80357-48-8Relevant academic research and scientific papers
Structure-Activity Relationship Studies of Tetrahydroquinolone Free Fatty Acid Receptor 3 Modulators
Ulven, Elisabeth Rexen,Quon, Tezz,Sergeev, Eugenia,Barki, Natasja,Brvar, Matjaz,Hudson, Brian D.,Dutta, Palash,Hansen, Anders H?jgaard,Bielefeldt, Line O.,Tobin, Andrew B.,McKenzie, Christine J.,Milligan, Graeme,Ulven, Trond
, p. 3577 - 3595 (2020/04/30)
Free fatty acid receptor 3 (FFA3, previously GPR41) is activated by short-chain fatty acids, mediates health effects of the gut microbiota, and is a therapeutic target for metabolic and inflammatory diseases. The shortage of well-characterized tool compounds has however impeded progress. Herein, we report structure-activity relationship of an allosteric modulator series and characterization of physicochemical and pharmacokinetic properties of selected compounds, including previous and new tools. Two representatives, 57 (TUG-1907) and 63 (TUG-2015), showed improved solubility and preserved potency. Of these, 57, with EC50 = 145 nM and a solubility of 33 μM, showed high clearance in vivo but is a preferred tool in vitro. In contrast, 63, with EC50 = 162 nM and a solubility of 9 μM, showed lower clearance and seems better suited for in vivo studies. Using 57, we demonstrate for the first time that FFA3 activation leads to calcium mobilization in murine dorsal root ganglia.
Synthesis of Pyridin-2(1H)-one derivatives: Temperature-dependent selectivity
Chikhalikar, Sandip,Bhawe, Vijay,Jachak, Madhukar,Ghagare, Maruti
experimental part, p. 6085 - 6091 (2011/12/02)
Two alternative methods for the synthesis of biologically important pyridin-2(1H)-one derivatives have been developed. The behavior of enamine 1 with aromatic amines in an aqueous solution of HCl resulted in the formation of substituted enamines 2a-f at ambient temperature. The obtained product enamines 2a-f, upon treatment with 2,2,6-trimethyl-4H-1,3-dioxin-4-one, generated pyridin-2(1H)-one derivatives 5a-f along with the unwanted side products 8a-f. However, the exclusive formation of pyridin-2(1H)-one derivatives 5a-f was achieved when starting from β-enaminones 3a-f, which were synthesized successfully from enamine 1 and aromatic amines at elevated temperatures. Compounds 2 and 3 have been used as precursors in the synthesis of pyridin-2(1H)-one derivatives. Temperature-dependent reaction diversity was observed for enamine 1 and the exclusive formation of pyridin-2(1H)-one derivatives 5 was possible.
Inter-and intra-molecular cyclisation reactions of azoacetates derived from aryl hydrazones of ethyl acetoacetate and acetoacetanilides
O'Halloran, Neil,James, John P.,Downey, Carol A.,O'Malley, Patrick,Duff, Thomas,Bertrand, Samuel
experimental part, p. 2681 - 2701 (2011/04/16)
The base induced cyclisations of azoacetates to azetidinones were investigated. In addition to the isolation of the desired products, it was found that 2-iminopyrrolidine-5-one derivatives as well as N-acyl hydrazides could be isolated when metal cyanides were employed as base. These entities were further modified to form pyrrolidine-2,5-diones and diazetidinones respectively. The Japan Institute of Heterocyclic Chemistry.
Synthesis, screening for antitubercular activity and 3D-QSAR studies of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxamides
Virsodia, Vijay,Pissurlenkar, Raghuvir R.S.,Manvar, Dinesh,Dholakia, Chintan,Adlakha, Priti,Shah, Anamik,Coutinho, Evans C.
, p. 2103 - 2115 (2008/12/23)
Multi-drug resistance to commonly used antitubercular drugs has propelled the development of new structural classes of antitubercular agents. This paper reports the synthesis, evaluation and 3D-QSAR analysis of a set of substituted N-phenyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamides as antitubercular agents. Substituted acetoacetanilides were reacted with various aromatic aldehydes and urea which yielded the tetrahydropyrimidine derivatives with a phenyl carbamoyl group at C5 position, and with various substitutions on the 4-phenyl and the N-phenyl aromatic rings. All compounds were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. The QSAR models were generated on a training set of 23 molecules. The molecules were aligned using the atom-fit and field-fit techniques. The CoMFA and CoMSIA models generated on the molecules aligned by the atom-fit method show a correlation coefficient (r2) of 0.98 and 0.95 with cross-validated r2(q2) of 0.68 and 0.58, respectively. The 3D-QSAR models were externally validated against a test set of 7 molecules for which the predictive r2 (rpred2) is recorded as 0.41 and 0.32 for the CoMFA and CoMSIA models, respectively. The CoMFA and CoMSIA contours helped to design some new molecules with improved activity.
