Category: 89793-12-4

Choi, Chulho; Nuhant, Philippe; Mousseau, James J.; Yang, Xiaojing; Gerstenberger, Brian S.; Williams, Jessica M.; Wright, Stephen W. published the artcile< Synthesis of Chiral Azabicycles from Pyroglutaminols>, Formula: C7H7ClN2O2, the main research area is chiral azabicycle morpholine piperazine derivative preparation; stereocontrolled intramol SN2 cyclization pyroglutaminol.

The stereocontrolled synthesis of a range of substituted bicyclic morpholine and piperazine derivatives is reported from substituted pyroglutaminols via an intramol. SN2 cyclization as the key step. This enantiospecific approach toward chiral bicyclic morpholines and piperazines offers new opportunities to access these challenging ring systems, which are becoming increasingly common motifs in drug discovery.

Organic Letters published new progress about Cyclization, stereoselective. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Formula: C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhang, Xuqing; Zhu, Bin; Sun, Weimei; Wang, Mina; Albarazanji, Kamal; Ghosh, Brahma; Cummings, Maxwell; Lenhard, James; Leonard, James; Macielag, Mark; Lanter, James published the artcile< Discovery of a novel series of guanidinebenzoates as gut-restricted enteropeptidase and trypsin dual inhibitors for the treatment of metabolic syndrome>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is guanidinebenzoates gutrestricted enteropeptidase trypsin dual inhibitor treatment metabolic syndrome; Enteropeptidase inhibitor; Guanidinebenzoate; Gut-restriction; Trypsin inhibitor.

Novel series of guanidinebenzoate enteropeptidase and trypsin dual inhibitors has been discovered and SAR studies were conducted. Optimization was focused on improving properties for gut restriction, including increased aqueous solubility, lower cellular permeability, and reduced oral bioavailability. Lead compounds were identified with efficacy in a mouse fecal protein excretion study.

Bioorganic & Medicinal Chemistry Letters published new progress about Biological permeation. 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

Yokoo, Hidetomo; Shibata, Norihito; Naganuma, Miyako; Murakami, Yuki; Fujii, Kiyonaga; Ito, Takahito; Aritake, Kosuke; Naito, Mikihiko; Demizu, Yosuke published the artcile< Development of a Hematopoietic Prostaglandin D Synthase-Degradation Inducer>, Quality Control of 89793-12-4, the main research area is prostaglandin D2 ubiquitin proteasome system protein knockdown PROTACs.

Although hematopoietic prostaglandin D synthase (H-PGDS) is an attractive target for treatment of a variety of diseases, including allergic diseases and Duchenne muscular dystrophy, no H-PGDS inhibitors have yet been approved for treatment of these diseases. Therefore, the development of novel agents having other modes of action to modulate the activity of H-PGDS is required. In this study, a chimeric small mol. that degrades H-PGDS via the ubiquitin-proteasome system, PROTAC(H-PGDS)-1(I), was developed. PROTAC(H-PGDS)-1 is composed of two ligands, TFC-007 (that binds to H-PGDS) and pomalidomide (that binds to cereblon). PROTAC(H-PGDS)-1 showed potent activity in the degradation of H-PGDS protein via the ubiquitin-proteasome system and in the suppression of prostaglandin D2 (PGD2) production Notably, PROTAC(H-PGDS)-1 showed sustained suppression of PGD2 production after the drug removal, whereas PGD2 production recovered following removal of TFC-007. Thus, the H-PGDS degrader-PROTAC(H-PGDS)-1-is expected to be useful in biol. research and clin. therapies.

ACS Medicinal Chemistry Letters published new progress about Allergy. 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

Homma, Daiki; Taketani, Shuhei; Shirai, Takeshi; Caytan, Elsa; Roussel, Christian; Elguero, Jose; Alkorta, Ibon; Kitagawa, Osamu published the artcile< Rotational Behavior of N-(5-Substituted-pyrimidin-2-yl)anilines: Relayed Electronic Effect in Two N-Ar Bond Rotations>, Electric Literature of 89793-12-4, the main research area is rotational barrier Substituted pyrimidinyl anilines NMR DFT.

N-Methyl-2-methoxymethylanilines 1 bearing various 5-substituted-pyrimidin-2-yl groups were prepared, and their rotational behaviors were explored in detail. the rotational barriers around two N-Ar bonds increase in proportion to the electron-withdrawing ability of substituents X at the 5-position.

Journal of Organic Chemistry published new progress about Bond angle. 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; San Jose-Eneriz, Edurne; Agirre, Xabier; Sanchez-Arias, Juan Antonio; de Miguel, Irene; Ordonez, Raquel; Garate, Leire; Miranda, Estibaliz; Saez, Elena; Vilas-Zornoza, Amaia; Pineda-Lucena, Antonio; Estella, Ander; Zhang, Feifei; Wu, Wei; Xu, Musheng; Prosper, Felipe; Oyarzabal, Julen published the artcile< Design and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with In Vivo Efficacy in Multiple Myeloma>, Category: pyrimidines, the main research area is histone deacetylases DNA methyltransferase G9a inhibitors multiple myeloma antitumor.

Concomitant inhibition of key epigenetic pathways involved in silencing tumor suppressor genes has been recognized as a promising strategy for cancer therapy. Herein, we report a first-in-class series of quinoline-based analogs that simultaneously inhibit histone deacetylases (from a low nanomolar range) and DNA methyltransferase-1 (from a mid-nanomolar range, IC50 < 200 nM). Addnl., lysine methyltransferase G9a inhibitory activity is achieved (from a low nanomolar range) by introduction of a key lysine mimic group at the 7-position of the quinoline ring. The corresponding epigenetic functional cellular responses are observed: histone-3 acetylation, DNA hypomethylation, and decreased histone-3 methylation at lysine-9. These chem. probes, multi-target epigenetic inhibitors, were validated against the multiple myeloma cell line MM1.S, demonstrating promising in vitro activity of 12a (CM-444) with GI50 of 32 nM, an adequate therapeutic window (>1 log unit), and a suitable pharmacokinetic profile. In vivo, 12a achieved significant antitumor efficacy in a xenograft mouse model of human multiple myeloma.

Journal of Medicinal Chemistry published new progress about Acetylation (histone H3). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kandalkar, Sachin R.; Kaduskar, Rahul D.; Ramaiah, Parimi Atchuta; Barawkar, Dinesh A.; Bhuniya, Debnath; Deshpande, Anil M. published the artcile< Highly efficient one-pot amination of carboxylate-substituted nitrogen-containing heteroaryl chlorides via Staudinger reaction>, Related Products of 89793-12-4, the main research area is carboxylate substituted heteroaryl amine preparation; Staudinger reaction carboxylate substituted heteroaryl chloride.

An efficient one-pot method for the synthesis of tert-Bu 6-aminonicotinate I is described. The key transformation involves displacement of the chloro group in tert-Bu 6-chloronicotinate with azide followed by a Staudinger reaction. The scope of this methodol. is further extended for the synthesis of a series of carboxylate-substituted heteroaryl amines e. g., II. In particular, we synthesized tert-Bu carboxylate-substituted amino-pyridine, -pyridazine, and -pyrazine. In addition to one-pot conversion, short reaction time, simplicity of operation, ease of purification, and good yields are the key advantages of this methodol.

Tetrahedron Letters published new progress about Amination. 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

Liu, Chunjian; Lin, James; Langevine, Charles; Smith, Daniel; Li, Jianqing; Tokarski, John S.; Khan, Javed; Ruzanov, Max; Strnad, Joann; Zupa-Fernandez, Adriana; Cheng, Lihong; Gillooly, Kathleen M.; Shuster, David; Zhang, Yifan; Thankappan, Anil; McIntyre, Kim W.; Chaudhry, Charu; Elzinga, Paul A.; Chiney, Manoj; Chimalakonda, Anjaneya; Lombardo, Louis J.; Macor, John E.; Carter, Percy H.; Burke, James R.; Weinstein, David S. published the artcile< Discovery of BMS-986202: A Clinical Tyk2 Inhibitor that Binds to Tyk2 JH2>, Synthetic Route of 89793-12-4, the main research area is BMS986202 Tyk2 JH2 inhibitor antiinflammatory inflammation.

A search for structurally diversified Tyk2 JH2 ligands from 6 (BMS-986165), a pyridazine carboxamide-derived Tyk2 JH2 ligand as a clin. Tyk2 inhibitor currently in late development for the treatment of psoriasis, began with a survey of six-membered heteroaryl groups in place of the N-Me triazolyl moiety in 6. The x-ray co-crystal structure of an early lead (12) revealed a potential new binding pocket. Exploration of the new pocket resulted in two front-runners for a clin. candidate. The potential hydrogen bonding interaction with Thr599 in the pocket was achieved with a tertiary amide moiety, confirmed by the x-ray co-crystal structure of 29. When the diversity search was extended to nicotinamides, a single fluorine atom addition was found to significantly enhance the permeability, which directly led to the discovery of 7 (BMS-986202) as a clin. Tyk2 inhibitor that binds to Tyk2 JH2. The preclin. studies of 7, including efficacy studies in mouse models of IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus, will also be presented.

Journal of Medicinal Chemistry published new progress about Acanthosis. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Synthetic Route of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ibrahim, Hany S.; Abdelsalam, Mohamed; Zeyn, Yanira; Zessin, Matthes; Mustafa, Al-Hassan M.; Fischer, Marten A.; Zeyen, Patrik; Sun, Ping; Buelbuel, Emre F.; Vecchio, Anita; Erdmann, Frank; Schmidt, Matthias; Robaa, Dina; Barinka, Cyril; Romier, Christophe; Schutkowski, Mike; Kraemer, Oliver H.; Sippl, Wolfgang published the artcile< Synthesis, Molecular Docking and Biological Characterization of Pyrazine Linked 2-Aminobenzamides as New Class I Selective Histone Deacetylase (HDAC) Inhibitors with Anti-Leukemic Activity>, Electric Literature of 89793-12-4, the main research area is pyrazine linked aminobenzamide preparation SAR docking antileukemic HDAC inhibitor; 2-aminobenzamides; HDAC1; HDAC2; HDAC3; SAR studies; acute myeloid leukemia (AML); docking; histone deacetylases.

Synthesis of a novel series of class-I selective HDAC inhibitors (HDACi) containing a 2-aminobenzamide moiety as a zinc-binding group connected with a central (piperazin-1-yl)pyrazine or (piperazin-1-yl)pyrimidine moiety I [R1 = H, Me, CH2-2-pridinyl, etc.; R2 = H, F; R3 = H, F, Cl; X = CH, N; Y = CH, N], II [R4 = H, Me; R5 = H, F, 2-FC6H4, etc.; R6 = H, F, Cl, etc.] was reported. Some of the compounds were addnl. substituted with an aromatic capping group. Compounds I and II were tested in vitro against human HDAC1, 2, 3, and 8 enzymes and compared to reference class I HDACi (Entinostat (MS-275), Mocetinostat, CI994 and RGFP-966). The most promising compounds were found to be highly selective against HDAC1, 2 and 3 over the remaining HDAC subtypes from other classes. Mol. docking studies and MD simulations were performed to rationalize the in vitro data and to deduce a complete structure activity relationship (SAR) anal. of this novel series of class-I HDACi. The most potent compounds, including I [R1 = CH2-3-indolyl, etc.; R2 = H; R3 = H; X = CH; Y = N], which blocked HDAC1, HDAC2, and HDAC3, as well as the selective HDAC1/HDAC2 inhibitors II [R4 = H, (CH2)2-1-methyl-indol-3-yl; R5 = 2-thienyl; R6 = H] were selected for further cellular testing against human acute myeloid leukemia (AML) and erythroleukemic cancer (HEL) cells, took into consideration their low toxicity against human embryonic HEK293 cells. Compound I [R1 = CH2-3-indolyl, etc.; R2 = H; R3 = H; X = CH; Y = N] was superior to the clin. tested class-I HDACi Entinostat (MS-275). Thus, I [R1 = CH2-3-indolyl, etc.; R2 = H; R3 = H; X = CH; Y = N] was a new and specific HDACi with the potential to eliminate blood cancer cells of various origins.

International Journal of Molecular Sciences published new progress about Acids 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, Electric Literature of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Li, Ruoxi; Ling, Dazheng; Tang, Tongke; Huang, Zhenghui; Wang, Manjiong; Mao, Fei; Zhu, Jin; Jiang, Lubin; Li, Jian; Li, Xiaokang published the artcile< Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is pyrimidine containing spirocyclic linker preparation cytotoxicity antimalarial human SAR.

Herein, 30 novel spirocyclic linker derivatives I [R = Ph, N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl, etc.] were designed and synthesized based on Quisinostat as lead compound and then evaluated for their antimalarial activities and cytotoxicity. Among them, compounds I [R = N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl] could effectively eliminate wild-type and multi-drug resistant P. falciparum parasites, and display weakened cytotoxicity and good metabolic stability. Western blot assay demonstrated that they could inhibit Plasmodium falciparum histone deacetylase (PfHDAC) activity like Quisinostat. In addition, both I [R = N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl] showed certain antimalarial efficacy in rodent malaria model, and the animal toxicity of I [R = N-Me-indolin-2-yl] was significantly improved compared with Quisinostat. Overall, I [R = N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl] were structurally novel PfHDAC inhibitors and provided prospective prototype for further antimalarial drug research.

Chinese Chemical Letters published new progress about Antimalarials. 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

Ohta, Kiminori; Kawachi, Emiko; Inoue, Noriko; Fukasawa, Hiroshi; Hashimoto, Yuichi; Itai, Akiko; Kagechika, Hiroyuki published the artcile< Retinoidal pyrimidinecarboxylic acids. Unexpected diaza-substituent effects in retinobenzoic acids>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is retinoid heterocyclic analog preparation retinoidal activity; structure activity relationship heterocyclic retinoid analog; antileukemia heterocyclic retinoid analog preparation.

Several pyridine- and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine-3-carboxylic acid and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]pyridine-3-carboxylic acid are more potent than the corresponding benzoic acid-type retinoids, Am80 and Am580, the replacement of the benzene ring of Am580, Am555, or Am55 with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]pyrimidine-5-carboxylic acid (PA013) is most active retinoid synergist in HL-60 assay.

Chemical & Pharmaceutical Bulletin published new progress about Antitumor agents. 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