- 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)
-
- Synthesis and anticonvulsant activity of some 1,4-dihydropyridine derivatives
-
A series of asymmetrical 4-alkyl/aryl-2,6-dimethyl-3-N-(aryl/heteroaryl)-carbamoyl-5-ethoxycarbonyl-1, 4-dihydropyridines 3a-d and symmetrical 4-alkyl/aryl-2,6-dimethyl-3,5-bis-(ethoxycarbonyl)-1,4-dihydropyridines 4a and 4b have been prepared by the condensation of various benzaldehydes, ethylacetoacetate, 2-aminopyridine or p-toludine in ethanol (Hantzch method). The structures of all the synthesized 1,4-dihydropyridine derivatives have been confirmed by spectral data (IR,1H NMR) and elemental analysis. Compounds 3a-c, 4a and 4b (10 mg/kg) have been evaluated for their anticonvulsant effect against pentylenetetrazole- induced convulsions with phenytoin (4 mg/kg) as the standard. The anticonvulsant potential of the newly synthesized compounds have been assessed on the basis of increase in latency (onset time) to induce convulsions; decrease in number of convulsions and increase in latency of death compared to control and standard.
- Begum, Safia,Sirisha, Kalam
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p. 433 - 438
(2021/09/28)
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- Ru-NHC-Catalyzed Asymmetric Hydrogenation of 2-Quinolones to Chiral 3,4-Dihydro-2-Quinolones
-
Direct enantioselective hydrogenation of unsaturated compounds to generate chiral three-dimensional motifs is one of the most straightforward and important approaches in synthetic chemistry. We realized the Ru(II)-NHC-catalyzed asymmetric hydrogenation of 2-quinolones under mild reaction conditions. Alkyl-, aryl- and halogen-substituted optically active dihydro-2-quinolones were obtained in high yields with moderate to excellent enantioselectivities. The reaction provides an efficient and atom-economic pathway to construct simple chiral 3,4-dihydro-2-quinolones. The desired products could be further reduced to tetrahydroquinolines and octahydroquinolones.
- Daniliuc, Constantin,Glorius, Frank,Hu, Tianjiao,Lückemeier, Lukas
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supporting information
p. 23193 - 23196
(2021/09/25)
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- HFIP-mediated strategy towards β-oxo amides and subsequent Friedel-Craft type cyclization to 2?quinolinones using recyclable catalyst
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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.
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supporting information
(2020/10/20)
-
- Enantioselective α-Amination of Acyclic 1,3-Dicarbonyls Catalyzed by N-Heterocyclic Carbene
-
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%.
- Santra, Surojit,Maji, Ujjwal,Guin, Joyram
-
supporting information
p. 468 - 473
(2020/02/04)
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- Structure-Activity Relationship Studies of Tetrahydroquinolone Free Fatty Acid Receptor 3 Modulators
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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)
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- 2- Amino -3,4-dihydropyran -3- formamide analogue as well as preparation method and application thereof
-
The invention relates to a preparation method 2 - of a compound containing, amino - 333384-dihydropyran - 3 3, which comprises the following step :1) of linking diketene with R. 2 NH2 The reaction is stirred in a solvent to complete. ;2) Is added R. 3 NH2 , R1 CHO And a of Compound, and adding elemental iodine to reaction solution to complete curing, and drying the filter cake to obtain compound 2 - containing. amino - 3333,4-dihydropyran - 3 3-carboxamide compound, according to the present invention as well as its use. without isolation of intermediate, in a simple.
- -
-
Paragraph 0082-0084
(2020/03/25)
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- 5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors
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Chronic hepatitis B virus (HBV) infection represents a major health threat. Current FDA-approved drugs do not cure HBV. Targeting HBV core protein (Cp) provides an attractive approach toward HBV inhibition and possibly infection cure. We have previously identified and characterized a 5-amino-3-methylthiophene-2,4-dicarboxamide (ATDC) compound as a structurally novel hit for capsid assembly effectors (CAEs). We report herein hit validation through studies on absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK), and hit optimization via analogue synthesis aiming to probe the structure-activity relationship (SAR) and structure-property relationship (SPR). In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC50 = 0.11 μM, CC50 > 100 μM, F = 25%) and 19k (EC50 = 0.31 μM, CC50 > 100 μM, F = 46%), displayed overall lead profiles superior to reported CAEs 7–10 used in our studies.
- Tang, Jing,Huber, Andrew D.,Pineda, Dallas L.,Boschert, Kelsey N.,Wolf, Jennifer J.,Kankanala, Jayakanth,Xie, Jiashu,Sarafianos, Stefan G.,Wang, Zhengqiang
-
supporting information
p. 179 - 192
(2019/01/04)
-
- Synthesis of β-Ketoamide Curcumin Analogs for Anti-Diabetic and AGEs Inhibitory Activities
-
Two different series of novel β-ketoamide curcumin analogs enriched in biological activities have been synthesized. The synthesized compounds were screened for their in?vitro anti-diabetic and AGEs inhibitory activities and exhibited potent to good anti-diabetic and AGEs inhibitory activities. The molecular docking study was also performed with the α-amylase enzyme.
- Banuppriya, Govindharasu,Sribalan, Rajendran,Fathima, Sulthan Alavudeen Rizwan,Padmini, Vediappen
-
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- Compounds having anticonvulsion activity, preparing methods thereof and applications of the compounds
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The invention provides 7-substituted-5-methyl-1,2,4-triazolo[4,3-a] quinoline and 7-substituted-5-ethoxy-[1,2,4]-triazolo[4,3-a] quinoline compounds having anticonvulsion activity, preparing methods thereof and applications of the compounds in the field of preparing anticonvulsion medicines.
- -
-
Paragraph 0041; 0042
(2017/10/05)
-
- 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.
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p. 3354 - 3358
(2017/05/22)
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- Selective exploitation of acetoacetate carbonyl groups using imidazolium based ionic liquids: synthesis of 3-oxo-amides and substituted benzimidazoles
-
An unprecedented Br?nsted base ionic liquid tuned selective aminolysis of ester carbonyl of acetoacetates is demonstrated to achieve acetoacetamide derivatives. Other imidazolium ionic liquid performs an efficient cyclization catalysis involving acetoacetate-carbonyl groups and o-phenylenediamine at elevated temperature to produce benzimidazoles via C–C bond cleavage of intermediate 1,5-benzodiazepinones under solvent-free conditions.
- Chakraborty, Ankita,Majumdar, Swapan,Maiti, Dilip K.
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p. 3298 - 3302
(2016/07/11)
-
- Design, Multicomponent Synthesis and Characterization of Diversely Substituted Pyrazolo[1,5-a] Pyrimidine Derivatives
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The synthesis of various heterocyclic compounds using acetoacetanilide[AAA], we have demonstrated that acetoactanilide are versatile intermediate for the synthesis of pyrazolopyrimidine derivatives. Thus, to explore further, we sought that the reaction of various acetoactanilide, an appropriate aldehyde and 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-carboxamide in the presence of base in isopropyl alcohol could be an effective strategy to furnish the novel pyrazolopyrimidine derivatives. Here we describe the novel synthetic methodology for the fused pyrazolopyrimidines.
- Ghelani, Satish M.,Naliapara, Yogesh T.
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p. 1843 - 1851
(2016/11/23)
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- Silver(I)-catalyzed tandem approach to β-oxo amides
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A facile and efficient AgI-catalytic approach is reported for the first time to synthesize β-oxo amides from β-oxo esters a with broad substrate scope in good to excellent yields. Crossover and in situ NMR studies confirmed that the reaction occurred through a new pathway and not by the traditional condensation reaction. The key advantages of this method are the readily available starting materials, the air-stable reaction, the simple protocol, and the environmental friendliness. A new, catalytic approach to the synthesis of β-oxo amides from β-oxo esters with a broad substrate scope in good to excellent yields was developed. In situ NMR spectroscopy and crossover experiments confirmed the reaction mechanism.
- Vandavasi, Jaya Kishore,Hsiao, Cheng-Tien,Hu, Wan-Ping,Boominathan, Siva Senthil Kumar,Wang, Jeh-Jeng
-
supporting information
p. 3171 - 3177
(2015/05/13)
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- Multicomponent strategy to indeno[2,1- C ]pyridine and hydroisoquinoline derivatives through cleavage of carbon-carbon bond
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A concise and efficient three-component domino reaction has been developed for the synthesis of polyfunctionalized indenopyridine and hydroisoquinoline derivatives via the cleavage of a C-C bond under transition-metal-free conditions. This reaction provides facile access to complex nitrogen-containing heterocycles by simply mixing three common starting materials in EtOH in the presence of 20 mol % NaOH under microwave irradiation conditions.
- Feng, Xian,Wang, Jian-Jun,Xun, Zhan,Huang, Zhi-Bin,Shi, Da-Qing
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p. 1025 - 1033
(2015/01/30)
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- An efficient green protocol for the preparation of acetoacetamides and application of the methodology to a one-pot synthesis of Biginelli dihydropyrimidines. Expansion of dihydropyrimidine topological chemical space
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The present study describes the preparation of N-aryl-(15) and N-alkyl-(17) acetoacetamides, in good to excellent yields, using both conventional and microwave heating, by reaction of amine derivatives (14 and 16) with 2,2,6-trimethyl-4H-1,3-dioxin-4-one (TMD, 12) in aqueous medium. The acetoacetamides were used to prepare novel Biginelli dihydropyrimidine derivatives. The introduction of the amino acid derivatives potentially allows for the exploration of new structural complexity and topologically diversifies the chemical space occupied by this versatile chemical scaffold.
- Gama, Fernando H. S.,De Souza, Rodrigo O. M. A.,Garden, Simon J.
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p. 70915 - 70928
(2015/09/08)
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- Facile eco-friendly synthesis of novel chromeno[4,3-b]pyridine-2,5-diones and evaluation of their antimicrobial and antioxidant properties
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Rapid and facileaccess to novel chromeno[4,3-b]pyridine-2,5-dione derivatives was achieved by a mild base catalysed reaction of 4-chloro-3-formylcoumarin and acetoacetamides in PEG-300 as recyclable solvent. The compounds were evaluated for their antimicrobial activities against 3 Gram-positive and 3 Gram-negative bacteria (Staphylococcus epidermis, Vibrio parahaemolyticus, Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia) with Cefotaxime control. They were further subjected to antioxidant studies using DPPH test with ascorbic acid control. While compounds 5d and 5k showed promising broad spectrum antibacterial properties against all the evaluated bacteria, compound 5g exhibited good antioxidant properties. Indian Academy of Sciences.
- Jaggavarapu, Satyanarayana Reddy,Kamalakaran, Anand Solomon,Jalli, Ventkata Prasad,Gangisetty, Sravan Kumar,Ganesh, Munusswamy Ramanujam,Gaddamanugu, Gopikrishna
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p. 187 - 195
(2014/04/03)
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- Facile eco-friendly synthesis of novel chromeno[4,3-b]pyridine-2,5-diones and evaluation of their antimicrobial and antioxidant properties
-
Rapid and facile access to novel chromeno[4,3-b]pyridine-2,5-dione derivatives was achieved by a mild base catalysed reaction of 4-chloro-3-formylcoumarin and acetoacetamides in PEG-300 as recyclable solvent. The compounds were evaluated for their antimicrobial activities against 3 Gram-positive and 3 Gram-negative bacteria (Staphylococcus epidermis, Vibrio parahaemolyticus, Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia) with Cefotaxime control. They were further subjected to antioxidant studies using DPPH test with ascorbic acid control. While compounds 5d and 5k showed promising broad spectrum antibacterial properties against all the evaluated bacteria, compound 5g exhibited good antioxidant properties. [Figure not available: see fulltext.]
- Jaggavarapu, Satyanarayana Reddy,Kamalakaran, Anand Solomon,Jalli, Ventkata Prasad,Gangisetty, Sravan Kumar,Ganesh, Munusswamy Ramanujam,Gaddamanugu, Gopikrishna
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p. 187 - 195
(2016/02/26)
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- Ligand-enabled γ-C-H olefination and carbonylation: Construction of β-quaternary carbon centers
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Monoselective γ-C-H olefination and carbonylation of aliphatic acids has been accomplished by using a combination of a quinoline-based ligand and a weakly coordinating amide directing group. The reaction provides a new route for constructing richly functionalized all-carbon quaternary carbon centers at the β-position of aliphatic acids.
- Li, Suhua,Chen, Gang,Feng, Chen-Guo,Gong, Wei,Yu, Jin-Quan
-
supporting information
p. 5267 - 5270
(2014/05/06)
-
- Palladium(II)-catalyzed sequential c-cl bond formation: A novel and efficient method for direct α,α-dichlorination of β-dicarbonyl compounds
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A simple and concise procedure for the synthesis of 2,2-dichloro-3-oxo-N- phenylbutanamides, via palladium-catalyzed C(sp3)-H dichlorination of 3-oxo-N-phenylbutanamides, is described. The protocol provides a direct route to α,α-dichlorinated products starting from β-dicarbonyl compounds. A plausible mechanism for this transformation involving two consecutive chlorination steps is described.
- Liu, Weibing,Tan, Liquan,Zhou, Peng,Chen, Cui,Zhang, Qing
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p. 2600 - 2604
(2013/09/24)
-
- Synthesis and in vitro anticancer and antitubercular activity of diarylpyrazole ligated dihydropyrimidines possessing lipophilic carbamoyl group
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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)
-
- Synthesis, antibacterial and antimycobacterial activities of some new 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(aryl)-carbamoyl-1,4-dihydropyridines
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A novel class of 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(phenyl/ substituted phenyl)-carbamoyl-1,4-dihydropyridines has been synthesized by simple, economical and eco-friendly, modified Hantzsch condensation reaction making use of N-arylacetoacetamides, aryl or heteroaryl aldehydes and ammonium acetate. The newly synthesized compounds were characterized by their spectral (IR, 1H NMR, Mass), elemental analyses data and evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H 37Rv ATCC 27294 and antibacterial activity against different Gram +ve and Gram -ve bacteria. The preliminary screening results revealed that some of the compounds possess promising antimicrobial activity. Amongst the new series of compounds, 6m containing pyrrolyl and 4-methylphenyl groups and 6r possessing 2-pyridyl and 2-methylphenyl groups were found to exhibit a significant antitubercular activity (MIC = 12.5-25 μg/mL) in comparison with the first line drug pyrazinamide.
- Sirisha, Kalam,Bikshapathi, Darna,Achaiah, Garlapati,Reddy, Vanga Malla
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experimental part
p. 1564 - 1571
(2011/05/06)
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- Diversity-oriented synthesis of quinolines via Friedlaender annulation reaction under mild catalytic conditions
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An efficient and practical method has been manifested for the diversity-oriented synthesis of quinolines via Friedlaender annulation reaction for the generation of a wide range of structurally interesting and pharmacologically significant compounds by using eerie ammonium, nitrate as a catalyst (10 mol %) at ambient temperature in 45 min, A variety of functional groups are introduced at various positions of the quinoline moiety, and further the diversity of the core skeleton was expanded at R1 and R 2 positions by the synthesis of various hybrids. Initial screening of the compounds for cytotoxicity against a series of cancer cell lines showed promising results.
- Subhas Bose,Idrees, Mohd,Jakka,Venkateswara Rao
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experimental part
p. 100 - 110
(2010/10/19)
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- Diastereoselective hydrogenation of substituted quinolines to enantiomerically pure decahydroquinolines
-
The stereoselective hydrogenation of auxiliary-substituted quinolines was used to build up saturated and partially saturated heterocycles. In a first step, the formation and diastereoselective hydrogenation of 2-oxazolidinone- substituted quinolines to 5,6,7,8-tetrahydroquinolines is reported. In this unprecedented process, stereocenters on the carbocyclic quinoline ring were formed with a dr of up to 89:11. Platinum oxide as a catalyst and trifluoroacetic acid as a solvent were found to be optimal for high levels of chemo- and stereoselectivity in this step. In a second hydrogenation step, the completely saturated decahydroquinolines with 4 newly formed stereocenters were obtained with enantioselectivities of up to 99%. Rhodium on carbon as a catalyst and acetic acid as a solvent gave the best results for this hydrogenation and allowed a traceless cleavage of the chiral auxiliary. Thus, this new method allows an efficient stereoselective synthesis of valuable 5,6,7,8-tetrahydro- and decahydroquinoline products.
- Heitbaum, Maja,Froehlich, Roland,Glorius, Frank
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supporting information; experimental part
p. 357 - 362
(2010/05/19)
-
- Multi-component synthesis of dihydropyrimidines by iodine catalyst at ambient temperature and in-vitro antimycobacterial activity
-
An efficient and simple three-component domino synthesis of some new dihydropyrimidines (DHPMs) from aromatic aldehydes, 1,3-dicarbonyl compounds and N-(3-chloro-4-fluorophenyl) urea using molecular iodine as catalyst is described. The 1-substituted dihydropyrimidines were isolated in good to excellent yields (78-90%) within a short reaction time (4-6 h) at ambient temperature. The biological evaluation revealed that the newly synthesized compounds (4a-i and 5a-i) exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis H37 RV.
- Zalavadiya, Paresh,Tala, Satish,Akbari, Jignesh,Joshi, Hitendra
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experimental part
p. 469 - 475
(2009/12/05)
-
- Inter-and intra-molecular cyclisation reactions of azoacetates derived from aryl hydrazones of ethyl acetoacetate and acetoacetanilides
-
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.
- O'Halloran, Neil,James, John P.,Downey, Carol A.,O'Malley, Patrick,Duff, Thomas,Bertrand, Samuel
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experimental part
p. 2681 - 2701
(2011/04/16)
-
- 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.
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p. 2103 - 2115
(2008/12/23)
-
- Unexpected formation of new bicyclic γ-lactams by dimerization of α-chloroacetoacetanilides
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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
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p. 5217 - 5219
(2008/12/20)
-
- Kinetics and mechanism of gas-phase pyrolysis of N-aryl-3-oxobutanamide ketoanilides, their 2-arylhydrazono derivatives, and related compounds
-
Rates and products of reaction and Arrhenius activation parameters were determined for the gas-phase thermolysis of 14 substrates of the title compounds using sealed pyrex reactor tubes and HPLC/UV-VIS to monitor substrate pyrolysis. The 14 compounds under study are N-phenyl-3-oxo- (1), N-(p-chlorophenyl)-3-oxo- (2). N-(p-methylphenyl)-3-oxo- (3). and N-(p-methoxyphenyl)-3-oxobutanamide (4). in addition to (i) four substrates (5-8) obtained by the replacement of the pairs of methylene hydrogens at the 2-position of compounds (1-4), each pair by a phenylhydrazono group; (ii) three arylhydrazono derivatives (9-11) in which Cl, CH3, or OCH3 groups are substituted at the para position of the phenylhydrazono moiety of compound 5, (iii) 3-oxobutanamide (acetoacetamide. 12), N-phenyl-3-oxo-3- phenylpropanamide (13), and N,N′-diphenylpropanediamide (14). The reactions were conducted over 374-546 K temperature range, and the values of the Arrhenius log A(s-1) and Ea(kJ mol-1) of these reactions were, respectively, 120±2.0 and 119.2 ± 17.0 for the ketoanilides (1-4, 12-14), and 13.0 ± 0.7 and 157.5 ± 8.6 for the arylhyrazono compounds (5-11). Kinetically. the arylhydrazono derivatives were found to be ca. 1.4 × 103 to 5.7 × 103 times less reactive than the parent ketoanilides. A mechanism is proposed to account for reaction products and to rationalize molecular reactivities.
- Malhas, Rana N.,Al-Awadi, Nouria A.,El-Dusouqui, Osman M.E.
-
-
- Ru(bpy)33+ electrochemiluminescence detection of aliphatic and aromatic amines with diketene
-
A new derivatization method for the detection of aliphatic and aromatic amines, based on electro-chemiluminescence (ECL) with Ru(bpy)32+ is proposed. Sample amines were derivatized to acetoacetylamide-type derivatives using diketene. The derivatives were detected by reversed-phase HPLC with ECL detection using Ru(bpy)32+.
- Uchikura, Kazuo
-
-
- Synthesis and immunosuppressant activity of pyrazole carboxamides
-
A series of novel pyrazole carboxamides sis disclosed that demonstrate strong immunosuppressant activity in rodent and human mixed leukocyte response (MLR) assays (IC50 1 μM). The synthesis, biological activity, mode of action, and pharmacokinetic properties of this new lead series are discussed.
- Wang, Alan X.,Xie, Qinghua,Lane, Ben,Mollison, Karl W.,Hsieh, Gin C.,Marsh, Kennan,Sheets, Michael P.,Luly, Jay R.,Coghlan, Michael J.
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p. 2787 - 2792
(2007/10/03)
-
- Drug-induced modifications of the immune response. 12. 4,5-Dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids and derivatives as novel antiallergic agents
-
The synthesis of a series of novel 4,5-dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids, salts, esters, and amides is described. The title compounds when tested in the mediator-induced dermal vascular permeability and active anaphylaxis assays in rats demonstrated moderate to potent antiallergic activity. The [2-trans-(4-methyl-phenyl)cyclopropyl]amino analogue 53 emerged as the most active derivative. Thus, when administered intraperitoneally to rate at a dose of 100 mg/kg, it inhibited the action of the mediators serotonin, histamine, and bradykinin by 100%. In the active anaphylaxis assay in rats, compound 30 suppressed the edema by 81% at a dose of 100 mg/kg, following intraperitoneal administration.
- Mck,Zazulak,Radov,baer,Steward,Elzer,Kinsolving,Georgiev
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p. 1910 - 1918
(2007/10/02)
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- Two Unusual Trimers of Diketene
-
Formation of two unknown, tricyclic trimers of diketene, 3 and 4, was observed in diketene solutions containing (CH3)3SiCl/NaI or TsOH.
- Ernest, Ivan,Fritz, Hans,Rihs, Grety
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p. 203 - 209
(2007/10/02)
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- Hydrogenolysis of the C-O Bond of the 1,2,4-Oxadiazine Ring. Adams Platinum Hydrogenation of 3-Aryl-5,6-dihydro-5-(substituted)-methylene-4H-1,2,4-oxadiazine Derivatives
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Adams platinum hydrogenation of Z-3-aryl-5,6-dihydro-5-(substituted)methylene-4H-1,2,4-oxadiazine (1a-f) proceeds very slowly through C-O bond fission to give N-(1-substitutedcarbonyl-2-propylidene)benzamide oxime derivative 2 as the main product.In the reaction of 5-(arylcarbamoyl)methylene analogues 1d-f, 5-(arylcarbamoyl)methyl-5,6-dihydro-3-phenyl-4H-1,2,4-oxadiazine (4) and N-aryl-3-hydroxybutanamide derivative 5 are also obtained as well as compound 2.
- Kawashima, Etsuko,Takada, Toyozo,Tabei, Katsumi
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p. 1409 - 1412
(2007/10/02)
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- MECHANISM OF ACETOACETYLATION OF SUBSTITUED ANILINES
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Kinetics have been studied of the reaction of diketene with substituted anilines, and the reaction rate has been found to depend on relative permitivity of the system.The rate and equilibrium constants have been calculated by combination of rate and equilibrium relations with the relation by Amis; the constants correlate with the Hammett substituent constants.The reaction does not proceed as a simple bimolecular process.A reaction mechanism has been suggested.
- Knizek, Jiri,Lejdar, Erhard,Vetesnik, Pavel
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p. 365 - 374
(2007/10/02)
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- Cyclocondensations of Acetoacetanilides with 1,3,5-Trinitrobenzene-Substituent Effect in the Formation of Bicyclononane Derivatives
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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.
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p. 1077 - 1081
(2007/10/02)
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