46268-56-8Relevant academic research and scientific papers
Five-membered azole heterocyclic compound and its preparation method, pharmaceutical composition and use thereof
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, (2017/02/28)
The present invention relates to a five-membered azole heterocycle compound represented by the following general formula (I), a preparation method of the five-membered azole heterocycle compound, a drug composition of the five-membered azole heterocycle compound, and a use of the five-membered azole heterocycle compound in preparation of drugs for prevention or treatment of TGR5-mediated diseases. The formula (I) is represented by the instruction.
Design, synthesis and biological evaluation of a novel class of potent TGR5 agonists based on a 4-phenyl pyridine scaffold
Zhu, Junjie,Ning, Mengmeng,Guo, Cen,Zhang, Lina,Pan, Guoyu,Leng, Ying,Shen, Jianhua
, p. 55 - 68 (2013/10/01)
TGR5, a GPCR, is involved in energy and glucose homeostasis, and as such, is a target for the treatment of diabetes, obesity and other metabolic syndromes. A new class of TGR5 agonists based on a 4-phenyl pyridine scaffold was designed, synthesized and evaluated in vitro and in vivo. Extensive structure-activity relationship studies are reported herein. The most potent compounds 15a, 18b and 18c showed comparable activity with the lead compound 2. 15a had the best potency in vitro but displayed an unfavorable pharmacokinetic profile and was found to be ineffective during an oral glucose tolerance test in imprinting control region mice at a dose of 50 mg/kg.
Design, synthesis, and structure-activity relationships of 3,4,5-trisubstituted 4,5-dihydro-1,2,4-oxadiazoles as TGR5 agonists
Zhu, Junjie,Ye, Yangliang,Ning, Mengmeng,Mandi, Attila,Feng, Ying,Zou, Qingan,Kurtan, Tibor,Leng, Ying,Shen, Jianhua
, p. 1210 - 1223 (2013/07/26)
Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor1 (TGR5) is considered a potential target for the treatment of type2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand-based pharmacophore model was built, and a new class of potent TGR5 agonists, based on the novel 3,4,5-trisubstituted 4,5-dihydro-1,2,4-oxadiazole core, was discovered by rational design. Three distinct synthetic methods for constructing 4,5-dihydro-1,2,4-oxadiazoles and extensive structure-activity relationship studies are reported herein. Compound (R)-54n, the structure of which was determined by single-crystal X-ray diffraction and quantum chemical solid-state TDDFT-ECD calculations, showed the best potency, with an EC50 value of 1.4nM toward hTGR5. Its favorable properties invitro warrant further investigation.
NOVEL SMALL MOLECULE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS I
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Page/Page column 26, (2011/10/13)
The present invention relates to small molecule potentiators of metabotropic receptors, in particular of the mGlu2 receptor. The present invention also relates to the use of these compounds for the prevention or treatment of neurological and psychiatric d
Vilsmeier-Haack reaction of tertiary alcohols: Formation of functionalised pyridines and naphthyridines
Thomas,Asokan
, p. 2583 - 2587 (2007/10/03)
Vilsmeier-Haack reaction of 2-arylpropan-2-ols proceeds with multiple iminoalkylations leading to the formation of conjugated iminium salts which on ammonium acetate-induced cyclisation afford 4-arylnicotinaldehydes in good yields. Tertiary alcohols derived from aliphatic or alicyclic ketones by the addition of methyl Grignard are converted into substituted pyridines and naphthyridines by the action of Vilsmeier's reagent in N,N-dimethylformamide followed by nucleophile-assisted cyclisation in the presence of ammonium acetate.
Regioselective Addition ofd Copper-Zinc Aryl Organometallic Reagents to 3-substituted Pyridinium Salts
Shiao, Min-Jen,Chia, Win-Long,Shing, Tai-Li,Chow, Tahsin J.
, p. 2101 - 2121 (2007/10/02)
A number of 3-substituted pyridinium salts are subjected to nucleophilic addition by copper-zinc aryl organometallic reagents.The adducts are oxidized subsequently to form the corresponding 4-arylpyridines.In all the cases 1,4-addition products are obtained predominantly.The regioselectivity can be rationalized according to the hard-soft acid-base principle.Calculations on both charge distributions and FMO coefficients indicate that these reactions may be classified on the basis of the type of soft acid-soft base reactions.The observed γ-attack complies very well with the orientation of the FMO coefficients as estimated by a semiempirical method.
SYNTHESIS OF SUBSTITUTED 3-PYRIDINECARBOXALDEHYDES
Comins, Daniel L.,Herrick, James J.
, p. 2159 - 2164 (2007/10/02)
Treatment of 3-substituted 1-(phenoxycarbonyl)-1,2-dihydropyridines with Vilsmeier reagent (POCl3/DMF) gave 3-substituted 5-formyl-1-(phenoxycarbonyl)-1,2-dihydropyridines, which were aromatized with hot sulfur to provide 5-substituted 3-pyridinecarboxaldehydes. The formylation of 4-substituted 1-(phenoxycarbonyl)-1,4-dihydropyridines and subsequent aromatization gave 4-substituted 3-pyridinecarboxaldehydes.
SYNTHESIS OF 3-HALO- AND 3-FORMYL-4-ALKYLPYRIDINES
Comins, Daniel L.,Smith, Roy K.,Stroud, Eric D.
, p. 339 - 344 (2007/10/02)
In the presence of a catalytic amount of cuprous iodide, the addition of Grignard reagents to the 1-phenoxycarbonyl salts of 3-halopyridines gives 4-alkyl-3-halo-1-phenoxycarbonyl-1,4-dihydropyridines.The crude dihydropyridines were aromatized with o-chloroanil to give 4-alkyl-3-halopyridines.Several 4-alkylnicotinaldehydes were synthesized in a similar manner from the cyclic acetal (1,3-dioxolane) of 3-pyridinecarboxaldehyde.After aromatization with sulfur, the crude acetals were hydrolyzed with oxalic acid to give the desired pyridinecarboxaldehydes.
