- Synthesis and Photodimerization of 2- And 2,3-Disubstituted Anthracenes: Influence of Steric Interactions and London Dispersion on Diastereoselectivity
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There is increased evidence that the effect of bulky groups in organic, organometallic, and inorganic chemistry is not only repulsive but can be attractive because of London dispersion interactions. The influence of the size of primary alkyl substituents in 2- and 2,3-positions of anthracenes on the diastereoselectivity (anti vs syn dimer) of the [π4s + π4s] photoinduced dimerization is investigated. The synthesis of the anthracene derivatives was achieved by Suzuki-Miyaura reaction of 2,3-dibromoanthracene with alkylboronic acids as well as by reduction of anthraquinones that were obtained from 2,3-disubstituted 1,3-butadienes and naphthoquinone followed by dehydrogenation. The mixtures of dianthracene isomers were analyzed with respect to the anti/syn-ratio of the products by X-ray crystallography and nuclear Overhauser effect spectroscopy. While for the 2,3-dimethylanthracene the anti and syn isomers were formed in equal amounts, the anti dimers are the major products in all other cases. A linear correlation (R2 = 0.98) between the steric size (Charton parameter) and the isomeric ratio suggests that the selectivity is dominated by classical repulsive steric effects. An exception is the iso-butyl substituent that produces an increased amount of the syn isomer. It is suggested that this is due to an exalted effect of London dispersion interactions.
- Geiger, Thomas,Haupt, Anne,Maichle-M?ssmer, C?cilia,Schrenk, Claudio,Schnepf, Andreas,Bettinger, Holger F.
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p. 10120 - 10135
(2019/08/26)
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- Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure
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A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10?μM?=?51.1%; FS?=?18.90; EF?=?12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation?=?53.3%; FS?=?30.04; EF?=?18.27) showed significant activity in?vitro and in?vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation?=?81.4%; FS?=?20.50; EF?=?13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation?=?44.0%; FS?=?24.79; EF?=?15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure.
- Manickam, Manoj,Jalani, Hitesh B.,Pillaiyar, Thanigaimalai,Sharma, Niti,Boggu, Pulla Reddy,Venkateswararao, Eeda,Lee, You-Jung,Jeon, Eun-Seok,Jung, Sang-Hun
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p. 379 - 391
(2017/04/24)
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- Compounds with cardiac myosin activating function and pharmaceutical composition containing the same for treating or preventing heart failure
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The present invention relates to a compound having a cardiotonic activating function and a pharmaceutical composition containing the same. The composition comprising the compound according to the present invention is effective in preventing or treating heart failure. In addition, the compound is represented by chemical formula 2 or is pharmaceutically acceptable salt thereof.COPYRIGHT KIPO 2016
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Paragraph 0629-0631
(2017/02/02)
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- Compounds with cardiac myosin activating function and pharmaceutical composition containing the same for treating or preventing heart failure
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Disclosed are a compound having cardiotonic activity and a pharmaceutical composition containing the same, and the composition containing the compound, according to the present invention, is useful for preventing and treating heart failure.COPYRIGHT KIPO 2016
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Paragraph 0629-0631
(2016/10/07)
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- The ouroborand: A cavitand with a coordination-driven switching device
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(Figure Presented) Molecular switch: The ouroborand coordinates an internal side chain in its cavity, just as it were swallowing its own tail. The presence or absence of zinc(II) in solution switches the cavity between open and closed states to external guests (see scheme: deep blue sphere: Zn).
- Durola, Fabien,Rebek Jr., Julius
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supporting information; experimental part
p. 3189 - 3191
(2010/07/15)
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- AMINE COMPOUND AND PHARMACEUTICAL USE THEREOF
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Provided is a novel amine compound represented by the following formula (I) having a superior peripheral blood lymphocyte decreasing action and superior in the immunosuppressive action, rejection suppressive action and the like, which shows decreased side effects of, for example, bradycardia and the like, or a pharmaceutically acceptable acid addition salt thereof, or a hydrate thereof, or a solvate thereof. wherein each symbol is as defined in the specification.
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Page/Page column 45
(2010/04/25)
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- Synthesis and biological studies of novel 2-aminoalkylethers as potential antiarrhythmic agents for the conversion of atrial fibrillation
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A series of 2-aminoalkylethers prepared as potential antiarrhythmic agents is described. The present compounds are mixed sodium and potassium ion channel blockers and exhibit antiarrhythmic activity in a rat model of ischemia-induced arrhythmias. Structure-activity studies led to the identification of three compounds 5, 18, and 26, which were selected based on their particular in vivo electrophysiological properties, for studies in two canine atrial fibrillation (AF) models. The three compounds converted AF in both models, but only compound 26 was shown to be orally bioavailable. Resolution of the racemate 26 into its corresponding enantiomers 40 and 41 and subsequent biological testing of these enantiomers led to the selection of (1S,2S)-1-(1-naphthalenethoxy)-2-(3- ketopyrrolidinyl)cyclohexane monohydrochloride (41) as a potential atrial selective antiarrhythmic candidate for further development.
- Plouvier, Bertrand,Beatch, Gregory N.,Jung, Grace L.,Zolotoy, Alexander,Sheng, Tao,Clohs, Lilian,Barrett, Terrance D.,Fedida, David,Wang, Wei Q.,Zhu, Jeff J.,Liu, Yuzhong,Abraham, Shlomo,Lynn, Leah,Dong, Ying,Wall, Richard A.,Walker, Michael J. A.
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p. 2818 - 2841
(2008/02/09)
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- DIARYL ETHERS AS OPIOID RECEPTOR ANTAGONIST
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A compound of the formula (I) wherein the variables X1 to X10, R1 to R7 including R3', E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.
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Page/Page column 69
(2008/06/13)
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- Inhibitors of protein isoprenyl transferases
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Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (d) —C(O)NH—CH(R14)—C(O)NHSO2R16, (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, and —P(W)RR3RR3′; R4is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4—L6—C(W)—N(R5)—L5—, (e) —L4—L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7—L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) and (m) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
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- Nucleosides and nucleotides. 107. 2-(cycloalkylalkynyl)adenosines: Adenosine A2 receptor agonists with potent antihypertensive effects
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Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosine (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100 μg/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3 position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.
- Abiru,Miyashita,Watanabe,Yamaguchi,Machida,Matsuda
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p. 2253 - 2260
(2007/10/02)
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- Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-Alkyl- and 6-cycloalkylalkyl derivatives
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A series of 6-alkyl- or 6-(cycloalkylalkyl)-[1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyr imidin-9(3H)-ones 1b-o was synthesized from the corresponding 1,3,4-thiadiazol-5-amines 3b-o and the antiallergic activities of the products were evaluated. Among the compounds 6-(2-cyclohexylethyl)-[1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]p yrimidin-9(3H)-one 1h, whose X-ray crystallographic stereostructure is shown, was found to be a promising new antiallergic agent, which has low toxicity and dual activity as a leukotriene D4 receptor antagonist and as an orally active mast cell stabilizer.
- Yokohama,Miwa,Aibara,Fujiwara,Matsumoto,Nakayama,Iwamoto,Mori,Moroi,Tsukada,Isoda
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p. 2391 - 2398
(2007/10/02)
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- The Copper Halide-Catalyzed Mono-Substitution of Bromine in α,ω-Dibromoalkanes by Grignard Reagents. A Reinvestigation
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α,ω-Dibromoalkanes have been converted into mono-bromides R(CH2)nBr by reaction with the Grignard compounds RMgBr in THF in the presence of 5 mol percent of copper(I)bromide.In contrast to what is suggested in the original literature, this method has a limited scope.
- Andringa, H.,Hanekamp, J.,Brandsma, L.
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p. 2349 - 2351
(2007/10/02)
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- 7-oxabicycloheptane imidazole prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease
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7-Oxabicycloheptane imidazole prostaglandin analogs are provided which are useful in treating thrombotic and vasospastic disease and have the structural formula STR1 wherein m is 0, 1, 2, 3 or 4; n is 1, 2 or 3; and p is 1, 2 or 3; Z is --CH=CH--, --CH2 CH2 -- or STR2 wherein Y is 1 or a single bond; R is CO2 H, CO2 lower alkyl, CO2 alkali metal, CONHSO2 R2 (wherein R2 is lower alkyl or aryl) or --CH2 -5-tetrazolyl; A is CHOH, C=O, STR3 (wherein R3 is H or lower alkyl), or a single bond; R1 is lower alkyl, aryl, cycloalkyl or H, R1 can be H only when A is a single bond.
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