Month: October 2022

On February 5, 1998, Murugesan, Natesan; Barrish, Joel C.; Stein, Philip D. published a patent.Computed Properties of 160377-42-4 The title of the patent was Preparation of heterocyclyl-substituted biphenylsulfonamide as endothelin antagonists. And the patent contained the following:

Compounds of formula (I; R1 and R2 are directly bonded to a ring carbon and are each independently hydrogen, alkyl or alkoxy, hydroxyl, halo, or amino; one of X and Y is N and the other is O: R3 and R4 are each directly bonded to a ring carbon and are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted or R3 and R4 together may also be alkylene or alkenylene, either of which may be substituted, completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; R11 – R14 are each independently are hydrogen alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl, aralkoxy, or heterocyclyl, any of which may be substituted, halo, OH, cyano, NO2, CHO, CO2H, etc.; J, K, L, T, and U are each independently N or C, provided that at least one is N, and at most two are N; and when only one of J, K, L, T, and U is N, the N may be substituted with O- so that N-oxide is formed), which inhibit the activity of endothelin (no data), are prepared Also claimed is a method for treating endothelin-related disorders in a mammal, such as (1) hypertension, (2) pulmonary hypertension, (3) renal, glomerular, or mesangial cell disorders, (4) endotoxemia, (5) ischemia, (6) atherosclerosis, (7) restenosis, (8) subarachnoid hemorrhage, (9) prostatic hypertrophy, and (10) congestive heart failure, and a method for inhibiting cell growth. Said compound I is used in combination with at least one angiotensin II receptor antagonist, renin inhibitor, angiotensin converting enzyme (ACE) inhibitor, or a dual neutral endopeptidase-ACE inhibitor for treating the endothelin-related disorder. A pharmaceutical composition for the treating the endothelin-related disorders comprises said compound optionally in combination with at least one angiotensin II receptor antagonist, renin inhibitor, angiotensin converting enzyme (ACE) inhibitor, or a dual neutral endopeptidase-ACE inhibitor. Thus, 2-(4-bromophenyl)pyrimidine is coupled with 2-borono-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]benzenesulfonamide in the presence of (Ph3P)4Pd in a mixture of toluene, 2 M aqueous Na2CO3, and 95% ethanol under reflux for 1.5 h to give the title compound, N-isoxazolylpyrimidinylbiphenylsulfonamide (II). The experimental process involved the reaction of 5-(4-Bromophenyl)pyrimidine(cas: 160377-42-4).Computed Properties of 160377-42-4

The Article related to angiotensin ii receptor antagonists, antiatherosclerotics, antihypertensives, benign prostatic hyperplasia, cell (renal, glomerular, or mesangial cell disorders), endotoxemia, growth inhibitors, animal role: spn (synthetic preparation), thu (therapeutic use), prep (preparation), biol (biological study), uses (uses), heart failure, ischemia, mesangium (disorders), subarachnoid hemorrhage and other aspects.Computed Properties of 160377-42-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Brawn, Ryan A.; Cook, Andrew; Omoto, Kiyoyuki; Ke, Jiyuan; Karr, Craig; Colombo, Federico; Virrankoski, Milena; Prajapati, Sudeep; Reynolds, Dominic; Bolduc, David M.; Nguyen, Tuong-Vi; Gee, Patricia; Borrelli, Deanna; Caleb, Benjamin; Yao, Shihua; Irwin, Sean; Larsen, Nicholas A.; Selvaraj, Anand; Zhao, Xuesong; Ioannidis, Stephanos published their research in ACS Medicinal Chemistry Letters in 2021. The article was titled 《Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3》.Product Details of 3764-01-0 The article contains the following contents:

Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clin. trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR anal. and structure-based drug design led to analogs with improved potency and drug metabolism and pharmacokinetics properties. The results came from multiple reactions, including the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Product Details of 3764-01-0)

2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Product Details of 3764-01-0

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Meng, Fan-Jie; Shao, Bing-Ru; Velopolcek, Maria K.; Guo, Xuan; Feng, Guang-Shou; Shi, Lei published their research in Organic & Biomolecular Chemistry in 2021. The article was titled 《Redox deracemization of phosphonate-substituted dihydropyrimidines》.Name: 2,4-Dichloropyrimidine The article contains the following contents:

An efficient redox deracemization of the phosphonic ester substituted 3,4-dihydropyrimidin-2-one (DHPM) derivatives I (R = Ph, Me, naphth-2-yl, etc.; R1 = H, Me, Ph) is described. The one-pot deracemization strategy consisted of the oxidization to destroy the stereocenter center and the following asym. transfer hydrogenation to regenerate the chiral carbon center with the vicinal phosphonic ester group, providing a series of optically active phosphonate substituted DHPMs with up to 96% ee. The results came from multiple reactions, including the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Name: 2,4-Dichloropyrimidine)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Name: 2,4-Dichloropyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Davis, Ryan R.; Li, Baoli; Yun, Sang Y.; Chan, Alice; Nareddy, Pradeep; Gunawan, Steven; Ayaz, Muhammad; Lawrence, Harshani R.; Reuther, Gary W.; Lawrence, Nicholas J.; Schonbrunn, Ernst published an article in 2021. The article was titled 《Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof》, and you may find the article in Journal of Medicinal Chemistry.Synthetic Route of C6H3Cl2N3 The information in the text is summarized as follows:

The discovery that aberrant activity of Janus kinase 2 (JAK2) is a driver of myeloproliferative neoplasms (MPNs) has led to significant efforts to develop small mol. inhibitors for this patient population. Ruxolitinib and fedratinib have been approved for use in MPN patients, while baricitinib, an achiral analog of ruxolitinib, has been approved for rheumatoid arthritis. However, structural information on the interaction of these therapeutics with JAK2 remains unknown. Here, we describe a new methodol. for the large-scale production of JAK2 from mammalian cells, which enabled us to determine the first crystal structures of JAK2 bound to these drugs and derivatives thereof. Along with biochem. and cellular data, the results provide a comprehensive view of the shape complementarity required for chiral and achiral inhibitors to achieve highest activity, which may facilitate the development of more effective JAK2 inhibitors as therapeutics. The results came from multiple reactions, including the reaction of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Synthetic Route of C6H3Cl2N3)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Synthetic Route of C6H3Cl2N3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia