171178-45-3Relevant articles and documents
Design, synthesis, and biological evaluation of 3-[4-(2-hydroxyethyl) piperazin-l-yl]7-(6-methoxypyridin-3-yl)-l-(2-propoxyethyl)pyrido[3,4-b] pyrazin-2(lH)-one, a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5 (PDE5)
Hughes, Robert O.,Rogier, D. Joseph,Jacobsen, E. Jon,Walker, John K.,Maclnnes, Alan,Bond, Brian R.,Zhang, Lena L.,Yu, Ying,Zheng, Yi,Rumsey, Jeanne M.,Walgren, Jennie L.,Curtiss, Sandra W.,Fobian, Yvette M.,Heasley, Steven E.,Cubbage, Jerry W.,Moon, Joseph B.,Brown, David L.,Acker, Brad A.,Maddux, Todd M.,Tollefson, Mike B.,Mischke, Brent V.,Owen, Dafydd R.,Freskos, John N.,Molyneaux, John M.,Benson, Alan G.,Blevis-Ba, Rhadika M.
, p. 2656 - 2660 (2010)
We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-l-yl]7-(6-methoxypyridin-3-yl)- l-(2-propoxyethyl)pyrido[3,4-è]pyrazin-2(l//)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials.
A Ruthenium(II) Complex as a Luminescent Probe for DNA Mismatches and Abasic Sites
Boynton, Adam N.,Marcélis, Lionel,McConnell, Anna J.,Barton, Jacqueline K.
, p. 8381 - 8389 (2017)
[Ru(bpy)2(BNIQ)]2+ (BNIQ = Benzo[c][1,7]naphthyridine-1-isoquinoline), which incorporates the sterically expansive BNIQ ligand, is a highly selective luminescent probe for DNA mismatches and abasic sites, possessing a 500-fold higher binding affinity toward these destabilized regions relative to well-matched base pairs. As a result of this higher binding affinity, the complex exhibits an enhanced steady-state emission in the presence of DNA duplexes containing a single base mismatch or abasic site compared to fully well-matched DNA. Luminescence quenching experiments with Cu(phen)22+ and [Fe(CN)6]3- implicate binding of the complex to a mismatch from the minor groove via metalloinsertion. The emission response of the complex to different single base mismatches, binding preferentially to the more destabilized mismatches, is also consistent with binding by metalloinsertion. This work shows that high selectivity toward destabilized regions in duplex DNA can be achieved through the rational design of a complex with a sterically expansive aromatic ligand.
Carbon-11 and Fluorine-18 Radiolabeled Pyridopyrazinone Derivatives for Positron Emission Tomography (PET) Imaging of Phosphodiesterase-5 (PDE5)
Chekol, Rufael,Gheysens, Olivier,Ahamed, Muneer,Cleynhens, Jan,Pokreisz, Peter,Vanhoof, Greet,Janssens, Stefan,Verbruggen, Alfons,Bormans, Guy
, p. 486 - 496 (2017)
The cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) plays an important role in various pathologies including pulmonary arterial hypertension and cardiomyopathy. PDE5 represents an important therapeutic and/or prognostic targ
PYRIDOPYRIMIDINES AS HISTAMINE H4-RECEPTOR INHIBITORS
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Page/Page column 32; 34-36, (2020/02/16)
The invention relates to compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof, to pharmaceutical compositions comprising them and to their use in the treatment and/or prevention of diseases or disorders mediated by histamine H4 receptor.
SULFONYL-SUBSTITUTED BICYCLIC COMPOUND WHICH ACTS AS ROR INHIBITOR
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Paragraph 0376; 0377, (2020/08/16)
Provided is a sulfonyl-substituted bicyclic compound (A) which acts as a RORγ inhibitor, said compound has good RORγ inhibitory activity and is expected to be used for treating diseases mediated by a RORγ receptor in mammals.
Discovery of Pyridopyrimidinones as Potent and Orally Active Dual Inhibitors of PI3K/mTOR
Yu, Tao,Li, Ning,Wu, Chengde,Guan, Amy,Li, Yi,Peng, Zhengang,He, Miao,Li, Jie,Gong, Zhen,Huang, Lei,Gao, Bo,Hao, Dongling,Sun, Jikui,Pan, Yan,Shen, Liang,Chan, Chichung,Lu, Xiulian,Yuan, Hongyu,Li, Yongguo,Li, Jian,Chen, Shuhui
supporting information, p. 256 - 261 (2018/03/21)
The identification and lead optimization of a series of pyridopyrimidinone derivatives are described as a novel class of efficacious dual PI3K/mTOR inhibitors, resulting in the discovery of 31. Compound 31 exhibited high enzyme activity against PI3K and mTOR, potent suppression of Akt and p70s6k phosphorylation in cell assays, and good pharmacokinetic profile. Furthermore, compound 31 demonstrated in vivo efficacy in a PC-3M tumor xenograft model.
MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES
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Paragraph 0563, (2017/08/01)
Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.
4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium as a neurokinin receptor modulator
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Page/Page column 33, (2016/08/29)
Compounds and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor, based on 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)3yridine-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium and pharmaceutically acceptable salts thereof.
SUBSTITUTED 4-PHENYL-PYRIDINES FOR TREATMENT OF NK-1 RECEPTOR RELATED DISEASES
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Paragraph 0164; 0165, (2018/10/31)
PROBLEM TO BE SOLVED: To provide new derivatives of 4-phenyl-pyridine compounds that are effective NK1 receptor antagonists, with enhanced physicochemical and/or biological properties, and methods for producing the 4-phenyl-pyridine compounds. SOLUTION: Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NKj) receptor. The compounds have the general formula (I). COPYRIGHT: (C)2015,JPOandINPIT
SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
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Paragraph 00478, (2016/04/26)
Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
