64373-43-9Relevant academic research and scientific papers
Dihydro pyridine compound, its composition, preparation method and use
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Paragraph 0252 - 0254, (2016/10/10)
Disclosed dihydropyridine compounds are the compounds possessing the following general formula (I) as shown in the specification, wherein R1 is selected from hydrogen, halogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic groups, substituted heterocyclic groups, ester group and amide group; R2 is selected from hydrogen, cyanogroup, alkyl, substituted alky, alkenyl, substituted alkenyl and acyl; or R2 and R3 form a fused ring; R3 is selected from alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl; or R3 and R2 or R4 form a fused ring; R4 is selected from hydrogen, alkyl and substituted alkyl; or R4 and R3 or R5 form a fused ring; R5 is selected form alkyl, substituted alky, aryl, substituted aryl, heteroaryl and substituted heteroaryl; or R5 and R4 form a fused ring. The invention also discloses a preparation method of the compounds of the general formula (I), compositions containing the compounds of the general formula (I), and applications of the compositions to medicaments for treating cancers.
Design and synthesis of 3-pyridylacetamide derivatives as dipeptidyl peptidase IV (DPP-4) inhibitors targeting a bidentate interaction with Arg125
Miyamoto, Yasufumi,Banno, Yoshihiro,Yamashita, Tohru,Fujimoto, Tatsuhiko,Oi, Satoru,Moritoh, Yusuke,Asakawa, Tomoko,Kataoka, Osamu,Takeuchi, Koji,Suzuki, Nobuhiro,Ikedo, Koji,Kosaka, Takuo,Tsubotani, Shigetoshi,Tani, Akiyoshi,Funami, Miyuki,Amano, Michiko,Yamamoto, Yoshio,Aertgeerts, Kathleen,Yano, Jason,Maezaki, Hironobu
experimental part, p. 172 - 185 (2011/03/17)
We have previously discovered nicotinic acid derivative 1 as a structurally novel dipeptidyl peptidase IV (DPP-4) inhibitor. In this study, we obtained the X-ray co-crystal structure between nicotinic acid derivative 1 and DPP-4. From these X-ray co-cryst
Discovery of potent, selective, and orally bioavailable quinoline-based dipeptidyl peptidase IV inhibitors targeting Lys554
Maezaki, Hironobu,Banno, Yoshihiro,Miyamoto, Yasufumi,Moritou, Yuusuke,Asakawa, Tomoko,Kataoka, Osamu,Takeuchi, Koji,Suzuki, Nobuhiro,Ikedo, Koji,Kosaka, Takuo,Sasaki, Masako,Tsubotani, Shigetoshi,Tani, Akiyoshi,Funami, Miyuki,Yamamoto, Yoshio,Tawada, Michiko,Aertgeerts, Kathleen,Yano, Jason,Oi, Satoru
experimental part, p. 4482 - 4498 (2011/09/19)
Dipeptidyl peptidase IV (DPP-4) inhibition is a validated therapeutic option for type 2 diabetes, exhibiting multiple antidiabetic effects with little or no risk of hypoglycemia. In our studies involving non-covalent DPP-4 inhibitors, a novel series of quinoline-based inhibitors were designed based on the co-crystal structure of isoquinolone 2 in complex with DPP-4 to target the side chain of Lys554. Synthesis and evaluation of designed compounds revealed 1-[3-(aminomethyl)-4-(4-methylphenyl)-2-(2-methylpropyl)quinolin-6-yl] piperazine-2,5-dione (1) as a potent, selective, and orally active DPP-4 inhibitor (IC50 = 1.3 nM) with long-lasting ex vivo activity in dogs and excellent antihyperglycemic effects in rats. A docking study of compound 1 revealed a hydrogen-bonding interaction with the side chain of Lys554, suggesting this residue as a potential target site useful for enhancing DPP-4 inhibition.
Discovery of a 3-pyridylacetic acid derivative (TAK-100as a potent, selective and orally active dipeptidyl peptidase IV (DPP-4) inhibitor
Miyamoto, Yasufumi,Banno, Yoshihiro,Yamashita, Tohru,Fujimoto, Tatsuhiko,Oi, Satoru,Moritoh, Yusuke,Asakawa, Tomoko,Kataoka, Osamu,Yashiro, Hiroaki,Takeuchi, Koji,Suzuki, Nobuhiro,Ikedo, Koji,Kosaka, Takuo,Tsubotani, Shigetoshi,Tani, Akiyoshi,Sasaki, Masako,Funami, Miyuki,Amano, Michiko,Yamamoto, Yoshio,Aertgeerts, Kathleen,Yano, Jason,Maezaki, Hironobu
experimental part, p. 831 - 850 (2011/04/12)
Inhibition of dipeptidyl peptidase IV (DPP-4is an exciting new approach for the treatment of diabetes. To date there has been no DPP-4 chemotype possessing a carboxy group that has progressed into clinical trials. Originating from the discovery of the str
Biocatalytic strategy toward asymmetric β-hydroxy nitriles and γ-amino alcohols
Nowill, Randall W.,Patel, Trisha J.,Beasley, David L.,Alvarez, Jose A.,Jackson III, Elizah,Hizer, Todd J.,Ghiviriga, Ion,Mateer, Scott C.,Feske, Brent D.
supporting information; experimental part, p. 2440 - 2442 (2011/05/16)
A library of 20 bakers' yeast reductases, that are overexpressed in Escherichia coli, were screened against a variety of β-keto nitriles. Enzymes from the aldose reductase and the short chain dehydrogenase family displayed activity toward these substrates. All of the seven substrates were reduced with high enantioselectivities and in some cases both antipodes could be synthesized in high ees. These whole-cell reactions afforded gram quantities of asymmetric compounds that could ultimately lead to scaleable and simple synthesis to new drug analogs of serotonin reuptake inhibitors and β-adrenergic blocking agents.
Facile iterative synthesis of 2,5-terpyrimidinylenes as nonpeptidic α-helical mimics
Anderson, Laura,Zhou, Mingzhou,Sharma, Vasudha,McLaughlin, Jillian M.,Santiago, Daniel N.,Fronczek, Frank R.,Guida, Wayne C.,McLaughlin, Mark L.
supporting information; experimental part, p. 4288 - 4291 (2010/08/06)
A facile iterative synthesis of 2,5-terpyrimidinylenes that are structurally analogous to α-helix mimics is presented. Condensation of amidines with readily prepared α,β-unsaturated α-cyanoketones gives 5-cyano-substituted pyrimidines. Iterative transformation of the 5-cyano group into an amidine allows synthesis of 2,5-terpyrimidinylenes with variable groups at the 4-, 4′-, and 4′′-positions. These compounds are designed to mimic the i, i + 4, and i + 7 sites of an α-helix.
ALPHA-HELIX MIMETIC USING A 2,5-OLIGOPYRIMIDINE SCAFFOLD
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Page/Page column 51, (2010/08/08)
Alpha-helix mimetics and associated methods of making are provided. These compounds are constructed using a 2,5-oligopyrimidine scaffold. The semi-rigid scaffold holds individual side chain-like residues in orientations that mimic the orientations of side chain residues of an ?-helical protein domain. The new scaffold is easier to make than previous scaffolds and has much more favorable physical properties than previous alpha-helix mimics. The amphiphilic alpha-helix mimetics have application for making libraries and for treating diseases or conditions effected by the inhibition or disruption of interactions with the alpha helix of a protein.
REMEDY FOR DIABETES
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Page/Page column 22, (2008/06/13)
The present invention provides an agent for increasing the pancreatic insulin content useful for the treatment of diabetes and the like. In one embodiment, the present invention provides an agent for increasing the pancreatic insulin content, which contai
A new class of small molecule RNA polymerase inhibitors with activity against Rifampicin-resistant Staphylococcus aureus1
Arhin, Francis,Belanger, Odette,Ciblat, Stephane,Dehbi, Mohammed,Delorme, Daniel,Dietrich, Evelyne,Dixit, Dilip,Lafontaine, Yanick,Lehoux, Dario,Liu, Jing,McKay, Geoffrey A.,Moeck, Greg,Reddy, Ranga,Rose, Yannick,Srikumar, Ramakrishnan,Tanaka, Kelly S.E.,Williams, Daniel M.,Gros, Philippe,Pelletier, Jerry,Parr Jr., Thomas R.,Far, Adel Rafai
, p. 5812 - 5832 (2007/10/03)
The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase.
PYRIDINE COMPOUNDS AS INHIBITORS OF DIPEPTIDYL PEPTIDASE IV
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Page/Page column 82, (2010/02/11)
A compound represented by the formula wherein R1 and R2 are the same or different and each is an optionally substituted hydrocarbon group or an optionally substituted hydroxy group; R3 is an optionally substituted aromatic group; R4 is an optionally substituted amino group; L is a divalent chain hydrocarbon group; Q is a bond or a divalent chain hydrocarbon group; and X is a hydrogen atom, a cyano group, a nitro group, an acyl group, a substituted hydroxy group, an optionally substituted thiol group, an optionally substituted amino group or an optionally substituted cyclic group; provided that when X is an ethoxycarbonyl group, then Q is a divalent chain hydrocarbon group. The compound has a peptidase inhibitory action, is useful as an agent for the prophylaxis or treatment of diabetes and the like, and is superior in efficacy, duration of action, specificity, lower toxicity and the like.
