264905-39-7Relevant articles and documents
Conjugate Addition of Perfluoroarenes to α,β-Unsaturated Carbonyls Enabled by an Alkoxide-Hydrosilane System: Implication of a Radical Pathway
Xie, Weilong,Park, Sung-Woo,Jung, Hoimin,Kim, Dongwook,Baik, Mu-Hyun,Chang, Sukbok
supporting information, p. 9659 - 9668 (2018/07/21)
Conjugate addition of organometallic reagents to α,β-unsaturated carbonyls is a key strategy for the construction of carbon-carbon bond in organic synthesis. Although direct C-H addition to unsaturated bonds via transition metal catalysis is explored in recent years, electron-deficient arenes that do not bear directing groups continue to be challenging. Herein we disclose the first example of a conjugate addition of perfluoroarenes to α,β-unsaturated carbonyls enabled by an alkoxide-hydrosilane system. The reaction is convenient to carry out at room temperature over a broad range of substrates and reactants to furnish synthetically versatile products in high to excellent yields. Mechanistic experiments in combination with computational studies suggest that a radical pathway is most likely operative in this transformation. The hypervalent silicate and silanide species, which are relevant to the proposed mechanism, were observed experimentally by NMR and single crystal X-ray diffraction analyses.
Quinazoline derivatives, composition and application thereof
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Paragraph 0205; 0206, (2018/07/06)
The invention relates to quinazoline derivatives as shown in a formula I as described in the specification, a composition and application thereof as a PGK1 inhibitor for preparing anti-tumor drugs andapplication thereof in treating malignant tumors.
MUSCARINIC AGONISTS
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Page/Page column 44; 52, (2017/02/28)
This invention relates to compounds that are agonists of the muscarinic receptor and/or M4 receptor and which are useful in the treatment of muscarinic M1/M4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula (1a) or a salt thereof, wherein p, q, r, s, Q, R3 and R4 are as defined herein.
Structure-based design of a new series of N-(piperidin-3-yl)pyrimidine-5-carboxamides as renin inhibitors
Imaeda, Yasuhiro,Tawada, Michiko,Suzuki, Shinkichi,Tomimoto, Masaki,Kondo, Mitsuyo,Tarui, Naoki,Sanada, Tsukasa,Kanagawa, Ray,Snell, Gyorgy,Behnke, Craig A.,Kubo, Keiji,Kuroita, Takanobu
, p. 5771 - 5780 (2016/10/30)
The action of the aspartyl protease renin is the rate-limiting initial step of the renin-angiotensin-aldosterone system. Therefore, renin is a particularly promising target for blood pressure as well as onset and progression of cardiovascular and renal diseases. New pyrimidine derivatives 5–14 were designed in an attempt to enhance the renin inhibitory activity of compound 3 identified by our previous fragment-based drug design approach. Introduction of a basic amine essential for interaction with the two aspartic acids in the catalytic site and optimization of the S1/S3 binding elements including an induced-fit structural change of Leu114 (‘Leu-in’ to ‘Leu-out’) by a rational structure-based drug design approach led to the discovery of N-(piperidin-3-yl)pyrimidine-5-carboxamide 14, a 65,000-fold more potent renin inhibitor than compound 3. Surprisingly, this remarkable enhancement in the inhibitory activity of compound 14 has been achieved by the overall addition of only seven heavy atoms to compound 3. Compound 14 demonstrated excellent selectivity over other aspartyl proteases and moderate oral bioavailability in rats.
CHEMOKINE RECEPTOR ANTAGONISTS AND METHODS OF USE THEREOF
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Paragraph 1426, (2016/02/21)
Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by: or physiologically acceptable salt thereof.
QUINOLONE DERIVATIVES AS FIBROBLAST GROWTH FACTOR RECEPTOR INHIBITORS
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Page/Page column 210, (2015/09/23)
Compounds that are Fibroblast Growth Factor Inhibitors (FGFR) and are therefore useful for the treatment of diseases treatable by inhibition of FGFR are disclosed. Also disclosed are pharmaceutical compositions containing such compounds and processes for
HETEROCYCLIC DERIVATIVE HAVING INHIBITORY ACTIVITY ON TYPE-I 11 -HYDROXYSTEROID DEHYDROGENASE
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Page/Page column 142, (2010/08/07)
Disclosed is a compound which is useful as an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. A compound represented by the formula: its pharmaceutically acceptable salt, or a solvate thereof, wherein X is O or S, a broken line and a wavy line represent the presence or the absence of a bond, (i) when a broken line represents the presence of a bond, a wavy line represents the absence of a bond, R2 and R3 are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like, (ii) when a broken line represents the absence of a bond, a wavy line represents the presence of a bond, R1 and R4 are each independently hydrogen, halogen or the like, R2 and R3 are each independently hydrogen, halogen, cyano, hydroxy, carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like, and R5 and R6 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or the like.
SUBSTITUTED ISOQUINOLINE AND ISOQUINOLINONE DERIVATIVES
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Page/Page column 57-58, (2008/12/06)
The invention relates to 6-substituted isoquinoline and isochinolone derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.
Discovery of a series of aminopiperidines as novel iNOS inhibitors
Bourdonnec, Bertrand Le,Leister, Lara K.,Ajello, Christopher A.,Cassel, Joel A.,Seida, Pamela R.,O'Hare, Heather,Gu, Minghua,Chu, Guo-Hua,Tuthill, Paul A.,DeHaven, Robert N.,Dolle, Roland E.
, p. 336 - 343 (2008/09/18)
Nitric oxide (NO), a mediator of various physiological and pathophysiological processes, is synthesized by three isozymes of nitric oxide synthase (NOS). Potential candidate clinical drugs should be devoid of inhibitory activity against endothelial NOS (eNOS), since eNOS plays an important role in maintaining normal blood pressure and flow. A new series of aminopiperidines as potent inhibitors of iNOS were identified from a HTS lead. From this study, we identified compound 33 as a potent iNOS inhibitor, with >25-fold selectivity over eNOS and 16-fold selectivity over nNOS.
BRADYKININ 1 RECEPTOR ANTAGONISTS
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Page/Page column 65, (2008/06/13)
The invention encompasses novel compounds and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for treatment of diseases mediated by B1 bradykinin receptor.