- Anticonvulsant and toxicity evaluation of newer 4H-benzo[1,4]oxazin-3-ones: The effect of two hydrogen bonding domains
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A series of (Z)-2-(substituted aryl)-N-(3-oxo-4-(substituted carbamothioyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl) hydrazine carboxamides (6a-r) was synthesized using 2-amino-5-nitrophenol as a starting material. All the synthesized compounds possessed two hydrogen-bonding domains and their effect on the activity was studied thereof. The anticonvulsant activity was assessed by the maximal electroshock test (MES), subcutaneous pentylenetetrazole test (scPTZ) and intraperitoneal thiosemicarbazide test (ipTSC). Compounds (6b, 6h, 6i, and 6p) were found to be the most potent of the series as they showed 83-100% protection in the MES test. They also displayed considerable activity in the chemically induced seizure tests. Most of the tested compounds were devoid of the neurotoxic and hepatotoxic effects. A series of (Z)-2-(substituted aryl)-N-(3-oxo-4-(substituted carbamothioyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin- 7-yl) hydrazine carboxamides (6a-r) was synthesized. Four compounds were found to be very promising as far as efficacy and safety is concerned. They may act as lead molecules for future investigations. Copyright
- Siddiqui, Nadeem,Ali, Ruhi,Arshad, M. Faiz,Ahsan, Waquar,Ahmed, Sharique,Alam, M. Shamsher
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- PHARMACOPHORES, COMPOUNDS AND METHODS HAVING APPLICATION IN THE TREATMENT OF CANCER THROUGH INHIBITION OF CYP17A1 AND CYP19A1
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The invention provides pharmacophores for use in the design, screening and identification of inhibitors of CYP17A1 and CYP19A1 enzymes. A preferred pharmacophore has a spatial arrangement of atoms as shown in the accompanying Figure 1, wherein: ? A represents hydrogen bond acceptors; ? D represents hydrogen bond donors; and ? R represents aromatic rings. Compounds conforming to the preferred pharmacophore are provided for use as medicaments in the treatment of cancer, especially prostate cancer and breast cancer. By way of example, these compounds include N-(4-ethylphenyl)-5-(2-hydroxy-5-methoxybenzoyl)-2-imino-2H-pyran-3-carboxamide and 2-(4-sulfamoylphenoxy) ethyl 2-amino-3-methylbenzoate. Also provided are methods for the treatment of prostate cancer and breast cancer using the compounds of the invention as well as their salts, solvates, hydrates, primary metabolites and prodrugs. Methods of inhibiting CYP17A1 and CYP19A1, and hence of inhibiting androgen activity in a subject, are disclosed. The invention also provides processes for designing, screening and identifying compounds which can inhibit CYP17A1 and CYP19A1.
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- ALKYL-SUBSTITUTED 3' COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, Ar, m and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 31
(2010/02/17)
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- CONDENSED HETEROCYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I) wherein R1, A, B, D, E, G, Q, Ar, n, m, and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 83-84
(2010/04/03)
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- ACYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, Q, G, Ar, m, and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 58
(2010/03/02)
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- 4'-AMINO CYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): formula (I) wherein Cy is selected from formula (Il) and wherein R1, R2, R3, Q, G, Ar, m, n and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 102
(2010/04/06)
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- PYRROLIDINE-SUBSTITUTED AZAINDOLE COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, A, B, D, E, G, Ar, and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 42
(2010/02/17)
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- Synthesis of 2-(4-substituted benzyl-1,4-diazepan-1-yl)-N-(3,4-dihydro-3- oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamides and their positive inotropic evaluation
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Herein we describe the discovery of compound 3g, a potent positive inotropic agent compared with the standard drug, milrinone. Compound 3g was developed from a series of 2-(4-substitutedbenzyl-1,4-diazepan-1-yl)-N-(3,4- dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl) acetamides found in an evaluation of inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activities, but 3g was the most potent, with 7.68 ± 0.14% increased stroke volume (milrinone 2.38 ± 0.05%) at 1 × 10-5 M in our in vitro study. The chronotropic effects of compounds having significant inotropic effects were also evaluated.
- Yang, Kun,Sun, Liang-Peng,Liu, Ji-Yong,Cui, Xun,Piao, Hu-Ri
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scheme or table
p. 4464 - 4467
(2010/10/02)
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- 3' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein Q, R1, R4, m and Ar are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 119
(2009/04/25)
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- Synthesis of 2-(4-substitutedmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamides and their positive inotropic evaluation
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In an attempt to search for more potent positive inotropic agents, a series of 2-(4-substitutedmethylpiperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamides were synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone, among which 2-(4-(4-methylbenzyl)piperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamide 4e showed the most potent activity with the 5.09 ± 0.00% increased stroke volume (milrinone 1.67 ± 0.64%) at a concentration of 1 × 10-5 M in our in vitro study. The chronotropic effects of those compounds having significant inotropic effects were also evaluated in this work.
- Liu, Xue-Kun,Cui, Xun,Hong, Lan,Sun, Liang-Peng,Quan, Zhe-Shan,Piao, Hu-Ri
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experimental part
p. 3027 - 3031
(2009/10/02)
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- 4' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, R6, B, D, E, G, Q, x and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 30
(2009/01/24)
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- FUSED THIAZOLE DERIVATIVES AS KINASE INHIBITORS
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A series of 5,5-dimethyl-5,6-dihydro-1,3-benzothiazol-7(4H)-one and 7,7-dimethyl-5,6,7,8-tetrahydro-4H-[1,3]thiazolo[5,4-c]azepin-4-one derivatives, and analogues thereof, which are substituted in the 2-position by an optionally substituted benzofused mor
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(2008/06/13)
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- Synthesis of novel 7-benzylamino-2H-1,4-benzoxazin-3(4H)-ones as anticonvulsant agents
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A series of 7-benzylamino-2H-1,4-benzoxazin-3(4H)-ones were synthesized using 2-amino-5-nitrophenol as a starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox.). The MES test showed that 7-(4-fluorobenzylamino)-2H-1,4-benzoxazin-3(4H)-one 4b was the most potent with ED50 value of 31.7 mg/kg and protective index (PI = TD50/ED50) value of 7.2. To explain the possible mechanism of anticonvulsant activity, the compound 4b was tested in sc-PTZ test, isoniazid test and strychnine test.
- Piao, Zhong-Tai,Guan, Li-Ping,Zhao, Li-Ming,Piao, Hu-Ri,Quan, Zhe-Shan
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p. 1216 - 1221
(2008/09/20)
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- 6' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1—R4 A, B, D, E, and G are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 52; 53
(2008/12/08)
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- BENZOXAZINES AND RELATED NITROGEN-CONTAINING HETEROBICYCLIC COMPOUNDS USEFUL AS MINERALOCORTICOID RECEPTOR MODULATING AGENTS
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The present invention relates to a compound, useful as a mineralocorticoid receptor-modulating agent, of the following formula [I]: wherein Ring A is a benzene ring optionally having a substituent(s) other than R1 etc, R1 is a group
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Page/Page column 75
(2008/06/13)
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- COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5HT6 receptor which are of the formula (I), wherein R1-R3 A, B, D, E, G, Q, and x are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 142-143
(2010/11/28)
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- 4-Piperidinecarboxamide modulators of vanilloid VR1 receptor
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This invention is directed to vanilloid receptor VR1 ligands. More particularly, this invention relates to hetero isonipecotic amides that are potent modulators of VR1 which are useful for the treatment and prevention of disease conditions in mammals.
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Page/Page column 67; 68
(2010/11/08)
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- Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N-aryl cinnamides
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The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators, particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert- butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1), an antagonist that blocks the capsaicin-induced and pH-induced uptake of 45Ca2+ in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 ± 5 and 150 ± 80 nM, respectively. In this report, we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (Foral = 39% and 17%, respectively).
- Doherty, Elizabeth M.,Fotsch, Christopher,Bo, Yunxin,Chakrabarti, Partha P.,Chen, Ning,Gavva, Narender,Han, Nianhe,Kelly, Michael G.,Kincaid, John,Klionsky, Lana,Liu, Qingyian,Ognyanov, Vassil I.,Tamir, Rami,Wang, Xianghong,Zhu, Jiawang,Norman, Mark H.,Treanor, James J. S.
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- 4-OXO-AND 4H-IMIDAZO(5,1-C)(1,4) BENZOXAZINES USEFUL AS BENZODIAZEPINE RECEPTOR-BINDING AGENTS
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Imidazo-benzoxazines of Formula (I) and pharmaceutically acceptable salts thereof. STR1 where Q is selected from (A) through (H) STR2 or pharmaceutically acceptable salts thereof wherein the R groups are as defined herein. The imidazo-benzoxazines, Formula (I), of the present invention are useful as anxiolytics and sedatives.
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- 6- OR 7-(2-IMINO-2-IMIDAZOLIDINE)-1,4-BENZOXAZINES AS ALPHA ADRENERGIC AGENTS
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Compounds having α adrenergic activity and useful for the treatment of glaucoma, renal and gastrointestinal disorders and vasoconstictors have the formula STR1 where R 1 is independently H, or lower alkyl or 1 to 6 carbons; R 2 is independently H, or lower alkyl of 1 to 6 carbons or the two R 2 symbols jointly represent a carbonyl oxygen; R 3 is H, lower alkyl of one to 6 carbons, O, OH and OR 7 where R 7 is lower alkyl of 1 to 6 carbons, or R 3 is COH or COR 8 where R 8 is lower alkyl of 1 to 6 carbons; R 4 and R 5 independently is H, Br, Cl, or lower alkyl of 1 to 6 carbons, lower alkenyl or lower alkynyl with the proviso that when the R 2 groups symbolize a carbonyl oxygen then R 4 and R 5 both cannot be hydrogen; R 6 is hydrogen, Br, Cl, or lower alkyl of 1 to 6 carbons, lower alkenyl or lower alkynyl, and the R 5 and the (2-imidazoline-2-yl)amino substituents are connected mutually exclusively to the 6 and 7 positions of the 1,4-benzoxazine nucleus.
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- Heteroaromatic Analogues of the α2-Adrenoreceptor Partial Agonist Clonidine
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A 1,4-dioxane analogue (1) of the α2-adrenoreceptor partial agonist clonidine (2) has previously been shown to possess an interesting but complex pharmacological profile.In this study, from a series of other heterocyclic analogues of clonidine,
- Chapleo, Christopher B.,Butler, Richard C. M.,England, David C.,Myers, Peter L.,Roach, Alan G.,et al.
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p. 1627 - 1630
(2007/10/02)
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- Synthesis and Anthelmintic Activity of Some New 6- and 7-Isothiocyanato-2H-1,4-benzoxa(thia)zin-3(4H)-ones and Benzoxa(thia)zin-3(4H)-thiones
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A series of 6- and 7-isothiocyanato-2H-1,4-benzoxa(thia)zin-3(4H)-ones (8a-n, 9a-c, 12a-i and 12l) and thiones (10a-h and 11a-c) has been prepared for anthelmintic testing.Some of these compounds possess a significant degree of activity against hookworm i
- Shridhar, D. R.,Rao, K. Srinivasa,Singh, A. N.,Rastogi, K.,Jain, M. L.,et al.
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p. 1263 - 1267
(2007/10/02)
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