- Discovery of BR102375, a new class of non-TZD PPARγ full agonist for the treatment of type 2 diabetes
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As a potential treatment of type 2 diabetes, a novel PPARγ non-TZD full agonist, compound 18 (BR102375) was identified from the original lead BR101549 by the SAR efforts of the labile metabolite control through bioisosteres approach. In vitro assessments
- Choung, Wonken,Yang, Deokmo,Kim,Choi, Hyukjoon,Lee, Bo Ram,Park, Min,Jang, Su Min,Lim, Jae Soo,Kim, Woo Sik,Kim, Kyung-Hee,Chin, Jungwook,Jung, Kyungjin,Lee, Geumwoo,Hong,Jang, Tae-ho,Joo, Jeongmin,Hwang, Hayoung,Myung, Jayhyuk,Kim, Seong Heon
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p. 2275 - 2282
(2019/06/27)
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- FUSED HETEROCYCLIC RING COMPOUND
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A compound represented by the following formula or a salt thereof, which has an GPR119 agonist action, is useful for the prophylaxis or treatment of diabetes, obesity and the like, and shows superior efficacy: wherein P: substituted 6-membered aromatic ring, Q: (substituted) 6-membered aromatic ring, A1: CR4aR4b, NR4c, O, S, SO or SO2 {R4a-4c: H etc.}, L1: (substituted) C1-5 alkylene, L2: a bond or (substituted) C1-3 alkylene, L3-4: (substituted) C1-3 alkylene, R1: H, X, CN, (substituted) hydrocarbon, (substituted) heterocycle or (substituted) OH, or (substituted) 4- to 8-membered (heterocyclic) ring together with A1, R2: H, CN, (substituted) hydrocarbon, and R3a: -COSRA1, (substituted) 5- or 6-membered aromatic ring {RA1: (substituted) hydrocarbon or (substituted) heterocycle}.
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Page/Page column 96
(2012/01/11)
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- CYCLOAMINO DERIVATIVES AS GPR119 ANTAGONISTS
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Therapeutic compounds are disclosed having the general formula (I) that are useful for the treatment of metabolic disorders, including type II diabetes. The compounds have activity as agonists of GPR119. Compounds having the stereochemistry of formula (la) may also demonstrate DPP-IV inhibitory activity.
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Page/Page column 103
(2011/12/14)
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- PTSA-ZnCl2: An efficient catalyst for the synthesis of 1,2,4-oxadiazoles from amidoximes and organic nitriles
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(Chemical Equation Presented) PTSA-ZnCl2 has been proved to be an efficient and mild catalyst for the synthesis of 3,5-disubstituted-1,2,4- oxadiazoles from amidoximes and organic nitriles.
- Augustine, John Kallikat,Akabote, Vani,Hegde, Shrivatsa Ganapati,Alagarsamy, Padma
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supporting information; experimental part
p. 5640 - 5643
(2009/12/08)
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- IMIDAZOLE-DERIVATIVES AS FACTOR Xa INHIBITORS
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The present invention relates to compounds of the formula (I), wherein R0 ; R1 ; R2 ; R3 ; R4; Q; V, G and M have the meanings indicated in the claims. The compounds of the formula (I) are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula (I), their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
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- Non-peptide antagonists of GLP-1 receptor and methods of use
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Non-peptide compounds that act as antagonists of the intestinal hormone glucagons-like peptide 1 (GLP-1) have a 9H-b-carboline central motif. The compounds exhibit advantageous physical, chemical and biological properties and inhibit GLP-1 peptide binding
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- Synthesis and biological characterization of 1,4,5,6- tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists
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Previous studies identified several novel tetrahydropyrimidine derivatives exhibiting muscarinic agonist activity in rat brain. Such compounds might be useful in treating cognitive and memory deficits associated with low acetylcholine levels, as found in Alzheimer's disease. To determine the molecular features of ligands important for binding and activity at muscarinic receptor subtypes, the series of tetrahydropyrimidines was extended. Several active compounds were examined further for functional selectivity through biochemical studies of muscarinic receptor activity using receptor subtypes expressed in cell lines. Several amidine derivatives displayed high efficacy at m1 receptors and lower activity at m3 receptors coupled to phosphoinositide (PI) metabolism in A9 L cells. Four ligands, including 1b, 1f, 2b, and 7b, exhibited marked functional selectivity for m1 vs m3 receptors. Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cyclase in A9 L cells. Molecular modeling studies also were initiated to help understand the nature of the interaction of muscarinic agonists with the m1 receptor using a nine amino model of the m1 receptor. Several important interactions were identified, including interactions between the ester moiety and Thr192. Additional interactions were found for oxadiazoles and alkynyl derivatives with Asn382, suggesting that enhanced potency and selectivity may be achieved by maximizing interactions with Asp105, Thr192, and Ash382. Taken together, the data indicate that several amidine derivatives display functional selectivity for m1 muscarinic receptors, warranting further evaluation as therapeutic agents for the treatment of Alzheimer's disease. In addition, several amino acid residues were identified as potential binding sites for m1 agonists. These data may be useful in directing efforts to develop even more selective m1 agonists.
- Messer Jr., William S.,Abuh, Yahaya F.,Liu, Yang,Periyasamy, Sumudra,Ngur, Dan O.,Edgar, Michael A. N.,El-Assadi, Afif A.,Sbeih, Sbeih,Dunbar, Philip G.,Roknich, Scott,Rho, Taikyun,Fang, Zheng,Ojo, Babatunde,Zhang, Hao,Huzl III, James J.,Nagy, Peter I.
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p. 1230 - 1246
(2007/10/03)
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- 4-phenylpiperidine compounds and their use
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Piperidine compounds having the formula STR1 wherein R1 is hydrogen, (C1-6 -alkoxyaryl)alkyl, diphenylmethozy-C1-6 -alkyl, C1-8 -alkyl, C4-10 -cycloalkylalkyl, phenoxy-C1-8 -alkyl, or C1-6 -alkoxy-C1-6 -alkyl; and R is STR2 or CH=NOR' wherein R' is C1-6 -alkyl, C3-7 -cycloalkyl, C1-6 -alkoxy-C1-6 -alkyl, aryl-C0-6 -alkyl, which may optionally be substituted with one or more halogen and (1-5 -alkoxy, thienyl, or C4-7 -cycloalkylalkyl. The novel compounds are useful for the treatment of pain conditions and as neuroleptics.
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