Co-reporter:Qing-Kun Shen, Chuan-Feng Liu, Hong-Jian Zhang, Yu-Shun Tian, Zhe-Shan Quan
Bioorganic & Medicinal Chemistry Letters 2017 Volume 27, Issue 21(Issue 21) pp:
Publication Date(Web):1 November 2017
DOI:10.1016/j.bmcl.2017.09.040
•Two novel series of xanthotoxin-triazole were designed and synthesized.•Compound 6p was found to have the better antiproliferative activity than the lead compound and the reference drug.•All compounds did not exhibit any remarkable cytotoxic activity against L02 normal cell.•Compound 6p exhibited better therapeutic activity and specificity compared with 5-Fu.•Compound 6p inhibited cell growth via the induction of S/G2 phase arrest in AGS cells.Two series of xanthotoxin-triazole derivatives were designed, synthesized, and studied for their antiproliferative properties. The in vitro cytotoxicity of the compounds in the AGS cancer cell line and the L02 normal cell line was evaluated via MTT assay. Among the synthesized compounds, 9-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-7H-furo[3,2-g]chromen-7-one (6p) was found to have the greatest antiproliferative activity against AGS cells (IC50 = 7.5 μM) and showed better activity than the lead compound (xanthotoxin, IC50 > 100 μM) and the reference drug (5-fluorouracil, IC50 = 29.6 μM) did. The IC50 value of 6p in L02 cells was 13.3 times higher than that in the AGS cells. Therefore, the compound exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil. Cell cycle analysis revealed that compound 6p inhibited cell growth via the induction of S/G2 phase arrest in AGS cells. Compound 6p was identified as a promising lead compound for the further development and identification of 1,2,3-triazole-based anticancer agents.Two novel series of xanthotoxin-triazole derivatives were designed, synthesized, characterized and evaluated for their antiproliferative activity.Download high-res image (124KB)Download full-size image
Co-reporter:Hong-Jian Zhang, Yan-Fei Li, Qi Cao, Yu-Shun Tian, Zhe-Shan Quan
Pharmacological Reports 2017 Volume 69, Issue 3(Volume 69, Issue 3) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.pharep.2016.12.006
•9,10-Dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives were synthesized.•Novel compounds were characterized by different spectral techniques.•The newly synthesized compounds have been tested for anti-inflammatory activity.•Compound B3 showed significant anti-inflammatory activity.BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are the most widely administered drugs for the treatment of inflammation. However, they usually cause some unexpected side effects. Coumarins and their derivatives exhibit broad-spectrum biological activities. In order to develop new anti-inflammatory drugs with high anti-inflammatory activity and less side effects, a series of 9-substituted-9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives were designed, synthesized, and screened for their anti-inflammatory activities.MethodsWe investigated the effect of compound 9-(2-chlorophenyl)-9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one (B3) on lipopolysaccharide (LPS)-induced cytokine levels in RAW 264.7 cells at concentrations between 6.25 μg/ml and 25 μg/ml. Concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Moreover, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation was investigated by western blot assay.ResultsCompound B3 could inhibit inflammatory responses via suppression of the NF-κB and MAPK signaling pathways. Docking study of the prepared compounds was performed for the study of interaction of molecules with the active site of TNF-α.Conclusion9,10-Dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives showed anti-inflammatory activity. Compound B3 was the most potent. The results of this study are encouraging further investigations to develop compound B3 as a novel therapeutic agent for inflammatory disorders.Download high-res image (165KB)Download full-size image
Co-reporter:Miao-Miao Li, Zheng-er Jiang, Ling-Yun Song, Zhe-Shan Quan, Hai-Ling Yu
Neuroscience Letters 2017 Volume 640(Volume 640) pp:
Publication Date(Web):15 February 2017
DOI:10.1016/j.neulet.2016.12.072
•TST and FST induced depression-like behaviors in mice.•EPMT and OFT induced anxiety-like behaviors in mice.•Erucamide, a bioactive fatty acid amide, ameliorated mouse depression and anxiety like behaviors.•ACTH and CORT serum levels in Erucamide treatment mice were reduced compared to the control group.•Erucamide may be involved in hypothalamus–pituitary–adrenal axis regulation.Erucamide (Era) is a bioactive fatty acid amide, which is similar to the classical endocannabinoid analogue oleoylethanolamide (OEA). In the present study, we hypothesized that Era may regulate the central nervous system and may have the potential to antagonize depression and anxiety. Therefore, we investigated the antidepressant and anxiolytic effects of Era in animal models in comparison with fluoxetine (Fxt). Fifty mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20 mL/kg, p.o.), Era (5, 10, 20 mg/kg, p.o.), or Fxt (20 mg/kg, p.o.) for 7 days. Immobility was used to evaluate depressive-like behavior in the forced swimming test (FST) and tail suspension test (TST). Animal activity and exploratory behavior as well as anxiety-like behaviors were measured in open field test (OFT) and elevated plus-maze test (EPMT) in mice. Additionally, serum adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) levels were determined using the ELISA method, and the total anti-oxidative capacity (T-AOC) was detected by ultraviolet spectrophotometry. Our data showed that Era (5, 10, or 20 mg/kg) induced a significant reduction in mouse immobility time in the TST and FST compared to the normal control group (vehicle group). The positive control, Fxt (20 mg/kg group), also induced a significant change in immobility time in the TST and FST compared to the control (vehicle) group. In the OFT, compared with the control group, Fxt (20 mg/kg) and Era (5, 10, or 20 mg/kg) did not significantly change the locomotive activity (locomotive time, immobility time, or locomotive distance) in mice, but Fxt (20 mg/kg) and Era (10, or 20 mg/kg) significantly increased the percentage of time spent and squares visited in the OFT central area. In regards to the EPMT, the data showed that Fxt (20 mg/kg) and Era (10, 20 mg/kg) significantly increased the ratio of time spent and entries in open arms, but did not significantly change the total locomotive distance (including open arms and closed arms) compared to the control group. Biochemical tests found that after 7 days of drug treatment, compared with the control group, ACTH and CORT serum levels in mice were significantly decreased, although T-AOC levels did not significantly change. In conclusion, Era (dose range of 5–20 mg/kg) administered orally may alleviate depression- and anxiety-like behaviors in mice, and the antidepressant and anti-anxiety effects of Era may be related to the regulation of the hypothalamus–pituitary–adrenal axis (HPA).Download high-res image (185KB)Download full-size image
Co-reporter:Da-Chuan Liu, Guo-Hua Gong, Cheng-Xi Wei, Xue-Jun Jin, Zhe-Shan Quan
Bioorganic & Medicinal Chemistry Letters 2016 Volume 26(Issue 6) pp:1576-1579
Publication Date(Web):15 March 2016
DOI:10.1016/j.bmcl.2016.02.008
The transcription factor nuclear factor-κB (NF-κB) controls many physiological processes including inflammation, immunity, and apoptosis. In this study, a novel series of 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives were synthesized as potent anti-inflammatory agents, which acted on tumor necrosis factor (TNF-α) as inhibitors of NF-κB activation. We showed that compounds 6h (6-(2,4-dichlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) and 6i (6-(3-tolyloxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) showed more prominent anti-inflammatory activity than other compounds, with similar activities as the reference drug dihydrotanshinone; compound 6i showed the lowest cellular toxicity among the tested compounds. In vivo evaluation of the anti-inflammatory activity showed that compound 6i exhibited excellent anti-inflammatory activity with 58.19% inhibition at 50 mg/kg intraperitoneal (i.p.), with equal efficacy as the positive control indomethacin (100 mg/kg i.p.; 59.21% inhibition).A new series of anti-inflammatory 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives were synthesized and their anti-inflammatory activities were evaluated by the luciferase reporter assay. 6-(3-Tolyloxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide (compound 6i) had comparable activity with the reference drug dihydrotanshinone with low cellular toxicity. Then, compound 6i was selected for anti-inflammatory evaluation in vivo. The activity screening indicated that compound 6i at 50 mg/kg showed 58.19% inhibition at 0.5 h after i.p. and 38.8% inhibition by p.o.
Co-reporter:Yan-Fei Li;Hong-Jian Zhang
Medicinal Chemistry Research 2016 Volume 25( Issue 10) pp:2280-2288
Publication Date(Web):2016 October
DOI:10.1007/s00044-016-1679-7
To discover new compounds with anti-inflammatory activity, a series of novel 3-alkyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine derivatives were synthesized and their structures were confirmed by spectroscopic techniques. In vivo anti-inflammatory activity of the synthesized compounds was determined using the xylene-induced mouse ear edema model. 3-Heptyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e] [1,3]oxazine and 3-p-tolyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine demonstrated higher anti-inflammatory activity (74.04 % and 64.99 %, respectively) at 0.5 h after intraperitoneal administration than the reference drug ibuprofen (62.65 %). Further, the time of peak effect after oral administration was 4 h for both compounds. Our results identify new compounds with anti-inflammatory activity in vivo that may have improved safety/side effect profiles relative to the currently approved nonsteroidal anti-inflammatory drugs.
Co-reporter:Hong-Jian Zhang;Shi-Ben Wang;Xiang Wen;Jin-Zi Li
Medicinal Chemistry Research 2016 Volume 25( Issue 7) pp:1287-1298
Publication Date(Web):2016 July
DOI:10.1007/s00044-016-1559-1
A series of pyrido[2,3-d]pyrimidine derivatives (4a–4n, 5a–5n, 6, and 7) were designed and synthesized as potential anticonvulsants and antidepressants. Their pharmacological activities were evaluated by maximal electroshock test, forced swimming test, and tail suspension test in mice. Pharmacological analyses showed that compounds 4-benzyl-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4a) and 4-(3-fluorobenzyl)-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4e) exhibited the greatest anticonvulsant activity (PI 12.02 and 12.25, respectively, 30 min after intraperitoneal injection), and were more efficient than the reference drug, carbamazepine. In addition, 4-(4-fluorobenzyl)-6,8-dimethylpyrido[3,2-e]tetrazolo[1,5-a]pyrimidin-5(4H)-one (4f) and 6-(4-fluorobenzyl)-2,4-dimethylpyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(6H)-one (5f) possessed potent antidepressant properties that lead to significant reduction in the duration of the immobility time than did the control (P < 0.001), which possessed activities similar to those of fluoxetine. 4f showed obvious antidepressant activity at doses of 10 mg/kg.
Co-reporter:Hong-Jian Zhang;Peng Jin;Shi-Ben Wang;Fu-Nan Li;Li-Ping Guan
Archiv der Pharmazie 2015 Volume 348( Issue 8) pp:564-574
Publication Date(Web):
DOI:10.1002/ardp.201500115
A series of 4-(substituted-phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones (6a–x) with triazole and other heterocyclic substituents (7–14) were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity by maximal electroshock (MES) and rotarod neurotoxicity tests. Among the compounds studied, 6o and 6q showed wide margins of safety with protective indices (PIs) that were much higher than those of currently used drugs (PI6o > 25.5, PI6q > 26.0). Compounds 6o and 6q showed significant oral activity against MES-induced seizures in mice, with ED50 values of 88.02 and 94.6 mg/kg, respectively. The two compounds were also found to have potent activity against seizures that were induced by pentylenetetrazole and bicuculline.
Co-reporter:Hong-Jian Zhang;Shi-Ben Wang
Molecular Diversity 2015 Volume 19( Issue 4) pp:817-828
Publication Date(Web):2015 November
DOI:10.1007/s11030-015-9623-1
A series of novel 4-(substituted-phenyl) tetrazolo[1,5-a]quinazolin-5(4H)-ones (6a–x) and their derivatives with tetrazole and other heterocyclic substituents (7–14) were designed, synthesized, and evaluated for antidepressant activities in mice. Pharmacological tests showed that three compounds (6l, 6u, and 6v) at a dose of 50 mg/kg significantly reduced the immobility time in the forced swimming test. The most active compound was 4-(p-tolyl)tetrazolo[1,5-a]quinazolin-5(4H)-one (6v), which decreased the immobility time by 82.69 % at 50 mg/kg. Moreover, 6v did not affect spontaneous activity in the open-field test, and this effect was comparable to the antidepressant effect of fluoxetine. Noradrenaline (NE) and 5-hydroxytryptamine (5-HT) levels in the brains of mice in the test sample groups significantly increased at a dose of 50 mg/kg compared with that in the control group. The monoamine oxidase (MAO) level of all test groups was reduced, but this result was not significantly different between the groups. Therefore, we can infer that their underlying mechanisms may involve the regulation of brain monoamine neurotransmitter homeostasis, based on the detected content of NE, 5-HT, and MAO in mouse brain tissue.
Co-reporter:Xian-Qing Deng, Ming-Xia Song, Yan Zheng, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2014 Volume 73() pp:217-224
Publication Date(Web):12 February 2014
DOI:10.1016/j.ejmech.2013.12.014
•Derivatives of triazole-containing quinolinones were synthesized and screened for antidepressant and anticonvulsant activity.•Compounds 5i, 5j, 5m, and 5n exhibited higher levels of efficacy than fluoxetine in the forced swimming test.•Compound 5i exhibited greater efficacy than fluoxetine in the tail suspension test.•Compounds 5c and 5d showed moderate levels of anticonvulsant activity in the maximal electroshock seizure screen.A series of 1-substituted-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydroquinolin-2(1H)-ones were designed, synthesized, and screened for their antidepressant and anticonvulsant activities. Interestingly, compounds 5i, 5j, 5m, and 5n led to significant reductions in the immobility time in the forced swimming test at a dose of 50 mg/kg, and exhibited higher levels of efficacy than the reference standard fluoxetine. In addition, compound 5i exhibited greater efficacy than fluoxetine in the tail suspension test. The results of an open field test further confirmed that compound 5i provided a good antidepressant effect. In the maximal electroshock seizure screen, compounds 5c and 5d showed moderate levels of anticonvulsant activity and protected 100% of the animals at a dose of 100 mg/kg. None of the synthesized compounds showed any neurotoxicity in the rotarod test at a dose of 100 mg/kg.A series of 1-substituted-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydroquinolin-2(1H)-ones were designed, synthesized, and screened for their antidepressant and anticonvulsant activities.
Co-reporter:Shi-Ben Wang, Peng Jin, Fu-Nan Li, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2014 Volume 84() pp:574-583
Publication Date(Web):12 September 2014
DOI:10.1016/j.ejmech.2014.07.074
•Purine derivatives were synthesized.•Their anticonvulsant activities were evaluated.•Compound 5e showed significant anticonvulsant activity.•Compound 5e was evaluated in the sc-PTZ-induced seizures tests.•Compound 5e was proposed to be a promising anticonvulsant agent.A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most potent compound, with a median effective dose of 23.4 mg/kg and a high protective index of more than 25.6 after intraperitoneal administration in mice. Compound 5e showed significant oral activity against MES-induced seizures in mice, with an ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound 5e possesses better anticonvulsant activity and is safer than the commercially available drugs carbamazepine and valproate in MES, scPTZ and TOX models.A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES) and rotarod tests.
Co-reporter:Da-Chuan Liu;Xian-Qing Deng;Shi-Ben Wang
Archiv der Pharmazie 2014 Volume 347( Issue 4) pp:268-275
Publication Date(Web):
DOI:10.1002/ardp.201300277
A new series of 7-alkoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-ones were synthesized and evaluated for their anticonvulsant activities. Among these compounds, 7-propoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4c) and 7-butoxy[1,2,4]triazolo[3,4-b]benzothiazol-3(2H)-one (4d) showed the highest activity against maximal electroshock (MES)-induced tonic extension [effective dose (ED)50: 11.4 and 13.6 mg/kg, respectively]. It is worth mentioning that compound 4d showed especially low neurotoxicity, which led to a high protective index (PI >51). The orally anticonvulsant activity data of compound 4d further confirmed its efficacy, in an MES test, and its high safety with a PI value of 50.2. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4d may exert its anticonvulsant activity through affecting the GABAergic system.
Co-reporter:Xu Cao;Shi-Ben Wang;Xian-Qing Deng;Da-Chuan Liu
Medicinal Chemistry Research 2014 Volume 23( Issue 4) pp:1829-1838
Publication Date(Web):2014 April
DOI:10.1007/s00044-013-0778-y
A novel series of 7-alkoxy-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]-thiazin-1-ones have been synthesized and tested for their anticonvulsant activity using the maximal electroshock (MES) method. The majority of the compounds prepared were effective in the MES screens at a dose level of 100 mg/kg. Of the compounds tested, the most promising was 7-[(4-fluorobenzyl)oxy]-2,4-dihydro-1H-[1,2,4]-triazolo[4,3-d][1,4]-benzothiazin-1-one (6m), which showed an ED50 value of 9.2 mg/kg in the MES test in mice. Furthermore, the compound exhibited a PI value of 15.4 which was superior to the standard drug carbamazepine (PI value of 6.4). As well as demonstrating the anti-MES efficacy of compound 6m, its potency against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline were also established, with the results suggesting that several different mechanisms of action might be involved in its anticonvulsant activity, including the inhibition of voltage-gated ion channels and the modulation of GABAergic activity.
Co-reporter:Bing Shu;Yan Zheng;Shi-Ben Wang;Xian-Qing Deng
Archiv der Pharmazie 2013 Volume 346( Issue 2) pp:127-133
Publication Date(Web):
DOI:10.1002/ardp.201200201
Abstract
A series of 4-(3-alkoxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-ones were synthesized using the appropriate synthetic route and evaluated experimentally in the maximal electroshock test; their neurotoxicities were evaluated by the rotarod neurotoxicity test. The structures of these compounds were confirmed by IR, MS, 1H-NMR, and elementary analysis. All target compounds exhibited anticonvulsant activity to varying degrees in the maximal electroshock test. 4-(3-Benzyloxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one (4i) was the most promising compound with an ED50 value of 30.5 mg/kg and a protective index (PI) of 18.63, showing a higher safety than the standard carbamazepine (PI = 6.45). In addition, the potency of compound 4i against seizures induced by pentylenetetrazole and 3-mercaptopropionic acid suggested its broad-spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might be involved in its anticonvulsant activity.
Co-reporter:Yan Zheng;Ming Bian;Xian-Qing Deng;Shi-Ben Wang
Archiv der Pharmazie 2013 Volume 346( Issue 2) pp:119-126
Publication Date(Web):
DOI:10.1002/ardp.201200376
Abstract
In the present study we describe the syntheses and anticonvulsant activity evaluation of 5-phenyl-[1,2,4]triazolo[4,3-c]quinazolin-3-amine derivatives. Their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock seizure test (MES) and the rotarod test, respectively. The majority of the compounds prepared were effective in the MES screens at a dose level of 100 mg/kg. Of these compounds, the most promising was compound 8h, which showed an ED50 value of 27.4 mg/kg and a protective index (PI) value of 5.8. These values were superior to those provided by valproate (ED50 and PI values of 272 and 1.6, respectively) in the MES test in mice. As well as its anti-MES efficacy, the potencies of compound 8h against seizures induced by pentylenetetrazole and thiosemicarbazide were also established, with the results suggesting that the GABAergic system-mediated mechanisms might be involved in its anticonvulsant activity.
Co-reporter:Shi-Ben Wang, Xian-Qing Deng, Yan Zheng, Yan-Ping Yuan, Zhe-Shan Quan, Li-Ping Guan
European Journal of Medicinal Chemistry 2012 Volume 56() pp:139-144
Publication Date(Web):October 2012
DOI:10.1016/j.ejmech.2012.08.027
A series of 5-alkoxytetrazolo[1,5-c]thieno[2,3-e]pyrimidine derivatives were synthesized and their anticonvulsant and antidepressant activities were evaluated. Pharmacological tests showed that four of the synthesized compounds had weak anticonvulsant activity, while most of the compounds had excellent antidepressant activity. The most active compound was 5-(2,4-dichlorobenzyloxy)tetrazolo[1,5-c] thieno[2,3-e]pyrimidine, which decreased the immobility time by 51.62% at a dose of 100 mg/kg. The results of open-field tests of this compound indicated that it had no significant effects on the locomotor activity compared with the control group at the doses assayed in the forced swimming tests test. This means that the antidepressant activity detected in the FST for the compound is not the result of central nervous system stimulant properties, and further confirms its antidepressant-like effect.Graphical abstractA series of 5-alkoxytetrazolo[1,5-c]thieno[2,3-e]pyrimidine derivatives were synthesized and their anticonvulsant and antidepressant activities were evaluated.Highlights► Tetrazolothienopyrimidine derivatives were synthesized. ► Their anticonvulsant and antidepressant activities were evaluated. ► Compound 5t showed significant antidepressant activity. ► Compound 5t was evaluated in the open-field test. ► Compound 5t was proposed to be a promising antidepressant agent.
Co-reporter:Xian-Qing Deng;Zheng-Qi Dong;Ming-Xia Song;Bing Shu;Shi-Ben Wang
Archiv der Pharmazie 2012 Volume 345( Issue 7) pp:565-573
Publication Date(Web):
DOI:10.1002/ardp.201100326
Abstract
The present study describes the synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (4a–4x) and their partially dehydrogenated products 5,6-dihydro-6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (5a–5n). The bioevaluation demonstrated that most compounds in the series of 4a–4x exhibited potent anticonvulsant activity in the maximal electroshock test. Among which, 6-(4-chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4h) emerged as the most promising candidate on the basis of its favorable ED50 value of 23.7 mg/kg and PI value of 10.8. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4h displayed broad-spectrum activity in several models, and it may exert its anticonvulsant activity through affecting the GABAergic system.
Co-reporter:Xian-Qing Deng, Li-Na Quan, Ming-Xia Song, Cheng-Xi Wei, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2011 Volume 46(Issue 7) pp:2955-2963
Publication Date(Web):July 2011
DOI:10.1016/j.ejmech.2011.04.020
Herein, we described the syntheses and anticonvulsant activities of 7-(substituted-phenyl)-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones (1a–1o) and their derivatives. Most of the synthesized compounds exhibited potent anticonvulsant activities in the maximal electroshock test (MES). The most promising compound 1i showed significant anticonvulsant activity in MES test with ED50 value of 19.7 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drugs. In addition, the potence of compound 1i against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide, 3-Mercaptopropionic acid, and Bicuculline in the chemical-induced seizure tests suggested that compound 1i displayed broad spectrum activity in several models, and it is likely to have several mechanisms of action including inhibiting voltage-gated ion channels and modulating GABAergic activity.A series of novel 7-phenyl-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones and its derivatives were synthesized and their anticonvulsant effects on mice were assessed. Their structure–activity relationships were also discussed.Highlights►7-(Substituted-phenyl)-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one derivatives were synthesized.►Their good anticonvulsant activities were found including the best one 1i (ED50 19.7 mg/kg and PI 34.8).►Compounds possessing a triazole displayed better activity and PI than others.►Compound 1i displayed broad spectrum activity in several models.
Co-reporter:Xian-Qing Deng;Di Wu;Cheng-Xi Wei
Medicinal Chemistry Research 2011 Volume 20( Issue 8) pp:1273-1279
Publication Date(Web):2011 November
DOI:10.1007/s00044-010-9470-7
This study described the chemical synthesis and pharmacological evaluation of a series of N-(2-hydroxyethyl) cinnamamide derivatives. The structures of them were characterized by IR, 1H-NMR, MS and elemental analysis. Their antidepressant activities were evaluated by the forced swimming test (FST) and tail suspension test (TST). Pharmacological results of these compounds showed that some of them, given orally, significantly reduced the immobility time in the FST and TST, indicating the antidepressant-like action. Among them, compounds N-(2-hydroxyethyl)cinnamamide (1g), (E)-3-(4-hydroxy-3-methoxyphenyl)-N-(2-hydroxyethyl)acrylamide (1i) and (E)-N-(2-hydroxyethyl)-3-(3-hydroxyphenyl)acrylamide (1n), active in the two models, were considered as the most promising compounds in this study.
Co-reporter:Li-Ping Guan, Xin Sui, Xian-Qing Deng, Ying-Chun Quan, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2010 Volume 45(Issue 5) pp:1746-1752
Publication Date(Web):May 2010
DOI:10.1016/j.ejmech.2009.12.077
A series of 6-alkoxy-[1,2,4]triazolo[4,3-b]pyridazine derivatives were synthesized. In initial screening and quantitative evaluation, compound 2r was among the most active agents, exhibiting in the same time the lowest toxicity. In the anti-maximal electroshock test, it showed median effective dose (ED50) of 17.3 mg/kg and median toxicity dose (TD50) of 380.3 mg/kg, and the protective index (PI) of 22.0, which is much better than PI of the reference drugs. In a subsequent test, compound 2r had median hypnotic dose (HD50) of 746.6 mg/kg, thus demonstrating much better margin of safety compared to reference drugs. Compound 2r also showed oral activity against MES-induced seizures and lower oral neurotoxicity. For explanation of the putative mechanism of action, compound 2r was tested in chemical induced models.6-Alkoxy-[1,2,4]triazolo[4,3-b]pyridazine derivatives were designed and synthesized. Their anticonvulsant activities were investigated by the maximal electroshock test and their neurotoxicity was evaluated by the rotarod neurotoxicity test.
Co-reporter:Xian-Yu Sun, Chuan Hu, Xian-Qing Deng, Cheng-Xi Wei, Zhi-Gang Sun, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2010 Volume 45(Issue 11) pp:4807-4812
Publication Date(Web):November 2010
DOI:10.1016/j.ejmech.2010.07.049
Starting from phthalic anhydride, several new 6-alkoxy(phenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine derivatives were synthesized as potent anti-inflammatory agent. The study showed that the compounds 6h (6-(2-chlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine) and 6s (6-(4-aminophenoxy)-[1,2,4] triazolo[3,4-a]phthalazine-3-amine) exhibited the highest anti-inflammatory activity (81% and 83% inhibition, respectively, at 0.5 h after i.p. administration) which were slightly more potent than the reference drug Ibuprofen (61%). Furthermore, the peak activity of 6h and 6s was observed at the 3 h after p.o. administration, and they exhibited stronger anti-inflammatory activity than Ibuprofen at the dose of 50 mg/kg at the peak time.Two promising compounds 6h (6-(2-chlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine) and 6s (6-(4-aminophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine) were found to possess slightly more potent anti-inflammatory activity than the reference drug Ibuprofen.
Co-reporter:Xian-Qing Deng, Cheng-Xi Wei, Fu-Nan Li, Zhi-Gang Sun, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2010 Volume 45(Issue 7) pp:3080-3086
Publication Date(Web):July 2010
DOI:10.1016/j.ejmech.2010.03.041
A series of novel 10-alkoxy-5, 6-dihydro-triazolo[4,3-d]benzo[f][1,4]oxazepine derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). In the MES test, compound 10-Heptyloxy-5, 6-dihydro-triazolo[4,3-d]benzo[f][1,4]oxazepine (8f) was found to possess better anticonvulsant activity and higher safety than marketed drugs carbamazepine and phenytoin with an ED50 value of 6.9 mg/kg a PI value of 9.5. To explain the possible mechanism of anticonvulsant activity, compound 8f was tested in pentylenetetrazole, isoniazid, thiosemicarbazide, 3-mercaptopropionic acid and Bicuculline induced seizures tests. The results suggest that compound 8f exerts anticonvulsant activity through GABA-mediated mechanism.A series of novel triazolo[4,3-d]benzo[f][1,4]oxazepine derivatives was synthesized and their anticonvulsant effects on mice were assessed. The mechanism of action of compound 8f was GABA-mediated.
Co-reporter:Cheng-Xi Wei;Di Wu;Zhi-Gang Sun;Kyu-Yun Chai
Medicinal Chemistry Research 2010 Volume 19( Issue 8) pp:925-935
Publication Date(Web):2010 November
DOI:10.1007/s00044-009-9239-z
A series of 6-(3-substituted-4H-1,2,4-triazol-4-yl)-2-phenylbenzo[d]oxazoles was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test, subcutaneous pentylenetetrazole (Sc-PTZ), and rotarod tests in intraperitoneally injected mice. Among the synthesized compounds, compound 2-phenyl-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazole (3a) could be considered the potentially most useful and safe therapeutic compound, with ED50 = 29.6 mg/kg, TD50 = 285 mg/kg, and PI = 9.7. Its neurotoxicity was the lowest of all the synthesized compounds and was also markedly lower than that of the reference drug carbamazepine with PI value of 6.4.
Co-reporter:Li-Ping Guan, Cheng-Xi Wei, Xian-Qing Deng, Xin Sui, Hu-Ri Piao, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2009 Volume 44(Issue 9) pp:3654-3657
Publication Date(Web):September 2009
DOI:10.1016/j.ejmech.2009.02.015
A series of novel N-(2-hydroxyethyl) cinnamamide derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The MES test showed that compounds I(N-(2-hydroxyethyl) cinnamamide) and 1d ((E)-3-(3-fluorophenyl)-N-(2-hydroxyethyl)acrylamide) were found to possess better anticonvulsant activity but also had lower toxicity. In the anti-MES potency test, these compounds exhibited median effective dose (ED50) of 17.7 and 17.0 mg/kg, respectively, and median toxicity dose (TD50) of 154.9 and 211.1, respectively, resulting in a protective index (PI) of 8.8 and 12.4, respectively, which is much greater than the PI of the marked antiepileptic drug carbamazepine. To further investigate the effects of the anticonvulsant activity in several different models, compounds I and 1d were tested against convulsions induced by chemical substances, including pentylenetetrazole (PTZ), isoniazid, 3-mercaptopropionic acid, and thiosemicarbazide.A series of novel N-(2-hydroxyethyl) cinnamamide derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox).
Co-reporter:Xian-Yu Sun, Lei Zhang, Cheng-Xi Wei, Hu-Ri Piao, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2009 Volume 44(Issue 3) pp:1265-1270
Publication Date(Web):March 2009
DOI:10.1016/j.ejmech.2008.09.003
A new series of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one derivatives were synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The results showed that 8-heptyloxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one 5t was the most potent with median effective dose (ED50) value of 11.4 mg/kg, median toxicity dose (TD50) of 114.1 mg/kg, providing a protective index (PI = TD50/ED50) value of 10.0, which is much greater than the PI of the prototype drug carbamazepine (PI = 6.4). To explain the possible mechanism of anticonvulsant activity, the compound 5t was tested in chemically induced seizures.A new series of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one derivatives were synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test.
Co-reporter:Li-Jun Guo, Cheng-Xi Wei, Jing-Hao Jia, Li-Ming Zhao, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2009 Volume 44(Issue 3) pp:954-958
Publication Date(Web):March 2009
DOI:10.1016/j.ejmech.2008.07.010
A series of 5-alkoxy-[1,2,4]triazolo[4,3-a]quinoline derivatives were synthesized using 4-hydroxyquinolin-2(1H)-one as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and their neurotoxicities were measured by the rotarod test. The results of these tests demonstrated that 5-hexyloxy-[1,2,4]triazolo[4,3-a]quinoline (3f) was the most potent anticonvulsant, with median effective dose (ED50) of 19.0 mg/kg and protective index (PI = TD50/ED50) values of 5.8 in the MES test. Compound 5-benzyloxy-[1,2,4]triazolo[4,3-a]quinoline (3j), exhibited a little weaker activity than compound 3f in controlling the seizure induced by MES test at the dose of 22.8 mg/kg, but it possessed lower neurotoxicity with PI value of 12.0, which was safer than marketed drug carbamazepine. To explain the possible mechanism of anticonvulsant activity, compound 3j was tested in pentylenetetrazole test, isoniazid test, thiosemicarbazide test, 3-mercaptopropionic acid and strychnine test.A new series of 5-alkoxy-[1,2,4]triazolo[4,3-a]quinoline derivatives are herein reported. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test.
Co-reporter:Lei Zhang;Li-Ping Guan;Xian-Yu Sun;Cheng-Xi Wei;Kyu-Yun Chai
Chemical Biology & Drug Design 2009 Volume 73( Issue 3) pp:313-319
Publication Date(Web):
DOI:10.1111/j.1747-0285.2009.00776.x
A new series of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines (3a–3v) were synthesized and their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock test and the rotarod test respectively. Significant anticonvulsant activity was displayed by a number of compounds. The most promising compounds 6-(4-chlorobenzyloxy)-[1,2,4]triazolo[3,4-a]phthalazine (3f) and 6-heptyloxy-[1,2,4]triazolo[3,4-a]phthalazine (3s) showed a median effective dose of 7.1 and 11.0 mg/kg, and had protective index value of 5.2 and 8.0 respectively. The two compounds were further found to have potent activity against seizures induced by pentylenetetrazole, isoniazid, thiosemicarbazide, 3-mercaptopropionic acid but not seizures induced by strychnine, indicating that the two compounds might function by enhancing gamma-aminobutyric acid neurotransmission.
Co-reporter:Li-Ping Guan;Dong-Hai Zhao;Jing-Hui Xiu;Xin Sui;Hu-Ri Piao
Archiv der Pharmazie 2009 Volume 342( Issue 1) pp:34-40
Publication Date(Web):
DOI:10.1002/ardp.200800153
Abstract
A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.
Co-reporter:Huo-Jian Wang;Cheng-Xi Wei;Xian-Qing Deng;Fu-Lan Li
Archiv der Pharmazie 2009 Volume 342( Issue 11) pp:671-675
Publication Date(Web):
DOI:10.1002/ardp.200900119
Abstract
Several 5-alkoxy-tetrazolo[1,5-a]quinazoline derivatives have been synthesized by reacting 2,4-dichloroquinazoline with various phenols or aliphatic alcohol and then with sodium azide. The structures of these compounds have been confirmed by IR, MS, 1H-NMR, and elementary analysis. Anticonvulsant activities were evaluated using the maximal electroshock (MES) test. Most of the synthesized compounds displayed weak anticonvulsant activity at a dose of 300 mg/kg. Antidepressant activities were investigated by forced swimming test. Two compounds, namely 5-(hexyloxy)tetrazolo[1,5-a]quinazoline and 5-(4-methoxyphenoxy)tetrazolo[1,5-a]quinazoline, showed significant antidepressant activity, which decreased the immobility time by 62.2 and 51.7% at 100 mg/kg dose level.
Co-reporter:Xiang-Shu Cui;Jing Chen;Kyu-Yun Chai;Jin Seok Lee
Medicinal Chemistry Research 2009 Volume 18( Issue 1) pp:49-58
Publication Date(Web):2009 February
DOI:10.1007/s00044-008-9106-3
A series of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazole derivatives (3a-s) were synthesized as open-chain analogues of 7-hexyloxyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines (1c) using 4-hexyloxyaniline, acyl hydrazines, and dimethoxy-N,N-dimethylmethanamine as the 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). MES test showed that all open-chain compounds exhibited strong anticonvulsant activity and lower neurotoxicity, and that some possessed obviously stronger activity than compound 1c. Compound 3d, 3-propyl-4-(4-hexyloxyphenyl)-4H-1,2,4-triazole was found to be the most potent with an ED50 value of 5.7 mg/kg and protective index (PI = TD50/ED50) value of 11.5, which was much greater than that of the prototype drug phenytoin (PI = 6.9).
Co-reporter:Zhong-Tai Piao, Li-Ping Guan, Li-Ming Zhao, Hu-Ri Piao, Zhe-Shan Quan
European Journal of Medicinal Chemistry 2008 Volume 43(Issue 6) pp:1216-1221
Publication Date(Web):June 2008
DOI:10.1016/j.ejmech.2007.08.006
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. A series of 7-benzylamino-2H-1,4-benzoxazin-3(4H)-ones was 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.)
Co-reporter:Xian-Yu Sun;Cheng-Xi Wei;Kyu-Yun Chai;Hu-Ri Piao
Archiv der Pharmazie 2008 Volume 341( Issue 5) pp:288-293
Publication Date(Web):
DOI:10.1002/ardp.200700182
Abstract
In this study, a novel series of 7-alkoxy-1-amino-4,5-dihydro[1,2,4]triazole[4,3-a]quinolines were synthesized by using 6-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. These compounds were evaluated for anti-inflammatory activity through monitoring their ability to inhibit xylene-induced ear edema in mice. Some of the tested compounds exhibited significant activity, and the compounds 5f (7-(benzyloxy)-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolin-1-amine) and 5i (7-(p-chlorobenzyloxy)-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolin-1-amine) showed the highest anti-inflammatory activity (52% and 58% inhibition, respectively, at 2 h pre-administration) which were comparable to or even slightly more potent than the reference drug ibuprofen (55%). Furthermore, the structure-activity relationship of these 1,2,4-triazole quinolines was demonstrated.
Co-reporter:Li-Ping Guan;Qing-Hao Jin;Shou-Feng Wang;Fu-Nan Li
Archiv der Pharmazie 2008 Volume 341( Issue 12) pp:774-779
Publication Date(Web):
DOI:10.1002/ardp.200800116
Abstract
A series of novel 5-phenyl-[1,2,4]-triazolo[4,3-a]quinoline derivatives was synthesized by the cyclization of 2-chloro-4-phenyl-1,2-dihydronaphthalene with formohydrazide. The starting material 2-chloro-4-phenyl-1,2-dihydronaphthalene was synthesized from ethyl-3-oxo-3-phenylpropanoate and substituted aniline. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The maximal electroshock test showed that 7-hexyloxy-5-phenyl-[1,2,4]-triazolo[4,3-a]quinoline 4f was found to be the most potent compound with an ED50 value of 6.5 mg/kg and a protective index (PI = ED50 / TD50) value of 35.1, which was much higher than the PI of the reference drug phenytoin.
Co-reporter:Jing Chen, Xian-Yu Sun, Kyu-Yun Chai, Jin-Seok Lee, Mi-Sun Song, Zhe-Shan Quan
Bioorganic & Medicinal Chemistry 2007 Volume 15(Issue 21) pp:6775-6781
Publication Date(Web):1 November 2007
DOI:10.1016/j.bmc.2007.08.004
A series of 4-(4-alkoxylphenyl)-3-ethyl-4H-1,2,4-triazole derivatives was synthesized as open-chain analogues of 7-alkoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). MES test showed that 3-ethyl-4-(4-octyloxyphenyl)-4H-1,2,4-triazole 3q was found to be the most potent with ED50 value of 8.3 mg/kg and protective index (PI = TD50/ED50) value of 5.5, but compound 3r, 3-ethyl-4-(4-octyloxyphenyl)-4H-1,2,4-triazole, exhibited better PI value of 9.3, which was much greater than PI value of the prototype drug phenytoin. For explanation of the possible mechanism of action, the compound 3r was tested in pentylenetetrazole test, isoniazid test, thiosemicarbazide test, 3-mercaptopropionic acid and strychnine test.A series of 4-(4-alkoxylphenyl)-3-ethyl-4H-1,2,4-triazole derivatives was synthesized as open-chain analogues of 7-alkoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox).
Co-reporter:Cheng-Xi Wei;Fu-Nan Li;Long-Xuan Zhao;Li-Ming Zhao
Archiv der Pharmazie 2007 Volume 340(Issue 9) pp:
Publication Date(Web):30 AUG 2007
DOI:10.1002/ardp.200700106
A series of 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1(2H)-ones was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, 2-propionyl-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-one 4b was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED50) of 8.2 mg/kg, median toxicity dose (TD50) of 318.3 mg/kg, and the protective index (PI) of 39.0 which is much greater than the PI of the reference drugs phenytoin and carbamazepine.
Co-reporter:Li-Ming Zhao, Hai-Shan Jin, Liang-Peng Sun, Hu-Ri Piao, Zhe-Shan Quan
Bioorganic & Medicinal Chemistry Letters 2005 Volume 15(Issue 22) pp:5027-5029
Publication Date(Web):15 November 2005
DOI:10.1016/j.bmcl.2005.08.039
In an effort to develop potent antiplatelet agents, a series of trihydroxychalcones was synthesized and screened in vitro for their inhibitory effects on washed rabbit platelet aggregation induced by arachidonic acid (100 μM) and collagen (10 μg/ml). Of five compounds with potent inhibitory effects on arachidonic acid- and collagen-induced platelet aggregation, compound 4e was found to be the most potent. The structure–activity relationships suggested that antiplatelet activity was governed to a greater extent by the substituent on B ring of the chalcone template, and most of the active compounds had methoxy or dimethoxy groups on B ring.A series of trihydroxychalcones was synthesized and screened in vitro for their inhibitory effects on washed rabbit platelet aggregation induced by arachidonic acid (100 μM) and collagen (10 μg/ml). Compound 4e exhibited a potent inhibitory effect on arachidonic acid- and collagen-induced platelet aggregation. The structure–activity relationships were also discussed in this paper.
Co-reporter:Hai-Ling Yu, Feng-Zhang, Ying-Jun Li, Guo-Hua Gong, Zhe-Shan Quan
Pharmacological Reports (September–October 2012) Volume 64(Issue 5) pp:1155-1165
Publication Date(Web):1 September 2012
DOI:10.1016/S1734-1140(12)70912-X
BackgroundQUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), a new phthalazine tetrazole derivative, was evaluated for the anti-inflammatory and analgesic effects.MethodsXylene-induced ear edema, carrageenan (Carr)-induced paw edema, and acetic acid-induced capillary permeability hyperactivity in mice were used to assess the anti-inflammatory effect; acetic acid-induced writhing and hot plate responses for the analgesic activity.ResultsIn the present study, QUAN-0808 (100, 200, 400 mg/kg) and indomethacin (Indo) significantly decreased xylene-induced ear edema by 33.3, 37.5, 46.6, and 45.1%, respectively, decreased Carr-induced paw edema at 1, 2, 4 h after Carr injection, and decreased the prostaglandin E2 (PGE2) and nitric oxide (NO) levels on the edema paw at 4 h after Carr injection; QUAN-0808 (100, 200, 400 mg/kg), and aspirin (Asp, 200 mg/kg) significantly decreased Evans blue exudation in acetic acid-induced capillary permeability hyperactivity model by 26.7, 28.7, 32.3 and 29.1%, respectively, and decreased the numbers of acetic acid-induced writhing response in 15 min by 40.4, 53.6, 66.4, and 64.5%, respectively. Morphine (10 mg/kg) significantly increased the latency of the hot plate response by 136.5,117.4,67.5, and 22.7%, respectively, at 30, 60, 90, 120 min after intraperitoneal injection of morphine; however, QUAN-0808 (100, 200 and 400 mg/kg) did not produce significantly antinociceptive effects in the hot plate test, suggesting that its antinociceptive action occurs via peripheral rather than a central-acting mechanism.ConclusionsThese results show that QUAN-0808 produced potential anti-inflammatory and peripheral antinociceptive effects, and indicated that the antinociceptive effects of QUAN-0808 were related to its anti-inflammatory activity in a dose-dependent manner. Therefore, as inflammation is a peripheral process, it is suggested that QUAN-0808 exerted peripheral effects. The peripheral effect mechanisms of QUAN-0808 may be related to a decrease in the production of PGE2, NO, bradykinin and other inflammatory mediators.
Co-reporter:Hai-Ling Yu, Xian-Qing Deng, Ying-Jun Li, Ying-Chun Li, ... Xian-Yu Sun
Pharmacological Reports (May–June 2011) Volume 63(Issue 3) pp:834-839
Publication Date(Web):1 May 2011
DOI:10.1016/S1734-1140(11)70596-5
The antidepressant-like effects of N-palmitoylethanolamide (PEA), a putative endocannabinoid, was investigated in mice using the tail suspension test (TST) and the forced swimming test (FST). In TST, PEA (10, 20, and 40 mg/kg) produced a statistically significant reduction in immobility (50, 32, and 34%, respectively, vs. the control group), whereas fluoxetine (20 mg/kg) reduced immobility by 38%. In FST, PEA (5, 10, and 20 mg/kg) produced a statistically significant reduction in immobility (15, 21, and 36%, respectively), whereas fluoxetine (20 mg/kg) reduced immobility by 18%. Moreover, PEA (20 mg/kg) did not significantly change motor activity in a spontaneous behavioral test. In conclusion, PEA (dose range of 5–40 mg/kg) administered orally reduced immobility in TST and FST, comparable to the antidepressant effect of fluoxetine, and had no effect on spontaneous activity in mice.
Co-reporter:Xian-Yu Sun, Cheng-Xi Wei, Xian-Qing Deng, Zhi-Gang Sun, Zhe-Shan Quan
Pharmacological Reports (March–April 2010) Volume 62(Issue 2) pp:273-277
Publication Date(Web):1 March 2010
DOI:10.1016/S1734-1140(10)70266-8
This study investigated the anticonvulsant activity of a new phthalazine tetrazole derivative, QUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), in the mouse maximal electroshock (MES) seizure model. The neurotoxicity of QUAN-0808 was investigated using the rotarod neurotoxicity test in mice. QUAN-0808 exhibited higher activity (median effective dose, ED50 = 6.8 mg/ kg) and lower neurotoxicity (median toxic dose, TD50 = 456.4 mg/kg), resulting in a higher protective index (PI = 67.1) compared with carbamazepine (PI = 6.4). In addition, QUAN-0808 exhibited significant oral anticonvulsant activity (ED50 = 24 mg/kg) against MES-induced seizure with low neurotoxicity (TD50 > 4500 mg/kg) in mice, resulting in a PI value of more than 187.5. QUAN-0808 was also tested in chemically induced animal models of seizure (pentylenetetrazole [PTZ], isoniazid [ISO], thiosemicarbazide [THIO] and 3-mercaptopropionic acid [3-MP]) to further investigate the anticonvulsant activity; QUAN-0808 produced significant anticonvulsant activity against seizures induced by ISO, THIO and 3-MP.
Co-reporter:Xian-Yu Sun, Lei Zhang, Cheng-Xi Wei, Hu-Ri Piao, Zhe-Shan Quan
Pharmacological Reports (March–April 2009) Volume 61(Issue 2) pp:245-251
Publication Date(Web):1 March 2009
DOI:10.1016/S1734-1140(09)70028-3
In this paper, the anticonvulsant characteristics of doxepin were evaluated in numerous experimental seizure models, including maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, isoniazid (ISO)-, 3-mercaptopropionic acid (3-MP)-, bicuculline (BIC)-, thiosemicarbazide (THIO)-, and strychnine (STR)-induced seizures. In addition, the acute adverse-effect profile of doxepin with respect to impairment of motor coordination was assessed with a mouse rotarod test. The evaluation of the time-course and doseresponse relationships for doxepin provided evidence that the peak maximum anticonvulsant activity and acute adverse effects occurred 5 min after intraperitoneal (ip) administration. The results also revealed that doxepin had excellent anticonvulsant activity against maximal electroshock-induced seizures in mice with a median effect value (ED50) of 6.6 mg/kg. The assessment of acute adverse effects in the rotarod test revealed that doxepin induced acute neurotoxicity, and its median toxic dose (TD50) was 26.4 mg/kg. Additionally, doxepin showed anticonvulsant activity in several chemically-induced seizure models, including ISO, 3-MP, BIC, and THI. Based on this study, we can conclude that the antidepressant drug doxepin may be useful for treatment of depression in patients with epilepsy due to its short time to peak maximum anticonvulsant activity after ip administration (5 min) and remarkable anticonvulsant activity (6.6 mg/kg).
Co-reporter:Chunliu Mi, Juan Ma, Ke Si Wang, Hong Xiang Zuo, Zhe Wang, Ming Yue Li, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Zhe Shan Quan, Xuejun Jin
Journal of Ethnopharmacology (5 May 2017) Volume 203() pp:27-38
Publication Date(Web):5 May 2017
DOI:10.1016/j.jep.2017.03.033
Ethnopharmacological relevanceAngelica dahurica is a commonly used traditional Chinese medicine to treat migraine headache, toothache and cancer. Imperatorin is an active natural furocoumarin component originating from Angelica dahurica and has been shown to exhibit multiple bioeffector functions, including anti-cancer activity. However, the mechanism by which imperatorin inhibits tumor growth is not fully understood.Aim of the studyThe aim of this study was to investigate the effectiveness of imperatorin as a treatment of cancer and to identify the underlying mechanisms of its anticancer activity.Materials and methodsHCT116, HeLa, and Hep3B cells were used in this study. Major assays were promoter-reporter gene assay, MTT, western blot analysis, immunofluorescence assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, clonogenic assay, EdU labeling and immunofluorescence, xenografted assay, and VEGF ELISA.ResultsWe here demonstrated the effect of imperatorin on hypoxia-inducible factor-1 (HIF-1) activation. Imperatorin showed a potent inhibitory activity against HIF-1 activation induced by hypoxia in various human cancer cell lines. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (Topo-I). Further analysis revealed that imperatorin inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), eIF4E binding protein-1 (4E-BP1), eukaryotic initiation factor 4E (eIF4E), extracellular signal-regulated kinase-1/2 (ERK1/2), SAPK/JNK and p38 were significantly suppressed by imperatorin. Furthermore, imperatorin prevented hypoxia-induced expression of HIF-1 target genes and flow cytometric analysis indicated that imperatorin induced G1 phase arrest in human colon cancer cell (HCT116). We found that imperatorin administration inhibits tumor growth and blocks tumor angiogenesis in a xenograft tumor model.ConclusionsThese results show that imperatorin inhibited HIF-1α protein synthesis by downregulating the mTOR/p70S6K/4E-BP1 and MAPK pathways. These conclusions suggest that imperatorin is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity.Download high-res image (169KB)Download full-size image
![1H-Benzimidazole, 2-chloro-1-[(3-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/875100/875004-98-1.png)
![1H-Benzimidazole, 2-chloro-1-[(3-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/875100/875004-98-1_b.png)
![Benzonitrile, 4-[(2-chloro-1H-benzimidazol-1-yl)methyl]-](http://img.cochemist.com/ccimg/875100/875004-97-0.png)
![Benzonitrile, 4-[(2-chloro-1H-benzimidazol-1-yl)methyl]-](http://img.cochemist.com/ccimg/875100/875004-97-0_b.png)
![1H-Benzimidazole, 2-chloro-1-[[3-(trifluoromethyl)phenyl]methyl]-](http://img.cochemist.com/ccimg/875100/875004-92-5.png)
![1H-Benzimidazole, 2-chloro-1-[[3-(trifluoromethyl)phenyl]methyl]-](http://img.cochemist.com/ccimg/875100/875004-92-5_b.png)
![1H-Benzimidazole, 2-chloro-1-[(4-nitrophenyl)methyl]-](http://img.cochemist.com/ccimg/875100/875004-91-4.png)
![1H-Benzimidazole, 2-chloro-1-[(4-nitrophenyl)methyl]-](http://img.cochemist.com/ccimg/875100/875004-91-4_b.png)
![9H-Purine, 6-chloro-9-[(2,4-dichlorophenyl)methyl]-](http://img.cochemist.com/ccimg/850800/850791-58-1.png)
![9H-Purine, 6-chloro-9-[(2,4-dichlorophenyl)methyl]-](http://img.cochemist.com/ccimg/850800/850791-58-1_b.png)
![1H-Benzimidazole, 2-chloro-1-[(4-methoxyphenyl)methyl]-](http://img.cochemist.com/ccimg/388600/388574-61-6.png)
![1H-Benzimidazole, 2-chloro-1-[(4-methoxyphenyl)methyl]-](http://img.cochemist.com/ccimg/388600/388574-61-6_b.png)
![1H-Benzimidazole, 2-chloro-1-[(4-methylphenyl)methyl]-](http://img.cochemist.com/ccimg/388600/388574-59-2.png)
![1H-Benzimidazole, 2-chloro-1-[(4-methylphenyl)methyl]-](http://img.cochemist.com/ccimg/388600/388574-59-2_b.png)
![Benzoic acid, 4-[(2,6-dichlorophenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/149300/149288-99-3.png)
![Benzoic acid, 4-[(2,6-dichlorophenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/149300/149288-99-3_b.png)
![1H-Benzimidazole, 2-chloro-1-[(4-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/131800/131705-80-1.png)
![1H-Benzimidazole, 2-chloro-1-[(4-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/131800/131705-80-1_b.png)
![Benzonitrile, 4-[(6-chloro-9H-purin-9-yl)methyl]-](http://img.cochemist.com/ccimg/112100/112089-36-8.png)
![Benzonitrile, 4-[(6-chloro-9H-purin-9-yl)methyl]-](http://img.cochemist.com/ccimg/112100/112089-36-8_b.png)
![4-[(4-Methoxybenzyl)oxy]benzaldehyde](http://img.cochemist.com/ccimg/77200/77182-73-1.png)
![4-[(4-Methoxybenzyl)oxy]benzaldehyde](http://img.cochemist.com/ccimg/77200/77182-73-1_b.png)
![7-ETHOXY-4H-BENZO[1,4]THIAZIN-3-ONE](http://img.cochemist.com/ccimg/71400/71387-69-4.png)
![7-ETHOXY-4H-BENZO[1,4]THIAZIN-3-ONE](http://img.cochemist.com/ccimg/71400/71387-69-4_b.png)
![4-[(2-CHLOROBENZYL)OXY]BENZALDEHYDE](http://img.cochemist.com/ccimg/70700/70627-21-3.png)
![4-[(2-CHLOROBENZYL)OXY]BENZALDEHYDE](http://img.cochemist.com/ccimg/70700/70627-21-3_b.png)
![4-[(2,4-DICHLOROBENZYL)OXY]BENZALDEHYDE](http://img.cochemist.com/ccimg/70700/70627-17-7.png)
![4-[(2,4-DICHLOROBENZYL)OXY]BENZALDEHYDE](http://img.cochemist.com/ccimg/70700/70627-17-7_b.png)
![9H-Purine, 6-chloro-9-[(2,6-dichlorophenyl)methyl]-](http://img.cochemist.com/ccimg/70100/70091-24-6.png)
![9H-Purine, 6-chloro-9-[(2,6-dichlorophenyl)methyl]-](http://img.cochemist.com/ccimg/70100/70091-24-6_b.png)
![BENZALDEHYDE, 4-[[4-(TRIFLUOROMETHYL)PHENYL]METHOXY]-](http://img.cochemist.com/ccimg/66800/66742-55-0.png)
![BENZALDEHYDE, 4-[[4-(TRIFLUOROMETHYL)PHENYL]METHOXY]-](http://img.cochemist.com/ccimg/66800/66742-55-0_b.png)
![BENZOIC ACID, 4-[(2-CHLOROPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/64000/63929-43-1.png)
![BENZOIC ACID, 4-[(2-CHLOROPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/64000/63929-43-1_b.png)
![BENZOIC ACID, 4-[(2,4-DICHLOROPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/56500/56441-85-1.png)
![BENZOIC ACID, 4-[(2,4-DICHLOROPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/56500/56441-85-1_b.png)
![Benzoic acid, 4-[(4-methoxyphenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-84-0.png)
![Benzoic acid, 4-[(4-methoxyphenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-84-0_b.png)
![BENZOIC ACID, 4-[(3-FLUOROPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/56500/56441-81-7.png)
![BENZOIC ACID, 4-[(3-FLUOROPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/56500/56441-81-7_b.png)
![BENZOIC ACID, 4-[(4-METHYLPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/56500/56441-63-5.png)
![BENZOIC ACID, 4-[(4-METHYLPHENYL)METHOXY]-, ETHYL ESTER](http://img.cochemist.com/ccimg/56500/56441-63-5_b.png)
![Benzoic acid, 4-[[3-(trifluoromethyl)phenyl]methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-60-2.png)
![Benzoic acid, 4-[[3-(trifluoromethyl)phenyl]methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-60-2_b.png)
![ETHYL 4-[(4-FLUOROPHENYL)METHOXY]BENZOATE](http://img.cochemist.com/ccimg/56500/56441-59-9.png)
![ETHYL 4-[(4-FLUOROPHENYL)METHOXY]BENZOATE](http://img.cochemist.com/ccimg/56500/56441-59-9_b.png)
![Benzoic acid, 4-[(3-chlorophenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-56-6.png)
![Benzoic acid, 4-[(3-chlorophenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-56-6_b.png)
![Benzoic acid, 4-[(4-chlorophenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-54-4.png)
![Benzoic acid, 4-[(4-chlorophenyl)methoxy]-, ethyl ester](http://img.cochemist.com/ccimg/56500/56441-54-4_b.png)
![5,7-dimethyl-2-sulfanylidene-1h-pyrido[2,3-d]pyrimidin-4-one](http://img.cochemist.com/ccimg/49700/49600-56-8.png)
![5,7-dimethyl-2-sulfanylidene-1h-pyrido[2,3-d]pyrimidin-4-one](http://img.cochemist.com/ccimg/49700/49600-56-8_b.png)
![1-Benzyl-2-chloro-1H-benzo[d]imidazole](http://img.cochemist.com/ccimg/43200/43181-78-8.png)
![1-Benzyl-2-chloro-1H-benzo[d]imidazole](http://img.cochemist.com/ccimg/43200/43181-78-8_b.png)
![2,4-dichloro-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine](http://img.cochemist.com/ccimg/40300/40277-35-8.png)
![2,4-dichloro-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidine](http://img.cochemist.com/ccimg/40300/40277-35-8_b.png)
![[1]Benzothieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,5,6,7,8-tetrahydro-](http://img.cochemist.com/ccimg/27300/27285-09-2.png)
![[1]Benzothieno[2,3-d]pyrimidine-2,4(1H,3H)-dione,5,6,7,8-tetrahydro-](http://img.cochemist.com/ccimg/27300/27285-09-2_b.png)
![6-Ethoxy-2-hydrazinylbenzo[d]thiazole](http://img.cochemist.com/ccimg/17000/16942-73-7.png)
![6-Ethoxy-2-hydrazinylbenzo[d]thiazole](http://img.cochemist.com/ccimg/17000/16942-73-7_b.png)
![7-benzyl-7H-tetrazolo[5,1-i]purine](http://img.cochemist.com/ccimg/10600/10553-44-3.png)
![7-benzyl-7H-tetrazolo[5,1-i]purine](http://img.cochemist.com/ccimg/10600/10553-44-3_b.png)
![2-Chloro-1H-benzo[d]imidazole](http://img.cochemist.com/ccimg/4900/4857-06-1.png)
![2-Chloro-1H-benzo[d]imidazole](http://img.cochemist.com/ccimg/4900/4857-06-1_b.png)
![Pyrido[2,3-d]pyridazine-5,8-diol](http://img.cochemist.com/ccimg/4500/4430-77-7.png)
![Pyrido[2,3-d]pyridazine-5,8-diol](http://img.cochemist.com/ccimg/4500/4430-77-7_b.png)
![7-benzyl-7H-[1,2,4]triazolo[3,4-i]purine](http://img.cochemist.com/ccimg/4100/4022-95-1.png)
![7-benzyl-7H-[1,2,4]triazolo[3,4-i]purine](http://img.cochemist.com/ccimg/4100/4022-95-1_b.png)
![2-Chloro-N-(6-methoxybenzo[d]thiazol-2-yl)acetamide](http://img.cochemist.com/ccimg/3500/3427-30-3.png)
![2-Chloro-N-(6-methoxybenzo[d]thiazol-2-yl)acetamide](http://img.cochemist.com/ccimg/3500/3427-30-3_b.png)
![5,8-DICHLOROPYRIDO[2,3-D]PYRIDAZINE](http://img.cochemist.com/ccimg/800/703-33-3.png)
![5,8-DICHLOROPYRIDO[2,3-D]PYRIDAZINE](http://img.cochemist.com/ccimg/800/703-33-3_b.png)
![9H-Purine, 6-chloro-9-[(2-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112089-33-5.png)
![9H-Purine, 6-chloro-9-[(2-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112089-33-5_b.png)
![9H-Purine, 6-chloro-9-[(3-fluorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-88-7.png)
![9H-Purine, 6-chloro-9-[(3-fluorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-88-7_b.png)
![9H-Purine, 6-chloro-9-[(3-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-84-3.png)
![9H-Purine, 6-chloro-9-[(3-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-84-3_b.png)
![9H-Purine, 6-chloro-9-[(4-methoxyphenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-76-3.png)
![9H-Purine, 6-chloro-9-[(4-methoxyphenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-76-3_b.png)
![9H-Purine, 6-chloro-9-[(4-fluorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-75-2.png)
![9H-Purine, 6-chloro-9-[(4-fluorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-75-2_b.png)
![9H-Purine, 6-chloro-9-[(4-methylphenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-73-0.png)
![9H-Purine, 6-chloro-9-[(4-methylphenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-73-0_b.png)
![9H-Purine, 6-chloro-9-[(4-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-71-8.png)
![9H-Purine, 6-chloro-9-[(4-chlorophenyl)methyl]-](http://img.cochemist.com/ccimg/112100/112088-71-8_b.png)
![9H-Purine, 6-chloro-9-[(2-fluorophenyl)methyl]-](http://img.cochemist.com/ccimg/101200/101155-08-2.png)
![9H-Purine, 6-chloro-9-[(2-fluorophenyl)methyl]-](http://img.cochemist.com/ccimg/101200/101155-08-2_b.png)
![4(1H)-Quinazolinone, 2,3-dihydro-3-[4-(pentyloxy)phenyl]-2-thioxo-](http://img.cochemist.com/ccimg/100900/100822-70-6.png)
![4(1H)-Quinazolinone, 2,3-dihydro-3-[4-(pentyloxy)phenyl]-2-thioxo-](http://img.cochemist.com/ccimg/100900/100822-70-6_b.png)
![Benzoic acid, 2-[[(phenylamino)thioxomethyl]amino]-, methyl ester](http://img.cochemist.com/ccimg/96300/96221-91-9.png)
![Benzoic acid, 2-[[(phenylamino)thioxomethyl]amino]-, methyl ester](http://img.cochemist.com/ccimg/96300/96221-91-9_b.png)
![[1,2,4]Triazolo[4,3-a]quinazolin-5(4H)-one, 4-phenyl-](http://img.cochemist.com/ccimg/67900/67811-46-5.png)
![[1,2,4]Triazolo[4,3-a]quinazolin-5(4H)-one, 4-phenyl-](http://img.cochemist.com/ccimg/67900/67811-46-5_b.png)
![[1,2,4]Triazolo[4,3-a]quinazoline-1,5-dione, 2,4-dihydro-4-phenyl-](http://img.cochemist.com/ccimg/67700/67629-33-8.png)
![[1,2,4]Triazolo[4,3-a]quinazoline-1,5-dione, 2,4-dihydro-4-phenyl-](http://img.cochemist.com/ccimg/67700/67629-33-8_b.png)
![1-Mercapto-4-phenyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one](http://img.cochemist.com/ccimg/67500/67442-90-4.png)
![1-Mercapto-4-phenyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one](http://img.cochemist.com/ccimg/67500/67442-90-4_b.png)
![TETRAZOLO[1,5-A]QUINAZOLIN-5(4H)-ONE, 4-PHENYL-](http://img.cochemist.com/ccimg/59400/59342-38-0.png)
![TETRAZOLO[1,5-A]QUINAZOLIN-5(4H)-ONE, 4-PHENYL-](http://img.cochemist.com/ccimg/59400/59342-38-0_b.png)
![6-Butoxybenzo[d]thiazol-2-amine](http://img.cochemist.com/ccimg/14400/14372-65-7.png)
![6-Butoxybenzo[d]thiazol-2-amine](http://img.cochemist.com/ccimg/14400/14372-65-7_b.png)
![6-Propoxybenzo[d]thiazol-2-amine](http://img.cochemist.com/ccimg/14400/14372-64-6.png)
![6-Propoxybenzo[d]thiazol-2-amine](http://img.cochemist.com/ccimg/14400/14372-64-6_b.png)
