Tag: M.W=150-200

Lin, Songnian published the artcileNovel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas as potent inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2), Product Details of C5H5ClN4O, the main research area is aminopyrazine amine isothiocyanate condensation; aminopyrazinylmethyl thiourea preparation antiinflammatory antiarthritis; protein kinase 2 inhibition structure activity.

Novel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas, i.e. I, are described as inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). These compounds demonstrate potent in vitro activity against the enzyme with IC50 values as low as 15 nM, and suppress expression of TNFα in THP-1 cells and in vivo in an acute inflammation model in mice. The synthesis, structure-activity relationship (SAR), and biol. evaluation of these compounds are discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about Anti-inflammatory agents. 1125-56-0 belongs to class pyrazines, name is 3-Amino-6-chloropyrazine-2-carboxamide, and the molecular formula is C5H5ClN4O, Product Details of C5H5ClN4O.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Long, Madeline F. published the artcileDiscovery of a novel 2,4-dimethylquinoline-6-carboxamide M4 positive allosteric modulator (PAM) chemotype via scaffold hopping, Safety of 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is dimethylquinoline carboxamide derivative preparation muscarinic M4 receptor CNS; M(4); Muscarinic acetylcholine receptor; Positive allosteric modulator (PAM); Structure-Activity Relationship (SAR).

This Letter details our efforts to replace the 3-amino moiety, an essential pharmacophore for M4 PAM activity in most M4 PAMs to date, within the thieno[2,3-b]pyridine core, as the β-amino carboxamide motif has been shown to engender poor solubility, varying degrees of P-gp efflux and represents a structural alert. A scaffold hopping exercise identified a novel 2,4-dimethylquinoline carboxamide core that provided M4 PAM activity and good CNS penetration without an amino moiety. In addition, MacMillan photoredox catalysis chem. was essential for construction of the 2,4-dimethylquinoline core.

Bioorganic & Medicinal Chemistry Letters published new progress about Central nervous system agents. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Safety of 2-Chloro-5-(trifluoromethyl)pyrazine.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Son, Se In published the artcileActivity-guided design of HDAC11-specific inhibitors, Application of 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is HDAC11 inhibitor histone dacetylase.

Mammalian histone deacetylases (HDACs) are a class of enzymes that play important roles in biol. pathways. Existing HDAC inhibitors target multiple HDACs without much selectivity. Inhibitors that target one particular HDAC will be useful for investigating the biol. functions of HDACs and for developing better therapeutics. Here, we report the development of HDAC11-specific inhibitors using an activity-guided rational design approach. The enzymic activity and biol. function of HDAC11 have been little known, but recent reports suggest that it has efficient defatty-acylation activity and that inhibiting it could be useful for treating a variety of human diseases, including viral infection, multiple sclerosis, and metabolic diseases. Our best inhibitor, SIS17(I), is active in cells and inhibited the demyristoylation of a known HDAC11 substrate, serine hydroxymethyl transferase 2, without inhibiting other HDACs. The activity-guided design may also be useful for the development of isoform-specific inhibitors for other classes of enzymes.

ACS Chemical Biology published new progress about Histone deacetylase inhibitors. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Application of 2-Chloro-5-(trifluoromethyl)pyrazine.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Preville, Cathy published the artcileSubstituted Azabicyclo[2.2.1]heptanes as Selective Orexin-1 Antagonists: Discovery of JNJ-54717793, Recommanded Product: 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is orexin OX1 OX2 SORA1 neuropeptides bioavailable brain OX1R antagonists.

The orexin system consists of two neuropeptides (orexin-A and orexin-B) that exert their mode of action on two receptors (orexin-1 and orexin-2). While the role of the orexin-2 receptor is established as an important modulator of sleep wake states, the role of the orexin-1 receptor is believed to play a role in addiction, panic, or anxiety. In this manuscript, we describe the optimization of a nonselective substituted azabicyclo[2.2.1]heptane dual orexin receptor antagonist (DORA) into orally bioavailable, brain penetrating, selective orexin-1 receptor (OX1R) antagonists. This resulted in the discovery of our first candidate for clin. development, JNJ-54717793.

ACS Medicinal Chemistry Letters published new progress about Bioavailability (orally bioavailable). 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Recommanded Product: 2-Chloro-5-(trifluoromethyl)pyrazine.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Guo, Qi published the artcileThe complete synthesis of favipiravir from 2-aminopyrazine, Related Products of pyrazines, the main research area is favipiravir preparation.

Favipiravir was synthesized from an inexpensive and com. available starting material, 2-aminopyrazine. The preferred route embedded within seven steps and was highlighted by the novel and efficient synthesis of 3,6-dichloropyrazine-2-carbonitrile. The intermediate 3,6-dichloropyrazine-2-carbonitrile was prepared in four successive steps which were regioselective chlorination of the pyrazine ring, bromination, Pd-catalyzed cyanation and Sandmeyer diazotization/chlorination. This protocol eliminated the hazardous POCl3 of previous synthetic methods and offered a better yield (48%) which was 1.3-fold higher than a recently published procedure. From intermediate 3,6-dichloropyrazine-2-carbonitrile, the subsequent nucleophilic fluorination, nitrile hydration and hydroxyl substitution efficiently afforded the target product. Another synthetic approach with the same starting material was also investigated to bypass the allergy-causing dichloro intermediate 3,6-dichloropyrazine-2-carbonitrile. The key step of monofluorination at the pyrazine C6 position of intermediate 6-chloro/bromo-3-aminopyrazine-2-carbonitriles and 6-chloro/bromo-3-hydroxylpyrazine-2-carbonitriles was not achieved.

Chemical Papers published new progress about. 356783-29-4 belongs to class pyrazines, name is 3,6-Difluoropyrazine-2-carboxamide, and the molecular formula is C5H3F2N3O, Related Products of pyrazines.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Liu, Feng-Liang published the artcileA practical and step-economic route to Favipiravir, Recommanded Product: 3,6-Difluoropyrazine-2-carboxamide, the main research area is favipiravir preparation.

A practical and step-economic route to Favipiravir, an antiviral drug, was developed. Favipiravir was synthesized in only six steps from 3-aminopyrazine-2-carboxylic acid with an overall yield of about 22.3%. Key intermediates Me 3-amino-6-bromopyrazine-2-carboxylate and 3,6-dichloropyrazine-2-carbonitrile were obtained in excellent purity via recrystallization from optimized solvents, which was beneficial to large-scale production In the key synthetic reaction, 3,6-dichloropyrazine-2-carbonitrile was reacted sequentially, in one pot, with KF and 30% H2O2 to give (after crystallization from 95% EtOH) favipiravir as colorless crystals, with a 60% yield for this final step of the synthesis.

Chemical Papers published new progress about. 356783-29-4 belongs to class pyrazines, name is 3,6-Difluoropyrazine-2-carboxamide, and the molecular formula is C5H3F2N3O, Recommanded Product: 3,6-Difluoropyrazine-2-carboxamide.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Patel, Meena V. published the artcileDiscovery of (R)-(3-fluoropyrrolidin-1-yl)(6-((5-(trifluoromethyl)pyridin-2-yl)oxy)quinolin-2-yl)methanone (ABBV-318) and analogs as small molecule Nav1.7/ Nav1.8 blockers for the treatment of pain, Application In Synthesis of 799557-87-2, the main research area is quinoline preparation sodium channel blocker SAR pharmacokinetic.

An effort to identify selective, CNS-penetrant Nav1.7 blockers with oral activity, improved selectivity, good drug-like properties, and safety led to the discovery of 2-substituted quinolines I [R = piperazine-1-carbonyl, cyclobutylcarbamoyl, 2-oxo-2-(1-piperidyl)ethoxy, etc.; R1 = 4-NCC6H4, 2-pyridyl, 5-(trifluoromethyl)-2-pyridyl, etc.] and quinolones II [R2 = 4-NCC6H4, 4-NCC6H4O; R3 = 1-piperidylmethyl, 1-piperidylmethyl] as potent small mol. Nav1.7 blockers. The design of these mols. focused on maintaining potency at Nav1.7, improving selectivity over the hERG channel, and overcoming phospholipidosis observed with the initial leads. The structure-activity relationship (SAR) studies leading to the discovery of compound I [R = (3R)-3-fluoropyrrolidine-1-carbonyl, R1 = 5-(trifluoromethyl)-2-pyridyl] were described herein. The compound I [R = (3R)-3-fluoropyrrolidine-1-carbonyl, R1 = 5-(trifluoromethyl)-2-pyridyl] displayed robust in vivo efficacy in both inflammatory and neuropathic rodent models of pain. The compound I [R = (3R)-3-fluoropyrrolidine-1-carbonyl, R1 = 5-(trifluoromethyl)-2-pyridyl] also inhibited Nav1.8, another sodium channel isoform that was an active target for the development of new pain treatments.

Bioorganic & Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Application In Synthesis of 799557-87-2.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem