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COA of Formula: C8H8N4. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Novel pyrazolopyrimidines as highly potent B-Raf inhibitors. Author is Di Grandi, Martin J.; Berger, Dan M.; Hopper, Darrin W.; Zhang, Chunchun; Dutia, Minu; Dunnick, Alejandro L.; Torres, Nancy; Levin, Jeremy I.; Diamantidis, George; Zapf, Christoph W.; Bloom, Jonathan D.; Hu, YongBo; Powell, Dennis; Wojciechowicz, Donald; Collins, Karen; Frommer, Eileen.

A novel series of pyrazolo[1,5-a]pyrimidines bearing a 3-hydroxyphenyl group at C(3) and substituted tropanes at C(7) have been identified as potent B-Raf inhibitors. Exploration of alternative functional groups as a replacement for the C(3) phenol demonstrated indazole to be an effective isostere. Several compounds possessing substituted indazole residues, such as 4e, 4p, and 4r, potently inhibited cell proliferation at submicromolar concentrations in the A375 and WM266 cell lines, and the latter two compounds also exhibited good therapeutic indexes in cells.

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Name: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine. The fused heterocycle is formed by combining a benzene ring with a single heterocycle, or two or more single heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Synthesis and study of the anti-inflammatory properties of some pyrazolo[1,5-a]pyrimidine derivatives. Author is Bruni, Fabrizio; Costanzo, Annarella; Selleri, Silvia; Guerrini, Gabriella; Fantozzi, Roberto; Pirisino, Renato; Brunelleschi, Sandra.

A series of pyrazolo[1,5-a]pyrimidin-7-ones I (R = bromophenyl, methoxyphenyl, thienyl, pyridyl, cyclohexyl, Bu, iso-Pr, nitrophenyl, aminophenyl hydrochloride, and ethylpyridinium iodide) were synthesized to evaluate in vivo and in vitro effects induced by structural modifications at the 2 position of 4,7-dihydro-4-ethyl-2-phenylpyrazolo[1,5-a]pyrimidin-7-one (FPP028). This substance, which has been previously studied, is a weak inhibitor of prostaglandin biosynthesis and a nonacid analgesic and anti-inflammatory agent devoid of ulcerogenic properties. To gain more insight into the mechanism of action of this class of compounds, several in vivo tests were carried out, such as carrageenan-induced rat paw edema and pleurisy. In vitro tests include some studies of leukocyte functions, such as superoxide production and myeloperoxidase release. In vitro effects on arachidonic acid-, ADP, and platelet-activating factor-induced platelet aggregation were also studied. Different anti-inflammatory activities were observed, depending on the nature of substituents at the 2 position; these differences are probably linked to the capacity of these compounds to inhibit leukotrienes and/or prostaglandin biosynthesis with different selectivity. 4,7-Dihydro-4-ethyl-2(2-thienyl)pyrazolo[1,5-a]pyrimidin-7-one proved to be the most interesting compound of the novel synthesized series, showing powerful pharmacol. activity in vivo as well as in vitro, together with very weak acute toxicity.

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Epoxy compounds usually have stronger nucleophilic ability, because the alkyl group on the oxygen atom makes the bond angle smaller, which makes the lone pair of electrons react more dissimilarly with the electron-deficient system. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201.Reference of 3-(Pyridin-4-yl)-1H-pyrazol-5-amine.

Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. The authors describe the discovery of APY0201, a unique small mol. IL-12/23 production inhibitor, from activated macrophages and monocytes, and demonstrate ameliorated inflammation in an exptl. model of colitis. Through a chem. proteomics approach using a highly sensitive direct nanoflow LC-MS/MS system and bait compounds equipped with the FLAG epitope associated regulator of PIKfyve (ArPIKfyve) was detected. Further study identified its associated protein phosphoinositide kinase, FYVE finger-containing (PIKfyve), as the target protein of APY0201, which was characterized as a potent, highly selective, ATP-competitive PIKfyve inhibitor that interrupts the conversion of phosphatidylinositol 3-phosphate (PtdIns3P) to PtdIns(3,5)P2. These results elucidate the function of PIKfyve kinase in the IL-12/23 production pathway and in IL-12/23-driven inflammatory disease pathologies to provide a compelling rationale for targeting PIKfyve kinase in inflammatory and autoimmune diseases.

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Category: pyrazines. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and characterization of the potent, selective, and orally efficacious agonist 5-(4-Acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-Methoxyphenyl)-1H-pyrazol-3-yl] amide (SEN15924, WAY-361789). Author is Zanaletti, Riccardo; Bettinetti, Laura; Castaldo, Cristiana; Cocconcelli, Giuseppe; Comery, Thomas; Dunlop, John; Gaviraghi, Giovanni; Ghiron, Chiara; Haydar, Simon N.; Jow, Flora; Maccari, Laura; Micco, Iolanda; Nencini, Arianna; Scali, Carla; Turlizzi, Elisa; Valacchi, Michela.

Alpha-7 nicotinic acetylcholine receptors (α7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, α7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer’s disease (AD) and schizophrenia. A medicinal chem. effort, around our previously reported chem. series, permitted the discovery of a novel class of α7 nAChR agonists with improved selectivity, in particular against the α3 receptor subtype and better ADME profile. The exploration of this series led to the identification of 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide [(I), SEN15924, WAY-361789], a novel, full agonist of the α7 nAChR that was evaluated in vitro and in vivo. Compound I proved to be potent and selective, and it demonstrated a fair pharmacokinetic profile accompanied by efficacy in rodent behavioral cognition models (novel object recognition and auditory sensory gating).

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Category: pyrazines. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Hit to lead optimization of pyrazolo[1,5-a]pyrimidines as B-Raf kinase inhibitors. Author is Gopalsamy, Ariamala; Ciszewski, Greg; Shi, Mengxiao; Berger, Dan; Hu, Yongbo; Lee, Frederick; Feldberg, Larry; Frommer, Eileen; Kim, Steven; Collins, Karen; Wojciechowicz, Donald; Mallon, Robert.

Our continued effort towards optimization of the pyrazolo[1,5-a]pyrimidine scaffold as B-Raf kinase inhibitors is described. Structure guided design was utilized to introduce kinase hinge region interacting groups in the 2-position of the scaffold. This strategy led to the identification of lead compound 9 with enhanced enzyme and cellular potency, while maintaining good selectivity over a number of kinases.

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A novel series of pyrazolo[1,5-a]pyrimidines bearing a 3-hydroxyphenyl group at C(3) and substituted tropanes at C(7) have been identified as potent B-Raf inhibitors. Exploration of alternative functional groups as a replacement for the C(3) phenol demonstrated indazole to be an effective isostere. Several compounds possessing substituted indazole residues, such as 4e, 4p, and 4r, potently inhibited cell proliferation at submicromolar concentrations in the A375 and WM266 cell lines, and the latter two compounds also exhibited good therapeutic indexes in cells.

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Product Details of 91912-53-7. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201. Author is Hayakawa, Nobuhiko; Noguchi, Masatsugu; Takeshita, Sen; Eviryanti, Agung; Seki, Yukie; Nishio, Hikaru; Yokoyama, Ryohei; Noguchi, Misato; Shuto, Manami; Shima, Yoichiro; Kuribayashi, Kanna; Kageyama, Shunsuke; Eda, Hiroyuki; Suzuki, Manabu; Hatta, Tomohisa; Iemura, Shun-ichiro; Natsume, Tohru; Tanabe, Itsuya; Nakagawa, Ryusuke; Shiozaki, Makoto; Sakurai, Kuniya; Shoji, Masataka; Andou, Ayatoshi; Yamamoto, Takashi.

Interleukin-12 (IL-12) and IL-23 are proinflammatory cytokines and therapeutic targets for inflammatory and autoimmune diseases, including inflammatory bowel diseases, psoriasis, rheumatoid arthritis, and multiple sclerosis. The authors describe the discovery of APY0201, a unique small mol. IL-12/23 production inhibitor, from activated macrophages and monocytes, and demonstrate ameliorated inflammation in an exptl. model of colitis. Through a chem. proteomics approach using a highly sensitive direct nanoflow LC-MS/MS system and bait compounds equipped with the FLAG epitope associated regulator of PIKfyve (ArPIKfyve) was detected. Further study identified its associated protein phosphoinositide kinase, FYVE finger-containing (PIKfyve), as the target protein of APY0201, which was characterized as a potent, highly selective, ATP-competitive PIKfyve inhibitor that interrupts the conversion of phosphatidylinositol 3-phosphate (PtdIns3P) to PtdIns(3,5)P2. These results elucidate the function of PIKfyve kinase in the IL-12/23 production pathway and in IL-12/23-driven inflammatory disease pathologies to provide a compelling rationale for targeting PIKfyve kinase in inflammatory and autoimmune diseases.

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COA of Formula: C8H8N4. So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Aminopyrazole-Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies.

Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid I, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P 450 or hERG liability. Compound I, together with its orally bioavailable Et ester prodrug II, were found to be suitable for in vivo proof-of-concept studies. Compound II displayed good efficacy in a mouse oral glucose tolerance test (OGTT). CompoundI showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

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Application of 91912-53-7. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Organocatalytic Stereoconvergent Synthesis of α-CF3 Amides: Triketopiperazines and Their Heterocyclic Metamorphosis. Author is Foster, Robert W.; Lenz, Eva N.; Simpkins, Nigel S.; Stead, Darren.

The highly enantioselective alkylation of α-CF3 enolates, generated from triketopiperazines, has been accomplished through use of a bifunctional thiourea organocatalyst to facilitate 1,4-addition to varied enone acceptors. On treatment with appropriate nitrogen nucleophiles, the chiral triketopiperazine products underwent metamorphosis, to provide novel fused heterocyclic lactams such as extended pyrazolopyrimidines.

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Recommanded Product: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine. Aromatic compounds can be divided into two categories: single heterocycles and fused heterocycles. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Design and Synthesis of the Potent, Orally Available, Brain-Penetrable Arylpyrazole Class of Neuropeptide Y5 Receptor Antagonists. Author is Sato, Nagaaki; Takahashi, Toshiyuki; Shibata, Takunobu; Haga, Yuji; Sakuraba, Aya; Hirose, Masaaki; Sato, Miki; Nonoshita, Katsumasa; Koike, Yuko; Kitazawa, Hidefumi; Fujino, Naoko; Ishii, Yasuyuki; Ishihara, Akane; Kanatani, Akio; Fukami, Takehiro.

Novel arylpyrazole derivatives were synthesized and evaluated as neuropeptide Y5 receptor antagonists. The 2,3-dihydro-1H-cyclopenta[a]naphthalene derivative I showed good binding affinity and antagonistic activity for the Y5 receptor. After intracerebroventricular administration in SD rats, (-)-I significantly inhibited food intake that was induced by the centrally administered Y5-preferring agonist, bovine pancreatic polypeptide, but had only a negligible effect on NPY-induced feeding.

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