93-68-5Relevant articles and documents
Design, parallel synthesis of Biginelli 1,4-dihydropyrimidines using PTSA as a catalyst, evaluation of anticancer activity and structure activity relationships via 3D QSAR studies
Faizan, Syed,Prashantha Kumar,Lalitha Naishima, Namburu,Ashok,Justin, Antony,Vijay Kumar, Merugumolu,Bistuvalli Chandrashekarappa, Revanasiddappa,Manjunathaiah Raghavendra, Nulgumnalli,Kabadi, Pradeep,Adhikary, Laxmi
, (2021/11/11)
Biginelli 1,4-dihydropyrimidines are extensively screened for their potential anticancer activity in the last decade. In this context, a series of Biginelli 1,4-dihydropyrimidines were designed and synthesised using PTSA as an efficient catalyst. The synthesised 1,4-dihydropyrimidines were screened for their anticancer activity against MCF-7 breast cancer cells by measuring cytotoxicity. The compounds exhibited activity ranging from weak to significant in terms of percentage cytotoxicity which is proportional to the anticancer activity. Amongst the screened compounds, compounds 4, 6 and 8 exhibited potential anticancer activity. Furthermore, CoMSIA studies were performed to derive the structure activity relationships in a 3D grid space by plotting experimental vs predicted cytotoxic activities. We have an opinion that, this developed model helps us in future to develop more potential 1,4-dihydropyrimidines for their cytotoxicity or anticancer activity.
Synthesis and in vitro Antidiabetic Screening of Novel Dihydropyrimidine Derivatives
Lalpara,Vachhani,Hadiyal,Goswami,Dubal
, p. 241 - 246 (2021/04/02)
Abstract: A series of N-substituted-6-methyl-4-{4-[5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl]methoxyphenyl}-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamides have been synthesized by the condensation of newly synthesized {4-[5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl]methoxy}benzaldehyde with variously substituted acetoacetanilides and urea in the presence of ethanol. The synthesized compounds have been characterized by 1H, 13C NMR, IR spectroscopy, and mass spectrometry. All synthesized compounds were evaluated for in vitro antidiabetic activity using the α-amylase inhibition assay with the 3,5-dinitrosalicylic acid (DNSA) reagent.
Enantioselective α-Amination of Acyclic 1,3-Dicarbonyls Catalyzed by N-Heterocyclic Carbene
Santra, Surojit,Maji, Ujjwal,Guin, Joyram
supporting information, p. 468 - 473 (2020/02/04)
Herein, we describe a method for the catalytic enantioselective α-amination of α-substituted acyclic 1,3-ketoamides and 1,3-amidoesters that affords the products possessing N-substituted quaternary stereocenters with a chiral N-heterocyclic carbene (NHC). The reaction is based on the utilization of an intrinsic Br?nsted base characteristic of NHC that enables the catalytic formation of a chiral ion pair comprising the enolate and the azolium ion. A series of challenging open-chain α-substituted 1,3-dicarbonyls are aminated via this method with ee's of ≤99%.
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.
A reduce the adjacent methyl-N-acetyl acetanil method for producing by-product in the
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Paragraph 0021-0024, (2017/05/16)
The invention discloses a method for reducing byproducts in o-methyl-N-acetoacetanilide production. The method comprises the following steps: adding alcohol into a reaction container, stirring, simultaneously adding diketene and o-toluidine in a dropwise manner at 0-30DEG C, carrying out a heat insulation reaction at 10-50DEG C for 1-5h, filtering, and drying to obtain finished o-methyl-N-acetoacetanilide; and adding an acidic catalyst into an alcohol filtrate obtained after filtration, distilling at 80-100DEG C to obtain an alcohol distillation liquid, and reusing the alcohol distillation liquid in a next batch reaction as alcohol, wherein a mass ratio of o-toluidine to the acidic catalyst is 1:0.0001-0.01. The method adopting alcohol as a solvent to optimize the crystal form of the above product prevents caking in the product disposal process, improves the appearance and the performances of the product, improves the yield of the product, and reduces the consumption of o-toluidine and diketene.
Targeting dormant tuberculosis bacilli: Results for molecules with a novel pyrimidone scaffold
Joshi, Rohit R.,Barchha, Avinash,Khedkar, Vijay M.,Pissurlenkar, Raghuvir R. S.,Sarkar, Sampa,Sarkar, Dhiman,Joshi, Rohini R.,Joshi, Ramesh A.,Shah, Anamik K.,Coutinho, Evans C.
, p. 201 - 207 (2015/01/30)
Our inability to completely control TB has been due in part to the presence of dormant mycobacteria. This also renders drug regimens ineffective and is the prime cause of the appearance of drug-resistant strains. In continuation of our efforts to develop novel antitubercular agents that especially target dormant mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and subsequently tested against both the dormant and virulent BCG strain of M. tuberculosis. Some novel compounds have been identified which selectively inhibit the dormant tuberculosis bacilli with significantly low IC50 values. This study reports the second molecule after TMC-207, having the ability to inhibit tuberculosis bacilli exclusively in its dormant phase. The synthesis was accomplished by a modified multicomponent Biginelli reaction. A classification model was generated using the binary QSAR approach - recursive partitioning (RP) to identify structural characteristics related to the activity. Physicochemical, structural, topological, connectivity indices, and E-state key descriptors were used for generation of the decision tree. The decision tree could provide insights into structure-activity relationships that will guide the design of more potent inhibitors. This paper reports the second molecule after TMC-207, with the ability to inhibit tuberculosis bacilli in its dormant phase. The paper reports molecules with a novel Pyrimidone Scaffold, the synthesis of which was accomplished with a modified multi-component Biginelli reaction. A classification model was generated using recursive partitioning (RP) technique to identify structural characteristics of the molecules with their varying activities.
Vinyl polymerizations of norbornene catalyzed by nickel complexes with acetoacetamide ligands
Feng, Qian,Chen, Dajun,Feng, Danyang,Jiao, Libin,Peng, Zhigang,Pei, Lixia
, p. 32 - 37 (2014/01/06)
On the basis of a remote effect, a series of acetoacetamide ligands and corresponding nickel complexes N-(R-phenyl) acetoacetamide Ni(CH2Ph) (PMe3) (R = H, 1; R = 2-methyl, 2; R = 2,6-dimethyl, 3; R = 2,6-diisopropyl, 4; R = 4-NO2, 5) were synthesized and characterized. The solid structure of complex 3 was confirmed by X-ray single-crystal analysis to be of cis form. 1H and 31P NMR spectroscopy confirmed that cis and trans isomers of nickel complexes were present in solution. Norbornene polymerizations with acetoacetamide nickel complexes activated with modified methylaluminoxane (MMAO) were investigated in detail. Remote steric and electronic effects of acetoacetamide ligand on catalytic activity and molecular weight of polynorbornenes (PNBs) were observed. Characterizations of the obtained PNBs show that the obtained polymer products are non-crystalline vinylic-addition polynorbornenes. Copyright
Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands
Hudson, Brian D.,Christiansen, Elisabeth,Murdoch, Hannah,Jenkins, Laura,Hansen, Anders H?jgaard,Madsen, Ole,Ulven, Trond,Milligan, Graeme
supporting information, p. 200 - 210 (2014/10/15)
Analysis of the roles of the short chain fatty acid receptor, free fatty acid 3 receptor (FFA3), has been severely limited by the low potency of its endogenous ligands, the crossover of function of these on the closely related free fatty acid 2 receptor, and a dearth of FFA3-selective synthetic ligands. From a series of hexahydroquinolone-3-carboxamides, we demonstrate that 4-(furan-2-yl)-2-methyl-5-oxo-N-(o-tolyl)-1,4,5,6,7, 8-hexahydroquinoline-3- carboxamide is a selective and moderately potent positive allosteric modular (PAM)-agonist of the FFA3 receptor. Modest chemical variations within this series resulted in compounds completely lacking activity, acting as FFA3 PAMs, or appearing to act as FFA3-negative allosteric modulators. However, the pharmacology of this series was further complicated in that certain analogs displaying overall antagonism of FFA3 function actually appeared to generate their effects via a combined positive allosteric binding cooperativity and negative allosteric effect on orthosteric ligand maximal signaling response. These studies show that various PAM-agonist and allosteric modulators of FFA3 can be identified and characterized. However, within the current chemical series, considerable care must be taken to define the pharmacological characteristics of specific compounds before useful predictions of their activity and their use in defining specific roles of FFA3 in either in vitro and in vivo settings can be made. Copyright
Vibrational, NMR and quantum chemical investigations of acetoacetanilde, 2-chloroacetoacetanilide and 2-methylacetoacetanilide
Arjunan,Kalaivani,Senthilkumari,Mohan
, p. 154 - 174 (2013/11/06)
The vibrational assignment and analysis of the fundamental modes of the compounds acetoacetanilide (AAA), 2-chloroacetoacetanilide (2CAAA) and 2-methylacetoacetanilide (2MAAA) have been performed. Density functional theory studies have been carried out with B3LYP method utilising 6-311++G ** and cc-pVTZ basis sets to determine structural, thermodynamic and vibrational characteristics of the compounds and also to understand the influence of chloro and methyl groups on the characteristic frequencies of amide (-CONH-) group. intramolecular hydrogen bond exists in acetoacetanilide and o-substituted acetoacetanilide molecules and the N?O distance is found to be around 2.7 ?. The 1H and 13C nuclear magnetic resonance chemical shifts of the molecules were determined and the same have been calculated using the gauge independent atomic orbital (GiAO) method. The energies of the frontier molecular orbitals have been determined. in AAA, 2CAAA and 2MAAA molecules, the nN → pπ*co Interaction between the nitrogen lone pair and the amide C=O antibonding orbital gives strong stabilization of 64.75, 62.84 and 64.18 kJ mol 1, respectively. The blue shift in amide-ii band of 2MAAA is observed by 45-50 cm1 than that of AAA. The steric effect of ortho methyl group significantly operating on the N-H bond properties. The amide-iii, the C-N stretching mode of methyl and chloro substituted aceto-acetanilide compounds are not affected by the substitution while the amide-V band, the N-H out of plane bending mode of 2-chloroacetoacetanilide compound is shifted to a higher frequency than that of AAA. The substituent chlorine plays significantly and the blue shift in o-substituted compounds than the parent in the amide-V vibration is observed. The amide-Vi, C=O out of plane bending modes of 2MAAA and 2CAAA are significantly raised than that of AAA. A blue shift of amide-Vi, C=O out of plane bending modes of 2MAAA and 2CAAA than AAA is observed.
One-pot synthesis of 3-hydroxyquinolin-2(1 H)-ones from N-phenylacetoacetamide via PhI(OCOCF3)2-mediated α-hydroxylation and H2SO4-promoted intramolecular cyclization
Yuan, Yucheng,Yang, Rui,Zhang-Negrerie, Daisy,Wang, Junwei,Du, Yunfei,Zhao, Kang
, p. 5385 - 5392 (2013/07/26)
A clean, one-pot synthesis of the biologically important 3-hydroxyquinolin-2(1H)-one compounds has been realized from the readily available N-phenylacetoacetamide derivatives through a PhI(OCOCF 3)2-mediated α-hydroxylation and a H 2SO4-promoted intramolecular condensation. The hydroxyl group in the generated α-hydroxylated intermediate can be well tolerated in the second H2SO4-promoted cyclization step.
