Tag: M.W=150-200

Jones, James Holden published the artcilePyrazine diuretics. IV. N-Amidino-3-amino-6-substituted pyrazinecarboxamides, Related Products of pyrazines, the main research area is PYRAZINECARBOXAMIDES; DIURETICS; SALURETICS.

cf. CA 67: 100105q. The synthesis of a series of N-amidino-3-amino-6-substituted pyrazinecarboxamides (I) (R = MeS, MeSO2, PhCH2S, and Me2N) is described. Since more direct synthetic routes were unsuccessful, the intermediate 3-amino-6-substituted pyrazinecarboxylic acids were synthesized by nucleophilic displacement of the Cl from 6-chloro-4(3H)-pteridinones or their 3-methyl derivatives, followed by alk. hydrolysis. These were cyclized to the 2-methyl-6-substituted 4H-pyrazino[2,3-d][1,3]oxazin-4-ones, which upon reaction with a guanidine followed by hydrolysis, afforded the desired compounds When the N-amidino-3-amino-6-substituted pyrazinecarboxamides were assayed for saluretic and diuretic activity in normal rats, the 6-methylthio and the 6-benzylthio derivatives proved to be the most potent, while in the corresponding 3-acetamido series, the outstanding members were the 6-methylthio and the 6-methoxy derivatives

Journal of Medicinal Chemistry published new progress about Diuretics. 1125-56-0 belongs to class pyrazines, name is 3-Amino-6-chloropyrazine-2-carboxamide, and the molecular formula is C5H5ClN4O, Related Products of pyrazines.

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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

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

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

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

Li, Jian-Yuan published the artcilePalladium-Catalyzed Hydroxycarbonylation of (Hetero)aryl Halides for DNA-Encoded Chemical Library Synthesis, Application In Synthesis of 69214-34-2, the main research area is palladium catalyzed hydroxycarbonylation heteroaryl halide DNA encoded library synthesis.

A strategy for DNA-compatible, palladium-catalyzed hydroxycarbonylation of (hetero)aryl halides on DNA-chem. conjugates has been developed. This method generally provided the corresponding carboxylic acids in moderate to very good conversions for (hetero)aryl iodides and bromides, and in poor to moderate conversions for (hetero)aryl chlorides. These conditions were further validated by application within a DNA-encoded chem. library synthesis and subsequent discovery of enriched features from the library in selection experiments against two protein targets.

Bioconjugate Chemistry published new progress about Carbonylation. 69214-34-2 belongs to class pyrazines, name is 8-Bromoimidazo[1,2-a]pyrazine, and the molecular formula is C6H4BrN3, Application In Synthesis of 69214-34-2.

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

Lumma, William C. Jr. published the artcilePiperazinylimidazo[1,2-a]pyrazines with selective affinity for in vitro α-adrenergic receptor subtypes, Name: 8-Bromoimidazo[1,2-a]pyrazine, the main research area is piperazinylimidazopyrazine preparation alpha adrenergic agonist; potential energy piperazinylimidazopyrazine; conformation piperazinylimidazopyrazine; NMR piperazinylimidazopyrazine; structure activity piperazinylimidazopyrazine.

The title compounds I (R = H, etc.; R1 = H, Cl, Me, etc.; R2 = H, piperazinyl, etc.; R3 = H, Cl, Ph, piperazinyl; R4 = H, piperazino or methylpiperazino) were prepared and evaluated in vitro for their affinity for α1- and α2-adrenergic receptors. 8-(1-piperazinyl)imidazo[1,2-a]pyrazine (II) [76537-53-6] was ∼70 times more selective than mianserin for the α2-receptor. Computer-assisted mol. modeling techniques were used to describe possible preferred conformations for receptor binding. Regioselective syntheses of the heterocyclic ring system are given. Literature NMR assignments for the imidazo[1,2-a]pyrazine ring system were made. Conformational energies for II and its 5-position isomer in relation to the semirigid mianserin were estimated Structure-activity relations are discussed.

Journal of Medicinal Chemistry published new progress about Molecular mechanics. 69214-34-2 belongs to class pyrazines, name is 8-Bromoimidazo[1,2-a]pyrazine, and the molecular formula is C6H4BrN3, Name: 8-Bromoimidazo[1,2-a]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