Category: 799557-87-2

Daniel, Matthieu published the artcileIntramolecular Metal-Free N-N Bond Formation with Heteroaromatic Amines: Mild Access to Fused-Triazapentalene Derivatives, Application of 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is triazapentalene preparation; heteroaromatic amine intramol cyclization bond formation; N−N bond formation; heteroaromatic amines; hypervalent compounds; iodine; triazapentalene derivatives.

Formation of N-N bonds may offer an original approach to various nitrogen-containing heterocycles I (R = CH, N; R1 = CH, N, C-CF3, C-OCH3; R2 = CH, N, C-CF3, C-Br, C-CN; R3 = CH, N, C-CF3; R4 = H, CH3; R5 = H, OCH3, CH3, CF3, Br; R6 = H, CH3) with numerous applications. For this purpose, it is found that readily available heteroaromatic amines II are appropriate substrates for providing an efficient and innovative approach for the formation of N-N bonds in the presence of iodine (III) reagent in very mild conditions. This method makes it possible to synthesize nitrogen rich triazapentalene derivatives exhibiting fluorescent properties, inaccessible with existing approaches.

Chemistry – A European Journal published new progress about Absorption. 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

Chen, Huifen published the artcileDiscovery of a Potent (4R,5S)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling, Recommanded Product: 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is preparation fluoro methylproline sulfonamide derivative TRPA1 inhibitor analgesic.

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in sensory neurons where it functions as an irritant sensor for a plethora of electrophilic compounds and is implicated in pain, itch, and respiratory disease. To study its function in various disease contexts, we sought to identify novel, potent, and selective small-mol. TRPA1 antagonists. Herein we describe the evolution of an N-isopropylglycine sulfonamide lead (1) to a novel and potent (4R,5S)-4-fluoro-5-methylproline sulfonamide series of inhibitors. Mol. modeling was utilized to derive low-energy three-dimensional conformations to guide ligand design. This effort led to compound 20, which possessed a balanced combination of potency and metabolic stability but poor solubility that ultimately limited in vivo exposure. To improve solubility and in vivo exposure, we developed methylene phosphate prodrug 22, which demonstrated superior oral exposure and robust in vivo target engagement in a rat model of AITC-induced pain.

Journal of Medicinal Chemistry published new progress about Analgesics. 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

Tsuno, Naoki published the artcilePharmacological evaluation of novel (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives as TRPV4 antagonists for the treatment of pain, Quality Control of 799557-87-2, 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. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Quality Control of 799557-87-2.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Thompson, Andrew M. published the artcileRepositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure-Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis, Quality Control of 799557-87-2, the main research area is dihydroimidazooxazole antitubercular leishmanicide leishmaniasis tuberculosis.

6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives were initially studied for tuberculosis within a backup program for the clin. trial agent pretomanid (PA-824). Phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of DNDI-VL-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (VL). Addnl. work was then conducted to delineate its essential structural features, aiming to improve solubility and safety without compromising activity against VL. While the 4-nitroimidazole portion was specifically required, several modifications to the aryloxy side chain were well-tolerated e.g., exchange of the linking oxygen for nitrogen (or piperazine), biaryl extension, and replacement of Ph rings by pyridine. Several less lipophilic analogs displayed improved aqueous solubility, particularly at low pH, although stability toward liver microsomes was highly variable. Upon evaluation in a mouse model of acute Leishmania donovani infection,phenylpyridine derivative I stood out, providing efficacy surpassing that of the original preclin. lead.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Quality Control of 799557-87-2.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Lucas-Hourani, Marianne published the artcileOriginal 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH), Name: 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is alkoxypyrazolylazine preparation inhibitor human dihydroorotate dehydrogenase SAR.

Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogs. As in our previous report, the structure-activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biol. evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine (I). Inhibition of DHODH by this compoundI was confirmed in an array of in vitro assays, including enzymic tests and cell-based assays for viral replication and cellular growth. I was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Name: 2-Chloro-5-(trifluoromethyl)pyrazine.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Thompson, Andrew M. published the artcileHeteroaryl ether analogues of an antileishmanial 7-substituted 2-nitroimidazooxazine lead afford attenuated hERG risk: In vitro and in vivo appraisal, COA of Formula: C5H2ClF3N2, the main research area is nitroimidazo oxazine heteroaryl ether analog preparation antileishmanial; Chagas disease; Leishmaniasis; Pharmacokinetics; Pretomanid; hERG inhibition; in vivo efficacy.

Previous investigation of the potent antileishmanial properties of antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines with biaryl side chains led to our development of a new clin. candidate for visceral leishmaniasis (DNDI-0690). Within a collaborative backup program, a racemic monoaryl lead (3) possessing comparable activity in mice but a greater hERG liability formed the starting point for our pursuit of efficacious second generation analogs having good solubility and safety. Asym. synthesis and appraisal of its enantiomers first established that chiral preferences for in vivo efficacy were species dependent and that neither form afforded a reduced hERG risk. However, in line with our findings in a structurally related series, less lipophilic heteroaryl ethers provided significant solubility enhancements (up to 16-fold) and concomitantly attenuated hERG inhibition. One promising pyridine derivative (49) displayed 100% oral bioavailability in mice and delivered a 96% parasite burden reduction when dosed at 50 mg/kg in a Leishmania donovani mouse model of visceral leishmaniasis.

European Journal of Medicinal Chemistry published new progress about Drug bioavailability. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, COA of Formula: C5H2ClF3N2.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Martin, Matthew W. published the artcileDiscovery of novel N-hydroxy-2-arylisoindoline-4-carboxamides as potent and selective inhibitors of HDAC11, Synthetic Route of 799557-87-2, the main research area is hydroxy arylisoindoline carboxamide derivative HDAC11 inhibitor antitumor antiinflammatory; HDAC11; HDACs; Hydroxamic acid; Inflammation; Isoindoline; Oncology.

N-Hydroxy-2-arylisoindoline-4-carboxamides are potent and selective inhibitors of HDAC11. The discovery, synthesis, and structure activity relationships of this novel series of inhibitors are reported. An advanced analog (FT895) displays promising cellular activity and pharmacokinetic properties that make it a useful tool to study the biol. of HDAC11 and its potential use as a therapeutic target for oncol. and inflammation indications.

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

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

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

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