共查询到20条相似文献,搜索用时 31 毫秒
1.
Natarajan Arumugam Raghavachary Raghunathan Vellaisamy Shanmugaiah Narayanasamy Mathivanan 《Bioorganic & medicinal chemistry letters》2010,20(12):3698-3702
Synthesis of novel β-lactam fused spiroisoxazolidine chromanones and tetralones ring systems has been achieved by intermolecular 1,3-dipolar cycloaddition reaction of bicyclic nitrone with unusual dipolarophiles, arylidene chromanones/tetralones under different reaction conditions. The synthesized compounds were evaluated for antimicrobial activities. It was observed that two of the synthesized compounds exhibited relatively good antibacterial and antifungal activities. 相似文献
2.
Wang X Bhatia PA Daanen JF Latsaw SP Rohde J Kolasa T Hakeem AA Matulenko MA Nakane M Uchic ME Miller LN Chang R Moreland RB Brioni JD Stewart AO 《Bioorganic & medicinal chemistry》2005,13(15):4667-4678
A series of 3-aryl piperidine analogs with 2-piperidinoalkylamino or 2-piperidinoalkyloxy fused bicyclic rings were prepared and found to be potent and efficacious human dopamine D4 agonists. The synthesis and structure-activity relationship (SAR) studies that led to the identification of these compounds are discussed. 相似文献
3.
Xiong Y Ullman B Choi JS Cherrier M Strah-Pleynet S Decaire M Feichtinger K Frazer JM Yoon WH Whelan K Sanabria EK Grottick AJ Al-Shamma H Semple G 《Bioorganic & medicinal chemistry letters》2012,22(5):1870-1873
A series of fused bicyclic heterocycles was identified as potent and selective 5-HT(2A) receptor antagonists. Optimization of the series resulted in compounds that had improved PK properties, favorable CNS partitioning, good pharmacokinetic properties, and significant improvements on deep sleep (delta power) and sleep consolidation. 相似文献
4.
《Bioorganic & medicinal chemistry》2020,28(9):115442
A unified synthetic approach was developed that enabled the synthesis of diverse tropane-related scaffolds. The key intermediates that were exploited were cycloadducts formed by reaction between 3-hydroxy-pyridinium salts and vinyl sulfones or sulfonamides. The diverse tropane-related scaffolds were formed by addition of substituents to, cyclisation reactions of, and fusion of additional ring(s) to the key bicyclic intermediates. A set of 53 screening compounds was designed, synthesised and evaluated in order to determine the biological relevance of the scaffolds accessible using the synthetic approach. Two inhibitors of Hedgehog signalling, and four compounds with weak activity against the parasite P. falciparum, were discovered. Three of the active compounds may be considered to be indotropane or pyrrotropane pseudo natural products in which a tropane is fused with a fragment from another natural product class. It was concluded that the unified synthetic approach had yielded diverse scaffolds suitable for the design of performance-diverse screening libraries. 相似文献
5.
Nishino N Shivashimpi GM Soni PB Bhuiyan MP Kato T Maeda S Nishino TG Yoshida M 《Bioorganic & medicinal chemistry》2008,16(1):437-445
Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that effect gene regulation. To know the interaction of aliphatic cap groups with HDACs, cyclic tetrapeptide and bicyclic peptide disulfide hybrids were synthesized without aromatic ring in their macrocyclic framework. Benzene ring of l-Phe in chlamydocin was replaced with several aliphatic amino acids and also a fused bicyclic tetrapeptide was synthesized by ring closing metathesis using Grubb's first generation catalyst. The inhibitory activities of the cyclic peptides against histone deacetylase enzymes were evaluated, which demonstrated most of them are interesting candidates as anticancer agents. 相似文献
6.
Salvati ME Balog A Shan W Wei DD Pickering D Attar RM Geng J Rizzo CA Gottardis MM Weinmann R Krystek SR Sack J An Y Kish K 《Bioorganic & medicinal chemistry letters》2005,15(2):271-276
A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). Co-crystallization of members of this family of inhibitors was successfully accomplished with the T877A AR LBD. A working model of how this class of compounds functions to antagonize the AR was created. Based on this model, it was proposed that expanding the bicyclic portion of the molecule should result in analogs which function as effective antagonists against a variety of AR isoforms. In contrast to what was predicted by the model, SAR around this new series was dictated by the aniline portion rather than the bicyclic portion of the molecule. 相似文献
7.
Nivsarkar M Thavaselvam D Prasanna S Sharma M Kaushik MP 《Bioorganic & medicinal chemistry letters》2005,15(5):1371-1373
A series of bicyclic N-substituted and unsubstituted beta-lactams were synthesized and evaluated as targeted potential antimalarials. The compounds MNR4 and MNR5 were found to have highest potency against Plasmodium falciparum in vitro. 相似文献
8.
9.
Chouteau F Ramanitrahasimbola D Rasoanaivo P Chibale K 《Bioorganic & medicinal chemistry letters》2005,15(12):3024-3028
An exploratory series of novel arylbromide and bicyclic chemosensitizers (modulators) against chloroquine-resistant Plasmodium falciparum were designed and synthesized on the basis of a basic chemosensitizing pharmacophore hypothesis in malaria. ortho-Substituted bromo and biphenyl ether compounds displayed the best activity from the series. 相似文献
10.
Xu R Banka A Blake JF Mitchell IS Wallace EM Bencsik JR Kallan NC Spencer KL Gloor SL Martinson M Risom T Gross SD Morales TH Wu WI Vigers GP Brandhuber BJ Skelton NJ 《Bioorganic & medicinal chemistry letters》2011,21(8):2335-2340
We describe the design and synthesis of novel bicyclic spiro sulfonamides as potent Akt inhibitors. Through structure-based rational design, we have successfully improved PKA selectivity of previously disclosed spirochromanes. Representative compounds showed favorable Akt potency while exhibiting up to 1000-fold selectivity against PKA. 相似文献
11.
Pelttari E Matikainen J Elo H 《Zeitschrift für Naturforschung. C, Journal of biosciences》2002,57(5-6):548-552
The marine alkaloids haminol A, haminol B and pulo'upone as well as 17 related compounds (twelve 2-substituted pyridine derivatives, four 3-substituted ones and one analogue of the bicyclic terminus of pulo'upone) were tested for antimicrobial activity against a panel of six microbes (Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Candida albicans and Saccharomyces cerevisiae) using the paper disc agar diffusion method. Six compounds were tested also against the mold Aspergillus niger. Some of the compounds displayed noteworthy antimicrobial activity, only one congener being completely devoid of activity. Nearly all compounds had activity against B. cereus and S. epidermidis. The growth of E. coli, C albicans and S. cerevisiae was also distinctly inhibited by many compounds. In contrast, most compounds were inactive or had minimal activity against P. aeruginosa. Interestingly, most of the compounds tested against the opportunistic pathogen A. niger were active, one of them having noteworthy inhibitory potency. 相似文献
12.
Jonathan M. Large Kristian Birchall Nathalie S. Bouloc Andy T. Merritt Ela Smiljanic-Hurley Denise J. Tsagris Mary C. Wheldon Keith H. Ansell Peter J. Coombs Catherine A. Kettleborough David Whalley Lindsay B. Stewart Paul W. Bowyer David A. Baker Simon A. Osborne 《Bioorganic & medicinal chemistry letters》2019,29(3):509-514
Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key sub-structural elements led to new compounds with good levels of inhibitory activity against the recombinant kinase and in vitro activity against the parasite. Key examples were shown to possess encouraging in vitro ADME properties, and computational analysis provided valuable insight into the origins of the observed activity profiles. 相似文献
13.
Luoni G McGuigan C Andrei G Snoeck R De Clercq E Balzarini J 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):931-933
We have recently discovered bicyclic furopyrimidines as potent and selective inhibitors of VZV. In order to investigate the structural requirements for antiviral activity we have succesfully synthesised some 3'-chloro and 5'-chloro derivatives. The compounds have been tested against VZV and CMV, but displayed no significant in vitro activity. 相似文献
14.
Johanna Faist Werner Seebacher Christian Schlapper Marcel Kaiser Reto Brun Robert Saf Robert Weis 《Bioorganic & medicinal chemistry》2009,17(10):3595-3603
Several bicyclic amides and esters of dialkylamino acids were prepared. Their activities against a multiresistant strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900) were examined. Structure–activity relationships were discussed. Particularly the ester compounds showed good antiplasmodial and antitrypanosomal activity and a single compound was tested in vivo against Plasmodium berghei. 相似文献
15.
The synthesis of a fused bicyclic thioglycoside analogue of mycothiol, (3R)-3-acetylamino-4-one-6,7-dihydro-(1',2'-dideoxy-beta-D-glucopyranoso)[2',1'-f]-1,5-thiazepane (5), is reported. Treatment of phthalimido-protected peracetylated glucosamine with N-acetyl-cysteine and boron trifluoride-etherate gave the beta-linked thioglycoside, which was deprotected and cyclized, using HOBt and EDCl to form the lactam and giving the target structure. This mycothiol mimic and its tri-O-acetate will be investigated as potential inhibitors of enzymes involved in the biosynthesis of mycothiol. The protected derivative also has the potential to be an alpha-selective N-cysteinyl glucosamine donor; however, initial glycosylation attempts failed due to the apparent stability of the fused bicyclic system. 相似文献
16.
Casagrande M Basilico N Parapini S Romeo S Taramelli D Sparatore A 《Bioorganic & medicinal chemistry》2008,16(14):6813-6823
To develop new classes of antimalarial agents, the possibility of replacing the phenolic ring of amodiaquine, tebuquine, and isoquine with other aromatic nuclei was investigated. Within a first set of pyrrole analogues, several compounds displayed high activity against both D10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. The isoquine structure was also modified by replacing the diethylamino group with more metabolically stable bicyclic moieties and by replacing the aromatic hydroxyl function with a chlorine atom. Among these compounds, two quinolizidinylmethylamino derivatives (6f and 7f) displayed high activity against both CQ-S and CQ-R strains. 相似文献
17.
Andrea Pinto Lucia Tamborini Eugenia Pennacchietti Antonio Coluccia Romano Silvestri Gregorio Cullia 《Journal of enzyme inhibition and medicinal chemistry》2016,31(2):295-301
The γ-aminobutyrate (GABA)-degradative enzyme GABA aminotransferase (GABA-AT) is regarded as an attractive target to control GABA levels in the central nervous system: this has important implications in the treatment of several neurological disorders and drug dependencies. We have investigated the ability of newly synthesized compounds to act as GABA-AT inhibitors. These compounds have a unique bicyclic structure: the carbocyclic ring bears the GABA skeleton, while the fused 3-Br-isoxazoline ring contains an electrophilic warhead susceptible of nucleophilic attack by an active site residue of the target enzyme. Out of the four compounds tested, only the one named (+)-3 was found to significantly inhibit mammalian GABA-AT in vitro. Docking studies, performed on the available structures of GABA-AT, support the experimental findings: out of the four tested compounds, only (+)-3 suitably orients the electrophilic 3-Br-isoxazoline warhead towards the active site nucleophilic residue Lys329, thereby explaining the irreversible inhibition of GABA-AT observed experimentally. 相似文献
18.
Todorov PT Wesselinova DW Pavlov ND Martinez J Calmes M Naydenova ED 《Amino acids》2012,43(4):1445-1450
The cytotoxic effects of novel racemic and optically active constrained N-phosphonoalkyl bicyclic β-amino acids were tested against a panel of human tumor cell lines. All of the compounds investigated exhibited different concentration-dependent antiproliferative effects against the HT-29, MDA-MB-231, HepG2 and HeLa cell lines after 24?h treatment. The most sensitive cells were the HeLa cells at various concentrations of the four compounds tested. The aminophosphonate 3 exerted the most pronounced antiproliferative effect against the HeLa cells (inhibition of the cell vitality up to 70% at 0.5?mg/ml) and was not toxic to the normal Lep3 cells at lower concentration. Furthermore, the N-phosphonophenyl derivatives 1 and 2 displayed antiproliferative effect against mainly the MDA-MB-231 tumour cells at higher concentration. 相似文献
19.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):931-933
Abstract We have recently discovered bicyclic furopyrimidines as potent and selective inhibitors of VZV. In order to investigate the structural requirements for antiviral activity we have succesfully synthesised some 3′-chloro and 5′-chloro derivatives. The compounds have been tested against VZV and CMV, but displayed no significant in vitro activity. 相似文献
20.
Guijun Wang Navneet Goyal Branden Hopkinson 《Bioorganic & medicinal chemistry letters》2009,19(14):3798-3803
Aeruginosins are a family of naturally occurring oligopeptides that share a common bicyclic amino acid core structure. Many compounds in the family are inhibitors of serine proteases, such as thrombin and trypsin. Thrombin is an important enzyme in the blood coagulation cascade, and is a promising target for anticoagulant drug development. In order to understand the structure–activity relationship (SAR) and to find selective thrombin inhibitors, we synthesized a series of aeruginosin 298-A analogs, in which the P2 bicyclic amino acid was replaced by a l-proline residue. The structure optimization was focused on modification of the P1 position. In choosing the P1 group, an effort was made to avoid using the highly basic guanidine groups present in nearly all naturally occurring aeruginosins. The synthesis and enzyme assays of these aeruginosin analogs against thrombin and trypsin are reported. We found that several compounds with neutral P1 groups exhibit excellent selectivity over trypsin and good potency against thrombin. The SAR data of the P1 groups obtained here can be used in preparing other thrombin inhibitors with better selectivity against trypsin. 相似文献