- Phosphorescence at Low Temperature by External Heavy-Atom Effect in Zinc(II) Clusters
-
Luminescent ZnII clusters [Zn4L4(μ3-OMe)2X2] (X=SCN (1), Cl (2), Br (3)) and [Zn7L6(μ3-OMe)2(μ3-OH)4]Y2 (Y=I? (4), ClO4? (5)), HL=methyl-3-methoxysalicylate, exhibiting blue fluorescence at room temperature (λmax=416≈429 nm, Φem=0.09–0.36) have been synthesised and investigated in detail. In one case the external heavy-atom effect (EHE) arising the presence of iodide counter anions yielded phosphorescence with a long emission lifetime (λmax=520 nm, τ=95.3 ms) at 77 K. Single-crystal X-ray structural analysis and time-dependent density-functional theory (TD-DFT) calculations revealed that their emission origin was attributed to the fluorescence from the singlet ligand-centred (1LC) excited state, and the phosphorescence observed in 4 was caused by the EHE of counter anions having strong CH?I interactions.
- Kobayashi, Fumiya,Ohtani, Ryo,Teraoka, Saki,Yoshida, Masaki,Kato, Masako,Zhang, Yingjie,Lindoy, Leonard F.,Hayami, Shinya,Nakamura, Masaaki
-
-
Read Online
- Evaluation of novel N′-(3-hydroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide derivatives as potential HIV-1 integrase inhibitors
-
In an attempt to identify potential new agents that are active against HIV-1 IN, a series of novel coumarin-3-carbohydrazide derivatives were designed and synthesised. The toxicity profiles of these compounds showed that they were non-toxic to human cells and they exhibited promising anti-HIV-1 IN activities with IC50 values in nM range. Also, an accompanying molecular modeling study showed that the compounds bind to the active pocket of the enzyme.
- Jesumoroti, Omobolanle J.,Faridoon,Mnkandhla, Dumisani,Isaacs, Michelle,Hoppe, Heinrich C.,Klein, Rosalyn
-
-
- Choleretic drug alibendol preparation method
-
The invention belongs to the field of drug synthesis, and provides an alibendol preparation method, which comprises: selecting 2-hydroxy-3-methoxybenzaldehyde as a raw material, selecting an efficientoxidative esterification catalyst, carrying out one-step oxidative esterification to obtain methyl 2-hydroxy-3-methoxybenzoate, carrying out a reaction on the methyl 2-hydroxy-3-methoxybenzoate and allyl bromide under the action of an alkali to generate methyl 2-allyloxy-3-methoxybenzoate, carrying out a para Claisen rearrangement reaction on the methyl 2-allyloxy-3-methoxybenzoate at a high temperature to obtain methyl 2-hydroxy-3-methoxy-5-allylbenzoate, and carrying out an aminolysis reaction in ethanolamine to generate alibendol. Compared with the traditional synthetic process, the new process of the present invention has characteristics of simple synthesis steps, convenient post-treatment and good product quality, and is suitable for industrial production.
- -
-
Paragraph 0017; 0020
(2019/06/30)
-
- Pharmaceutical composition for use in preventing or treating poly(ADP-ribose)polymerase-1 related diseases containing the same as an active ingredient
-
The present invention relates to a novel compound, a method for manufacturing the same, and a pharmaceutical composition for preventing or treating poly(ADP-ribose)polymerase-1 (PARP-1) related diseases containing the compound as an active ingredient. The novel PARP-1 inhibitory compound according to the present invention exhibits an excellent PARP-1 inhibitory effect at a concentration of nanomol unit and further exhibits an excellent cytoprotective effect (cell death inhibitory effect) on ophthalmic diseases or disorders, especially on retinal diseases. The composition containing the compound as an active ingredient is useful as a composition for preventing or treating PARP-1 related diseases, for example, ophthalmic diseases or disorders.(AA) Example 37(BB) Example 39COPYRIGHT KIPO 2018
- -
-
Paragraph 0441; 0453-0455
(2018/06/29)
-
- Chromatography-free, Mitsunobu-triggered heterocyclizations of salicylhydroxamic acids to 3-hydroxybenzisoxazoles
-
The Mitsunobu reaction has become one of the most powerful tools to alkylate acidic pronucleophiles. A significant caveat of Mitsunobu chemistry, however, is that the reaction mixture is often plagued with purification problems owing to the phosphine oxide and hydrazine dicarboxylate by-products. In addition to the development of more readily separable Mitsunobu reagents, the product's physicochemical properties may be exploited to facilitate purification. In this regard, we present a swift and efficient preparation of 3-hydroxybenzisoxazoles by the Mitsunobu-triggered heterocyclizations of salicylhydroxamic acids, which can be isolated by an acid–base work-up. As expected, a range of functional groups was compatible with the chemistry.
- Van Eker, Daniel,Chauhan, Jay,Murphy, William A.,Conlon, Ivie L.,Fletcher, Steven
-
p. 5301 - 5303
(2016/11/16)
-
- Computational and Experimental Studies of Phthaloyl Peroxide-Mediated Hydroxylation of Arenes Yield a More Reactive Derivative, 4,5-Dichlorophthaloyl Peroxide
-
The oxidation of arenes by the reagent phthaloyl peroxide provides a new method for the synthesis of phenols. A new, more reactive arene oxidizing reagent, 4,5-dichlorophthaloyl peroxide, computationally predicted and experimentally determined to possess enhanced reactivity, has expanded the scope of the reaction while maintaining a high level of tolerance for diverse functional groups. The reaction proceeds through a novel "reverse-rebound" mechanism with diradical intermediates. Mechanistic insight was achieved through isolation and characterization of minor byproducts, determination of linear free energy correlations, and computational analysis of substituent effects of arenes, each of which provided additional support for the reaction proceeding through the diradical pathway.
- Camelio, Andrew M.,Liang, Yong,Eliasen, Anders M.,Johnson, Trevor C.,Yuan, Changxia,Schuppe, Alex W.,Houk,Siegel, Dionicio
-
p. 8084 - 8095
(2015/09/01)
-
- CYCLIC PEROXIDE OXIDATION OF AROMATIC COMPOUND PRODUCTION AND USE THEREOF
-
The present invention provides a method for converting an aromatic hydrocarbon to a phenol by providing an aromatic hydrocarbon comprising one or more aromatic C-H bonds and one or more activated C-H bonds in a solvent; adding a phthaloyl peroxide to the solvent; converting the phthaloyl peroxide to a di-radical; contacting the di-radical with the one or more aromatic C-H bonds; oxidizing selectively one of the one or more aromatic C-H bonds in preference to the one or more activated C-H bonds; adding a hydroxyl group to the one of the one or more aromatic C-H bonds to form one or more phenols; and purifying the one or more phenols.
- -
-
Page/Page column 10
(2014/10/15)
-
- Expeditious synthesis of benzopyrans via lewis acid-catalyzed C-H functionalization: Remarkable enhancement of reactivity by an ortho substituent
-
An expeditious construction of a benzopyran skeleton via Lewis acid-catalyzed C-H functionalization was achieved. In this process, a [1,5] hydride shift and 6-endo cyclization successively occurred to give benzopyrans. The presence of substituents ortho to the alkoxy group significantly enhanced the reactivity, affording the desired compounds in excellent chemical yields with short reaction times.
- Mori, Keiji,Kawasaki, Taro,Sueoka, Shosaku,Akiyama, Takahiko
-
supporting information; experimental part
p. 1732 - 1735
(2010/09/05)
-
- Synthesis and structure activity relationship studies of benzothieno[3,2-b]furan derivatives as a novel class of IKKβ inhibitors
-
As a novel class of IKKβ inhibitors, a series of tricyclic furan derivatives was designed and synthesized based on the structure of known thiophene IKKβ inhibitors. Among the various fused furan derivatives synthesized, a benzothieno[3,2-b]furan derivative 13a displayed potent inhibitory activity towards IKKβ in enzymatic and cellular assays. The potent inhibitory activity originates from an intramolecular non-bonded S...O interaction which was confirmed by the X-ray structure of JNK3 with 16k. The introduction of further substituents on the core structure led to the discovery of the 6-alkoxy derivatives, which possessed a comparable IKKβ inhibitory activity to 13a and an improved metabolic stability. Among these, appropriately lipophilic compounds 16a, h, i, and 13g (logD>2) were found to possess good oral bioavailability.
- Sugiyama, Hideyuki,Yoshida, Masato,Mori, Kouji,Kawamoto, Tomohiro,Sogabe, Satoshi,Takagi, Terufumi,Oki, Hideyuki,Tanaka, Toshimasa,Kimura, Hiroyuki,Ikeura, Yoshinori
-
p. 613 - 624
(2008/02/13)
-
- Efficient synthesis of salicylates by catalytic [3 + 3] cyclizations of 1,3-bis(silyl enol ethers) with 1,1,3,3-tetramethoxypropane
-
(Chemical Equation Presented) Salicylic acid derivatives were prepared by Me3SiOTf-catalyzed [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 1,1,3,3-tetramethoxypropane.
- Sher, Muhammad,Tam Dang,Ahmed, Zafar,Rashid, Muhammad A.,Fischer, Christine,Langer, Peter
-
p. 6284 - 6286
(2008/02/10)
-
- Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum
-
A parallel synthetic strategy to the 9-aminoacridine scaffold of the classical anti-malarial drug quinacrine (2) is presented. The method features a new route to 9-chloroacridines that utilizes triflates of salicylic acid derivatives, which are commercially available in a variety of substitution patterns. The route allows ready variation of the two diversity elements present in this class of molecules: the tricyclic aromatic heterocyclic core, and the disubstituted diamine sidechain. In this study, a library of 175 compounds was designed, although only 93 of the final products had purities acceptable for screening. Impurity was generally due to incomplete removal of 9-acridones (18), a degradation product of the 9-chloroacridine synthetic intermediates. The library was screened against two strains of Plasmodium falciparum, including a model of the drug-resistant parasite, and six novel compounds were found to have IC50 values in the low nanomolar range.
- Anderson, Marc O.,Sherrill, John,Madrid, Peter B.,Liou, Ally P.,Weisman, Jennifer L.,DeRisi, Joseph L.,Guy, R. Kiplin
-
p. 334 - 343
(2007/10/03)
-
- Facile and regioselective dealkylation of alkyl aryl ethers using niobium(V) pentachloride
-
A simple and facile method for the cleavage of carbon-oxygen bonds promoted by niobium pentachloride(V) is described. Excellent yields and regioselectivities were observed with various alkyl aryl ethers to give the phenols. NMR studies revealed the formation of monoaryloxy niobium salt(V), and a neighboring-group effect may play a significant role in the regioselectivity. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Sudo, Yukinori,Arai, Shigeru,Nishida, Atsushi
-
p. 752 - 758
(2007/10/03)
-
- Aminoalkoxybenzoyl-benzofuran or benzothiophene derivatives, method for preparing same and compositions containing same
-
The invention relates to benzofuran or benzothiophene derivatives of general formula: 1These compounds are of use as medicinal products, in particular in the treatment of pathological syndromes of the cardiovascular system.
- -
-
Page/Page column 29
(2010/02/05)
-
- A simple and regioselective carbon-oxygen bond cleavage using Niobium(V)
-
A simple and convenient method for the differentiation of alkoxy groups on aromatic rings is described. Niobium(V) is found to possess a strong Lewis acid property to transform alkyl arylethers smoothly to the corresponding phenols in high yields. The excellent regioselectivity was also observed in dialkoxy benzene derivatives under mild conditions.
- Arai, Shigeru,Sudo, Yukinori,Nishida, Atsushi
-
p. 1104 - 1106
(2007/10/03)
-
- Synthetic studies of the phosphatidylinositol 3-kinase inhibitor LY294002 and related analogues
-
Synthetic methodologies have been developed for the direct and high-yielding preparation of the phosphatidyl-inositol 3-kinase inhibitor LY294002. These methods are readily amenable to the efficient generation of analogues, which will facilitate a detailed investigation of this important family of enzymes.
- Abbott, Belinda,Thompson, Philip
-
p. 1099 - 1106
(2007/10/03)
-
- Aminoalkoxybenzoyl-benzofuran or benzothiophene derivatives, method of preparing same and compositions containing same
-
Benzothiophenes and related compounds of formula (1), wherein A, B, Z are independently —CH═, —CR4═ or ═N—; X is —S—, —O—, —NH—, —NR2, —CH2—CH2—, CH2—CH2—CH2—, —CH2—O—; —OCH2—, —CH2—S—, —CO—, —SCH2—. —N═CR2— or —R2C═N—; Y is optionally substituted phenyl, alkyl, cycloalkyl, cycloalkenyl, heterocycle or bicyclic ring system; D is —CO—, CR2R3—, —CONH—, —NHCO—, —CR2(OH)—, —CONR2, NOR1 CH—NO2 N—CN —NR2—CO—, —C—, —C—, —C—; E is a single bond, optionally substituted phenyl, heterocycle; Z1 is —(CH2)p W(CH2)q—, —O(CH2)p CR5R6— or —O(CH2)p W(CH2)q; G is —NR7R8, (a), (b), (c), a 5- or 6-membered saturated, unsaturated or partially unsaturated and optionally substituted heterocycle or a bicyclic amine containing 5 to 12 carbon atoms either bridged or fused and optionally substituted and R is halogen, —NR2R3, —NHCOR2, —NHSO2R2, —CR2R3OH, —CONR2R3, —SO2NR2R3, OH, —OR1, —O—COR1; are estrogen agonists which are useful for treating syndromes and diseases caused by estrogen deficiency.
- -
-
-
- Endothelin receptor antagonists: Synthesis and structure-activity relationships of substituted benzothiazine-1,1-dioxides
-
The development of benzothiazine-1,1-dioxide derivatives as a new structural class of potent endothelin receptor antagonists is described. Structure-activity relationships (SAR) revealed that PD164800 (1) is a potent antagonist of the ET(A) receptor subtype. Copyright (C) 1998 Elsevier Science Ltd.
- Berryman,Edmunds,Bunker,Haleen,Bryant,Welch,Doherty
-
p. 1447 - 1456
(2007/10/03)
-
- Synthesis and 5-HT-3 receptor binding activity of 5-[125I]iodo-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl]benzamide and its 5-halogen-2-alkoxyl homologues
-
(S)-5-Iodo-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide (MIZAC) was prepared from 5-iodo-2,3-dimethoxybenzoyl chloride and (S)-3-aminoquinuclidine. [125I]Iodode-stannylation of its corresponding 5-tri-n-butyltin derivative gave [125I]-MIZAC at 1800 Ci/mmol. Binding of [125I]-MIZAC in rat entorhinal cortex revealed a K(D) of 1.37 ± 0.21 nM. A series of racemic 2-O-alkyl derivatives of MIZAC were prepared and 5-HT-3 receptor affinities were determined by inhibition of [125I]-MIZAC binding. Optimal affinity for the receptor was obtained with small, electron-withdrawing substituents in the aromatic 5-position and with bulky substituents in the 3-position. [125I]-MIZAC is a selective radioligand useful for in vitro identification of the 5-HT-3 receptor.
- De Paulis,Hewlett,Schmidt,Mason,Trivedi,Ebert
-
p. 385 - 396
(2007/10/03)
-
- A practical preparation of 7-methoxy-3(2H)-benzofuranone
-
A practical new synthesis suitable for large-scale production of 7-methoxy-3(2H)-benzofuranone by conversion of commercially available 2-hydroxy-3-methoxybenzoic acid to 7-methoxy-3-acetoxybenzofuran followed by hydrolysis is described.
- Bryant III,Huhn
-
p. 915 - 920
(2007/10/02)
-
- Metabolic pathways of 4-[(3-methoxyphenyl)methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6-disila cyclohexane (MPSC) hydrochloride, a silicon-containing xenobiotic, in rat, dog, and man
-
The metabolic pathways of Sandoz compound 58-112, 4-[(3-methoxyphenyl)methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6-disila cyclohexane (MPSC) hydrochloride were evaluated in rat, dog, and man after a single oral dose. In rat, dog and man the major route of elimination was renal. In the dog, renal excretion of unchanged MPSC represented a substantial portion of the dose whereas in rat and man MPSC was completely metabolized prior to excretion. In rat and man, the major end-product metabolite was 3'-[{(hydroxydimethylsilyl)methylamino}methyl]-phenol glucuronide; 4-[(3-hydroxyphenyl)-methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6-disil acyclohexane and 4-[(4-hydroxy-3-methoxyphenyl)methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza- 2,6-disilacyclohexane and their conjugates were also present. In dog, the major end-product metabolites were the hippurate of 3-methoxybenzoic acid and 3-hydroxybenzoic acid.
- Dain,Nicoletti
-
p. 951 - 961
(2007/10/03)
-
- Synthesis and in vitro evaluation of 2,3-dimethoxy-5-(fluoroalkyl)-substituted benzamides: High-affinity ligands for CNS dopamine D2 receptors
-
A number of 2,3-dimethoxy-5-(fluoroalkyl)-N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamides (with or without a 6-hydroxy group) were synthesized and evaluated as dopamine D2 receptor ligands. The parent acids were synthesized via the Claisen rearrangement of the appropriate O-allyl ethers, which were derived from o-vanillic acid or 2,3-dimethoxysalicylic acid. A decrease in reactivity was found to be characteristic of pentasubstituted benzoates, and difficulties were encountered with the introduction of fluorine onto the ethyl side chains. The (fluoroethyl)- and (fluoropropyl)salicylamides were 5 times more potent than the corresponding benzamides in inhibiting [3H]spiperone binding to the D2 receptor. These (fluoroalkyl)salicylamides are of potential value for in vivo positron emission tomography (PET) studies upon the basis of their relatively selective, high potency binding affinity for the D2 receptor.
- Bishop,Mathis,Gerdes,Whitney,Eaton,Mailman
-
p. 1612 - 1624
(2007/10/02)
-
- Benzofuro[3,2-c]pyrazol-3-amine derivatives
-
Herein is disclosed benzofuro[3,2-c]pyrazol-3-amine derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions. The derivatives are useful for producing analgesia in a mammal. In addition, some of the derivatives are useful for inhibiting gastric acid secretion, convulsions, anxiety and aggression, and producing muscle relaxation, hypnosis and sedation in a mammal.
- -
-
-