2067-84-7Relevant articles and documents
Regioselective one-pot synthesis of 9-alkyl-6-chloropyrido[3,2-e][1,2,4] triazolo-[4,3-a]pyrazines. Reactivity of aliphatic and aromatic hydrazides
Unciti-Broceta, Asier,Pineda-de-las-Infantas, Maria J.,Diaz-Mochon, Juan J.,Romagnoli, Romeo,Baraldi, Pier G.,Gallo, Miguel A.,Espinosa, Antonio
, p. 2878 - 2880 (2005)
(Chemical Equation Presented) The one-pot synthesis of new 9-alkyl-6-chloropyrido[3,2-e]-[1,2,4]triazolo[4,3-a]pyrazines has been achieved. Hydrazides regioselectively reacted as nucleophiles with the 3-chloro substituent of 2,3-dichloropyrido[2,3-6]pyrazine. An intramolecular cyclization afforded the tricycle nonxanthine adenosine receptor antagonists.
Cyclopentadienopyrazine organic compound and application thereof
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Paragraph 0209-0210; 0213-0214, (2021/03/30)
The invention relates to a cyclopentadienopyrazine organic compound and application thereof. The organic compound has a structure as shown in a general formula (1). The organic compound according to the present invention has excellent hole transport properties and stability, can be used as a hole injection layer material in an organic electroluminescent element, and can also be doped in a hole injection layer or a hole transport layer as a doping agent, so that a device can be driven at a low voltage, the electroluminescent efficiency can be improved, and the service life of the device can beprolonged.
Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis
Ko, Kwangseok,Kim, Hye-Jung,Ho, Pil-Su,Lee, Soon Ok,Lee, Ji-Eun,Min, Cho-Rong,Kim, Yu Chul,Yoon, Ju-Han,Park, Eun-Jung,Kwon, Young-Jin,Yun, Jee-Hun,Yoon, Dong-Oh,Kim, Jung-Sook,Park, Woul-Seong,Oh, Seung-Su,Song, Yu-Mi,Cho, Woon-Ki,Morikawa, Kazumi,Lee, Kyoung-June,Park, Chan-Hee
supporting information, p. 2949 - 2961 (2018/04/23)
The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido[2,3-e]tetrazolo[1,5-a]pyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.
Rationalization of benzazole-2-carboxylate versus benzazine-3-one/ benzazine-2,3-dione selectivity switch during cyclocondensation of 2-aminothiophenols/phenols/anilines with 1,2-biselectrophiles in aqueous medium
Dhameliya, Tejas M.,Chourasiya, Sumit S.,Mishra, Eshan,Jadhavar, Pradeep S.,Bharatam, Prasad V.,Chakraborti, Asit K.
, p. 10077 - 10091 (2018/05/31)
The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via the 5-endo-trig process contrary to Baldwin's rule. On the other hand, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via the 6-exo-trig process in compliance with Baldwin's rule. The mechanistic insights of these cyclocondensation reactions using the hard-soft acid-base principle, quantum chemical calculations (density functional theory), and orbital interaction studies rationalize the selectivity switch of benzothiazole-2-carboxylates versus benzazine-3-ones/ benzazine-2,3-diones. The presence of water facilitates these cyclocondensation reactions by lowering of the energy barrier.
Discovery and analgesic evaluation of 8-chloro-1,4-dihydropyrido[2,3- b ]pyrazine-2,3-dione as a novel potent d -amino acid oxidase inhibitor
Xie, Dongsheng,Lu, Jun,Xie, Jin,Cui, Junjun,Li, Teng-Fei,Wang, Yan-Chao,Chen, Yuan,Gong, Nian,Li, Xin-Yan,Fu, Lei,Wang, Yong-Xiang
, p. 19 - 32 (2016/05/11)
A series of 5-azaquinoxaline-2,3-dione derivatives were synthesized and evaluated on d-amino acid oxidase (DAAO) inhibition as potential α-hydroxylactam-based inhibitors. The potent inhibitory activities in vitro suggested that 5-nitrogen could significantly enhance the binding affinity by strengthening relevant hydrogen bond interactions. The analgesic effects of intrathecal and systemic injection of 8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione, a representative molecule of 5-azaquinoxaline-2,3-dione, were investigated in rodents. This research not only confirmed the analgesic effect of the DAAO inhibitors but provided a new class of chemical entities with oral application potential for the treatment of chronic pain and morphine analgesic tolerance.
A series of pyrido[2,3-b[pyrazin-3(4 H)-one derivatives as aldose reductase inhibitors with antioxidant activity
Han, Zhongfei,Hao, Xin,Ma, Bing,Zhu, Changjin
, p. 308 - 317 (2016/07/06)
A series of pyrido[2,3-b]pyrazin-3(4H)-one based derivatives were designed as inhibitors of aldose reductase (ALR2), the enzyme which plays a key role in the development of diabetes complications as well as in the oxidative stress processes associated with diabetes and other pathologies. Most of the derivatives, having a substituted C2 aromatic group and a N4 acetic acid group on the core structure, were found to be potent and selective aldose reductase inhibitors with submicromolar IC50 values, and 9c was the most active with IC50 value 0.009 μM. Particularly, a number of the designed compounds bearing phenolic hydroxyl substituted C2-styryl side chain showed excellent not only in ALR2 inhibition but also in antioxidant, and among these 11i was proved to be the top one with an antioxidant ability even comparable to that of the well-known antioxidant Trolox. Structure-activity relationship and molecular docking studies highlighted the importance of phenolic hydroxyl substituents and vinyl spacer in C2 side chain of the scaffold for the construction of efficient and multifunctional ALR2 inhibitors.
Synthesis and evaluation of F-18 labeled pyrido[3,2-B]pyrazine derivative as a potential imaging agent for non-small-cell lung cancer
Park, Jeong Hoon,Kim, Heejung,Kim, Dong-Yeon,Yang, Seung Dae,Hur, Min Goo,Kim, Sang Wook,Yu, Kook Hyun
, p. 1778 - 1783 (2015/07/15)
Pyridopyrazine derivatives have been known as Wnt-2/β-catenin signaling pathway inhibitors. Wnt-2 overexpression may be involved in non-small-cell lung cancer (NSCLC). A novel 2-(4-[18 F]fluorobutoxy)-3-(phenylethynyl)pyrido[3,2-b]pyrazine was prepared to demonstrate the feasibility of NSCLC imaging agent by uptake of Wnt-2 protein. It was synthesized with tosylated precursor using [18F]fluoride in radiochemical yield of 44-48%. In cellular uptake evaluation, H460 and H1299, Wnt-2 expressed cancer cell lines, showed 2.5-folds higher cellular uptake than that of MCF10A as a control.
FUSED PIPERIDINES AS IP RECEPTOR AGONISTS FOR THE TREATMENT OF PAH AND RELATED DISORDERS
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Page/Page column 101, (2013/07/25)
The present invention provides heterocyclic derivatives which activate the IP receptor. Activating the IP receptor signaling pathway is useful to treat many forms of PAH, pulmonary fibrosis and exert beneficial effects in fibrotic conditions of various organs in animal models and in patients. Pharmaceutical compositions comprising such derivatives are also encompassed.
IP RECEPTOR AGONIST HETEROCYCLIC COMPOUNDS
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Page/Page column 129, (2012/02/02)
The present invention provides heterocyclic derivatives which activate the IP receptor. Activating the IP receptor signaling pathway is useful to treat many forms of PAH, pulmonary fibrosis and exert beneficial effects in fibrotic conditions of various organs in animal models and in patients. Pharmaceutical compositions comprising such derivatives are also encompassed.
A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/β-catenin pathway inhibitors in non-small-cell lung cancer cell lines
Gong, Young-Dae,Dong, Mi-Sook,Lee, Sang-Bum,Kim, Nayeon,Bae, Mi-Seon,Kang, Nam-Sook
experimental part, p. 5639 - 5647 (2011/10/13)
We developed Wnt/β-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cancer cell proliferation. In the optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b] pyrazine core skeletons showed were shown to higher activity than 2,3,6-trisubstituted quinoxaline's and thus hold promise for use as potential small-molecule inhibitors of the Wnt/β-catenin signal pathway in non-small-cell lung cancer cell (NSCLC) lines. And we have studied the pharmacophore mapping for compound 954, which presented the highest activity with a fit value of 2.81. The pharmacophore mapping for the compounds including 954, pyrido[2,3,-b]pyrazine core had hydrogen-bond acceptor site and hydrophobic center roles.
