- Design, synthesis, and potential CNS activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-methyl- 4H-quinazolin-3-yl)-urea
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Twelve new 1-(4-substituted-phenyl)-3-(4-oxo- 2-methyl-4H-quinazolin-3-yl)- urea were synthesized and screened for anticonvulsant, CNS depressant, and sedativehypnotic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2,3-Disubstitutedquinazolin- 4(3H)-one were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. M3, M4 and M10 were found to be active in both MES screen and scPTZ screen at 0.5 h. All except M11 showed more than 44% decrease in locomotor activity after 1 h of compound administration via actophotometer screen. CNS-depressant activity screened with the help of the forced swim method resulted into some potent compounds. Except for M6 and M11 other tested compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed sedative-hypnotic and CNS depressant activities. Springer Science+Business Media, LLC 2010.
- Kashaw, Sushil K.,Kashaw, Varsha,Mishra, Pradeep,Jain,Stables
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experimental part
p. 738 - 745
(2012/05/20)
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- Oxidation of arylthiourea by cetyltrimethylammonium dichromate
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With a view to investigate the oxidation behaviors of cetyltrimethylammonium dichromate on multifunctional groups, some arylthioureas were subjected to oxidation, both in neutral and in acidic conditions. In neutral conditions, the products were found to be a mixture of corresponding urea and isonitrile. In acidic conditions, the products were corresponding ureas only. A probable mechanism was proposed for the formation of the product, wherein the first step involves coupling of-NH2 and-SH of one molecule to the-NH2 and-SH of another molecule, respectively, which is followed by removal of nitrogen and sulfur. The microwave irradiation resulted in great yield of isonitrile than urea in neutral conditions. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Sahu, Sandhyamayee,Sahoo, Prangya Rani,Patel, Sabita,Mishra
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experimental part
p. 3268 - 3273
(2010/12/24)
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- Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea
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Several new 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea were synthesized and screened for anticonvulsant, CNS depressant and sedative-hypnotic activity in the mice. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight synthesized compounds were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. Compounds E1, E6, E9, E12, P3, P4 and P6 were found to be active in the MES screen whereas E1, P4, P6 and P11 were found to be active in the scPTZ screen. All except E6, E11 and P6 showed more than 50% decrease in locomotor activity at 1 h of compound administration via actophotometer screen. CNS depressant activity screened with the help of the forced swim method resulted into some potent compounds. All the compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed promising CNS activities.
- Kashaw, Sushil K.,Kashaw, Varsha,Mishra, Pradeep,Jain,Stables
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experimental part
p. 4335 - 4343
(2009/12/24)
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- COMPOUND LIBRARIES OF N-(AMINOCARBONYL)-PIPERIDINE-4-CARBOXAMIDE DERIVATIVES CAPABLE OF BINDING TO G-PROTEIN COUPLED RECEPTORS
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The present invention provides a compound library targeted to receptors with a requirement for a positively charged amine in their structure activity relationships. It is designed to produce both agonists and antagonists and so is expected to be especially useful in producing ligands for orphan receptors. The library is designed around an acylurea coupled to a piperidine moiety. A combination of specific motifs R2 and R1 are appended from the central scaffold and are designed to pick up different interactions at a receptor site. The library comprises or consists of a set of structurally related compounds of general formula (I).
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Page/Page column 27-28
(2008/06/13)
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- Synthesis of sulofenur analoges as antitumour agents: Part II
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A series of N-aryl-N′-heteroaryl or N,N′-diheteroaryl sulfonylurea has been prepared using two different methods. All the intermediates were prepared including heteroarylsulfonyl chlorides and aryl- or hetero-arylurea derivatives. Structural elucidation of the newly synthesized compounds were based on elementary analysis, IR, 1H & 1C NMR and mass spectra. The antitumor screening of the prepared compounds were performed at the National Cancer Institute (NCI) Bethesda, Maryland, USA. Compound N-(3-methylbenzothiazol-2-yl)-N′ -(1-benzodiazolyl-sulfonyl)urea (13) with GI50, TGI, LC50 (MG-MID) values of 25.1, 77.5, 93.3 μM, respectively is the most active compound in this study. It showed a broad spectrum antitumor activity as well as selective activity toward individual cell lines. It showed distinctive activities compared to that of sulofenur against RPMI-8226 leukemia, EKVX Non-small lung cancer, PC-3 prostate cancer, OVCAR-4 Ovarian cancer, CAKI-1Renal cancer, MDA-MB-435 and T-47D Breast cancer with GI50 values of 21.5, 1.7, 28.7, 25.9, 15.9, 27.9, 15.1 μM, respectively.
- Youssef, Khairia M.,Al-Abdullah, Ebtihal,El-Khamees, Hamad
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p. 481 - 503
(2007/10/03)
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- Synthesis of certain diarylsulfonylureas as antitumor agents
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A new series of N-aryl-N′-heteroaryl or N,N′-diheteroaryl sulfonylurea or sulfonylthiourea was synthesized and screened for their antitumor activity at the National Cancer Institute (NCI). N-(3-Chlorophenyl)-N′-(6-methyl-uracil-2-sulfonyl)urea (28) with GI50, TGI, LC50 (MG-MID) values of 66.1, 83.2, 93.3 μM, respectively is the most active compound in this study. It showed a remarkable activity more than sulofenur against HL-60 (TB) and RPMI-8226 leukemia, HOP-92 Non small lung cancer, KM12 colon cancer, SF-295 CNS cancer, PC-3 prostate cancer, OVCAR-4 Ovarian cancer, CAKI-1 and UO-31 Renal cancer, and MDA-MB-435 Breast cancer with GI50 values of 0.3, 2.7, 6.9, 14.7, 8.2, 9.3, 2.0, 2.1, 3.4, 11.3 μM, respectively.
- Youssef,Al-Abdullah,El-Khamees
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p. 404 - 418
(2007/10/03)
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- A kinetic study of the denitrosation and hydrolysis reactions of N-nitrosophenylureas
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The kinetics of the decomposition of N-nitroso-phenylurea in aqueous solution have been studied in the acidity range 0.035-0.36 mol.l-1-HCIO4 and in buffer solutions of pH 3.98-6.14.Below pH 3 the decomposition proceeds mainly by acid catalysed denitrosation, but a small uncatalysed contribution has also been detected.The general acid catalysis, the absence of nucleophilic catalysis by halides and the isotopic effect (kH:kD ca. 1.5) allow a mechanism to be proposed in which the protonation of N-nitrosophenylurea is the rate determining step.The results obtained on studying the denitrosation of some ring-derivatives of N-nitrosophenylurea show a little effect on reaction rate.The mechanism proposed for the hydrolysis reaction (studied at pH > 3.9) involves the formation of a nitrosourea hydrate under steady state conditions, which undergoes an OH(1-) catalysed reaction yielding benzenediazonium ion and an uncatalysed reaction yielding an unidentified product.This latter pathway is virtually negligible at the highest values of pH worked with.
- Casado, Julio,Castro, Albino,Lorenzo, Francisco Manuel,Meijide, Francisco,Mosquera, Manuel
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p. 597 - 601
(2007/10/02)
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