共查询到20条相似文献,搜索用时 78 毫秒
1.
Hartmann RW Palusczak A Lacan F Ricci G Ruzziconi R 《Journal of enzyme inhibition and medicinal chemistry》2004,19(2):145-155
Regioselectively fluorinated 1-(naphth-2-ylmethyl)imidazoles 1a-h have been synthesized starting from the corresponding (naphth-2-yl)methanols (2). 2a-d have been obtained by LiAlH4-promoted reduction of fluorinated 1-methyl-2-naphthaldehydes. The latter were easily prepared in fairly good overall yields by ceric ammonium nitrate (CAN)-promoted oxidative addition of the suitable 3-(fluoroaryl)-1-trimethylsilyloxy-1-butenes to ethyl vinyl ether in methanol followed by cyclization of the resulting acetals in strongly acidic medium in the presence of DDQ. 2e-h were prepared by LiAlH4-promoted reduction of the corresponding fluorinated methyl 2-naphthoates. The latter were more profitably obtained by reacting the suitable benzyl bromide with the sodium salt of dimethyl 2-(2,2-dimethoxyethyl)malonate in DMF followed by demethoxycarbonylation and acid catalysed cyclization of the resulting acetals. Compared with the nonfluorinated parent compounds 1i-1, fluorinated 1-(naphth-2-yl)methylimidazoles 1a-h turned out to be potent inhibitors of CYP17 and CYP19 enzymes. The most active inhibitor of CYP17 is 1c, whereas CYP19 is strongly inhibited by 1b, 1e, and 1g. Interestingly, 1g is a potent dual inhibitor also being very active towards CYP19. 相似文献
2.
E. Rajanarendar M. Nagi Reddy K. Rama Murthy K. Govardhan Reddy S. Raju M. Srinivas B. Praveen M. Srinivasa Rao 《Bioorganic & medicinal chemistry letters》2010,20(20):6052-6055
A series of 1-aryl-4-methyl-3,6-bis-(5-methylisoxazol-3-yl)-2-thioxo-2,3,6,10b-tetrahydro-1H-pyrimido[5,4-c]quinolin-5-ones (6a–h) have been synthesized by cyclization of ethyl-3-aryl-4-(2-chlorophenyl)-6-methyl-1-(5-methylisoxazol-3-yl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates 4a–h with 3-amino-5-methylisoxazole 5. Compounds 4a–h were obtained by Biginelli reaction, by condensation of aromatic aldehyde 1, ethyl acetoacetate 2, and isoxazolyl thioureas 3 in a one-pot reaction catalyzed by ceric ammonium nitrite (CAN). Compounds 6a–h were tested for their antibacterial and antifungal activities against various bacterial and fungal strains. The results showed that these compounds exhibited good antibacterial and antifungal activity compared with that of standard antibiotics. Mosquito larvicidal activity of the newly synthesized compounds 6a–h is also studied against fourth instar larvae Culex quinquefasciatus. Some of the compounds are proved to be lethal for mosquito larvae. 相似文献
3.
Abderrahim Ben Saïd Anis Romdhane Nicolas Elie David Touboul 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1277-1285
The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes 2a–e has been accomplished by reaction of 2-acetonitrile derivatives 1a–e with hydroxylamine. Cyclocondensation reaction of precursors 2a–e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a–e, 4a–e, and 5a–e, respectively. On the other hand, the reaction of precursors 2a–e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a–e which evolve under reflux of toluene to the new oxadiazoles 7a–e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i) 5a was the most active (IC50?=?4.0?μM) and selective against MCF-7 and (ii) 2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50?=?17 and 12?μM, respectively) while 2e is highly selective against OVCAR-3 (IC50?=?10?μM). 相似文献
4.
Hardesh K. Maurya Ruby Verma Saba Alam Shweta Pandey Vinay Pathak Sandeep Sharma Kishore K. Srivastava Arvind S. Negi Atul Gupta 《Bioorganic & medicinal chemistry letters》2013,23(21):5844-5849
Various substituted 5,6-dihydro-8-methoxybenzo[h]quinazolin-2-amine, 1-(3-(4-alkoxyphenyl)-7-methoxy-3,3a,4,5-tetrahydro-2H benzo[g]indazol-2-yl)ethanone, pyrazole and 2,6-diarylpyridine derivatives have been synthesized in good yields by an efficient methodology. The synthesized compounds (4–23) were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. Compounds 6a, 6c, 8a, 19a and 19e exhibited significant anti-tubercular activity at MIC values 50, 100, 50, 25 and 100 μM concentration. In vitro cytotoxicity data using THP-1 cells indicated that most active compound 19a is safe as its MIC value is much lower than the cytotoxic value. 相似文献
5.
G. Santhosh Kumar Y. Poornachandra Shravan Kumar Gunda K. Ratnakar Reddy Jaheer Mohmed Kamal Shaik C. Ganesh Kumar B. Narsaiah 《Bioorganic & medicinal chemistry letters》2018,28(13):2328-2337
A series of novel furo[2,3-b]pyridine-2-carboxamide 4a–h/pyrido[3′,2′:4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives 5a–p were prepared from pyridin 2(1H) one 1 via selective O-alkylation with α-bromoethylester followed by cyclization, then reaction with different aliphatic primary amines to obtain 4 and further reaction with triethyl orthoacetate/triethyl orthoformate. Also prepared novel furo[2,3-b]pyridine-2-carbohydrazide Schiff’s bases 7a–h and pyrido [3′,2′:4,5]furo[3,2-d]pyrimidin-4(3H)-one derivatives 8a–h starting from furo[2,3-b]pyridine carboxylate derivatives 3 by reaction with hydrazine hydrate to form 6 and reaction with diverse substituted aldehydes and cyclization. Products 4a–h, 5a–p, 7a–h and 8a–h were screened against four human cancer cell lines (HeLa, COLO205, Hep G2 and MCF 7) and one normal cell line (HEK 293). Compounds 4e, 4f, 4g, 5h, 7c, 7d, 7e and 7f showed significant anticancer activity against all the cell lines at micro molar concentration and found to be non-toxic to normal cell line. Studies for HeLa, COLO205 and MCF-7 using CoMFA and CoMSIA. Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205 and MCF-7 cell line inhibitors. 相似文献
6.
Zimmer C Hafner M Zender M Ammann D Hartmann RW Vock CA 《Bioorganic & medicinal chemistry letters》2011,21(1):186-190
A series of 23 N-(Pyridin-3-yl)benzamides was synthesized and evaluated for their potential to inhibit human steroid-11β-hydroxylase (CYP11B1) and human aldosterone synthase (CYP11B2). The most potent and selective CYP11B2 inhibitors (IC50 values 53-166 nM) were further evaluated for their potential to inhibit human CYP17 and CYP19, and no inhibition was observed. Clear evidence was shown for N-(Pyridin-3-yl)benzamides to be a highly selective class of CYP11B2 inhibitors in vitro. 相似文献
7.
《Bioorganic & medicinal chemistry》2016,24(11):2486-2503
Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents, and numerous drug discovery programs are dedicated to finding small-molecule MCH receptor 1 (MCHR1) antagonists. We recently reported novel pyridine-2(1H)-ones as aliphatic amine-free MCHR1 antagonists that structurally featured an imidazo[1,2-a]pyridine-based bicyclic motif. To investigate imidazopyridine variants with lower basicity and less potential to inhibit cytochrome P450 3A4 (CYP3A4), we designed pyridine-2(1H)-ones bearing various less basic bicyclic motifs. Among these, a lead compound 6a bearing a 1H-benzimidazole motif showed comparable binding affinity to MCHR1 to the corresponding imidazopyridine derivative 1. Optimization of 6a afforded a series of potent thiophene derivatives (6q–u); however, most of these were found to cause time-dependent inhibition (TDI) of CYP3A4. As bioactivation of thiophenes to form sulfoxide or epoxide species was considered to be a major cause of CYP3A4 TDI, we introduced electron withdrawing groups on the thiophene and found that a CF3 group on the ring or a Cl adjacent to the sulfur atom helped prevent CYP3A4 TDI. Consequently, 4-[(5-chlorothiophen-2-yl)methoxy]-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (6s) was identified as a potent MCHR1 antagonist without the risk of CYP3A4 TDI, which exhibited a promising safety profile including low CYP3A4 inhibition and exerted significant antiobesity effects in diet-induced obese F344 rats. 相似文献
8.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):267-274
Claisen-Schmidt condensation of 3-(1,2,3,6-tetrahydro-1-methylpyridin-4-yl)-2,4,5- trimethoxybenzaldehyde 3 and various aromatic, heterocyclic and alicyclic amides of 3- aminoacetophenone 6(a–s) afforded novel curcumin mimics. All the synthesized compounds were characterized by IR, 1H NMR, Mass spectroscopy and evaluated for antioxidant, cytotoxicity and antimicrobial activity. Out of the 20 compounds screened, compounds 7i, 7l, 7q, and 7n have shown excellent radical scavenging activity, compounds 7o, 7t, 7f, and 7r have shown significant xanthine oxidase inhibition, and compounds 7a, 7k and 7l were found to be potent inhibitors of selected cancer cell lines. Compounds 7h, 7t, 7l, 7i, and 7e have shown good antibacterial activity, whereas compounds 7j, 7f, 7o, 7h, and 7t exhibited significant antifungal activity. 相似文献
9.
As part of an effort to generate broad-spectrum inhibitors of rhinovirus replication, novel series of (E)-3-[(E)-3-phenylallylidene]chroman-4-ones 1a–e, (E)-3-(3-phenylprop-2-yn-1-ylidene)chroman-4-ones 2a and 2b, (Z)-3-[(E)-3-phenylallylidene]chromans 3a–e, and (E)-3-(3-phenylprop-1-en-1-yl)-2H-chromenes 4a–d were designed and synthesized. All the compounds were tested in vitro for their efficacy against infection by human rhinovirus (HRV) 1B and 14, two representative serotypes for rhinovirus group B and A, respectively. Most of the analogues were found to be potent and selective inhibitors of both HRVs, although HRV 1B was generally more susceptible than HRV 14. Mechanism of action studies of (E)-6-chloro-3-(3-phenylprop-1-en-1-yl)-2H-chromene 4b, the most potent compound on HRV 1B infection, suggested that 4b behaves as a capsid-binder probably acting at the uncoating level. 相似文献
10.
A series of new N′-[N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)thiocarbamoyl]-2-[(1-aryl-1H-tetrazol-5-yl)sulfanyl]acetohydrazides 5a–5e were synthesized rapidly in high yields from 2-(1-aryl-1H-tetrazol-5-ylsulfanyl)acetohydrazides 3a–3e and 2,3,4-tri-O-acetyl-β-d-xylopyranosyl isothiocyanate 4, then 5a–5e were converted to a series of new 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-1,3,4-oxadiazole-2-amines 6a–6e and 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-1,3,4-thiadiazole-2-amines 7a–7e, respectively under mercuric acetate/alcohol system or acetic anhydride/phosphoric acid system, then deacetylated in the solution of CH3ONa/CH3OH. All of the novel compounds were characterized by IR, 1H NMR, 13C NMR, MS and elemental analysis. The structures of compounds 2e, 3e, 5a and 5c have been determined by X-ray diffraction analysis. Some of the synthesized compounds displayed PTP1B inhibition and microorganism inhibition. 相似文献
11.
Luz María Torres Espíndola Daniela Rojo-Serrato Antonio Álvaro-Heredia Manuel de Jesús Castillejos López Armando de Uña-Flores Martin Pérez-García 《Biomarkers》2020,25(4):331-340
AbstractContext: Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide.Materials and methods: A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan–Meier curves.Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin.Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity.Clinical trial registration: 068/2013 相似文献
12.
Rideg O Háber A Botz L Szücs F Várnai R Miseta A Kovács GL 《Cell biochemistry and function》2011,29(7):562-568
Polymorphisms of CYP450 metabolizer enzymes and transport proteins play crucial roles in the inter‐individual variability of drug efficiency. The aim of our study was to predict the frequency of functional variants of CYP2D6, CYP2C19 and ABCB1 genes in the Hungarian population. One hundred twelve unrelated healthy subjects donated DNA sample in the study. ABCB1 C3435T and G2677T/A single‐nucleotide polymorphisms (SNPs) were determined by LightCycler polymerase chain reaction. Because only limited amount of data is available on the rare allelic variants of CYP2D6 in the European populations, our study applied an expanded set of CYP2D6 and CYP2C19 alleles by using AmpliChip test. Our results show that the CYP2D6 phenotypes were 1.9% ultra‐rapid metabolizer, 6.5% intermediate metabolizer (IM), 8.3% poor metabolizer (PM) and 83.3% extensive metabolizer (EM), and the CYP2C19 phenotypes were 1.8% PM, 31.2% IM and 67% EM. The prevalence of the commonly observed CYP2D6 and CYP2C19 alleles in our study corresponds with that of other European populations. Nevertheless, our study confirms that extending the CYP2D6 allele set with loss‐of‐function variants such as CYP2D6*7, *9, *41 is worth considering. Frequency of the wild type ABCB1 3435C was 42.8% whereas the prevelance of 2677 G was 50.4%. Although frequency data of G2677T/A SNP in the European area are limited, some discrepancies with other studies were found. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
13.
Supattra Boonruang Khanistha Prakobsri Phisit Pouyfung Ekaruth Srisook Aruna Prasopthum Pornpimol Rongnoparut 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1136-1142
The human liver cytochrome P450 (CYP) 2A6 and the respiratory CYP2A13 enzymes play role in nicotine metabolism and activation of tobacco-specific nitrosamine carcinogens. Inhibition of both enzymes could offer a strategy for smoking abstinence and decreased risks of respiratory diseases and lung cancer. In this study, activity-guided isolation identified four flavonoids 1–4 (apigenin, luteolin, chrysoeriol, quercetin) from Vernonia cinerea and Pluchea indica, four hirsutinolide-type sesquiterpene lactones 5–8 from V. cinerea, and acetylenic thiophenes 9–11 from P. indica that inhibited CYP2A6- and CYP2A13-mediated coumarin 7-hydroxylation. Flavonoids were most effective in inhibition against CYP2A6 and CYP2A13, followed by thiophenes, and hirsutinolides. Hirsutinolides and thiophenes exhibited mechanism-based inhibition and in irreversible mode against both enzymes. The inactivation kinetic KI values of hirsutinolides against CYP2A6 and CYP2A13 were 5.32–15.4 and 0.92–8.67 µM, respectively, while those of thiophenes were 0.11–1.01 and 0.67–0.97 µM, respectively. 相似文献
14.
《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》2000,125(2):203-214
The catalytic activity of CYP1A isoforms and the effect of mammalian CYP1A-specific inhibitors in liver S9 fractions were studied in an agnathan (River lamprey, Lampetra fluviatilis, 30–33 cm) and in two species of teleost fish (European flounder, Pleuronectes flesus, 11–18 cm and common eel, Anguilla anguilla, 31–48 cm). Ethoxyresorufin O-deethylation (EROD), caffeine N-demethylation/C-oxidation and phenacetin O-deethylation (POD) activity increased 3–4-fold in flounders and 17–46-fold in eels, 5 days after fish were injected (i.p.) with 100 mg kg−1 benzo(a)pyrene (B[a]P). In lampreys, basal EROD activity was very low and no increase in activity was observed following exposure to B[a]P. While the apparent Michaelis constant (Km) for each assay showed only small changes after B[a]P injection, maximum reaction velocity (Vmax) values increased by up to 19- and 84-fold for EROD activity, 4- and 35-fold for caffeine-related metabolism and 4- and 19-fold for POD activity in flounders and eels, respectively. The mammalian CYP1A2 inhibitor furafylline (50 μM–1 mM) reduced activity in the EROD, caffeine and POD assays to 65, 21 and 20% of control values in flounders and to 85, 10 and 5% of control values in eels, respectively. By contrast, low concentrations (0.025–0.050 μM) of the mammalian CYP1A1 inhibitor ellipticine completely abolished EROD activity, but had no effect (up to 1 mM) on caffeine metabolism or POD activity in either species. While the inhibitor studies strongly suggest that two separate enzymes are present in flounders and eels, the monophasic Michaelis–Menten kinetics obtained in all the assays imply that only a single CYP1A protein is present that has substrate and inhibitor specificities characteristic of both mammalian CYP1A1 and CYP1A2 isoforms. 相似文献
15.
Katarzyna Skupinska Irena Misiewicz‐Krzeminska Rafal Stypulkowski Katarzyna Lubelska Teresa Kasprzycka‐Guttman 《Journal of biochemical and molecular toxicology》2009,23(1):18-28
CYP1A1 and CYP1A2 enzymes metabolize polycyclic aromatic hydrocarbons (PAHs) to the reactive oxyderivatives. PAHs can induce the activity of both enzymes, which increases its conversion and enhances risk of carcinogenesis. Thus, the inhibition of CYP enzymes is recognized as a cancer chemoprevention strategy. A well‐known group of chemopreventive agents is isothiocyanates, which occur naturally in Brassica vegetables. In this paper, a naturally occurring sulforaphane and its two synthetic analogues isothiocyanate‐2‐oxohexyl and alyssin were investigated. The aim of the study was to determine whether the differences in the isothiocyanate structure change its ability to inhibit CYP1A1 and CYP1A2 activity induced by benzo[a]pyrene in HepG2 and Mcf7 cells. Also a mechanistic study was performed including isothiocyanates' influence on CYP1A1 and CYP1A2 catalytic activity, enzymatic protein level, and AhR translocation. It was shown that both enzymes were significantly induced by benzo[a]pyrene, and isothiocyanates were capable of decreasing the induced activity. The inhibitory properties depend on the types of isothiocyanate and enzyme. In general, CYP1A2 was altered in the more meaningful way than CYP1A1 by isothiocyanates. Sulforaphane exhibited weak inhibitory properties, whereas both analogues were capable of inhibiting BaP‐induced activity with the similar efficacy. The mechanistic study revealed that analogues decreased the CYP1A2 activity via the protein‐level reduction and CYP1A1 directly. The results indicate that isothiocyanates can be considered as potent chemopreventive substances and the change in the sulforaphane structure increases its chemopreventive potency. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:18–28, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20259 相似文献
16.
Neill J. Horley Kenneth J.M. Beresford Supriya Kaduskar Prashant Joshi Glen J.P. McCann Ketan C. Ruparelia Ibidapo S. Williams Linda Gatchie Vinay R. Sonawane Sandip B. Bharate Bhabatosh Chaudhuri 《Bioorganic & medicinal chemistry letters》2017,27(24):5409-5414
The overexpression of CYP1 family of enzymes is reported to be associated with development of human carcinomas. It has been well reported that CYP1A1 specific inhibitors prevents carcinogenesis. Herein, thirteen pyridine-4-yl series of chalcones were synthesized and screened for inhibition of CYP1 isoforms 1A1, 1B1 and 1A2 in Sacchrosomes? and live human HEK293 cells. The structure-activity relationship analysis indicated that chalcones bearing tri-alkoxy groups (8a and 8k) on non-heterocyclic ring displayed selective inhibition of CYP1A1 enzyme, with IC50 values of 58 and 65?nM, respectively. The 3,4,5-trimethoxy substituted derivative 8a have shown >10-fold selectivity towards CYP1A1 with respect to other enzymes of the CYP1 sub-family and >100-fold selectivity with respect to CYP2 and CYP3 family of enzymes. The potent and selective CYP1A1 inhibitor 8a displayed antagonism of B[a]P mediated activation of aromatic hydrocarbon receptor (AhR) in yeast cells, and also protected human cells from CYP1A1-mediated B[a]P toxicity in human cells. This potent and selective inhibitor of CYP1A1 enzyme have a potential for development as cancer chemopreventive agent. 相似文献
17.
Wataru Hamaguchi Naoyuki Masuda Mai Isomura Satoshi Miyamoto Shigetoshi Kikuchi Yasushi Amano Kazuya Honbou Takuma Mihara Toshihiro Watanabe 《Bioorganic & medicinal chemistry》2013,21(24):7612-7623
A novel class of phosphodiesterase 10A (PDE10A) inhibitors with reduced CYP1A2 inhibition were designed and synthesized starting from 2-{[(1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (1). Introduction of an isopropyl group at the 2-position and a methoxy group at the 5-position of the benzimidazole ring of lead compound 1 resulted in the identification of 2-{[(2-isopropyl-5-methoxy-1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (25b), which exhibited potent PDE10A inhibitory activity with reduced CYP1A2 inhibitory activity compared to compound 1. 相似文献
18.
《Bioorganic & medicinal chemistry letters》2014,24(23):5423-5427
A chemical study of the roots of Euphorbia fischeriana resulted in the isolation of seven triterpenes (1–7), including two new compounds: (24R,S)-3β-24,31-epoxy-24-methylcycloartane (1) and (24R,S)-3β,31-dihydroxy-24-methoxy-24-methylcycloartane (2). Their structures were elucidated through extensive spectroscopic analyses. Cycloartanes 1–4 showed significant human CYP3A4 promoter activity through a series of luciferase reporter assays. Of these compounds, 3 and 4 activated the pregnane X receptor (PXR) and induced CYP3A4 mRNA expression in human primary hepatocytes. However, despite showing the most potent human CYP3A4 promoter activity via a PXR-independent pathway, 2 did not affect CYP3A4 mRNA expression in human primary hepatocytes. This difference is correlated to substitutions in C-24 and C-25 of the cycloartane structure. 相似文献
19.
20.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):141-148
A series of substituted azole derivatives (3a–e, 4a–e and 5a–e) were synthesised by the cyclisation of N1(diphenylethanoyl)-N4-substituted phenyl thiosemicarbazides under various reaction conditions. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen, were screened for their analgesic, ulcerogenic and lipid peroxidation activities. The compounds 5-(diphenylmethyl)-N-(4-fluorophenyl)-1,3,4-oxadiazol-2-amine (3b) and 5-(diphenylmethyl)-N-(3-chloro-4-fluorophenyl)-1,3,4-oxadiazol-2-amine (3c) emerged as the most active compounds of the series, and were moderately more potent than the standard drug, ibuprofen. (This abstract was published in Inflammation Research, Supplement 2, Volume 56, page A101, 2008.) 相似文献