- Synthesis, in silico study and cholinesterases inhibition activity of 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives
-
We have synthesized and evaluated a number of 2, 3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases. In vitro assay results revealed that all synthesized compounds are active against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and few compounds having longer alkyl chain at C-2 position showed better inhibition activity than standard drug galantamine. Moreover, bromo derivatives 6a-d were more active than nitro 5a-d and their un-substituted counterparts 4a-d. Amongst all, compound 6d, with IC50 values of 4.8±1.01 μM (AChE) and 11.1±1.15 μM (BChE) can be considered as good cholinesterase (AChE/BChE), inhibitor with greater selectivity towards BChE. In silico calculations revealed that all compounds have good pharmacokinetic profile along with having high probabilities for penetration across blood brain barrier (BBB), human intestinal absorption (HIA), non-AMES toxicity and non-carcinogenicity except nitro substituted derivatives which were predicted to show AMES toxicity. The synthesized compounds may lead toward development of new potent cholinesterase inhibitors.
- Sarfraz, Muhammad,Sultana, Nargis,Jamil, Muhammad,Tariq, Muhammad Ilyas
-
p. 227 - 234
(2018/08/03)
-
- Nitrile Hydration Reaction Using Copper Iodide/Cesium Carbonate/DBU in Nitromethane-Water
-
The catalytic nitrile hydration (amide formation) in a copper iodide/cesium carbonate/1,8-diazabicyclo[5.4.0]undec-7-ene/nitromethane-water system is described. The protocol is robust and reliable; it can be applied to a broad range of substrates with high chemoselectivity.
- Kuwabara, Jun,Sawada, Yoshiharu,Yoshimatsu, Mitsuhiro
-
supporting information
p. 2061 - 2065
(2018/09/14)
-
- Design and synthesis of 3-(3-((9 H-carbazol-4-yl)oxy)-2-hydroxypropyl)-2-phenylquinazolin-4(3 H)-one derivatives to induce ACE inhibitory activity
-
In an attempt to develop a new class of cardiovascular drugs, a series of novel carbazolyloxy phenylquinazoline derivatives 9a-g have been synthesized and evaluated as angiotensin converting enzyme (ACE) inhibitors. Most of these compounds exhibited activity as significant ACE inhibitors and three compounds (9b, 9c & 9e) showed maximum inhibitory potency in enzyme based assays. To render support to the experimental results, a series of quinazolinone derivatives were docked into active site of ACE and identified the probable binding modes compared to Lisinopril. Also we have identified common pharmacophore hypothesis (AAADDRR) among the best docked conformers of most potent compounds in a series of compounds. The most potent 9b, 9c, 9e compounds shared common active site with the Lisinopril binding site and retained the key active site residue interactions. The obtained results from pharmacological and molecular modeling studies can be utilized for further optimization of identified hits for selective inhibition of ACE.
- Venkatesh, Ramineni,Kasaboina, Suresh,Gaikwad, Hanmant K.,Janardhan, Sridhara,Bantu, Rajashaker,Nagarapu, Lingaiah,Sastry, G. Narahari,Banerjee, Sanjay K.
-
-
- Convenient N-acetylation of amines in N,N-dimethylacetamide with N,N-carbonyldiimidazole
-
Dimethylacetamide (DMAc) acts as an efficient source of acetyl and dimethylamine gas in the presence of N,N-carbonyldiimidazole (CDI). Addition of amines to the reaction mixture delivers the corresponding amides in good to excellent yields. The acetylation of amines reported herein, which relies on the in situ generation of N-acetylimidazole on warming of DMAc with CDI at 120-125 °C, serves as a convenient alternative to other acetylation methods.
- Chikkulapalli, Anil,Aavula, Sanjeev Kumar,Mona Np, Rifahath,Karthikeyan, Karthikeyan,Kumar C.H., Vinodh,Sulur G., Manjunatha,Sumathi, Shanmugam
-
supporting information
p. 3799 - 3803
(2015/06/08)
-
- COMPOSITIONS AND METHODS FOR MODULATING GATED ION CHANNELS
-
Disclosed are compounds that modulate the activity of the gated ion channels. Compounds that modulate these gated ion channels are useful in the treatment of diseases and disorders related to pain, inflammation, the neurological system, the gastrointestinal system and genitourinary system. Preferred compounds include compounds of the Formulae 1, 2, 3, 4, and 5.
- -
-
Page/Page column 64-65
(2009/02/11)
-
- Microwave-assisted synthesis in aqueous medium of new quinazoline derivatives as anticancer agent precursors
-
Fast and eco-friendly microwave-irradiated reactions permitting the "green synthesis" of new 2-substituted quinazoline derivatives in aqueous medium via S-alkylation or SRN1 reaction from 2-chloromethyl-3-methylquinazolin-4(3H)-one derivatives with different benzenesulfinic acids and nitronate anions, are reported herein.
- Kabri,Gellis,Vanelle
-
experimental part
p. 201 - 208
(2010/04/22)
-
- Synthesis leading to novel 2,4,6-trisubstituted quinazoline derivatives, their antibacterial and cytotoxic activity against thp-1, hl-60 and a375 cell lines
-
A series of novel 2,4,6-trisubstituted quinazoline derivatives 6 have been synthesized from anthranilic acids 1 in five steps via benzoxazinones 2, N-benzoyl benzamides 3, quinazol-4-ones 4, 4-chloroquinazolines 5. Products 6 have been screened for antibacterial and cytotoxic activity, promising compounds have been identified.
- Chandrika, P Mani,Yakaiah,Narsaiah,Sridhar,Venugopal,Rao, J Venkateshwara,Kumar, K Pranay,Murthy,Rao, A Raghu Ram
-
experimental part
p. 840 - 847
(2009/12/24)
-
- The study of cyclization of N-acylphenacyl anthranilates with ammonium salts under various conditions
-
N-Acylphenacyl anthranilates were heated with ammonium salts in organic acid or NMP, and formation of various heterocyclic compounds was observed. Reaction results are strongly influenced by reaction conditions. The most interesting are imidazole derivati
- Hradil, Pavel,Grepl, Martin,Hlavac, Jan,Lycka, Antonin
-
p. 269 - 280
(2008/02/09)
-
- Rapid synthesis of 2,3-disubstituted-quinazolin-4-ones enhanced by microwave-assisted decomposition of formamide
-
An efficient methodology for the preparation of a series of 2,3-disubstituted-quinazolin-4(3H)-ones is described via a three step reaction from anthranilic acid. The obtained results also reveal that microwave-assisted rapid decomposition of formamide under controlled conditions of power, temperature and time is a very convenient source of ammonia for the synthesis of 2-substituted-quinazolin-4(3H)-ones and other rings.
- Kostakis, Ioannis K.,Elomri, Abdelhakim,Seguin, Elisabeth,Iannelli, Mauro,Besson, Thierry
-
p. 6609 - 6613
(2008/03/12)
-
- Syntheses of Some 4-Anilinoquinazoline Derivatives
-
Some 4-N-(3′- or 4′-substituted-phenyl)amino-6,7- dimethoxyquinazolines and the corresponding unsubstituted compounds were synthesized from 2-amino-4,5-dimethoxybenzoic acid and the appropriate substituted anilines. Other related quinazolines or their synthetic intermediates were also obtained. A large number of the described quinazolines are new compounds, while the remaining were prepared by a more efficient procedure. The main goal for the synthesis of these compounds comes from the fact that the 4-anilinoquinazoline pharmacophore is an important unit, which is found among the ATP-competitive inhibitors of several protein kinase enzymes.
- Rocco, Silvana A.,Barbarini, Jose Eduardo,Rittner, Roberto
-
p. 429 - 435
(2007/10/03)
-
- Phosphodiesterase inhibitory properties of losartan. Design and synthesis of new lead compounds
-
A 4-centre PDE 4 pharmacophore search has been carried out in several 3D-databases containing compounds belonging to different therapeutic areas. Losartan, an angiotensin-II antagonist, has been identified as a new lead compound for developing PDE 4 inhibitors. New families of compounds derived from losartan has been synthesized and their PDE inhibition has been measured.
- Segarra, Victor,Crespo, M. Isabel,Pujol, Ferran,Beleta, Jorge,Domenech, Teresa,Miralpeix, Montserrat,Palacios, Jose M.,Castro, Ana,Martinez, Ana
-
p. 505 - 510
(2007/10/03)
-
- Acyl Trimethylsilyl Polyphosphates as Activated Esters in Acylation Reactions
-
The preparation and application of a new class of activated esters, acyl trimethylsilyl polyphosphates, are described.These complexes, prepared by the reaction of trimethylsilyl carboxylates with phosphorus pentoxide, are versatile acylating agents under relatively mild conditions.Sodium or potassium halides and imidazole are very effective catalysts leading to the in situ generation of reactive acyl halides and acyl imidazolides.Amines, amides, alcohols and phenols, p-thiocresol, carboxylic acids and trimethylsilyl carboxylates, and hexamethyldisilazane have been acylated to give high yields of amides, imides, esters, thioesters, anhydrides and nitriles, respectively.
- Rao, C. Someswara,Rambabu, M.,Srinivasan, P. S.
-
p. 407 - 411
(2007/10/02)
-
- Acylanthranils. 9. Influence of Hydrogen Bonding on the Reaction of Acetylanthranil with Ammonia
-
It was shown that hydrogen bonding has a marked influence on the reaction of acetylanthranil (1) with ammonia.The product of the reaction in anhydrous benzene is 2-methylquinazolin-4-one (5, R = H) which is formed via pathway A as shown in Scheme I, but the rate of formation is unusually slow.The rate of this conversion is about 6 times faster in pyridine than in benzene.If water is added to the benzene system, the rate of reaction is increased by orders of magnitude, but the product is o-acetamidobenzamide (4, R = H) and not 5.In contrast to this result, the addition of water to the pyridine system causes a small decrease in rate and only a slight change in selectivity.These results are consistent with postulated mechanisms whereby 1 reacts with molecular clusters of ammonia, i.e. with (NH3)n in benzene, with N(H*S)3 in strong proton acceptor solvents S, and with (NH3)n*H2O in benzene plus added water.It was verified that cyclodehydration of 4 to give 5 occurs at an appreciable rate in aqueous solution at elevated temperatures and that this rate is accelerated considerably by the presence of strong base even at room temperature.It was also observed that o-acetamidobenzamide exists in at least two crystalline forms, α and β, which have different physical properties.
- Errede, L. A.,Martinucci, P. D.,McBrady, J. J.
-
p. 3009 - 3017
(2007/10/02)
-
