- Catalytic Ring-Opening of Cyclic Alcohols Enabled by PCET Activation of Strong O-H Bonds
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We report a new photocatalytic protocol for the redox-neutral isomerization of cyclic alcohols to linear ketones via C-C bond scission. Mechanistic studies demonstrate that key alkoxy radical intermediates in this reaction are generated via the direct homolytic activation of alcohol O-H bonds in an unusual intramolecular PCET process, wherein the electron travels to a proximal radical cation in concert with proton transfer to a weak Br?nsted base. Effective bond strength considerations are shown to accurately forecast the feasibility of alkoxy radical generation with a given oxidant/base pair.
- Yayla, Hatice G.,Wang, Huaiju,Tarantino, Kyle T.,Orbe, Hudson S.,Knowles, Robert R.
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p. 10794 - 10797
(2016/09/09)
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- TREATMENT OF HYPERPROLIFERATIVE DISEASES WITH N-OXIDES OF ESTROGEN RECEPTOR MODULATORS
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The invention relates to N-oxides of tamoxifen analogs having activity for treating hyperproliferative disorders. Pharmaceutical compositions comprising therapeutically effective amount of an N-oxide of an estrogen receptor modulator, or a pharmaceuticall
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Page/Page column 64
(2008/06/13)
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- α-fluoro-benzylphosphonates as reagents for the preparation of 1-fluoro-1-aryl alkenes and α-fluorostilbenes
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The preparation of several fluoro-benzylphosphonates Ar-CHF-PO(OEt) 2 and their Wadsworth-Emmons type olefination with aldehydes and ketones are described affording fluorostyrenes and fluorostilbenes. Some of these compounds are incorporated in
- Allmendinger, Thomas,Fujimoto, Roger,Gasparini, Fabrizio,Schilling, Walter,Satoh, Yoshi
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p. 133 - 137
(2007/10/03)
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- Synthesis and pharmacological properties of benzamide derivatives as selective serotonin 4 receptor agonists
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A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamides with a polar substituent group at the 1-position of the piperidine ring was synthesized and evaluated for its effect on gastrointestinal motility. The benzoyl, phenylsulfonyl, and benzylsulfonyl derivatives accelerated gastric emptying and increased the frequency of defecation. One of them, 4-amino-N-[1-[3-(benzylsulfonyl)propyl]piperidin-4-ylmethyl]-5-chloro-2- methoxybenzamide (13a, Y-36912), was a selective 5-HT4 receptor agonist offering potential as a novel prokinetic with reduced side effects derived from 5-HT3- and dopamine D2 receptor-binding affinity. In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and the lower gastrointestinal tract.
- Sonda, Shuji,Katayama, Kenichi,Kawahara, Toshio,Sato, Noriko,Asano, Kiyoshi
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p. 2737 - 2747
(2007/10/03)
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- Triarylpyrazoles with basic side chains: Development of pyrazole-based estrogen receptor antagonists
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Recently, we developed a novel triaryl-substituted pyrazole ligand system that has high affinity for the estrogen receptor (ER) (Fink, B. E.; Mortenson, D. S.; Stauffer, S. R.; Aron, Z. D.; Katzenellenbogen, J. A. Chem. Biol. 1999, 6, 205). Subsequent wor
- Stauffer, Shaun R.,Huang, Ying R.,Aron, Zachary D.,Coletta, Christopher J.,Sun, Jun,Katzenellenbogen, Benita S.,Katzenellenbogen, John A.
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p. 151 - 161
(2007/10/03)
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- Synthesis of 5-(ω-sulfhydrylalkyl)salicylaldehydes as precursors for the preparation of alkanethiol-modified metal salens
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Using multistep syntheses, we obtained two alkanethiol-modified salicylaldehydes, namely 5-(2-sulfhydrylethyl)salicylaldehyde and 5-(6-sulfhydrylhexyl)salicylaldehyde. These compounds are precursors for the preparation of alkanethiol-substituted metal sal
- Ji, Chang,Peters, Dennis G
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p. 6065 - 6067
(2007/10/03)
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- BENZOIC ACID COMPOUNDS AND USE THEREOF AS MEDICAMENTS
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Benzoic acid compounds of the formula STR1 wherein each symbol is as defined in the specification, optical isomers thereof and pharmaceutically acceptable salts thereof; pharmaceutical composition comprising this compound and pharmaceutically acceptable additive; and serotonin 4 receptor agonists, gastrointestinal prokinetic agents and therapeutic agents for various gastrointestinal diseases, which comprise this compound as active ingredient. The compounds of the present invention have high and selective affinity for serotonin 4 receptor, and show agonistic effects thereon. Accordingly, they are useful medications for the prophylaxis and treatment of various gastrointestinal diseases, central nervous disorders, cardiac function disorders, urinary diseases, and the like, as well as useful anti-nociceptors for analgesic use which increase threshold of pain.
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- Potentiation of cADPR-induced Ca2+-release by methylxanthine analogues
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Caffeine and other methylxanthines are known to induce Ca2+-release from intracellular stores via the ryanodine receptor. In the present work, a range of caffeine analogues, in which methyl groups at the 1 and 7 positions were replaced with alkyl chains containing different functional groups (oxo, hydroxyl, propargyl, ester, and acids), were synthesized. These compounds were then screened for their ability to potentiate Ca2+-release induced by cADPR (an endogenous modulator of ryanodine receptors) in sea urchin egg homogenates. Two of the synthesized methylxanthines, 1,3-dimethyl-7-(7- hydroxyoctyl)xanthine (37) and 3-methyl-7-(7-oxooctyl)-1-propargylxanthine (66), were shown to be more potent than caffeine in potentiating cADPR- induced Ca2+-release, while 1,3-dimethyl-7-(5-ethylcarboxypentyl)xanthine (14) was shown to be more efficacious. The development of new methylxanthine analogues may lead to a better understanding of ryanodine receptor function and could possibly provide novel therapeutic agents.
- Cavallaro, Rosaria A.,Filocamo, Luigi,Galuppi, Annamaria,Galione, Antony,Brufani, Mario,Genazzani, Armando A.
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p. 2527 - 2534
(2007/10/03)
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- BENZOIC ACID COMPOUNDS AND MEDICINAL USE THEREOF
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A benzoic acid compound of the formula wherein each symbol is as defined in the specification, an optical isomer thereof and a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising this compound and a pharmaceutically acceptable additive, a serotonin 4 receptor agonist comprising this compound as an active ingredient, a gastrointestinal prokinetic agent and a therapeutic agent for gastrointestinal diseases. The compound of the present invention shows selective and high affinity for serotonin 4 receptors, activates same, is useful as a pharmaceutical agent for the prophylaxis and treatment of gastrointestinal diseases (e.g., reflux esophagitis; gastroesophageal reflux such as that accompanying cystic fibrosis; Barrett syndrome; intestinal pseudoileus; acute or chronic gastritis; gastric or duodenal ulcer; Crohn's disease; non-ulcer dyspepsia; ulcerative colitis; postgastrectomy syndrome; postoperative digestive function failure; delayed gastric emptying caused by gastric neurosis, gastroptosis, diabetes, and the like; gastrointestinal disorders such as indigestion, meteorism, abdominal indefinite complaint, and the like; constipation such as atonic constipation, chronic constipation, and that caused by spinal cord injury, pelvic diaphragm failure and the like; and irritable bowel syndrome), central nervous disorders (e.g., schizophrenia, depression, anxiety, disturbance of memory and dementia), cardiac function disorders (e.g., cardiac failure and myocardial ischemia), urinary diseases (e.g., dysuria caused by urinary obstruction, ureterolith, prostatomegaly, spinal cord injury, pelvic diaphragm failure, etc.), and shows superior absorption.
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- Aryl substituted diketones
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Aryl substituted diketones and keto-esters, useful as antiviral agents and insecticides, are prepared by reacting an arylalkyl or arylalkenyl iodide with a metal salt of the appropriate diketone or keto-ester.
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- Methylenedioxyphenyl substituted aliphatic diketones
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Aryl substituted diketones and keto-esters, useful as antiviral agents and insecticides, are prepared by reacting an arylalkyl or arylalkenyl iodide with a metal salt of the appropriate diketone or keto-ester.
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