共查询到20条相似文献,搜索用时 15 毫秒
1.
Nida N. Farshori Mudasir R. Banday Anis Ahmad Asad U. Khan Abdul Rauf 《Bioorganic & medicinal chemistry letters》2010,20(6):1933-1938
The long-chain alkenoic acid hydrazides (1a–d) on reaction with phenylisocyanate and phenylthiocyanate gave their corresponding semicarbazides (2a–d) and thiosemicarbazides (4a–d), which on further refluxing with POCl3 and Ac2O yielded corresponding 1,3,4-oxadiazoles (3a–d) and thiadiazoles (5a–d), respectively.The structure elucidation of synthesized compounds is based on the elemental analysis and spectral data (IR, 1H NMR, 13C NMR and MS). The synthesized oxadiazoles and thiadiazoles have been screened for antibacterial and antifungal activities. The investigation of antimicrobial screening revealed that compounds 3c, 3d, 5c, 5d and compounds 3b, 5b, showed good antibacterial and antifungal activities, respectively. 相似文献
2.
Krzysztof Kamiński Jolanta Obniska Iwona Chlebek Beata Wiklik Sabina Rzepka 《Bioorganic & medicinal chemistry》2013,21(21):6821-6830
The synthesis and anticonvulsant properties of new N-Mannich bases of 3-phenyl- (9a–d), 3-(2-chlorophenyl)- (10a–d), 3-(3-chlorophenyl)- (11a–d) and 3-(4-chlorophenyl)-pyrrolidine-2,5-diones (12a–d) were described. The key synthetic strategies involve the formation of 3-substituted pyrrolidine-2,5-diones (5–8), and then aminoalkylation reaction (Mannich-type) with formaldehyde and corresponding secondary amines, which let to obtain the final compounds 9a–d, 10a–d, 11a–d and 12a–d in good yields. Initial anticonvulsant screening was performed in mice (ip) using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The most effective compounds in mice were tested after oral administration in rats. The acute neurological toxicity was determined applying the minimal motor impairment rotarod test. The in vivo results revealed that numerous compounds were effective especially in the MES test (model of human tonic-clonic seizures). The most active in the MES seizures in rats was 1-[(4-benzyl-1-piperidyl)methyl]-3-(2-chlorophenyl)pyrrolidine-2,5-dione (10c) which showed ED50 value of 37.64 mg/kg. It should be stressed that this molecule along with 9a, 9d and 10d showed protection in the psychomotor seizure test (6-Hz), which is known as an animal model of therapy-resistant epilepsy. Furthermore compounds 9a, 9d and 10d were also tested in the pilocarpine-induced status prevention (PISP) test to assess their potential effectiveness in status epilepticus. For the most promising molecule 9d an influence on human CYP3A4 isoform of P-450 cytochrome was studied in vitro. 相似文献
3.
Imran Ali Ashanul Haque Kishwar Saleem Ming Fa Hsieh 《Bioorganic & medicinal chemistry》2013,21(13):3808-3820
Pyrazolealdehydes (4a–d), Knoevenagel’s condensates (5a–d) and Schiff’s bases (6a–d) of curcumin-I were synthesized, purified and characterized. Hemolysis assays, cell line activities, DNA bindings and docking studies were carried out. These compounds were lesser hemolytic than standard drug doxorubicin. Minimum cell viability (MCF-7; wild) observed was 59% (1.0 μg/mL) whereas the DNA binding constants ranged from 1.4 × 103 to 8.1 × 105 M?1. The docking energies varied from ?7.30 to ?13.4 kcal/mol. It has been observed that DNA-compound adducts were stabilized by three governing forces (Van der Wall’s, H-bonding and electrostatic attractions). It has also been observed that compounds 4a–d preferred to enter minor groove while 5a–d and 6a–d interacted with major grooves of DNA. The anticancer activities of the reported compounds might be due to their interactions with DNA. These results indicated the bright future of the reported compounds as anticancer agents. 相似文献
4.
Anand R. Saundane Katkar Vijaykumar A. Verma Vaijinath 《Bioorganic & medicinal chemistry letters》2013,23(7):1978-1984
As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitriles (2a–i), 4,5-diamino-6-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-8-aryl-2-oxo-2,6-dihydrodipyrano [2,3-b:3,2-e]pyridine-3-carbonitriles (3a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-ones (4a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-thiones (5a–i), 4-(5′-subtituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-1,4-dihydropyrano[2,3-c]pyrazol-3-amines (6a–i) and 5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-3H-pyrano[2,3-d]pyrimidin-4(5H)-ones (7a–i). Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa. Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus. In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe3+) reducing antioxidant power (FRAP) and metal chelating activity. 相似文献
5.
Liangwei Zhang Xuemei Cui Jinyu Sun Yuli Wang Weishuang Li Jianguo Fang 《Bioorganic & medicinal chemistry letters》2013,23(12):3511-3514
PMQA, an 8-aminoquinoline-based ratiometric fluorescent sensor, demonstrates the Zn2+-induced red-shift of emission (85 nm), and was successfully applied to image zinc in living cells. Compared to 2:1 stoichiometry in PMQA–Zn2+, PMQA–Cu2+ shows 1:1 composition. Both nitrogen atoms from the aminoquinoline are missing in binding of zinc, while they are critically involved in Cu2+ chelation. The structure difference between PMQA–Zn2+ and PMQA–Cu2+ might shed light in designing novel zinc probes without suffering from copper interference. 相似文献
6.
Masato Oikawa Minoru Ikoma Makoto Sasaki Martin B. Gill Geoffrey T. Swanson Keiko Shimamoto Ryuichi Sakai 《Bioorganic & medicinal chemistry》2010,18(11):3795-3804
Here, we report our second-generation synthesis of 12 artificial glutamate analogs, starting from heterotricycle intermediates 3a–3d, readily prepared in three steps including tandem Ugi/Diels-Alder reactions. The new synthesis employs imidate intermediates for the deoxygenation of pyrrolidones (10a–10d to 6a–6d), and each advanced intermediate 6a–6d was diversified into three glutamate analogs (1a–1d, 5a–5d, 7a–7d) in 1–2 steps.In vitro electrophysiological assays revealed that the new piperidine-type analog 7c alters neuronal function with lower potency than 1a. Conversely, intracranial injection of 7c into mice produced a greater degree of hypoactivity than 1a. Our recent investigation has revealed that this series of compounds antagonizes AMPA-type glutamate receptor-mediated currents in a subtype selective manner. The more efficient syntheses of this novel set of neuroactive molecules will facilitate their pharmacological characterization. 相似文献
7.
Zhe Chen Bryan D. Cox Ethel C. Garnier-Amblard Tamara R. McBrayer Steven J. Coats Raymond F. Schinazi Franck Amblard 《Bioorganic & medicinal chemistry letters》2017,27(23):5296-5299
Several β-d-2′-deoxy-2′-substituted nucleoside analogs have displayed potent and selective anti-HCV activities and some of them have reached human clinical trials. In that regard, we report herein the synthesis of a series of 2′-deoxy,2′-dibromo substituted U, C, G and A nucleosides 10a–d and their corresponding phosphoramidate prodrugs 13a–d. The synthesized nucleosides 10a–d and prodrugs 13a–d were evaluated for their inhibitory activity against HCV as well as cellular toxicity. The results showed that the most potent compound was prodrug 13a, which exhibited micromolar inhibitory activity (EC50?=?1.5?±?0.8?µM) with no observed toxicity. In addition, molecular modeling and free energy perturbation calculations for the 5′-triphosphate formed from 13a and related 2′-modified nucleotides are discussed. 相似文献
8.
Dóra Ondré János Wölfling István Tóth Mihály Szécsi János Julesz Gyula Schneider 《Steroids》2009,74(13-14):1025-1032
17β-Oxazolinyl steroids 7a–g and 8a–g were synthesized. The Lewis acid-catalysed reactions of (20R)-3β-acetoxy-21-azidomethyl-20-hydroxypregn-5-ene with substituted aromatic aldehydes led to the formation of 3β-acetoxyandrost-5-enes substituted in position 17β with oxazolinyl residues (7a–g). Oppenauer oxidation of the 3β-hydroxy-exo-heterocyclic steroids yielded the corresponding Δ4-3-ketosteroids. The inhibitory effects (IC50) of both 3-hydroxy compounds 7a–g and their Δ4-3-keto counterparts 8a–g on rat testicular C17,20-lyase were investigated with an in vitro radioligand incubation technique. The 3-chlorophenyl- (8d), and the 4-bromophenyl-17β-(2-oxazolin-5-yl)androst-4-en-3-one derivatives (8f) were found to be modest inhibitors (IC50 = 4.8 and 5.0 μM, respectively). 相似文献
9.
Syntheses, characterization and antitumor activities of transition metal complexes with isoflavone 总被引:1,自引:0,他引:1
Five new complexes were synthesized by the reaction of 4′-methoxy-5,7-dihydroxy-isoflavone ligand (a) with transition metal ions zinc (Zn2+) (complex b), manganese (Mn2+) (complex c), copper (Cu2+) (complex d), cobalt (Co2+) (complex e) and nickel (Ni2+) (complex f). The composition of the complexes has been characterized by elemental analysis, IR, mass spectrometry (MS) and 1H NMR spectrometric techniques. Their antitumor properties were evaluated against five human cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. The results indicated that the complexes possess higher growth inhibitory effects than free isoflavone and corresponding metal ions. Complex c and f showed greater antitumor activity and selectivity than other described complexes, even more effective than the positive control cisplatin against the selected cell lines. In addition, DNA flow cytometric analysis demonstrated that complexes display a significant G2/M phase arrest, which then progressed to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). 相似文献
10.
《Bioorganic & medicinal chemistry letters》2014,24(7):1808-1811
The halogenated and oxidized derivatives (1a–1e, 1a′–1c′, 2a–2d, 2a′–2b′, 3a–3e, 3′ and 3a′–3b′) of schizandrin (1), schizandrin B (2) and schisanhenol (3) were synthesized. The hepatoprotective effects of these dibenzocyclooctadiene lignan analogues against CCl4-induced injury were preliminarily evaluated. Most of the analogues exhibited higher protective effects than the positive control biphenyldicarboxylate (DDB). Among these active analogues, dichloroschisanhenol (3a) exhibited the strongest protective activity (cell survival rate exceeding 98.0%). 相似文献
11.
Daniele Lecis Eloise Mastrangelo Laura Belvisi Martino Bolognesi Monica Civera Federica Cossu Michelandrea De Cesare Domenico Delia Carmelo Drago Giacomo Manenti Leonardo Manzoni Mario Milani Elisabetta Moroni Paola Perego Donatella Potenza Vincenzo Rizzo Cinzia Scavullo Carlo Scolastico Federica Servida Francesca Vasile Pierfausto Seneci 《Bioorganic & medicinal chemistry》2012,20(22):6709-6723
Novel pro-apoptotic, homodimeric and heterodimeric Smac mimetics/IAPs inhibitors connected through head–head (8), tail–tail (9) or head–tail linkers (10), were biologically and structurally characterized. In vitro characterization (binding to BIR3 and linker-BIR2–BIR3 domains from XIAP and cIAP1, cytotoxicity assays) identified early leads from each dimer family. Computational models and structural studies (crystallography, NMR, gel filtration) partially rationalized the observed properties for each dimer class. Tail–tail dimer 9a was shown to be active in a breast and in an ovary tumor model, highlighting the potential of dimeric Smac mimetics/IAP inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold as potential antineoplastic agents. 相似文献
12.
Stefania Butini Emanuele Gabellieri Margherita Brindisi Alice Casagni Egeria Guarino Paul B. Huleatt Nicola Relitti Valeria La Pietra Luciana Marinelli Mariateresa Giustiniano Ettore Novellino Giuseppe Campiani Sandra Gemma 《Bioorganic & medicinal chemistry letters》2013,23(1):85-89
Aiming at identifying new scaffolds for BACE-1 inhibition devoid of the pharmacokinetic drawbacks of peptide-like structures, we investigated a series of novel peptidomimetics based on a 1,4-benzodiazepine (BDZ) core 1a–h and their seco-analogues 2a–d. We herein discuss synthesis, molecular modeling and in vitro studies which, starting from 1a, led to the seco-analogues (R)-2c and (S)-2d endowed with BACE-1 inhibition properties in the micromolar range both on the isolated enzyme and in cellular studies. These data can encourage to pursue these analogues as hits for the development of a new series of BACE-1 inhibitors active on whole-cells. 相似文献
13.
《Bioorganic & medicinal chemistry letters》2020,30(17):127376
A series of benzo[d]thiazole analogs were synthesized and evaluated for their anti-inflammatory and analgesic effects. Using an ear edema model, except for compounds 2k, 2m-2q and 3a, other compounds showed the anti-inflammatory effects. Among them, compounds 2c, 2d, and 2g showed the best anti-inflammatory activity (inhibition rate: 86.8%, 90.7% and 82.9%, respectively). By the acetic acid-induced abdominal writhing test, except for compounds 2e, 2l, 2m, 2o, 2p and 3a, other compounds showed the analgesic effects with inhibition rate values of 51.9–100% (2a-2r) and 68.6–100% (3a-3g). Next, compounds 2c, 2d, 2g, 3d, 3f, 3g that displayed the excellent anti-inflammatory and analgesic activities were evaluated for their inhibitory effect against ovine COX-1 and COX-2. Compounds 2c, 2d, 2g, 3d, 3f, 3g were weak inhibitors of the COX-1 isozyme but exhibited the moderate COX-2 isozyme inhibitory effects IC50 from 0.28 to 0.77 μM and COX-2 selectivity indexes (SI: 18.6 to 7.2). This benzo[d]thiazole moiety will be proved to be of great significance for developing more potent COX-2 inhibitors. 相似文献
14.
15.
Junghun Lee Hoyong Jung Minjung Kim Eunkyu Lee Daseul Im Waqar Aman Jung-Mi Hah 《Bioorganic & medicinal chemistry》2018,26(8):1628-1637
A series of 4-aryl-thieno[1,4]diazepin-2-one were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Several compounds showed very potent antiproliferative activities toward both cell lines and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide (8a–8i, 9a–9m) and urea (10a–10d, 11a–11d) with diverse hydrophobic moieties. One of the most potent inhibitor 10d, 1-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-(2-oxo-2,3-dihydro-1H-thieno [3,4-b][1,4]diazepin-4-yl)phenyl)urea was found to be very potent inhibitor of multi-protein kinases including FMS kinase (IC50?=?3.73?nM) and is a promising candidate for further development in therapeutics for cancer. 相似文献
16.
Mingzhang Gao Min Wang Qi-Huang Zheng 《Bioorganic & medicinal chemistry letters》2018,28(13):2234-2238
The reference standards methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate (5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide (5c), and their corresponding desmethylated precursors 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoic acid (6a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-hydroxybenzamide (6b), were synthesized from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively. Carbon-11-labeled casein kinase 1 (CK1) inhibitors, [11C]methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate ([11C]5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-[11C]methoxybenzamide ([11C]5c), were prepared from their O-desmethylated precursor 6a or 6b with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40–45% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ~40-min from EOB. 相似文献
17.
《Carbohydrate research》1999,315(1-2):98-105
Syntheses of five ‘direct linked’ C-disaccharides 8a–e were reported. The (Et3SiH/BF3·Et2O) reduction of pyranulose glycoside 1 yielded (6S)- and (6R)-6-(2,3,5-tri-O-benzoyl-β-d-ribofuranosyl)pyran-3(2H,6H)-one (2a and 2b) in a ratio of ca. 2:1 and in 88% combined yield. The absolute stereochemistry of each was determined from its CD spectrum. The reduction of 2a with NaBH4 in methanol afforded two allylic alcohols 6a and 6b in 14 and 73% yield, respectively. The reduction of 2b with NaBH4 afforded 6c and 6d in 30 and 56% yield, respectively. Cis hydroxylation of the double bond in compounds 6a–d with osmium tetroxide gave 7a–e. The stereoisomers 7a–e were separated and their configuration was established by 1H NMR spectroscopy. Debenzoylation of compounds 7a–e with aqueous sodium carbonate produced deprotected C-disaccharides 8a–e. 相似文献
18.
In this paper we describe the chemoenzymatic synthesis of new enantiomerically enriched (R)- and (S)-1-(2-arylthiazol-4-yl)ethanols and their acetates by enzymatic enantioselective acetylation of the racemic alcohols rac-2a–d and by methanolysis of the corresponding racemic esters rac-3a–d mediated by lipase B from Candida antarctica (CaL-B) in non-aqueous media. In terms of stereoselectivity and activity, both procedures, acylation and alcoholysis, gave similar good results (50% conversion, E ≫ 200). The absolute configuration of the kinetic resolution products was determined by a detailed 1H NMR study of the Mosher's derivatives of (S)-2b. 相似文献
19.
Mingzhang Gao Min Wang Kathy D. Miller Gary D. Hutchins Qi-Huang Zheng 《Bioorganic & medicinal chemistry》2010,18(6):2099-2106
Cannabinoids have been recently proposed as a new family of potential antitumor agents, and cannabinoid receptor 2 (CB2) is believed to be over-expressed in tumor cells. This study was designed to develop new radioligands for imaging of CB2 receptor in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled 2-oxoquinoline and 2-chloroquinoline derivatives, [11C]6a–d and [11C]9a–d, were prepared by O-[11C]methylation of their corresponding precursors using [11C]CH3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 40–50% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15–20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111–185 GBq/μmol. Radioligand binding assays indicated compounds 6f, 6b, and 9f display potent in vitro binding affinities with nanomolar Ki values and at least 100–2000-fold selectivity for CB2. 相似文献
20.
Srikantamurthy Ningaiah Umesha K. Bhadraiah Shubakara Keshavamurthy Chethan Javarasetty 《Bioorganic & medicinal chemistry letters》2013,23(16):4532-4539
A novel series of pyrazoline amidoxime (2a–d) and pyrazoly-1,2,4-oxadiazole (3a–p) and (4) of pharmacological significance have been synthesised. Structures of newly synthesised compounds were characterized by spectral studies. New compounds were screened for their in vitro antioxidant, antimicrobial and antiinflammatory activities. Among the synthesized compounds, compound 2a, 3l and 3o were found to be active antimicrobial agents in addition to having potent antioxidant activity, while the compound 3f showed promising antiinflammatory activity in comparison with standard drug. 相似文献