- Compound as potassium channel modulator
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The invention relates to a compound as a potassium channel modulator, which is a compound of a formula (I) or a pharmaceutically acceptable salt thereof. The compound or the pharmaceutically acceptable salt thereof is effective for curing and preventing diseases and symptoms influenced by the activity of potassium ion channels.
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Paragraph 0195; 0197; 0200; 0201
(2018/07/30)
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- Identification and preliminary structure–activity relationships of 1-Indanone derivatives as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors
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Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein. The preliminary SAR was further explored and the binding mode with IDO1 protein was predicted by experiment along with molecular docking. Subsequent ADME properties of these active compounds were analyzed in silico, and the results showed good pharmacokinetic efficiencies. We believe this study contributes a lot to the structural diversity for the future development of highly potent IDO1 inhibitors.
- Gao, Dingding,Li, Yingxia
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p. 3780 - 3791
(2017/06/13)
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- A general route to the synthesis of 1,5-methano- and 1,5-ethano-2, 3,4,5-tetrahydro-1h-3-benzazepines
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A general approach to preparing 1,5-methano-(1) and l,5-ethano-2,3,4,5- tetrahydro-lff-3-benzazepine (2) is discussed. This strategy involves converting an indanone or tetralone (4) to a cyanohydrin (3) which is subjected to hydrogenolysis followed by lac
- O'Donnell, Christopher J.,Singer, Robert A.,Brubaker, Jason D.,McKinley, Jason D.
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p. 5756 - 5759
(2007/10/03)
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- Synthesis of new 6-substituted purinyl-5′-nor-1′- homocarbanucleosides based on indanol
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A series of new 6-substituted purinyl-5′-nor-1′- homocarbanucleosides based on indanol were synthesized from (±)-cis-3- hydroxymethyl-1-indanol, an appropriately functionalized derivative of which was reacted with 6-chloropurine in the presence of NaH and
- Fernández, Franco,García-Mera, Xerardo,Morales, Melvin,Vilari?o, Leonardo,Caama?o, Olga,De Clercq, Eric
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p. 9245 - 9253
(2007/10/03)
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- Aminoindanes
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The present invention relates to therapeutically active novel aminoindanes of formula (I). Also provided is a method of preparing compounds of formula (I), and pharmaceutical compositions comprising the compounds. The novel compounds act as modulators of
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Page/Page column 29-31
(2010/02/05)
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- Photochemical preparation of highly functionalized 1-indanones
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A series of o-alkylphenyl alkyl ketones 1 were synthesized by different methods. The presence of a leaving group X adjacent to the carbonyl group is the special peculiarity of these ketones. Upon irradiation the keto carbonyl group of these compounds undergoes an n-π* excitation followed by a 1,5-hydrogen migration from the o-alkyl substituent to the carbonyl oxygen atom. The thus formed 1,4-diradicals are subject to a very rapid elimination of acid HX, giving 1,5-diradicals. We called this process spin center shift. After intersystem crossing these diradicals cyclize to 1-indanones 20 in good yields. Depending on the solvent and on substituents, o-alkoxyalkyl ketones 22 or benzo-[c]furanes 21 are obtained as byproducts. The mechanism of the cyclization was elucidated by quantum chemical calculations and kinetic measurements.
- Wessig, Pablo,Glombitza, Clemens,Mueller, Gunnar,Teubner, Janek
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p. 7582 - 7591
(2007/10/03)
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- Kinetic resolution of 3-hydroxymethylbenzocycloalkanols by selective asymmetric hydrogen-transfer oxidation
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Kinetic resolution of 3-hydroxymethylbenzocycloalkanols was performed by selective asymmetric hydrogen-transfer oxidation using the Ru(II)-(S,S)-TsDPEN catalyst. Thus, several 3-hydroxymethyl-1-tetralols 7a-d afforded (1R,3R)-3-hydroxymethyl-1-tetralols (
- Caro, Yolanda,Torrado, Maria,Masaguer, Christian F.,Ravina, Enrique
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p. 3689 - 3696
(2007/10/03)
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- Aryl fused azapolycyclic compounds
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Compounds of the formula and their pharmaceutically acceptable salts, wherein R1, R2, and R3are as defined herein; intermediates for the synthesis of such compounds, pharmaceutical compositions containing such compounds; a
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- A short, efficient synthesis of substituted uracil: An indane carbocyclic nucleoside
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(±)-cis-1-(3-Hydroxymethyl-1-indanyl)-1,2,3,4-tetrahy-dropyrimidine-2, 4-dione (1) was synthesised in two steps and with an overall yield of 51percent from (±)-cis-3-amino-1-indanylmethanol (4) and 3-ethoxy-2-propenoyl isocyanate (3). The isocyanate 3 was prepared in 76percent overall yield by reacting silver cyanate with 3-ethoxy-2-propenoyl chloride (2), which was obtained in one pot from ethyl vinyl ether and oxalyl chloride. The aminoalcohol (4) was prepared from phenylsuccinic anhydride in four steps.
- Ferna?ndez,Garci?a-Mera,Morales,Rodri?guez-Borges
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p. 239 - 242
(2007/10/03)
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- Conformationally constrained butyrophenones with mixed dopaminergic (D2) and serotoninergic (5-HT2(A), 5-HT2(C)) affinities: Synthesis, pharmacology, 3D-QSAR, and molecular modeling of (aminoalkyl)benzo- and - thienocycloa
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A series of novel conformationally restricted butyrophenones (2- (aminoethyl)- and 3-(aminomethyl)thieno- or benzocycloalkanones bearing (6- fluorobenzisoxazolyl)piperidine, (p-fluorobenzoyl)piperidine, (o- methoxyphenyl)piperazine, or linear butyrophenon
- Ravi?a, Enrique,Negreira, Jesús,Cid, José,Masaguer, Christian F.,Rosa, Elizabeth,Rivas, M. Emilia,Fontenla, José A.,Loza, M. Isabel,Tristán, Helena,Cadavid, M. Isabel,Sanz, Ferran,Lozoya, Estrella,Carotti, Angelo,Carrieri, Antonio
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p. 2774 - 2797
(2007/10/03)
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- Palladium-catalyzed carbonylative cyclization of 1-iodo-2-alkenylbenzenes
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The Pd-catalyzed carbonylation of ω-vinyl-substituted o-iodoalkenylbenzenes 1-4 can provide up to modest yields (50-60%) of 5- and 6-membered Type I cyclic acylpalladation products, i.e., α,β-unsaturated cyclic ketones, in the absence of an external nucleophile and high yields of 5- and 6-membered Type II cyclic acylpalladation products, i.e., α- or β-((alkoxycarbonyl)methyl)substituted cyclic ketones in the presence of an alcohol, e.g., MeOH. In cases where no such processes are available, other side reactions, such as cyclic carbopalladation, polymeric acylpalladation, and trapping of acylpalladiums via esterification and other processes may become predominant. Neither smaller, i.e., 3- or 4-membered, nor 7-membered or larger cyclic ketones appear to be accessible by the reaction. In most cases, the exo-mode cyclic acylpalladation takes place exclusively. However, the cyclic acylpalladation of 3 proceeds exclusively via endo-mode cyclization to give 5-membered ketones. Substitution of one or more hydrogens in the ω-vinyl group with carbon groups has significant effects on the reaction course. Those substrates containing a 1,2-disubstituted alkenyl group in place of a vinyl group, i.e., 19-22 and 24 excluding 25, can give monomeric cyclic acylpalladation products in high yields. These results represent a major deviation from those obtained with 1 and 2. In the absence of an external nucleophile, formation of Type I cyclic acylpalladation products is, in some cases, accompanied by Type III cyclic acylpalladation involving trapping of acylpalladiums by internal enolates. In the presence of MeOH or other alcohols, Type II acylpalladation products have been obtained in respectable yields from 19-20, 23, and 24. In the presence of an alcohol, premature esterification can be a serious side reaction. However, this problem can be alleviated using i-PrOH or t-BuOH in place of MeOH in combination with appropriate solvents, typically those of lower polarity. Heteroatom-containing substituents on the ω-vinyl groups also exert significant effects on cyclic acylpalladation. Electron-donating substituents tend to lead to high yields of cyclic acylpalladation products, while electron-withdrawing alkoxycarbonyl groups conjugated with the ω-alkenyl group tend to give lower yields of cyclic acylpalladation products. With Me3Si and alkoxycarbonyl groups products of apparent endo-mode cyclic acylpalladation, i.e., naphthols, have been obtained in significant yields (25-50%). Free OH and other nucleophilic heteroatom groups can seriously interfere with cyclic acylpalladation, and they must be appropriately protected in most cases, although there are indications that acylpalladation-lactonization tandem processes similar to Type II cyclic acylpalladation might be developed.
- Negishi, Ei-Ichi,Copéret, Christophe,Ma, Shengming,Mita, Takeshi,Sugihara, Takumichi,Tour, James M.
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p. 5904 - 5918
(2007/10/03)
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- Synthesis and biochemical evaluation of baclofen analogues locked in the baclofen solid-state conformation
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The synthesis of six close analogues of baclofen [3-(4-chlorophenyl)-4-aminobutyric acid] (BAC), a potent GABA(B) agonist, are reported. The compounds were designed starting from the structural informations contained in the solid state of BAC, regarded as
- Mann,Boulanger,Brandau,Durant,Evrard,Heaulme,Desaulles,Wermuth
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p. 1307 - 1313
(2007/10/02)
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- Conformational and steric aspects of the inhibition of phenylethanolamine N-methyltransferase by benzylamines
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Compounds of the benzylamine (BA) class are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). Restriction of the aminomethyl side chain through its incorporation into a cyclic framework as in 1,2,3,4-tetrahydroisoquinoline (
- Grunewald,Sall,Monn
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p. 433 - 444
(2007/10/02)
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- SYNTHESE DU METHOXYCARBONYL-3 INDENE ET DE METHOXYCARBONYL-4 DIHYDRO-1,2 NAPHTALENES. OBTENTION DES β-TETRALONES A PARTIR DES α-TETRALONES CORRESPONDANTES
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The synthesis of variously substituted 3-methoxycarbonylindene and 4-methoxycarbonyl-1,2-dihydronaphthalenes is described.A simple and efficient method for the transformation of 1-tetralone into 2-tetralone is reported.
- Vebrel, Joel,Carrie, Robert
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p. 161 - 166
(2007/10/02)
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