55314-29-9Relevant academic research and scientific papers
Discovery and preclinical characterization of 1-methyl-3-(4-methylpyridin- 3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo-[3,4-b]pyrazine (PF470): A highly potent, selective, and efficacious metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator
Zhang, Lei,Balan, Gayatri,Barreiro, Gabriela,Boscoe, Brian P.,Chenard, Lois K.,Cianfrogna, Julie,Claffey, Michelle M.,Chen, Laigao,Coffman, Karen J.,Drozda, Susan E.,Dunetz, Joshua R.,Fonseca, Kari R.,Galatsis, Paul,Grimwood, Sarah,Lazzaro, John T.,Mancuso, Jessica Y.,Miller, Emily L.,Reese, Matthew R.,Rogers, Bruce N.,Sakurada, Isao,Skaddan, Marc,Smith, Deborah L.,Stepan, Antonia F.,Trapa, Patrick,Tuttle, Jamison B.,Verhoest, Patrick R.,Walker, Daniel P.,Wright, Ann S.,Zaleska, Margaret M.,Zasadny, Kenneth,Shaffer, Christopher L.
, p. 861 - 877 (2014)
A novel series of pyrazolopyrazines is herein disclosed as mGluR5 negative allosteric modulators (NAMs). Starting from a high-throughput screen (HTS) hit (1), a systematic structure-activity relationship (SAR) study was conducted with a specific focus on balancing pharmacological potency with physicochemical and pharmacokinetic (PK) properties. This effort led to the discovery of 1-methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b] pyrazine (PF470, 14) as a highly potent, selective, and orally bioavailable mGluR5 NAM. Compound 14 demonstrated robust efficacy in a 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP)-rendered Parkinsonian nonhuman primate model of l-DOPA-induced dyskinesia (PD-LID). However, the progression of 14 to the clinic was terminated because of a potentially mechanism-mediated finding consistent with a delayed-type immune-mediated type IV hypersensitivity in a 90-day NHP regulatory toxicology study.
Alkylidene Dihydropyridines Are Surrogates for Pyridylic Anions in the Conjugate Addition to α,β-Unsaturated Ketones
Shi, Jiaqi,Sayyad, Ashik,Fishlock, Dan,Orellana, Arturo
, p. 48 - 52 (2021/12/27)
We show that alkylidene dihydropyridines, readily prepared from 4-alkylpyridines, behave as soft nucleophiles toward a range of α,β-unsaturated ketones under the influence of silyl Lewis acids to give the products of conjugate addition. In contrast to existing methods, which use strongly basic pyridylic anions, this reaction tolerates a wide array of functional groups, providing access to useful heterocyclic scaffolds.
Synthesis of regioisomeric pyrido[c]azocanones from azaindanone derivatives
Penning, Miriam,Christoffers, Jens
, p. 2140 - 2149 (2014/04/17)
A ring enlargement reaction with methylamine gave new pyrido[2,3-c]-, pyrido[3,4-c]- and pyrido[3,2-c]azocanone derivatives from cyclic β-oxo esters with a cyclopentapyridine skeleton and a 1,4-diketone moiety. The starting materials for this ring transformation were either prepared from halogenopyridine carboxylates by Heck reaction and subsequent hydrogenation, or (halogenomethyl)pyridine carboxylates were submitted to SN reaction with diethyl malonate. Both routes were completed by Dieckmann condensation to build the cyclic β-oxo ester structure and alkylation with phenacylbromide to install the 1,4-diketone motif. Copyright
Evaluation of the first cytostatically active 1-aza-9-oxafluorenes as novel selective CDK1 inhibitors with P-glycoprotein modulating properties
Brachwitz, Kristin,Voigt, Burkhardt,Meijer, Laurent,Lozach, Olivier,Sch?chtele, Christoph,Molnár, Josef,Hilgeroth, Andreas
, p. 876 - 879 (2007/10/03)
The first series of synthetic 1-aza-9-oxafluorenes with cytostatic activities in the micromolar range was evaluated as cyclin-dependent kinase (CDK1) inhibitors. Activity was found to be selective in comparison to the inhibition of other kinases within th
Immunopotentiator agents
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Page column 21, (2010/02/05)
Novel compounds and methods for preparing same, immunopotentiating compositions, and a method for potentiating the immune system of a host animal. The method comprises administering to the animal an effective amount of an immunopotentiating compound of Formula I or Formula II, or a physiologically acceptable salt.
Observations on the DDQ oxidation of 1-acyldihydropyridines - A synthetic application
Wallace,Gibb,Cottrell,Kennedy,Brands,Dolling
, p. 1784 - 1789 (2007/10/03)
A synthetic application of the rate difference in oxidation of regioisomerically substituted N-acyldihydropyridines is reported. This has allowed for isolation of pure 4-substituted pyridine isomers without the need for chromatography. Diels-Alder adducts between a dihydropyridine and DDQ were isolated and formation of novel hydroquinone ethers was also observed during some reactions.
Regioselective formation of novel functionalized 1-aza-9-oxafluorenes
Hilgeroth, Andreas,Brachwitz, Kristin,Baumeister, Ute
, p. 661 - 669 (2007/10/03)
A small series of novel 1-aza-9-oxafluorenes have been prepared by regioselective cycloaddition reaction of p-benzoquinone to the sterically unhindered side of unsymmetrically substituted N-acyl-1,4-dihydropyridines (1). The stereochemistry of the product
Preparation of some Thiopyranopyridine Derivatives
Clarke, Kenneth,Goulding, John,Scrowston, Richard M.
, p. 1501 - 1505 (2007/10/02)
In the first systematic study of thiopyranopyridines in which the sulphur atom is separated from the pyridine ring by one carbon atom, the four isomeric enol esters, ethyl 5-hydroxy-8H-thiopyranopyridine-6-carboxylate (4b), ethyl 8-hydroxy-5H-thiopyranopyridine-7-carboxylate (5b), and ethyl 4-hydroxy-1H-thiopyrano- and pyridine-3-carboxylate (6b) and (7b), have been synthesised.Improved methods for the preparation of their pyridine precursors are described.With phenylhydrazine, the enol esters (4b) - (7b) give condensed pyrazole derivatives (15) - (18), which have dipolar structures; with hot mineral acid they undergo decarboxylative hydrolysis, to give the corresponding oxothiopyranopyridines (4a) - (7a).
