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1.
Atul Kumar Siddharth Sharma Vishwa Deepak Tripathi Ram Awatar Maurya Swayam Prakash Srivastava Gitika Bhatia A.K. Tamrakar Arvind Kumar Srivastava 《Bioorganic & medicinal chemistry》2010,18(11):4138-4148
A series of 2,4-disubstituted polyhydroquinoline were synthesized and evaluated for their in vivo antihyperglycemic as well as antidyslipidemic activities. Several synthesized compounds have exhibited promising in vivo antihyperglycemic in SLM, STZ-S, and db/db mice model along with significant lipid and TG modulating activity. All these compounds were evaluated in various in vitro models of diabetes to know the possible mechanism of their antihyperglycemic action. Interestingly, compounds 3a–r (diaryl substitution) have exhibited promising protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity whereas, compounds 5a–d (acid substituted) have shown significant glycogen phosphorylase activity. 相似文献
2.
Shukla P Singh AB Srivastava AK Pratap R 《Bioorganic & medicinal chemistry letters》2007,17(3):799-802
A series of chalcone based aryloxypropanolamines were synthesized and evaluated for their antihyperglycemic activity in SLM and STZ rat models. Most of the compounds exhibited moderate to good activity ranging from 6.5% to 31.1% in SLM and 8.3% to 22.6% in STZ models, respectively. The most potent compound 5 g exhibited glucose lowering of 26.7% in SLM and 22.6% in STZ models. A definite structure-activity relationship was observed while varying the nature as well as the position of the amine in ring B. 相似文献
3.
Yanagisawa H Takamura M Yamada E Fujita S Fujiwara T Yachi M Isobe A Hagisawa Y 《Bioorganic & medicinal chemistry letters》2000,10(4):373-375
Oximes having 5-benzyl-2,4-thiazolidinedione were prepared, and their PPAR gamma agonistic activities and blood glucose lowering activities were evaluated. Biaromatic and methyl groups, attached to the oxime moiety, and the ethylene bridge between oxime and phenoxy groups are favorable to biological activities. 相似文献
4.
Discovery and synthesis of novel substituted benzocoumarins as orally active lipid modulating agents
Sashidhara KV Kumar M Modukuri RK Srivastava A Puri A 《Bioorganic & medicinal chemistry letters》2011,21(22):6709-6713
The synthesis of a series of benzocoumarin keto-enamine schiff bases is reported. The novel compounds were evaluated for their antihyperlipidemic activity in the hyperlipidemic hamster model. The compound 11 at a dose of 10 mg/kg body weight significantly lowered the plasma triglyceride levels (TG) by 70%, total cholesterol (TC) by 47%, accompanied by an increase in HDL-C/TC ratio by 80% in hyperlipidemic hamsters to a greater degree than the reference drugs atorvastatin and lovastatin. 相似文献
5.
Nucleoside analogues as antiviral agents 总被引:1,自引:0,他引:1
E de Clercq 《Acta microbiologica Academiae Scientiarum Hungaricae》1981,28(3):289-306
6.
De Clercq E 《Nucleosides, nucleotides & nucleic acids》2000,19(10-12):1531-1541
Several guanosine analogues, i.e. acyclovir (and its oral prodrug valaciclovir), penciclovir (in its oral prodrug form, famciclovir) and ganciclovir, are widely used for the treatment of herpesvirus (i.e. HSV-1, HSV-2, VZV and HCMV) infections. In recent years, several new guanosine analogues have been developed, including the 3-membered (cyclopropyl) sugar derivative A-5021 and the 6-membered D- and L-cyclohexenyl derivatives. Prominent features shared by all guanosine analogues are the following. They depend for their phosphorylation on the virus-encoded thymidine kinase (TK), which makes them particularly effective against those viruses (HSV-1, HSV-2 and VZV) that encoded for such TK. They are also active against HCMV, whether or not they are subject of phosphorylation by the HCMV-induced UL97 protein kinase. Their antiviral activity can be markedly potentiated by mycophenolic acid, an IMP dehydrogenase inhibitor, and they hold great promise, not only as antiviral agents for the treatment of herpesvirus infections, but also as antitumor agents for the combined gene therapy/chemotherapy of cancer, provided that (part of) the tumor cells have been transfected by the viral TK gene. 相似文献
7.
Sharma VM Adi Seshu KV Vamsee Krishna C Prasanna P Chandra Sekhar V Venkateswarlu A Rajagopal S Ajaykumar R Deevi DS Rao Mamidi NV Rajagopalan R 《Bioorganic & medicinal chemistry letters》2003,13(10):1679-1682
A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21 and 28 exhibited good pharmacokinetic properties. These compounds were further evaluated for their in vivo efficacy in modified hollow fibre assay (HFA). 相似文献
8.
Paul S. Humphries Ross Bersot John Kincaid Eric Mabery Kerryn McCluskie Timothy Park Travis Renner Erin Riegler Tod Steinfeld Eric D. Turtle Zhi-Liang Wei Erik Willis 《Bioorganic & medicinal chemistry letters》2018,28(3):293-297
A series of novel carbazole-containing amides and ureas were synthesized. A structure–activity relationship study of these compounds led to the identification of potent cryptochrome modulators. Based on the desired pharmacokinetic/pharmacodynamic parameters and the results of efficacy studies in db/db mice, compound 50 was selected for further profiling. 相似文献
9.
Fateh V. Singh Amrita Parihar Sumit Chaurasia Amar B. Singh Salil P. Singh Akhilesh K. Tamrakar Arvind K. Srivastava Atul Goel 《Bioorganic & medicinal chemistry letters》2009,19(8):2158-2161
Various functionalized mono- and diarylanthranilo-1,3-dinitriles were synthesized and evaluated for their in vitro antihyperglycemic activity against the PTP-1B, glucose-6-phosphatase, glycogen phosphorylase and α-glucosidase enzymes. Among various screened compounds, 5,6-diaryl substituted anthranilo-1,3-dinitriles 3a, 3b, and 3d showed good inhibitory activity against PTP-1B with IC50 values of 58–72 μM. Three of the test compounds showed significant (25–37%) lowering of plasma glucose level at 24 h in sucrose-challenged streptozotocin-induced diabetic Sprague–Dawley rat model. 相似文献
10.
Coppola GM Damon RE Eskesen JB France DS Paterniti JR 《Bioorganic & medicinal chemistry letters》2002,12(17):2439-2442
A series of gemfibrozil analogues with a thiourea moiety embedded in the side chain was prepared and evaluated as HDL-elevating agents. Derivatives 8b, 9b, 9c, and 9d were found to be approximately as effective as gemfibrozil (1) for HDL cholesterol elevation. 相似文献
11.
Ling L Urichuk LJ Sloley BD Coutts RT Baker GB Shan JJ Pang PK 《Bioorganic & medicinal chemistry letters》2001,11(20):2715-2717
A series of N(1)- and N(2)-propargylphenelzine derivatives and analogues (1-7) was synthesized. In addition to their activity as monoamine oxidase inhibitors, two of the compounds, N(1)- and N(2)-propargylphenelzines (3 and 6), were found to be potent at preventing DSP-4-induced noradrenaline (NA) depletion in mouse hippocampus, suggesting that they have neuroprotective properties. 相似文献
12.
Sit SY Huang Y Antal-Zimanyi I Ward S Poindexter GS 《Bioorganic & medicinal chemistry letters》2002,12(3):337-340
The dihydropyridine is currently one of the lead compounds in the neuropeptide-Y(1) (NPY-Y(1)) receptor antagonist program. Compound is a selective, high affinity ligand at the NPY-Y(1) receptors (IC(50)=4.2 nM) in SK-N-MC cells. To further expand the SAR study surrounding this dihydropyridine core structure we succeeded in synthesizing an analogous series of dihydropyrazine derivatives. This structural modification yielded compounds substantially different from the parent molecules in terms of molecular polarization and electron distribution while the overall molecular structure was generally preserved. This altered property should therefore provide us with additional SAR information on the optimal binding requirement with NPY receptors. 相似文献
13.
Mahajan A Kumar V Mansour NR Bickle Q Chibale K 《Bioorganic & medicinal chemistry letters》2008,18(7):2333-2336
New analogues of the potent antihelmintic meclonazepam were prepared and evaluated against Schistosoma mansoni. The biological data suggests substitution at positions 2 and 4 of meclonazepam could provide promising analogues for prophylactic and therapeutic activity against S. mansoni. 相似文献
14.
Dang HT Lee HJ Yoo ES Hong J Bao B Choi JS Jung JH 《Bioorganic & medicinal chemistry》2008,16(24):10228-10235
In an effort to develop new anti-inflammatory agents, methyl jasmonate analogues (2-20) were synthesized and evaluated for their inhibitory effects on the production of pro-inflammatory mediators (NO, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophage cells. The introduction of an enone functionality to the structure of a plant hormone (1) rendered the product (2) a significant anti-inflammatory activity. Analogues further derived from 2 (7, 9, 13, and 15) exhibited even more enhanced activity, and these compounds were much more potent than natural anti-inflammatory prostaglandins (PGA(1), PGA(2), and 15-deoxy-Delta(12,14)-PGJ(2)). Among them, compounds 9 and 15 showed the highest potency, while compounds 7 and 13 would be more desirable with respect to safety. This is the first study demonstrating the anti-inflammatory potential of jasmonate derivatives, and the present results suggest that alpha-haloenone jasmonates (7, 9, 13, and 15) may serve as potential anti-inflammatory leads. 相似文献
15.
Ethambutol analogues as potential antimycobacterial agents. 总被引:1,自引:0,他引:1
H H?usler R P Kawakami E Mlaker W B Severn A E Stütz 《Bioorganic & medicinal chemistry letters》2001,11(13):1679-1681
A range of new ethambutol analogues was synthesised and their inhibitory potencies were probed with Mycobacterium smegmatis. Interestingly, apparently even minor deviation from the structure of the parent compound resulted in reduced antimycobacterial activity. 相似文献
16.
(3-substituted benzyl)thiazolidine-2,4-diones as structurally new antihyperglycemic agents 总被引:9,自引:0,他引:9
Nomura M Kinoshita S Satoh H Maeda T Murakami K Tsunoda M Miyachi H Awano K 《Bioorganic & medicinal chemistry letters》1999,9(4):533-538
A series of 3-[(2,4-dioxothiazolidin-5-yl)methyl]benzamide derivatives was prepared as part of a search for antidiabetic agents. A structure-activity relationship study of these compounds led to the identification of 5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[4-(trifluorome thyl)-phenyl]methyl]benzamide (KRP-297) as a candidate drug for the treatment of diabetes mellitus. 相似文献
17.
Gupta L Talwar A Nishi Palne S Gupta S Chauhan PM 《Bioorganic & medicinal chemistry letters》2007,17(14):4075-4079
A series of marine alkaloid 8,9-dihydrocoscinamide B, its analogues and indolylglyoxylamide derivatives have been synthesized and screened for their in vitro antileishmanial activity profile in promastigote and amastigote models. Compounds 7 and 10 have shown 99-100% inhibition against promastigotes and 97-98% inhibition against amastigotes at a concentration of 10 microg/ml. 相似文献
18.
Satoshi Miyanaga Hiroaki Sakurai Ikuo Saiki Hiroyasu Onaka Yasuhiro Igarashi 《Bioorganic & medicinal chemistry》2009,17(7):2724-2732
Myxochelin A (1) is an inhibitor of tumor cell invasion produced by the bacterium belonging to the genus Nonomuraea. In order to obtain more potent inhibitors, a series of myxochelin analogues [2 and (S)-3–17] were synthesized through the coupling of lysine or diaminoalkane derivatives and appropriately protected hydroxybenzoate, followed by modification of functional groups and deprotection. These compounds were evaluated for their inhibitory activity against invasion of murine colon 26-L5 carcinoma cells. Among the synthetic analogues tested, compound (S)-6 which possesses carbamoyl group at C-1 was found to be the most potent antiinvasive agent and is considered to be a promising lead molecule for the antimetastasis. Compound (S)-6 was also shown to inhibit gelatinase activities of MMP-2 and MMP-9 and in vivo lung metastasis in mice. 相似文献
19.
Ismail MA Bialy SA Brun R Wenzler T Nanjunda R Wilson WD Boykin DW 《Bioorganic & medicinal chemistry》2011,19(2):978-984
A series of phenyl-2,2’-bichalcophene diamidines 1a-h were synthesized from the corresponding dinitriles either via a direct reaction with LiN(TMS)2, followed by deprotection with ethanolic HCl or through the bis-O-acetoxyamidoxime followed by hydrogenation in acetic acid and EtOH over Pd-C. These diamidines show a wide range of DNA affinities as judged from their ??Tm values which are remarkably sensitive to replacement of a furan unit with a thiophene one. These differences are explained in terms of the effect of subtle changes in geometry of the diamidines on binding efficacy. Five of the eight compounds were highly active (below 6 nM IC50) in vitro against Trypanosoma brucei rhodesiense (T. b. r.) and four gave IC50values less than 7 nM against Plasmodium falciparum (P. f.). Only one of the compounds was as effective as reference compounds in the T. b. r. mouse model for the acute phase of African trypanosomiasis. 相似文献
20.
Novel phomactin analogues as PAF receptor ligands 总被引:1,自引:0,他引:1
Goldring WP Alexander SP Kendall DA Pattenden G 《Bioorganic & medicinal chemistry letters》2005,15(13):3263-3266
A range of natural and unnatural phomactins, recently synthesised in our laboratory, were found to exhibit PAF antagonism with pIC(50) values in the range 5.6-6.2. The variation in structural and stereochemical features between the phomactins was found to have only a modest effect on the inhibition of binding of PAF to its human platelet receptors. 相似文献