cas 93-70-9, 2'-Chloroacetoacetanilide | Articles data

Articles about 93-70-9Total 18 be found

Article title
Article abstract
Author
Journal number and time
Download

Synthesis and in vitro Antidiabetic Screening of Novel Dihydropyrimidine Derivatives
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.
Lalpara,Vachhani,Hadiyal,Goswami,Dubal
p. 241 - 246
(2021/04/02)

HFIP-mediated strategy towards β-oxo amides and subsequent Friedel-Craft type cyclization to 2?quinolinones using recyclable catalyst
A simple and cost-effective 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)-mediated protocol for the synthesis of β-oxo amides has been described by using amines and β-keto esters as substrates. The reaction conditions were found to be highly efficient towards the cleavage of C[sbnd]O bond and consequent formation of the products in excellent yields and selectivity. The obtained β-oxo amides were further transformed in to the synthetically useful 2?quinolinones via intramolecular Friedel-Craft type cyclization of aromatic ring using ferrites as a recyclable catalyst. A spectrum of substrates bearing broad range of functional groups were well tolerated under the reaction conditions. The proposed mechanistic pathways were substantially verified by literature and mass-spectroscopic evidences.
Kabi, Arup K.,Gujjarappa, Raghuram,Vodnala, Nagaraju,Kaldhi, Dhananjaya,Tyagi, Ujjawal,Mukherjee, Kalisadhan,Malakar, Chandi C.
supporting information

(2020/10/20)

Structure-Activity Relationship Studies of Tetrahydroquinolone Free Fatty Acid Receptor 3 Modulators
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.
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)

Effective microwave synthesis of bioactive thieno[2,3-d]pyrimidines
A series of novel 2-Amino-3-cyanothiophenes (2a-2j) were synthesized using heterogeneous base (K2CO3) supported Gewald reaction. Cyclization of 2a-j with formamide and urea in conventional heating as well as microwave irradiation gave thieno[2,3-d]pyrimidines (3a-3j) and thieno[2,3-d]pyrimidin-2(1H)-ones(4a-4j) respectively. The reaction rates were faster and yields were higher in the microwave conditions. The structures of the compounds were confirmed with elemental analysis, mass spectral analysis, FTIR, 1H NMR and 13C NMR techniques. All the synthesized compounds were subjected to antimicrobial activity (MIC) in vitro by broth dilution method and exhibited a moderate antimicrobial activity.
Khatri, Taslimahemad T.,Shah, Viresh H.
p. 3354 - 3358
(2017/05/22)

Discovery and Optimization of Novel, Selective Histone Methyltransferase SET7 Inhibitors by Pharmacophore- and Docking-Based Virtual Screening
Histone methyltransferases are involved in various biological functions, and these methylation regulating enzymes' abnormal expression or activity has been noted in several human cancers. Within this context, SET domain-containing (lysine methyltransferase) 7 (SET7, also called KMT7, SETD7, SET9) is of increasing significance due to its diverse roles in biological functions and diseases, such as diabetes, cancers, alopecia areata, atherosclerotic vascular disease, HIV, and HCV. In this study, DC-S100, which was discovered by pharmacophore- and docking-based virtual screening, was identified as the hit compound of SET7 inhibitor. Structure-activity relationship (SAR) analysis was performed on analogs of DC-S100 and according to the putative binding mode of DC-S100, structure modifications were made to improve its activity. Of note, compounds DC-S238 and DC-S239, with IC50 values of 4.88 and 4.59 μM, respectively, displayed selectivity for DNMT1, DOT1L, EZH2, NSD1, SETD8, and G9a. Taken together, DC-S238 and DC-S239 can serve as leads for further investigation as SET7 inhibitors and the chemical toolkits for functional biology studies of SET7.
Meng, Fanwang,Cheng, Sufang,Ding, Hong,Liu, Shien,Liu, Yan,Zhu, Kongkai,Chen, Shijie,Lu, Junyan,Xie, Yiqian,Li, Linjuan,Liu, Rongfeng,Shi, Zhe,Zhou, Yu,Liu, Yu-Chih,Zheng, Mingyue,Jiang, Hualiang,Lu, Wencong,Liu, Hong,Luo, Cheng
p. 8166 - 8181
(2015/11/09)

Targeting dormant tuberculosis bacilli: Results for molecules with a novel pyrimidone scaffold
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.
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)

Vibrational, NMR and quantum chemical investigations of acetoacetanilde, 2-chloroacetoacetanilide and 2-methylacetoacetanilide
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.
Arjunan,Kalaivani,Senthilkumari,Mohan
p. 154 - 174
(2013/11/06)

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
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.
Yuan, Yucheng,Yang, Rui,Zhang-Negrerie, Daisy,Wang, Junwei,Du, Yunfei,Zhao, Kang
p. 5385 - 5392
(2013/07/26)

Synthesis and in vitro anticancer and antitubercular activity of diarylpyrazole ligated dihydropyrimidines possessing lipophilic carbamoyl group
A series of dihydropyrimidine derivatives were synthesized by utilizing Biginelli reaction and evaluated for their in vitro anticancer activity against MCF-7 human breast cancer (HBC) cell line using sulforhodamine B (SRB) assay and antitubercular activity against Mycobacterium tuberculosis (MTB) H 37Rv using Microplate Alamar Blue Assay (MABA). Compounds 13p, 13t were exhibited 70.6% and 63.7% of HBC cell growth inhibition at 10 μM concentration. Interestingly compound 13p was also found to be the most potent in the series against MTB H37Rv with MIC value of 0.125 μg/mL.
Yadlapalli, Rama Krishna,Chourasia,Vemuri, Kiranmayi,Sritharan, Manjula,Perali, Ramu Sridhar
supporting information; experimental part
p. 2708 - 2711
(2012/05/20)

Novel Biginelli dihydropyrimidines with potential anticancer activity: A parallel synthesis and CoMSIA study
Novel Biginelli dihydropyrimidines of biological interest were prepared using p-toluene sulphonic acid as an efficient catalyst. All the thirty-two synthesised dihydropyrimidines were evaluated for their in vitro antioxidant activity using DPPH method. Only, compounds 28 and 29 exhibited reasonably good antioxidant activity. Furthermore, the synthesised Biginelli compounds were subjected for their in vitro anticancer activity against MCF-7 human breast cancer cells. The title compounds were tested at the concentration of 10 μg. Compounds exhibited activity ranging from weak to moderate and, from moderate to high in terms of percentage cytotoxicity. Among them, compounds 10 and 11 exhibited significant anticancer activity. In order to elucidate the three-dimensional structure-activity relationships (3D QSAR) towards their anticancer activity, we subjected them for comparative molecular similarity indices analysis (CoMSIA). Illustration regarding their synthesis, analysis, antioxidant activity, anticancer activity and 3D QSAR study is described.
Prashantha Kumar,Sankar, Gopu,Nasir Baig,Chandrashekaran, Srinivasan
experimental part
p. 4192 - 4198
(2009/12/06)

Discovery of inducible nitric oxide synthase (iNOS) inhibitor development candidate KD7332, part 1: Identification of a novel, potent, and selective series of quinolinone iNOS dimerization inhibitors that are orally active in rodent pain models
There are three isoforms of dimeric nitric oxide synthases (NOS) that convert arginine to citrulline and nitric oxide. Inducible NOS is implicated in numerous inflammatory diseases and, more recently, in neuropathic pain states. The majority of existing NOS inhibitors are either based on the structure of arginine or are substrate competitive. We describe the identification from an ultra high-throughput screen of a novel series of quinolinone small molecule, nonarginine iNOS dimerization inhibitors. SAR studies on the screening hit, coupled with an in vivo lipopolysaccharide (LPS) challenge assay measuring plasma nitrates and drug levels, rapidly led to the identification of compounds 12 and 42 - potent inhibitors of the human and mouse iNOS enzyme that were highly selective over endothelial NOS (eNOS). Following oral dosing, compounds 12 and 42 gave a statistical reduction in pain behaviors in the mouse formalin model, while 12 also statistically reduced neuropathic pain behaviors in the chronic constriction injury (Bennett) model.
Bonnefous, Céline,Payne, Joseph E.,Roppe, Jeffrey,Zhuang, Hui,Chen, Xiaohong,Symons, Kent T.,Nguyen, Phan M.,Sablad, Marciano,Rozenkrants, Natasha,Zhang, Yan,Wang, Li,Severance, Daniel,Walsh, John P.,Yazdani, Nahid,Shiau, Andrew K.,Noble, Stewart A.,Rix, Peter,Rao, Tadimeti S.,Hassig, Christian A.,Smith, Nicholas D.
supporting information; experimental part
p. 3047 - 3062
(2010/01/16)

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
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.
Virsodia, Vijay,Pissurlenkar, Raghuvir R.S.,Manvar, Dinesh,Dholakia, Chintan,Adlakha, Priti,Shah, Anamik,Coutinho, Evans C.
p. 2103 - 2115
(2008/12/23)

Unexpected formation of new bicyclic γ-lactams by dimerization of α-chloroacetoacetanilides
Novel and unusual dimerization reaction of α-chloroacetoacetanilide under basic reaction condition to give structurally unique 6-oxa-3-azabicyclo[3.1.0]hexane was described.
Han, Minsoo,Nam, Kee-Dal,Hahn, Hoh-Gyu,Shin, Dongyun
p. 5217 - 5219
(2008/12/20)

Synthesis and bronchodilatory activity of new 4-aryl-3,5-bis(2- chlorophenyl)-carbamoyl-2,6-dimethyl-1,4-dihydropyridines & their 1-substituted analogues
Thirty five different 4-aryl-1-substituted 2,6-dimethyl-3, 5-bis-N-[(substituted) carbamoyl] 1,4-dihydropyridines have been prepared from a three component condensation reaction of N-(2-chlorophenyl)-acetoacetamide; an aromatic aldehyde and a primary amine under four different experimental conditions. Except for conventional, all the experimental conditions are simple, eco-friendly, economical, and the reactions are rapid and high yielding. All the compounds have been purified and characterized by their spectral and elemental analysis data. The methods employed have been compared in terms of yields, cost and simplicity. All the compounds have been tested for their acute toxicity, gross behavioural studies and screened for their bronchodilatory activity by standard methods.
Suresh,Swamy,Reddy
p. 115 - 121
(2008/02/09)

Synthesis and characterization of N-acylaniline derivatives as potential chemical hybridizing agents (CHAs) for wheat (Triticum aestivum L.)
Induction of male sterility by deployment of chemical hybridizing agents (CHAs) are important in heterosis breeding of self-pollinated crops like wheat, wherein the male and female organs are in the same flower. Taking a lead from the earlier work on rice, a total of 25 N-acylanilines comprising of malonanilates, acetoacetanilides, and acetanilides (including halogenated acetanilides) were synthesized and screened as CHAs on three genotypes of wheat, viz., PBW 343, HD 2046, and HD 2733 at 1500 ppm in the winter of 2001-2002. The N-acylanilines containing variations at the acyl and aromatic domain were synthesized by condensation of substituted anilines with appropriate diesters, acid chlorides, or monoesters. The test compounds with highly electronegative groups such as F/Br at the para position of the aryl ring were identified as the most potent CHAs, causing higher induction of male sterility. A variation of N-substitution at the side chain generally furnished analogues like 4′-fluoroacetoacetanilide (7) and ethyl 4′-fluoromalonanilate (1), which induced 89.12 and 84.66% male sterility, respectively, in PBW 343. Among halogenated acetanilides, the increasing number of chlorine atoms in the side chain led to an increase in the activity of 4′-fluoro (23) and 4′-bromo (24) derivatives of trichoroacetanilides, which induced >87% male sterility. Quantitative structure-activity relationship (QSAR) models indicated the positive contributions of the field effect exemplified by the Swain-Lupton constant (Fp) and negative contributions of the Swain-Lupton resonance constant (R) for the aromatic substitution. The positive influences of parachor (P) for the acyl domain have been underlined. These leads will be significant in explaining the CHA fit in the macromolecular receptor site. The CHAs appeared to act by causing an imbalance in the acid-base equilibrium in pollen mother cells resulting in dissolution of the callose wall by premature callase secretion.
Chakraborty, Kajal,Devakumar
p. 6800 - 6808
(2007/10/03)

Synthesis and structural assignment of oxanilo-N-arylhydrazonoyl chlorides
Oxanilo-N-arylhydrazonoyl chlorides have been prepared from appropriate N-aryl-2-chloro-3-oxobutanamides by the Japp-Klingemann reaction. The structures of the title compounds have been established in the solid state by single-crystal X-ray structure determination and IR spectroscopy, and in solution by IR, UV, and 1H and 13C NMR spectroscopy. The results indicate that the hydrazonoyl chloride moiety adopts the (Z)-configured form. In the crystal, intramolecular hydrogen bonds generally exist between the chloride function and the hydrazone hydrogen atom, and also between the amide hydrogen atom and the double-bonded nitrogen atom of the hydrazone moiety. In solution, this intramolecular hydrogen bonding could not be detected. In compounds with an ortho-chloro-substituted NH-aryl moiety, however, the chlorine atom is involved in hydrogen bonding to the NH hydrogen atom both in the crystal and in solution. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
Frohberg, Petra,Drutkowski, Guntram,Wagner, Christoph
p. 1654 - 1663
(2007/10/03)

Synthesis and biological activity of some haloanilido pyrazoline and isoxazoline derivatives
-
Mandal,Sinha,Banerjee
p. 979 - 981
(2007/10/02)

Cyclocondensations of Acetoacetanilides with 1,3,5-Trinitrobenzene-Substituent Effect in the Formation of Bicyclononane Derivatives
Kinetics of cyclicondensation reaction of acetoacetanilide and substituted acetoacetanilides with 1,3,5-trinitrobenzene in the presence of triethylamine have been studied in 75percentDMSO-water(v/v) at 30, 35 and 40 deg C.Electron donating groups accelerate the rate of the reaction.Strongly electron withdrawing groups in the para-position require the use of ?--values for a better correlation of the rate constants.The reaction constants and the resonance parameters have been calculated.Isokinetic relationship has been established.Equilibrium constants for the formationof sodium salts of bicyclononane derivatives from sodium salts of acetoacetanilides and TNB have been calculated.
Gnanadoss, Lalitha,Radha, N.
p. 1077 - 1081
(2007/10/02)