共查询到20条相似文献,搜索用时 15 毫秒
1.
Kelvin Cooper M. Jonathan Fray M. John Parry Kenneth Richardson John Steele 《Bioorganic & medicinal chemistry letters》1995,5(24):3085-3090
The PAF antagonist activity of a series of enantiomeric dihydropyridines is described. In the first example, 1, the PAF antagonist activity and calcium channel blocking activity reside in opposite enantiomers. Subsequent examples also display enantioselectivity and the SAR of the series is described. 相似文献
2.
Yong H Gu YG Clark RF Marron T Ma Z Soni N Stone GG Nilius AM Marsh K Djuric SW 《Bioorganic & medicinal chemistry letters》2005,15(10):2653-2658
A novel series of 6-O-arylpropargyl diazalides was synthesized and evaluated for their antibacterial activity. Members of this series exhibited potent activity against erythromycin-resistant respiratory tract pathogens. 相似文献
3.
Two series of triazaspiroalkanedienes, bearing a substituted phenoxy propyloxy side chain, were identified as potent mammalian DHFR inhibitors. One series has a 6,5-spiro bicyclic ring system and the other series has a 6,6-spiro bicyclic system. Both series were synthesized and tested for in vitro mammalian DHFR inhibitory activity and antiproliferative activity against A549 human lung-cancer cells. Compound 3c showed the highest antiproliferative activity against A549 cells with an IC50 value of 27.1 nM. Rescue experiment confirmed its antifolate antiproliferative mechanism. The excellent antifolate and antiproliferative activity of selected analogues presented in this study warrants further investigation as potential leads in the anticancer drug discovery. 相似文献
4.
A series of novel 6-O-substituted and 6,12-di-O-substituted 8a-aza-8a-homoerythromycin A and 9a-aza-9a-homoerythromycin A ketolides were synthesized and evaluated for in vitro antibacterial activity against a panel of representative erythromycin-susceptible and erythromycin-resistant test strains. Another series of ketolides based on 14-membered erythromycin oxime scaffold was also synthesized and their antibacterial activity compared to those of 15-membered azahomoerythromycin analogues. In general, structure-activity studies have shown that 14-membered ketolides displayed favorable antibacterial activity in comparison to their corresponding 15-membered analogues within 9a-azahomoerythromycin series. However, within 8a-azahomoerythromycin series, some compounds incorporating a ketolide combined with either quinoline or quinolone pharmacophore substructures showed significantly potent activity against a variety of erythromycin-susceptible and macrolide-lincosamide-streptogramin B (MLS(B))-resistant Gram-positive pathogens as well as fastidious Gram-negative pathogens. The best compounds in this series overcome all types of resistance in relevant clinical Gram-positive pathogens and display hitherto unprecedented in vitro activity against the constitutively MLS(B)-resistant strain of Staphylococcus aureus. In addition, they also represent an improvement over telithromycin (2) and cethromycin (3) against fastidious Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis. 相似文献
5.
Guohua Zhao Chet Kwon Aiying Wang James G. Robertson Jovita Marcinkeviciene Rex A. Parker Mark S. Kirby Lawrence G. Hamann 《Bioorganic & medicinal chemistry letters》2013,23(6):1622-1625
Synthesis and structure–activity relationship of a series of substituted piperidinyl glycine 2-cyano-4,5-methano pyrroline DPP-IV inhibitors are described. Improvement of the inhibitory activity and chemical stability of this series of compounds was respectively achieved by the introduction of bulky groups at the 4-position and 1-position of the piperidinyl glycine, leading to a series of potent and stable DPP-IV inhibitors. 相似文献
6.
Elliott RL Oliver RM LaFlamme JA Gillaspy ML Hammond M Hank RF Maurer TS Baker DL DaSilva-Jardine PA Stevenson RW Mack CM Cassella JV 《Bioorganic & medicinal chemistry letters》2003,13(20):3593-3596
A series of 2-heteroaryl-4-arylimidazoles with potent in vitro activity at the NPY5 receptor was developed. Introduction of electron-withdrawing groups on the 4-aryl ring led to a significant improvement of in vitro potency. Several analogues from this series had anorectic activity in rodent feeding models, but were also found to have undesired behavioral effects in spontaneous locomotor activity. 相似文献
7.
L A Sumbatov L B Novoderezhkina A M Lekhtman 《Biulleten' eksperimental'no? biologii i meditsiny》1975,80(12):14-17
Two series of experiments were conducted on dogs. In the first series of experiments dogs were subjected to deep hypothermia with an external chilling of the organism; in the second series-to the isolated deep hypothermia of the head with the maintenance of normothermia in the organism. Bioelectrical activity of the brain and circulation minute volume were recorded in the animals of both series. As revealed, depression of the bioelectrical activity was more pronounced and a prevalence of slow waves was observed in general hypothermia; at the same time a more even reduction of the electrical activity in all the EEG frequencies under study was seen in the series with local hypothermia. A reduction of the circulation minute volume was also more pronounced in the first series of experiments; in the authors' opinoin this was associated with the difference in the character of the EEG evolution with the same depth of hypothermia of the brain. 相似文献
8.
Skinner PJ Cherrier MC Webb PJ Sage CR Dang HT Pride CC Chen R Tamura SY Richman JG Connolly DT Semple G 《Bioorganic & medicinal chemistry letters》2007,17(23):6619-6622
A series of 3-nitro-4-substituted-aminobenzoic acids were prepared and found to act as potent and highly selective agonists of the orphan human GPCR GPR109b, a low affinity receptor for niacin. No activity was observed at the closely homologous high affinity niacin receptor, GPR109a. A second series, comprising 6-amino-substituted nicotinic acids was, also prepared and several analogues showed comparable activity to the nitroaryl series. 相似文献
9.
We report the design, semisynthesis, and biological activity of a series of fredericamycin (1) derivatives. Within this series compound 1e combines low nanomolar cytotoxic potency in vitro, increased tumor cell line selectivity, and in vivo activity in a human xenograft model. 相似文献
10.
Francavilla C Turtle ED Kim B O'Mahony DJ Shiau TP Low E Alvarez NJ Celeri CE D'Lima L Friedman LC Ruado FS Xu P Zuck ME Anderson MB Najafi RR Jain RK 《Bioorganic & medicinal chemistry letters》2011,21(10):3029-3033
Antimicrobial compounds with broad-spectrum activity and minimal potential for antibiotic resistance are urgently needed. Toward this end, we prepared and investigated a novel series of N-chloroheterocycles. Of the compounds examined, the N-chloroamine series were found superior over N-chloroamide series in regards to exhibiting high antimicrobial activity, low cytotoxicity, and long-term aqueous stability. 相似文献
11.
Design, synthesis, and structure-activity relationship studies of new phenolic DNA gyrase inhibitors
Lübbers T Angehrn P Gmünder H Herzig S 《Bioorganic & medicinal chemistry letters》2007,17(16):4708-4714
Starting from a biased needle screening hit 3a, we report herein the design and synthesis of a series of novel 2,3-dihydroisoindol-1-ones structurally related to cyclothialidine 2 with DNA gyrase inhibitory activity. In this series, some compounds exhibited promising antibacterial activity against gram-positive bacterial strains. 相似文献
12.
Yuan L Li Y Zou C Wang C Gao J Miao C Ma E Sun T 《Bioorganic & medicinal chemistry letters》2012,22(6):2216-2220
In an effort to improve the aqueous solubility and the antitumor activity of natural product asperphenamate, we have designed and synthesized three series of asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. 相似文献
13.
Kim IH Combrink KD Ma Z Chapo K Yan D Renick P Morris TW Pulse M Simecka JW Ding CZ 《Bioorganic & medicinal chemistry letters》2007,17(5):1181-1184
A novel series of spirorifamycins was synthesized and their antibacterial activity evaluated both in vitro and in vivo. This new series of rifamycins shows excellent activity against Staphylococcus aureus that is equivalent to rifabutin. However, some compounds of the series exhibit lower MICs than rifabutin against rifampin-resistant strains of S. aureus. Further, compound 2e exhibits comparable efficacy in vivo in a murine model of S. aureus septicemia model following administration by either oral or parenteral dosing routes. 相似文献
14.
Effect of low frequency fatigue on human muscle strength and fatigability during subsequent stimulated activity 总被引:3,自引:0,他引:3
M. J. Stokes R. H. T. Edwards R. G. Cooper 《European journal of applied physiology and occupational physiology》1989,59(4):278-283
Fatiguing contractions of the adductor pollicis muscle were produced by intermittent supramaximal stimulation of the ulnar nerve in a set frequency pattern, in six normal subjects. At the end of an initial fatiguing contraction series, low frequency fatigue (LFF) had been induced and persisted at 15 min of recovery. Stimulated fatiguing activity was then repeated in an identical fashion to the initial series. At high frequencies, declines in force were similar for both series. At low frequencies, declines in force were greater during the second series despite similar changes in compound muscle action potential amplitude. This confirmation that LFF persists during subsequent stimulated activity, and reduces low but not high frequency fatigue resistance, suggests that the impaired endurance of fatigued muscle during voluntary activity primarily results from peripheral changes at low frequency. These findings also have implications for therapeutic electrical stimulation of muscle. 相似文献
15.
Rajamohan R. Poondra Ratnam V. Nallamelli Chandana Lakshmi Teja Meda B.N.V. Srinivas Anushka Grover Jyotsna Muttabathula Sreedhara R. Voleti Balasubramanian Sridhar Manojit Pal Kishore V.L. Parsa 《Bioorganic & medicinal chemistry letters》2013,23(4):1104-1109
Substituted 1,4-dihydropyridines were discovered as a novel and potent series of phosphodiesterase 4 (PDE4) inhibitors. Structure–activity relationships within this series have been carried out and studies revealed that the dihydropyridine core, with indole moiety and 3,4-dimethoxybenzyl group, is a potent analogue for PDE4 inhibition. These novel series of compounds were prepared via a 3-component reaction in a single pot. In vitro biological activity, modeling studies and crystallography data are also reported. 相似文献
16.
Colabufo NA Berardi F Cantore M Perrone MG Contino M Inglese C Niso M Perrone R Azzariti A Simone GM Paradiso A 《Bioorganic & medicinal chemistry》2008,16(7):3732-3743
Starting from lead compound 1 (EC(50)=1.64 microM), its non-basic nucleus has been conformationally restricted by 4-biphenyl and 2-naphthyl moieties. In each series we investigated if the presence of H-bond donor or acceptor substituents, the basicity and the lipophilicity (clogP) were correlated with the P-gp inhibiting activity of tested compounds. In the biphenyl series, derivative 4d displayed the best results (EC(50)=0.05 microM). The corresponding amide 3d was found less active (EC(50)=3.5 microM) ascertaining the importance of basicity in this series whilst the presence of hydroxy or methoxy substituents seems to be negligible. In the naphthyl series, both the basicity and the presence of H-bond donor or acceptor groups seem to be negligible. Moreover, the lipophilicity did not influence the P-gp inhibition activity of each series. Specific biological assays have been carried out to establish the P-gp interacting mechanism of tested compounds discriminating between substrates and inhibitors. Moreover, compound 4d displayed a potent P-gp inhibition activity with good selectivity towards BCRP pump. 相似文献
17.
C Pandey K P Dwivedi G D Yadava V K Singh A K Srivastava V K Agrawal 《Indian journal of biochemistry & biophysics》1989,26(6):405-409
QSAR studies using molecular connectivity and van der Waal volume have been performed on a new series of hydroxyguanidine derivatives and a series of isoindolediones. Regression analysis has shown that anticancer and antiviral activity of hydroxyguanidines as well as cytostatic activity of isoindolediones correlate well with both the structural parameters. 相似文献
18.
Ashish T. Baviskar Uttam C. Banerjee Mukesh Gupta Rajveer Singh Sunil Kumar Manish K. Gupta Sanjeev Kumar Satish K. Raut Madhu Khullar Sandeep Singh Raj Kumar 《Bioorganic & medicinal chemistry》2013,21(18):5782-5793
Design, synthesis and anticancer activity of a series of imine-pyrazolopyrimidinones is reported for the first time. Compounds 9d, 9n and 9o in the series show encouraging in vitro anticancer activity with low micromolar IC50 values against prostate (PC3) and breast (MCF7) cancer cell lines. Some notions about structure–activity relationships and plausible mechanism of biological activity are presented. 相似文献
19.
Wallén EA Christiaans JA Saario SM Forsberg MM Venäläinen JI Paso HM Männistö PT Gynther J 《Bioorganic & medicinal chemistry》2002,10(7):2199-2206
New 4-phenylbutanoyl-2(S)-acylpyrrolidines and 4-phenylbutanoyl-L-prolyl-2(S)-acylpyrrolidines were synthesized. Their inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. In the series of 4-phenylbutanoyl-2(S)-acylpyrrolidines, the cyclopentanecarbonyl and benzoyl derivatives were the best inhibitors having IC(50) values of 30 and 23 nM, respectively. This series of compounds shows that the P1 pyrrolidine ring, which is common in most POP inhibitors, can be replaced by either a cyclopentyl ring or a phenyl ring, causing only a slight decrease in the inhibitory activity. In the series of 4-phenylbutanoyl-L-prolyl-2(S)-acylpyrrolidines the cyclopentanecarbonyl and benzoyl derivatives were not as active as in the series of 4-phenylbutanoyl-2(S)-acylpyrrolidines. The hydroxyacetyl derivative did however show high inhibitory activity. This compound is structurally similar to JTP-4819, which is one of the most potent prolyl oligopeptidase inhibitors. The acyl group in the two series of new compounds seems to bind to different sites of the enzyme, since the second series of new compounds did not show the same cyclopentanecarbonyl or benzoyl specificity as the first series. 相似文献
20.
Weide T Arve L Prinz H Waldmann H Kessler H 《Bioorganic & medicinal chemistry letters》2006,16(1):59-63
In the course of studies directed toward the discovery of novel scaffolds for medicinal application, we synthesized a series of 3-substituted indolizine-1-carbonitrile derivatives. Some of them displayed activity against MPtpA/MPtpB phosphatases which are involved in infectious diseases. We report here the solid-phase synthesis and antiphosphatase activity of a series of indolizines. 相似文献