- Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening
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Highly diastereoselective synthesis of chromeno β-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired β-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4-hydroxycoumarin in the presence of 1,4-diazabicyclo [2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1D and 2D NMR spectra, X-ray analysis, H–H COSY and H–C HSQC two-dimensional NMR experiments, and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. β-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. β-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.
- Borazjani, Nassim,Sepehri, Saghi,Behzadi, Maryam,Jarrahpour, Aliasghar,Rad, Javad Ameri,Sasanipour, Maryam,Mohkam, Milad,Ghasemi, Younes,Akbarizadeh, Amin Reza,Digiorgio, Carole,Brunel, Jean Michel,Ghanbari, Mohammad Mehdi,Batta, Gyula,Turos, Edward
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Read Online
- Methyl 2-(2-(4-formylphenoxy)acetamido)-2-substituted acetate derivatives: A new class of acetylcholinesterase inhibitors
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A new class of inhibitors of acetylcholinesterase (methyl 2-(2-(4-formylphenoxy)acetamido)-2-substituted acetate derivatives) is described. Compounds 4b and 4i were found to be more potent than galanthamine in inhibiting acetylcholinesterase.
- Wen, Huan,Zhou, Yayao,Lin, Chonglan,Ge, Hui,Ma, Lin,Wang, Zihou,Peng, Wenlie,Song, Huacan
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Read Online
- Synthesis, structural characterization, and antibacterial activity of tricyclohexyltin aryloxyacetates
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Three tricyclohexyltin aryloxyacetates, p-YC6H4OCH2COOSn(C6H11-c)3 (where Y=H, 1; CHO, 2; CH2OH, 3), have been synthesized and characterized by means of elemental analysis, IR, and NMR (1H, 13C, and 119Sn) spectroscopy. The crystal structures of complexes 1 and 3 are determined by X-ray single-crystal diffraction. The carboxylate in the compounds is monodentate. The tin atom of compound 1 adopts distorted tetrahedral coordination geometry. In the crystal lattice of compound 3, there is a four-coordinated tin and a five-coordinated tin in which the fifth coordination site is occupied by a water molecule, and the molecules are linked by R33(30) and R55(28) hydrogen bonds into a two-dimensional supramolecular network. Bioassay results have shown that the compounds have good in vitro antibacterial activity against Escherichia coli.
- Zhang, Hao,Yu, Haixia,Liu, Xijie,Tian, Laijin
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Read Online
- Discovery of Novel Dual-Target Inhibitor of Bromodomain-Containing Protein 4/Casein Kinase 2 Inducing Apoptosis and Autophagy-Associated Cell Death for Triple-Negative Breast Cancer Therapy
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Bromodomain-containing protein 4 (BRD4) is an attractive epigenetic target in human cancers. Inhibiting the phosphorylation of BRD4 by casein kinase 2 (CK2) is a potential strategy to overcome drug resistance in cancer therapy. The present study describes the synthesis of multiple BRD4–CK2 dual inhibitors based on rational drug design, structure–activity relationship, and in vitro and in vivo evaluations, and 44e was identified to possess potent and balanced activities against BRD4 (IC50 = 180 nM) and CK2 (IC50 = 230 nM). In vitro experiments show that 44e could inhibit the proliferation and induce apoptosis and autophagy-associated cell death of MDA-MB-231 and MDA-MB-468 cells. In two in vivo xenograft mouse models, 44e displays potent anticancer activity without obvious toxicities. Taken together, we successfully synthesized the first highly effective BRD4–CK2 dual inhibitor, which is expected to be an attractive therapeutic strategy for triple-negative breast cancer (TNBC).
- Chen, Juncheng,Chiang, Cheng-Ming,He, Gu,Liu, Bo,Liu, Jie,Ouyang, Liang,Tang, Pan,Wang, Guan,Yang, Chengcan,Ye, Tinghong,Zhang, Jifa,Zhang, Jin,Zou, Ling
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p. 18025 - 18053
(2022/01/03)
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- Application of bioorthogonal hetero-Diels-Alder cycloaddition of 5-arylidene derivatives of 1,3-dimethylbarbituric acid and vinyl thioether for imaging inside living cells
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New bioorthogonal cycloaddition of 5-arylidene derivatives of 1,3-dimethylbarbituric acid as 1-oxa-1,3-butadienes and vinyl thioether as a dienophile has been applied to imaging inside living cells. The reaction is high yielding, selective, and fast in aqueous media. The proposed 1-oxa-1,3-butadiene derivative conjugated to a FITC fluorochrome selectively and rapidly labels the cancer cells pretreated with the dienophile-taxol. The second order rate constants k2 for various proposed bioorthogonal cycloadditions were estimated to be in the range from 0.9 × 10-2 M-1 s-1 to 1.4 M-1 s-1, which is much better than in the case of the first generation TQ-ligation (o-quinolinone quinone methide and vinyl thioether ligation, k2 = 1.5 × 10-3 M-1 s-1) and comparable or better to that for the second generation TQ-ligation (k2 = 2.8 × 10-2 M-1 s-1). The reaction rate constants k2 of proposed ligation reactions are in the range of the rate constants k2 for tetrazines and norbornenes or tetrazines and cyclopropenes. These findings indicate that this chemistry is suitable for in vitro imaging experiments.
- Bazan, Bart?omiej,Pa?asz, Aleksandra,Skalniak, ?ukasz,Cie?, Dariusz,Buda, Szymon,J?drzejowska, Katarzyna,G?omb, Sonia,Kamzol, Daniel,Czarnota, Kinga,Latos, Krystian,Kozie?, Krzysztof,Musielak, Bogdan
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supporting information
p. 6045 - 6058
(2021/07/25)
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- Rational Design, Synthesis, and In Vitro Neuroprotective Evaluation of Novel Glitazones for PGC-1α Activation via PPAR-γ: a New Therapeutic Strategy for Neurodegenerative Disorders
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In the present study, two structurally diverse novel glitazones were designed and synthesized for activation of central PGC-1α signaling through stimulation of PPAR-γ receptor. The functional interaction between PGC-1α and PPAR-γ is a key interaction in the normal physiology of neuroprotective mechanism. Therefore, activation of PPAR-γ–dependent PGC-1α co-activator signaling could be an effective strategy to exhibit neuroprotection in several neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. As part of rational design, analogs were designed manually based on principles of bioisosterism, followed by virtually screened using docking to predict the mode of interaction of compound towards the binding site and molecular dynamic simulation to observe the structural changes that occur during compound interaction with active site. The designed two glitazones (G1, G2) were synthesized and structurally analyzed. As part of evaluation, synthesized glitazones were subjected for preliminary neuroprotective evaluation in Lipopolysaccharide (LPS) intoxicated SH-SY5Y neuroblastoma cells. The results indicate that pre-treatment with synthesized glitazones have increased the percentage cell viability, protected the cell morphology, and decreased the release of pro-inflammatory cytokines (IL-1β, TNF-α), lipid peroxide (LPO), and nitric oxide (NO) level in LPS intoxicated SH-SY5Y cells. Interestingly, among the two glitazones, G2 has shown significant neuroprotection in comparison to G1 and neuroprotective effect exerted by G2 was similar and comparable with the standard pioglitazone. Altogether, neuroprotection exhibited by this non-thiazolidione–based glitazones during neuroinflammatory conditions may be attributed to the activation of central PGC-1α signaling via PPAR-γ receptor.
- Bharathi, Jeyabalan Jeyaram,Dhivya, S.,Divakar, Selvaraj,Durai, Priya,Justin, Antony,Kabadi, Pradeep,Mandal, Subhankar,Prabitha, P.,Prashantha Kumar, B. R.,Sandhya, C. H.,Sekhar, Satheesh John,Wadhwani, Ashish D.,Yuvaraj, S.
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- Chalcone aryloxyacetamide compound as well as preparation method and application thereof
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The invention relates to the field of pharmaceutical chemistry, in particular to a chalcone aryloxyacetamide compound (I) or (II) and a preparation method thereof. As proved by a pharmacodynamic test,the compound has the effects of reducing blood glucose, reducing triglyceride and reducing cholesterol, and can be used for treating abnormal glucolipid metabolism and obesity. A general formula of the compound is shown in the description.
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Paragraph 0031-0032; 0038-0042
(2018/03/26)
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- Design, synthesis chalcone derivatives as AdipoR agonist for type 2 diabetes
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Two structurally novel series of chalcone derivatives were designed and synthesized as potential agents against type 2 diabetes. As a result of the antidiabetic biological evaluation in streptozotocin (STZ)-induced type 2 diabetes animal model, 13e, 13g, and 19f showed more significant reduction in serum Glu, TG, TC levels by contrast to the positive control AdipoRon. In addition to upregulating the expression of AdipoR1 and AdipoR2, 13e and 19f treatment also increased expression of AMPK and PPAR-α. Taken together, these results suggested that 13e and 19f might be a promising compound for type 2 diabetes treatment.
- Zhu, Panhu,Huang, Weijun,Li, Jiaming,Ma, Xiaodong,Hu, Mengqi,Wang, Yujun,Xu, Qinlong,Wang, Xianna
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p. 1525 - 1536
(2018/06/04)
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- Carbon nitride assisted chemoselective C-H bond photo-oxidation of alkylphenolethoxylates in water medium
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The unprecedented ability of g-C3N4 to chemoselectively photo-oxidise the methyl group of 2-(4-methylphenoxy)ethanol instead of the easily oxidised oxyethanol fragment has been demonstrated. When g-C3N4 is treat
- Ilkaeva,Krivtsov,Bartashevich,Khainakov,García,Díaz,Ordó?ez
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supporting information
p. 4299 - 4304
(2017/09/29)
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- Synthetic method of p-hydroxymethylphenoxyacetic acid serving as linker
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The invention relates to a synthetic method of p-hydroxymethylphenoxyacetic acid serving as a linker and aims at solving the technical problems that a traditional method is higher in cost, is unfavorable for body health and the like. The technical scheme adopted by the invention is that the synthetic method of the p-hydroxymethylphenoxyacetic acid serving as the linker comprises the following steps of condensing p-hydroxy benzaldehyde and chloroacetic acid under the alkaline condition to obtain p-formylphenoxyacetic acid; reducing the p-formylphenoxyacetic acid by using a reducing agent to obtain the p-hydroxymethylphenoxyacetic acid. The synthetic method disclosed by the invention is low in synthetic cost and is suitable for scale production.
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Paragraph 0005; 0013
(2017/03/08)
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- Design, synthesis, and biological evaluation of thiazolidine-2,4-dione conjugates as PPAR-γ agonists
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A library of synthesized conjugates of phenoxy acetic acid and thiazolidinedione 5a-m showed potent peroxisome proliferator activated receptor-γ (PPAR-γ) transactivation as well as significant blood glucose lowering effect comparable to the standard drugs pioglitazone and rosiglitazone. Most of the compounds showed higher docking scores than the standard drug rosiglitazone in the molecular docking study. Compounds 5l and 5m exhibited PPAR-γ transactivation of 54.21 and 55.41%, respectively, in comparison to the standard drugs pioglitazone and rosiglitazone, which showed 65.94 and 82.21% activation, respectively. Compounds 5l and 5m significantly lowered the blood glucose level of STZ-induced diabetic rats. Compounds 5l and 5m lowered the AST, ALT, and ALP levels more than the standard drug pioglitazone. PPAR-γ gene expression was significantly increased by compound 5m (2.00-fold) in comparison to the standard drugs pioglitazone (1.5-fold) and rosiglitazone (1.0-fold). Compounds 5l and 5m did not cause any damage to the liver and could be considered as promising candidates for the development of new antidiabetic agents.
- Nazreen, Syed,Alam, Mohammad Sarwar,Hamid, Hinna,Yar, Mohammad Shahar,Dhulap, Abhijeet,Alam, Perwez,Pasha, Mohammad Abdul Qadar,Bano, Sameena,Alam, Mohammad Mahboob,Haider, Saqlain,Kharbanda, Chetna,Ali, Yakub,Pillai, Kolakappi
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p. 421 - 432
(2015/06/08)
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- Targeting quorum sensing by designing azoline derivatives to inhibit the N-hexanoyl homoserine lactone-receptor CviR: Synthesis as well as biological and theoretical evaluations
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To counteract bacterial resistance, we investigated the interruption of quorum sensing mediated by non-classical bioisosteres of the N-hexanoyl homoserine lactone with an azoline core. For this purpose, a set of selected 2-substituted azolines was synthesized, establishing the basis for a new protocol to synthesize 2-amino imidazolines. The synthesized compounds were evaluated as inhibitors of violacein production in Chromobacterium violaceum. Theoretical studies on bioisostere-protein interactions were performed using CviR. The results show that some azolines decreased violacein production, suggesting an antiquorum sensing profile against Gram-negative bacteria. Docking and molecular dynamic simulations together with binding free energy calculations revealed the exact binding and inhibitory profiles. These theoretical results show relationship with the in vitro activity of the azoline series.
- Bucio-Cano, Alejandro,Reyes-Arellano, Alicia,Correa-Basurto, José,Bello, Martiniano,Torres-Jaramillo, Jenifer,Salgado-Zamora, Héctor,Curiel-Quesada, Everardo,Peralta-Cruz, Javier,Avila-Sorrosa, Alcives
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p. 7565 - 7577
(2015/12/18)
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- SIGMA-2 RECEPTOR LIGAND DRUG CONJUGATES AS ANTITUMOR COMPOUNDS, METHODS OF SYNTHESIS AND USES THEREOF
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Methods and compositions for treating cancers such as pancreatic cancer and synovial sarcoma are disclosed. Compounds comprising a sigma-2 receptor-binding moiety and a ferroptosis-inducing moiety are described. At least one described molecular species exhibits an IC50 value below 5 μΜ against human pancreatic cancer cells in vitro. Administration of this species promoted shrinkage of pancreatic cancer tumors in a murine model system in vivo, and led to 100% survival of experimental animals over a time course in which control therapies provided only 30% or 40% survival. Methods of synthesis of molecular species are also disclosed.
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Page/Page column 0159
(2016/01/29)
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- IMIDAZOPYRIDINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
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A series of substituted 3H imidazo[4,5-b]pyridine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
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Page/Page column 92; 93
(2015/06/25)
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- Synthesis and in vitro antiplasmodial evaluation of 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone conjugates
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Abstract The manuscript describes the synthesis of novel amide tethered 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone bifunctional hybrids and their evaluation as antimalarial agents against W2 resistant strain of Plasmodium falciparum. The antiplasmodial activity of 7-chloroquinoline-ferrocenylchalcones was found to be less than their corresponding simple chalcone conjugates. The presence of a methoxy substituent at para position of ring B on chalcones and longer alkyl chain length markedly improved the antiplasmodial profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC50 value of 17.8 nM. Synthesis of 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone conjugates.Antimalarial potency of synthesized conjugates was evaluated against W2 strain.Most potent and non-cytotoxic conjugate exhibited IC50 of 17.8 nM.
- Raj, Raghu,Saini, Anu,Gut, Jiri,Rosenthal, Philip J.,Kumar, Vipan
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p. 230 - 239
(2015/04/14)
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- IMIDAZO [4, 5 - B] PYRIDINE DERIVATIVES AS ALK AND JAK MODULATORS FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
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This application relates to compounds of the Formula I as defined herein, and/or salts thereof. This application further relates to compositions and methods of using these compounds and/or salts thereof. The compounds of Formula I are useful as ALK and JAK modulators for the treatment of proliferative disorders.
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Page/Page column 225; 226
(2013/08/15)
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- An efficient one pot syntheses of aryl-3,3′-bis(indolyl)methanes and studies on their spectral characteristics, DPPH radical scavenging-, antimicrobial-, cytotoxicity-, and antituberculosis activity
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An efficient one-pot syntheses of aryl-3,3′-bis(indolyl)methanes (BIMs) from indole/2-methylindole and formylphenoxyaliphatic acid(s) is described. Esterification of carboxylic acid and aromatic electrophilic substitution reactions are achieved simultaneous in the presence of potash alum as a catalyst. This catalyst could be recovered and reused without substantial loss in its catalytic activity and the methodology could be applied on a range of closely related substrates. The solvation characteristics in ground and excited states of the compounds by monitoring the absorbance and fluorescence band maxima have been studied. The fluorescence studies in protic and aprotic solvents were rationalized on the basis of solute-solvent interaction and substituents effect on these photophysical processes analyzed. The compounds prepared showed efficient antimicrobial effect against human pathogens, cytotoxicity against A431 cell line, and DPPH radical scavenging effect. Single crystal XRD studies have been carried out for a few compounds synthesized in this work.
- Suresh Kumar,Kumaresan,Antony Muthu Prabhu,Bhuvanesh,Seethalakshmi
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supporting information
p. 254 - 263
(2013/02/23)
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- Synthesis and Hypolipidemic Activity of Novel 2-(4-(2-Amino-6-(4-Substituted Phenyl) Pyrimidin-4-yl)-2-Substituted Phenoxy) Acetic Acid Derivatives
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A novel series of 2-(4-(2-amino-6-(4-substituted phenyl) pyrimidin-4-yl)-2-substituted phenoxy) acetic acid derivatives were efficiently synthesized. The synthesized compounds were evaluated for their in vivo hypolipidemic activity, using high-fat-diet-induced hyperlipidemia in rats. Some of these compounds showed significant antihyperlipidemic activity.
- Mokale, Santosh N.,Shete, Maheshwari T.,Shaikh, Sameer I.,Shinde, Devanand B.
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experimental part
p. 548 - 552
(2012/06/29)
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- Synthesis and antimicrobial activity of some novel benzimidazole hydrazides
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The present study was undertaken to synthesize some 4-(5,6-dichloro-1H- benzimidazole-2-yl)phenoxyacetic acid-4-substituted benzylidene hydrazide derivatives and investigate their possible antimicrobial activity. Chemical structures of the synthesized compounds were elucidated by IR, 1H NMR and ES-MS spectral data and elemental analysis. Some of the compounds in the series exhibited notable antibacterial activity against various bacterial strains. Besides, most of them displayed significant antifungal activity against different Candida yeasts. Microbiological studies revealed that the most active compounds in the series were 6d and 6n, which were also evaluated in Brine-Shrimp lethality assay. The compound 6d was found as non-toxic in addition to its significant antimicrobial activity, whereas the compound 6n was determined as harmful.
- ?zkay,Tunali,Karaca,Isikdag
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scheme or table
p. 1503 - 1508
(2012/01/05)
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- Synthesis of novel unsymmetric bisbenzimidazoles
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Using chloroacetic acid, p-hydroxyl aromatic aldehydes 1 and aromatic diamines 3 as starting materials, novel bisbenzimidazoles 5 with unsymmetric structure were synthesized via aryloxyacetic acid intermediates 2. Four new intermediates 4 and ten target molecules 5 were characterized by FTIR, 1H NMR, 13C NMR, MS and elemental analysis. Different synthetic methods, including one-pot synthesis and intermittent microwave promotion, were investigated. The research provides a new method and idea for the synthesis of bisbenzimidazoles.
- Mao, Zhengzhoua,Wang, Zhaoyang,Mei, Wenjie,Yang, Kai
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scheme or table
p. 818 - 824
(2010/11/02)
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- Novel N-O type oxazoline ligands
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We describe here the synthesis of three novel N-O type oxazoline compounds from readily available 3-hydroxy-2-naphthoic acid and pamoic acid (BINOL-box type) and 2-naphthol (Xabox type).
- Ergunes, Duygu,Kokce, Zeynep,Sirkecioglu, Okan,Talinli, Naciye
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experimental part
p. 455 - 458
(2011/09/12)
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- Synthesis and biological evaluation of novel 4-hydroxybenzaldehyde derivatives as tyrosinase inhibitors
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A series of novel 4-hydroxybenzaldehyde derivatives were synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were investigated. Most of target compounds had more potent inhibitory activities than the parent compound 4-hydroxybenzaldehyde (IC50 = 1.22 mM). Interestingly, compound 3c bearing a dimethoxyl phosphate was found to be the most potent inhibitor with IC50 value of 0.059 mM. The inhibition kinetics analyzed by Lineweaver-Burk plots revealed that compound 3c was a non-competitive inhibitor (KI = 0.0368 mM). In particular, compound 3c showed no side effects at dose of 1600 mg/kg in mice. These results suggested that such compounds might be served as lead compounds for further designing new potential tyrosinase inhibitors.
- Yi, Wei,Cao, Rihui,Peng, Wenlie,Wen, Huan,Yan, Qin,Zhou, Binhua,Ma, Lin,Song, Huacan
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experimental part
p. 639 - 646
(2010/04/02)
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- Adenosine A2A receptor-antagonist/dopamine D2 receptor-agonist bivalent ligands as pharmacological tools to detect A 2A-D2 receptor heteromers
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Adenosine A2A (A2AR) and dopamine D2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease.Here, a family of heterobivalent ligands containing a D2R agonist and an A 2AR antagonist linked through a spacer of variable size was designed and synthesized to study A2AR-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A2AR with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A2AR-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A2AR-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy.
- Soriano, Aroa,Ventura, Ruben,Molero, Anabel,Hoen, Rob,Casado, Vicent,Corte, Antoni,Fanelli, Francesca,Albericio, Fernando,Lluís, Carmen,Franco, Rafael,Royo, Miriam
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supporting information; experimental part
p. 5590 - 5602
(2010/03/24)
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- Heterocyclic analogs of prostaglandines: IV. Synthesis of 3,7-interphenylene 3,10(11)-dioxa-13-azaprostanoids and 9-oxa-7-azaprostanoids based on tetronic acid and aromatic aldehydes
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An approach was developed to the synthesis of stable in metabolism 3,7-interphenylene 3,10-dioxa-13-aza-and 3,11-dioxa-13-azaprostanoids, and also 9-oxa-7-azaprostanoids with interphenylene and terminal phenyl fragments in the ω-chain based on 3-(alkoxybenzylidene)-and 3-(3-phenylallylidene) tetrahydrofuran-2,4-diones obtained by Knoevenagel condensation of tetronic acid with alkoxy-substituted aromatic aldehydes and cinnamic aldehyde.
- Pashkovskii,Shchukina,Gribovskii,Lakhvich
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scheme or table
p. 657 - 670
(2009/04/07)
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- Microwave-Accelerated SPOT-synthesis on cellulose supports
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Equation presented. We demonstrate that microwave irradiation can dramatically accelerate reaction rates for spatially addressable library synthesis on planar membrane supports. The development of a robust support/linker system, microwave-assisted synthesis of small molecule test libraries, and methods for solid-phase scale-up on cellulose are described.
- Bowman, Matthew D.,Jeske, Ryan C.,Blackwell, Helen E.
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p. 2019 - 2022
(2007/10/03)
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- ROSIGLITAZONE DERIVATIVES AS ANTIDIABETIC AGENTS
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The present invention relates to rosiglitazone derivatives of Formula VI and their pharmaceutically acceptable salts. The invention concerns methods for the preparation of such derivatives, pharmaceutical compositions comprising the same and methods of treatment comprising administration of such compositions. These derivatives are putative metabolites of rosiglitazone.
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- Enediyne derivatives useful for the synthesis of conjugates of methyltrithio antitumor agents
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This invention describes carrier-drug conjugates prepared from disulfide analogs of the calicheamicin family of potent antitumor antibiotics and their derivatives, as well as similar analogs from related antitumor antibiotics such as the esperamicins. The carrier can be an antibody, growth factor, or steroid which targets an undesired population of cells, such as those of a tumor. Whole protein carriers as well as their antigen-recognizing fragments and their chemically or genetically manipulated counterparts are useful for the targeting portion of the conjugates. This invention includes compounds required for the synthesis of these conjugates, appropriate pharmaceutical compositions of the carrier-drug conjugates, and their method of use.
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- Designing of resorcinol-p-hydroxybenzaldehyde tetramer for uranophilic activity
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Resorcinol-p-hydroxybenzaldehyde tetramer (1) has been obtained under acidic conditions, separated into its conformations and characterized by 1H NMR and 13C NMR spectra and through the preparation of its octaacetate. The direct carboxymethylation of 1 has been attempted with chloroacetic acid under basic conditions but due to steric repulsions, the tetramer 2a could not be obtained. Using the reverse approach p-hydroxybenzaldehyde is carboxymethylated first to get 6 which is then cyclized under acidic conditions to yield the tetramer 2b. Compound 2a has been characterized as its acetylated ethyl ester 3 by 1H NMR spectral data and elemental analysis. The two conformations of 3 have been separated by repeated recrystallization from acetonitrile and their purity has been checked by 1H NMR spectra. The tetramer 2a is obtained by hydrolysis of 3 with NaOH (1N). The coplanar arrangement of carboxylate groups in 2a is utilized to bind uranyl ion. The binding as shown by Job's plot does not show 1:1 (2a: UO22+) ratio due to fourth carboxylate group, but it acts as a good uranophile as indicated by an increase in the intensity of UO22+ ions in UV absorption in the presence of 3.
- Singh, Harmit,Singh, Serjinder
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p. 409 - 412
(2007/10/03)
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- Porphyrin synthesis in surfactant solution: Multicomponent assembly in micelles
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A synthesis of meso-substituted porphyrins in anionic sodium dodecyl sulfate micelles has been developed. Polar, functionalized aromatic aldehydes condense reversibly with pyrrole in the micellar phase. Oxidation of the porphyrinogen then provides functionalized porphyrins in yields of 10-48%. Hydrophobic aldehydes condense irreversibly to give low yields at practical substrate concentrations. Synthesis in D2O solution results in per-β-deuterated porphyrins. A two-phase model is used to rationalize the dependence of porphyrin yield on reactant and surfactant concentration. Micelles are viewed as potential wells which promote porphyrinogen assembly by binding products more tightly than reactants.
- Bonar-Law, Richard P.
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p. 3623 - 3634
(2007/10/03)
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- 1,4-dihydropyridine derivatives
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Compounds a formula (I) STR1 wherein the substituents and symbols have the meanings given in the specification, are new compounds with marked cardiovascular activity.
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- BIOLOGICALLY-ACTIVE 1,3-DIPROPYL-8-PHENYLXANTHINE DERIVATIVES
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Certain functionalized congeners of 1,3-dialkylxanthine exhibit high potency and selectivity as antagonists for A 1-and A. sub.2-adenosine receptors and are suitable for attachment to probes, drug carriers, or solid supports. These derivatives are characterized by the presence of a phenyl at the 8 position para-substituted with a functionalized chain to provide high water solubility and high receptor affinity to such an extent that these compounds are suitable for use as antiallergenic, antiasthmatic, or cardiotonic drugs, central nervous system stimulants, and diuretics.
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- Functionalized Congeners of 1,3-Dialkylxanthines: Preparation of Analogues with High Affinity for Adenosine Receptors
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A series of functionalized congeners of 1,3-dialkylxanthines has been prepared as adenosine receptor antagonists.On the basis of high potency of 8-(p-hydroxyphenyl)-1,3-dialkylxanthines, the parent compounds were 8-phenyl> derivatives of theophylline and 1,3-dipropylxanthine.A series of analogues including esters of ethanol and N-hydroxysuccinimide, amides, a hydrazide, an acylurea, and anilides were prepared.The potency in blocking A1-adenosine receptors (inhibition of binding of N6-cyclohexyladenosine to brain membranes) and A2-adenosine receptors (inhibition of 2-chloroadenosine-elicited accumulations of cyclic AMP in brain slices) was markedly affected by structural changes distal to the primary pharmacophore (8-phenyl-1,3-dialkylxanthine).Potencies in the dipropyl series at the A1 receptor ranged from Ki values of 1.2 nM for a congener with a terminal amidoethyleneamine moiety to a Ki value of 58 nM for the parent carboxylic acid to a Ki of 96 nM for the bulky ureido congener.Certain congeners were up to 145-fold more active at A1 receptors than at A2 receptors.Various derivatives of the congeners should be useful as receptor probes and for radioidodination, avidin binding, and preparation of affinity columns.
- Jacobson, Kenneth A.,Kirk, Kenneth L.,Padgett, William L.,Daly, John W.
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p. 1334 - 1340
(2007/10/02)
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