- DERIVATIVES OF THE N-(PYRID-2-YL)AMIDES OF 3-AMINOCROTONIC ACID AS CHELATING LIGANDS
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New chelating ligands, N-(pyrid-2-yl)amides of 4,4,4-trichloro-3-amino-2-cyanocrotonic acid have been synthesized from N-(pyrid-2-yl)amides of cyanoacetic acid and CCl3CN.It has been demostrated that by the action of butylthiodibutylborane they form binuclear boron chelate complexes.Analogous chelates have been obtained from the N-(pyrid-2-yl)amides of acetoacetic and 4,4,4-trichloro-3-aminocrotonic acids. Keywords: acylaminopyridines, trichloroacetonitrile, boron chelates
- Dorokhov, V. A.,Baranin, S. V.,Dib, A.,Cherkasova, K. L.,Bochkareva, M. N.,Bogdanov, V. S.
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- Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study
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A series of novel pyrazole linked triazolo-pyrimidine hybrids were synthesized and evaluated for their anti-tuberculosis activity against M.tb H37Rv strain. Some of the screened entities rendered promising anti-tb activity (MIC: 0.39 μg/mL) and were found non toxic against Vero cells (IC50: ≥20 μg/mL). Further, the docking study against wild type InhA enzyme of Mycobacterium tuberculosis using Glide reproduced the most active inhibitors (J21 and J27) with lowest binding energies and highest Glide XP scores demonstrating efficient binding to the active pocket. Additionally, the enzyme inhibition assay and ADME prediction of the active proved to be an attest to the possibility of developing compound J27 as a potent anti-tubercular lead.
- Bhatt, Jaimin D.,Chudasama, Chaitanya J.,Patel, Kanuprasad D.
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- Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors
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Classic galactosemia is a rare disease caused by inherited deficiency of galactose-1 phosphate uridylyltransferase (GALT). Accumulation of galactose-1 phosphate (gal-1P) is thought to be the major cause of the chronic complications associated with this disease, which currently has no treatment. Inhibiting galactokinase (GALK1), the enzyme that generates galactose-1 phosphate, has been proposed as a novel strategy for treating classic galactosemia. Our previous work identified a highly selective unique dihydropyrimidine inhibitor against GALK1. With the determination of a co-crystal structure of this inhibitor with human GALK1, we initiated a structure-based structure-activity relationship (SAR) optimization campaign that yielded novel analogs with potent biochemical inhibition (IC50 100 nM). Lead compounds were also able to prevent gal-1P accumulation in patient-derived cells at low micromolar concentrations and have pharmacokinetic properties suitable for evaluation in rodent models of galactosemia.
- Liu, Li,Tang, Manshu,Pragani, Rajan,Whitby, Frank G.,Zhang, Ya-Qin,Balakrishnan, Bijina,Fang, Yuhong,Karavadhi, Surendra,Tao, Dingyin,LeClair, Christopher A.,Hall, Matthew D.,Marugan, Juan J.,Boxer, Matthew,Shen, Min,Hill, Christopher P.,Lai, Kent,Patnaik, Samarjit
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p. 13551 - 13571
(2021/09/28)
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- Synthesis and anticonvulsant activity of some 1,4-dihydropyridine derivatives
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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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- 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)
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- Metal and Solvent-Free Synthesis of 2H-Pyrido[1,2-a]pyrimidin-2-ones Catalyzed by Elemental Sulfur
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The efficiency of elemental sulfur for the synthesis of 2H-pyrido[1,2-a]pyrimidin-2-ones has been demonstrated. This strategy involves coupling of 2-aminopyridines and β-oxo esters under neat condition in the absence of external oxidant. The reaction does not require pre-functionalization of the substrates, thus making it an alternate approach for the synthesis of 2H-pyrido[1,2-a]pyrimidin-2-ones. The reaction was tolerant to several substituted 2-aminopyridines and β-oxo esters.
- Pavithra, Thangavel,Devi, E. Sankari,Nagarajan, Subbiah,Sridharan, Vellaisamy,Maheswari, C. Uma
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supporting information
p. 6884 - 6887
(2019/11/11)
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- Targeting dormant tuberculosis bacilli: Results for molecules with a novel pyrimidone scaffold
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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.
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p. 201 - 207
(2015/01/30)
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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
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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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- Synthesis of some new 1,2,3,4-tetrahydropyrimidine-2-thione and their thiazolo[3,2-a]pyrimidine, thiazino and benzothiazepine derivatives
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The starting N-(2-pyridyl)-6-methyl-4-phenyl-2-thioxo-1,2,3,4- tetrahydropyrimidine-5-carboxamide (4) was used as a key intermediate for the synthesis of new 1,2,3,4-tetrahydropyrimidine-2-thione and their thiazolo[3,2-a]pyrimidine, thiazino and benzothiazipen derivatives. The reaction of 4 with haloketones in ethanol catalyzed by base afforded the corresponding thiophenopyrimidine and pyrimidothiazipine derivatives 5-10. Methylation and formylation of 4 led to the pyrimidine derivatives 15 and 16, respectively. The preventative compounds were established on the basis of elemental and spectral data.
- Fadda,Bondock,Khalil,Tawfik, Eman H.
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p. 838 - 843
(2013/08/23)
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- Antimycobacterial agents: Synthesis and biological evaluation of novel 4-(substituted-phenyl)-6-methyl-2-oxo-N-(pyridin-2-yl)-1,2,3, 4-tetrahydropyrimidine-5-carboxamide derivatives by using one-pot multicomponent method
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The aim of this work was to synthesize a series of compounds to study their antimycobacterial potential. Eight compounds were found to be most active with minimum inhibitory concentration of less than 6μM and were more active than Isoniazid (INH) against Mycobacterium tuberculosis H37Rν (MTB). Compounds with electron withdrawing group substituted on the aryl ring were showing better activity. Among the fifteen newly synthesized compounds, compound 6-methyl-4-(4-nitrophenyl)-2-oxo-N-(pyridin-2-yl)-1,2,3,4tetrahydropyrimidine-5- carboxamide (B) was found to be the most active agent against MTB and INH resistant Mycobacterium tuberculosis (INHR-MTB) with minimum inhibitory concentration of 0.35 μM.
- Almansour, Abdulrahman I.,Ali, Mohamed Ashraf,Ali, Sadath,Wei, Ang Chee,Yoon, Yeong Keng,Ismail, Rusli,Choon, Tan Soo,Pandian, Suresh,Kumar, Raju Suresh,Arumugam, Natarajan,Osman, Hasnah
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p. 953 - 957
(2013/02/22)
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- Facile synthesis and antibacterial, antitubercular, and anticancer activities of novel 1,4-dihydropyridines
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A series of twenty new 4-substituted-2,6-dimethyl-3,5-bis-N-(heteroaryl)- carbamoyl-1,4-dihydropyridines have been prepared from a three-component one-pot condensation reaction of N-heteroaryl acetoacetamide, an aromatic/ heteroaromatic aldehyde, and ammonium acetate under four different experimental conditions. Except for the conventional method, all the experimental conditions were simple, eco-friendly, economical, and the reactions were rapid and high-yielding. The methods employed have been compared in terms of yields, cost, and simplicity. The synthesized compounds were characterized by different spectroscopic techniques and evaluated for their in-vitro anticancer, antibacterial, and antitubercular activities. Amongst the compounds tested, compound 25 exhibited the highest anticancer activity while compounds 14 and 18 exhibited significant antibacterial and antitubercular activities.
- Sirisha, Kalam,Achaiah, Garlapati,Reddy, Vanga Malla
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experimental part
p. 342 - 352
(2011/07/30)
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- New α-amido-α-aminonitrones as building blocks for constructing heterocyclic systems
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New, stable α-amido-α-aminonitrones were obtained in good yields from 3-oxobutyric acid N-pyridin-2-ylamides and nitrosobenzene. The α-amido-α-aminonitrones were then used as new, versatile building blocks to obtaining various heterocycles with both bielectrophilic and binucleophilic reagents. With diiodomethane as reagent, 1,2,5-oxadiazine derivatives were formed, whereas reactions with aromatic 1,2-, 1,3- and 1,4-diamines yielded quinoxaline, quinazoline, perimidine, and dibenzo[d,f][1,3]diazepine derivatives, respectively. Georg Thieme Verlag Stuttgart.
- Trzewik, Bartosz,Ciez, Dariusz,Hodorowicz, Maciej,Stadnicka, Katarzyna
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experimental part
p. 2977 - 2985
(2009/04/05)
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- One-pot synthesis of 3,4-dihydro-2H-pyrido[1,2-α][1,3,5]triazin-2-one derivatives from N-(2′-pyridinyl)benzoylacetamide and nitrosobenzenes
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A convenient method leading to fused pyrido[1,2-α] [1,3,5]triazine-2-ones is described. It consists in a one-pot, two-step reaction of N-(2′-pyridinyl)benzoylacetamide with nitrosobenzenes. On the other hand, N-(2′-pyridinyl)acetoacetamide provides a C-2 condensation/addition product with nitrosobenzene. N-(2′-Pyridinyl)benzoylthioacetamide and N-(2′-pyridinyl)acetothioacetamide with nitrosobenzene undergo oxidative heterocyclisation leading to [1,2,4]thiadiazqlo[2,3-a]pyridine derivatives.
- Zaleska, Barbara,Trzewik, Bartosz,Stodolak, Ewa,Grochowski, Jacek,Serda, Pawel
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p. 2975 - 2979
(2007/10/03)
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- Microwave induced acetoacetylation of hetaryl and aryl amines
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Acetoacetylation of hetaryl and aryl amines by interaction with ethyl acetoacetate under microwave irradiation, without any catalyst and/or solvent, is reported.
- Suri,Satti,Suri
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p. 3709 - 3718
(2007/10/03)
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- Further Reactions of t-Butyl 3-Oxobutanthioate and t-Butyl 4-Diethylphosphono-3-oxobutanthioate: Carbonyl Coupling Reactions, Amination, Use in The Preparation of 3-Acyltetramic Acids and Application to The Total Synthesis of Fuligorubin A.
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Key words: Acyltetramic acid; Phosphonate; Wadsworth-Emmons; Dieckmann cyclisation; Fuligorubin A. Abstract: The use of t-butyl-3-oxobutanthioate (1) and t-butyl 4-diethylphosphono-3-oxobuthanthioate (2) for the preparation of homologated derivatives suitable for amination in the presence of silver(I) trifluoroacetate to afford the corresponding β-ketoamides is discussed.In particular Wadsworth-Emmons coupling reactions of (2) with various carbonyl compounds gave good yields of E-substituted products.Many of the β-ketoamides were shown to be suitable precursors for 3-acyltetramic acids using a Dieckman cyclisation with tetra-n-butyl ammonium fluoride as the cyclising base.These new reactions were applied to the total synthesis of the polyene 3-acyltetramic acid fuligorubin A.
- Ley, Steven V.,Smith, Stephen C.,Woodward, Peter R.
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p. 1145 - 1174
(2007/10/02)
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- THE USE OF β-KETOTHIOESTERS FOR THE EXCEPTIONALLY MILD PREPARATION OF β-KETOAMIDES
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Transamination of t-butylacetothioacetate derivatives with primary and secondary amines in the presence of silver(I) trifluoroacetate gives high yields of the corresponding β-ketoamides.
- Ley, Steven V.,Woodward, Peter R.
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p. 3019 - 3020
(2007/10/02)
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- Synthesis and Biological Activity of some Pyrido-2-carboxamido-pyrazoline and -isoxazoline Derivatives
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2-Acetoacetamidopyridine on condensation with aromatic aldehydes yielded the corresponding pyrido-2-carboxamido-α,β-unsaturated ketones which on heating with hydrazine hydrate/phenylhydrazine and hydroxylamine hydrochloride gave the corresponding pyrido-2-carboxamido pyrazoline and isoxazoline derivatives.The biological activity of some representative compounds were tested.
- Mandal, N. K.,Sinha, R.,Banerjee, K. P.
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p. 221 - 222
(2007/10/02)
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