential vanilloid 4 (TRPV4) channel antagonist and showed analgesic effect in Freund’s Complete Adjuvant (FCA) induced mech. hyperalgesia model in guinea pig and rat. Modification of right part based on the compound I which was disclosed in the previous communication led to the identification of compound II as a flagship compound In this paper, the authors described the details about design, synthesis and structure-activity relationship (SAR) anal.

Bioorganic & Medicinal Chemistry published new progress about Analgesics. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Application In Synthesis of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sanchez-Arias, Juan A.; Rabal, Obdulia; Cuadrado-Tejedor, Mar; de Miguel, Irene; Perez-Gonzalez, Marta; Ugarte, Ana; Saez, Elena; Espelosin, Maria; Ursua, Susana; Haizhong, Tan; Wei, Wu; Musheng, Xu; Garcia-Osta, Ana; Oyarzabal, Julen published the artcile< Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer's Disease>, Computed Properties of 89793-12-4, the main research area is histone deacetylase phosphodiesterase 5 inhibitor preparation Alzheimer treatment; Alzheimer’s disease; HDACs; PDE5; dual inhibitor; tadalafil; vardenafil.

A novel systems therapeutics approach, involving simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylase (HDAC), has been validated as a potentially novel therapeutic strategy for the treatment of Alzheimer’s disease (AD). First-in-class dual inhibitors bearing a sildenafil core have been very recently reported, and the lead mol. CM-414 has proven this strategy in AD animal models. Because scaffolds may play a critical role in primary activities and ADME-Tox profiling as well as on intellectual property, the authors have explored alternative scaffolds (vardenafil- and tadalafil-based cores) and evaluated their impact on critical parameters such as primary activities, permeability, toxicity, and in vivo (pharmacokinetics and functional response in hippocampus) to identify a potential alternative lead mol. bearing a different chemotype for in vivo testing.

ACS Chemical Neuroscience published new progress about Alzheimer disease. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Computed Properties of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhao, Chao; Choi, You Hee; Khadka, Daulat Bikram; Jin, Yifeng; Lee, Kwang-Youl; Cho, Won-Jea published the artcile< Design and synthesis of novel androgen receptor antagonists via molecular modeling>, SDS of cas: 89793-12-4, the main research area is androgen receptor antagonist preparation cancer; AR antagonist; Bioisostere; Molecular modeling; Nicotinamide; Pyrazinamide; Pyrimidinamide.

Several androgen receptor (AR) antagonists are clin. prescribed to treat prostate cancer. Unfortunately, many patients become resistant to the existing AR antagonists. To overcome this, a novel AR antagonist candidate called DIMN was discovered by our research group in 2013. In order to develop compounds with improved potency, we designed novel DIMN derivatives based on a docking study and substituted carbons with heteroatom moieties. Encouraging in vitro results for compounds 1b, 1c, 1e, 3c, and 4c proved that the new design was successful. Among the newly synthesized compounds, 1e exhibited the strongest inhibitory effect on LNCaP cell growth (IC50 = 0.35 μM) and also acted as a competitive AR antagonist with selectivity over the estrogen receptor (ER) and the glucocorticoid receptor (GR). A docking study of compound 1e fully supported these biol. results. Compound 1e is considered to be a novel, potent and AR-specific antagonist for treating prostate cancer. Thus, our study successfully applied mol. modeling and bioisosteric replacement for hit optimization. The methods here provide a guide for future development of drug candidates through structure-based drug discovery and chem. modifications.

Bioorganic & Medicinal Chemistry published new progress about Androgen receptor antagonists. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, SDS of cas: 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chen, Junwei; Cao, Xin; An, Quanlin; Zhang, Yao; Li, Ke; Yao, Wenting; Shi, Fuchun; Pan, Yanfang; Jia, Qiong; Zhou, Wenwen; Yang, Fang; Wei, Fuxiang; Wang, Ning; Yu, Biao published the artcile< Inhibition of cancer stem cell like cells by a synthetic retinoid>, Quality Control of 89793-12-4, the main research area is cancer stem cell synthetic retinoid WYC209 anticancer.

Developing novel drugs that can abrogate the growth and metastasis of malignant tumors is a major challenge for cancer researchers. Here we describe a novel synthetic retinoid, namely WYC-209, which inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs), known to resist conventional drug treatment, with an IC50 of 0.19 μM in a dose-dependent manner. WYC-209 also inhibits proliferation of TRCs of human melanoma, lung cancer, ovarian cancer, and breast cancer in culture. Interestingly, the treated TRCs fail to resume growth even after the drug washout. Importantly, the mol. abrogates 87.5% of lung metastases of melanoma TRCs in immune-competent wild-type C57BL/6 mice at 0.22 mg kg-1 without showing apparent toxicity. Pretreating the melanoma TRCs with retinoic acid receptor (RAR) antagonists or with RAR siRNAs blocks or reduces the inhibitory effect of the mol., suggesting that the target of the mol. is RAR. WYC-209 induces TRC apoptosis and pretreating the TRCs with caspase 3 inhibitor or depleting caspase 3 with siRNAs substantially rescues growth of TRCs from WYC-209 inhibition, suggesting that WYC-209 induces TRCs apoptosis primarily via the caspase 3 pathway. Our findings demonstrate the promise of the new retinoid WYC-209 in treating malignant melanoma tumors with high efficacy and little toxicity.

Nature Communications published new progress about Antiproliferative agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Quality Control of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Watterson, Scott H.; Xiao, Zili; Dodd, Dharmpal S.; Tortolani, David R.; Vaccaro, Wayne; Potin, Dominique; Launay, Michele; Stetsko, Dawn K.; Skala, Stacey; Davis, Patric M.; Lee, Deborah; Yang, Xiaoxia; McIntyre, Kim W.; Balimane, Praveen; Patel, Karishma; Yang, Zheng; Marathe, Punit; Kadiyala, Pathanjali; Tebben, Andrew J.; Sheriff, Steven; Chang, Chieh Ying Y.; Ziemba, Theresa; Zhang, Huiping; Chen, Bang-Chi; DelMonte, Albert J.; Aranibar, Nelly; McKinnon, Murray; Barrish, Joel C.; Suchard, Suzanne J.; Murali Dhar, T. G. published the artcile< Small Molecule Antagonist of Leukocyte Function Associated Antigen-1 (LFA-1): Structure-Activity Relationships Leading to the Identification of 6-((5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic Acid (BMS-688521)>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is spirocyclic hydantoin derivative preparation LFA1 antagonist SAR.

Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18 or αLβ2, belongs to the β2 integrin subfamily and is constitutively expressed on all leukocytes. The major ligands of LFA-1 include three intercellular adhesion mols. 1, 2, and 3 (ICAM 1, 2, and 3). The interactions between LFA-1 and the ICAMs are critical for cell adhesion, and preclin. animal studies and clin. data from the humanized anti-LFA-1 antibody efalizumab have provided proof-of-concept for LFA-1 as an immunol. target. This article will detail the structure-activity relationships (SAR) leading to a novel second generation series of highly potent spirocyclic hydantoin antagonists of LFA-1. With significantly enhanced in vitro and ex vivo potency relative to our first clin. compound (1, I), as well as demonstrated in vivo activity and an acceptable pharmacokinetic and safety profile, 6-((5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro-[4.4]nonan-7-yl)nicotinic acid (2e) was selected to advance into clin. trials.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 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