Tag: M.W=150-200

Yang, Jiao; Chen, Kai; Zhang, Guo; Yang, Qiu-Yuan; Li, Yue-Shan; Huang, Shen-Zhen; Wang, Yan-Lin; Yang, Wei; Jiang, Xiao-Juan; Yan, Heng-Xiu; Zhu, Jing-Qiang; Xiang, Rong; Luo, You-Fu; Li, Wei-Min; Wei, Yu-Quan; Li, Lin-Li; Yang, Sheng-Yong published the artcile< Structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of inhibitors of RET and its drug resistance mutants>, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine, the main research area is phenyldihydro pyrimido oxazinamine derivative preparation RET inhibitor cancer; Drug resistance mutant; Medullary thyroid cancer; RET kinase; Structure-activity relationship.

The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of RET inhibitors. Among all the obtained kinase inhibitors, 1-(5-(tert-butyl)isoxazol-3-yl)-3-(4-((6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-yl)amino)phenyl)urea (17d) is a multi-kinase inhibitor and potently inhibits RET and its drug resistance mutants. It showed IC50 (half maximal inhibitory concentration) values of 0.010 μM, 0.015 μM, and 0.009 μM against RET-wild-type, RET-V804M, and RET-V804L, resp. 17d displayed significant anti-viability potencies against various RET-driving tumor cell lines. In a xenograft mouse model of NIH3T3-RET-C634Y, 17d exhibited potent in vivo anti-tumor activity, and no obvious toxicity was observed Mechanisms of action were also investigated by Western blot and immunohistochem. assays. Collectively, 17d could be a promising agent for the treatment of MTC, hence deserving a further investigation.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Dudfield, Philip J.; Le, Van-Duc; Lindell, Stephen D.; Rees, Charles W. published the artcile< Synthesis of C-ribosyl imidazo[2,1-f ][1,2,4]triazines as inhibitors of adenosine and AMP deaminases>, Name: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is imidazotriazine C nucleoside preparation adenosine deaminase inhibitor; C ribosyl imidazotriazine preparation adenosine deaminase inhibition.

A 3-β-D-ribofuranoside of the new imidazo[2,1-f][1,2,4]triazine is isomeric and isoelectronic with the nucleoside deaminoformycin which is a good inhibitor of adenosine deaminase (ADA) while its 5′-monophosphate is a good inhibitor of AMP deaminase (AMPDA). The 6-methylsulfanyl derivative is synthesized by condensation of the monocyclic 1,2,4-triazine with a bromo aldehyde, which is accompanied by cyclization to give the protected C-nucleoside; the 8-methylsulfanyl group is removed by replacement by hydrazine and oxidation The 1,2,4-triazine cyclizes similarly with chloroacetaldehyde or its di-Me acetal to give 6,8-bis(methylsulfanyl)imidazo[2,1-f ][1,2,4]triazine, which is converted into the parent heterocycle by two routes, into mono- and di-substituted derivatives of the new ring system. 6-Methylsulfanyl-3-β-D-ribofuranosylimidazo[2,1-f][1,2,4]triazine is an inhibitor of mammalian ADA (IC50 40 μM).

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry published new progress about C-nucleosides Role: BAC (Biological Activity or Effector, Except Adverse), BSU (Biological Study, Unclassified), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Name: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Karimian, Azam; Karimi, Zahra published the artcile< Synthesis of A Novel Heterocyclic System of 3,8-Disubstituted-5H-Pyrimido[5',4':5,6][1,4]Thiazino[3,2-e][1,2,4]Triazine>, COA of Formula: C3H2BrN3O2, the main research area is chloro amino pyrimidothiazinotriazine preparation secondary amine nucleophilic substitution; pyrimidothiazinotriazinediyl diamine preparation.

The new compounds 6-methyl-8-morpholino-2H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2e][1,2,4]triazin-3(5H)-one and 6-methyl-8-(piperidin-1-yl)-2H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazin-3(5H)-one were obtained from cyclocondensation of 6-bromo-1,2,4-triazine-3,5(2H,4H)-dione with appropriate 5-amino-6-methylpyrimidine-4-thiol in DMF and in the presence of potassium carbonate under reflux. Reaction of compounds with phosphorous oxychloride gave 4-(3-chloro-6-methyl-5H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazin-8-yl)morpholine and 3-chloro-6-methyl-8-(piperidin-1-yl)-5H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazine. Nucleophilic substitution of chlorine atom of compounds with typical secondary amines in DMF and K2CO3 produced the new derivatives of the 3,8-disubstituted-5H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazine ring systems . All the synthesized products were characterized and confirmed by their spectroscopic and microanal. data.

Polycyclic Aromatic Compounds published new progress about Fused heterocyclic compounds Role: SPN (Synthetic Preparation), PREP (Preparation). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, COA of Formula: C3H2BrN3O2.

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

Trenker, Stefan; Grunenberg, Lars; Banerjee, Tanmay; Savasci, Goekcen; Poller, Laura M.; Muggli, Katharina I. M.; Haase, Frederik; Ochsenfeld, Christian; Lotsch, Bettina V. published the artcile< A flavin-inspired covalent organic framework for photocatalytic alcohol oxidation>, Formula: C4H4N2O5, the main research area is diethyl bis formylphenyl alloxazine covalent organic framework preparation; aryl aldehyde preparation; alc oxidation catalyst FEAx COF.

Herein, the construction and use of a novel COF (FEAx-COF) photocatalyst, inspired by natural flavin cofactors was reported. The functionality of the alloxazine chromophore incorporated into the COF backbone was retained and study the effects of this heterogenization approach by comparison with similar mol. photocatalysts. The integration of alloxazine chromophores into the framework significantly extended the absorption spectrum into the visible range, allowing for photocatalytic oxidation of benzylic alcs. to aldehydes RC(O)H [R = 4-MeC6H4, 4-MeOC6H4, 4-t-BuC6H4, 2-thienyl] even with low-energy visible light. In addition, the activity of the heterogeneous COF photocatalyst was less dependent on the chosen solvent, making it more versatile compared to mol. alloxazines. Finally, the use of oxygen as the terminal oxidant renders FEAx-COF a promising and green heterogeneous photocatalyst.

Chemical Science published new progress about Alcohols Role: RCT (Reactant), RACT (Reactant or Reagent). 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Formula: C4H4N2O5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

John, Joyamma published the artcile< Evaluate the hypoglycemic effect of vinca rosea leaf extracts in alloxan induced diabetic rats>, HPLC of Formula: 2244-11-3, the main research area is allaxon induced diabetic Vinca rosea leaf extract hypoglycemic effect.

The present study was carried out to evaluate the antidiabetic activity of aqueous leaf extract of Vinca rosea. The aqueous extract at high dose (300mg/100g) body weight showed a significant hypoglycemic activity. Improvement in the body weight and water and food consumption is also observed after the treatment with herbal extract

International Journal of Science and Nature published new progress about Antidiabetic agents. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, HPLC of Formula: 2244-11-3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Prusoff, William H.; Gaito, Raymond A. published the artcile< Effect of 6-azathymine, an analog of thymine, on the urinary excretion of uracil>, Recommanded Product: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is NUCLEOSIDES AND NUCLEOTIDES/pharmacology; URACIL/urine.

Administration of 6-azathymine, an analog of thymine, to mice resulted in the excretion of large amounts of uracil in urine. 6-Azathymine and 5-bromo-6-azauracil, but not 6-azauracil, 5-ethyl-6-azauracil or 5-propyl-6azauracil inhibited the degradation of uracil by a particle-free fraction of rat liver. The enzyme degradation of uracil was inhibited by 6-azathymine to a greater extent than by thymine.

Biochimica et Biophysica Acta, Specialized Section on Nucleic Acids and Related Subjects published new progress about Enzymes Role: BIOL (Biological Study). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Recommanded Product: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ma, Bin; Metrick, Claire M.; Gu, Chungang; Hoemberger, Marc; Bajrami, Bekim; Bame, Eris; Huang, Jiansheng; Mingueneau, Michael; Murugan, Paramasivam; Santoro, Joseph C.; Tang, Hao; Wang, Ti; Hopkins, Brian T. published the artcile< Optimization of a novel piperazinone series as potent selective peripheral covalent BTK inhibitors>, HPLC of Formula: 5018-38-2, the main research area is piperazinone antiinflammatory BTK inhibitor autoimmune disease; B cell; BTK; Covalent inhibitor; Piperazinone; Selectivity; X-ray.

BTK is a tyrosine kinase playing an important role in B cell and myeloid cell functions through B cell receptor (BCR) signaling and Fc receptor (FcR) signaling. Selective inhibition of BTK has the potential to provide therapeutical benefits to patients suffering from autoimmune diseases. Here we report the design, optimization, and characterization of novel potent and highly selective covalent BTK inhibitors. Starting from a piperazinone hit derived from a selective reversible inhibitor, we solved the whole blood cellular potency issue by introducing an electrophilic warhead to reach Cys481. This design led to a covalent irreversible BTK inhibitor series with excellent kinase selectivity as well as good whole blood CD69 cellular potency. Optimization of metabolic stability led to representative compounds like 42, which demonstrated strong cellular target occupancy and inhibition of B-cell proliferation measured by proximal and distal functional activity.

Bioorganic & Medicinal Chemistry Letters published new progress about Autoimmune disease. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, HPLC of Formula: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kashiwagi, Michio published the artcile< Electron spin resonance of irradiated single crystals of alloxan monohydrate>, Related Products of 2244-11-3, the main research area is ALLOXAN IRRADIATED ESR; ESR IRRADIATED ALLOXAN.

X-ray irradiated single crystals of alloxan monohydrate were subjected to E.S.R. studies. Irradiation gives rise to radicals I by the abstraction of a hydroxyl group. The principal values of g-factors of the radicals are g1 = 2.0021, g2 = 2.0042, and g3 = 2.0060. The principal values of coupling constants with hydroxyl H are A1 = 3.1, A2 = -5.9, and A3 = -7.4 gauss. Spin ds. on the C and H atoms of •C-OH were evaluated from the 13C coupling constant Under the assumption of a planar structure for •C-OH and from consideration of the electronic structure of the radical, the directions of the principal values were concluded as follows. The directions of g1 and A2 are perpendicular to the radical plane, while that of g3 bisects the exterior angle of •COH. The direction of A1 is parallel to the OH bond.

Nippon Kagaku Zasshi published new progress about ESR (electron spin resonance). 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Related Products of 2244-11-3.

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