- An improved process for the synthesis of 5-bromo-3-(1-methylpiperidin-4-yl) -1 H-indole: A key intermediate in the synthesis of naratriptan hydrochloride
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An improved process has been developed for the synthesis of 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole, a key intermediate of naratriptan hydrochloride, which is used as a drug for migraine. A novel one-pot synthetic procedure using triethyl silane was developed for scale-up.
- Shashikumar, Nellisara D.,Krishnamurthy, Ganga Naika,Rao K, Sundara Raj,Shridhara, Kanakamajalu,Naik, Halehatti S. Bhojya,Nagarajan, Kuppuswamy
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- Discovery and characterization of novel indole and 7-azaindole derivatives as inhibitors of β-amyloid-42 aggregation for the treatment of Alzheimer's disease
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The aggregation of amyloid-β peptides into cytotoxic oligomeric and fibrillary aggregates is believed to be one of the major pathological events in Alzheimer disease. Here we report the design and synthesis of a novel series of indole and 7-azaindole derivatives containing, nitrile, piperidine and N-methyl-piperidine substituents at the 3-position to prevent the pathological self-assembly of amyloid-β. We have further demonstrated that substitution of the azaindole and indole derivatives at the 3 positions is required to obtain compounds with improved physicochemical properties to allow brain penetration.
- Sreenivasachary, Nampally,Kroth, Heiko,Benderitter, Pascal,Hamel, Anne,Varisco, Yvan,Hickman, David T.,Froestl, Wolfgang,Pfeifer, Andrea,Muhs, Andreas
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supporting information
p. 1405 - 1411
(2017/03/08)
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- Novel Compounds for the Treatment of Diseases Associated with Amyloid or Amyloid-Like Proteins
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The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.
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Page/Page column 45
(2011/11/30)
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- COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5HT6 receptor which are of the formula (I), wherein R1-R3 A, B, D, E, G, Q, and x are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 84
(2010/11/28)
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- PIPERIDINE-INDOLE COMPOUNDS HAVING 5-HT6 AFFINITY
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Described herein are indole compounds with affinity for the 5-HT6 receptor, which have general formula (I) wherein, R is selected from the group consisting of H and C1-4alkyl; R is selected from the group consisting of H, C1-4alkyl and benzyl; -----
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Page/Page column 13
(2010/11/28)
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- Conformationally restricted homotryptamines 3. Indole tetrahydropyridines and cyclohexenylamines as selective serotonin reuptake inhibitors
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A series of indole tetrahydropyridine and indole cyclohexenylamines was prepared, and their binding affinities at the human serotonin transporter (SERT) were determined. In particular, a nitrile substituent at the C5 position of the indole ring gave poten
- Deskus, Jeffrey A.,Epperson, James R.,Sloan, Charles P.,Cipollina, Joseph A.,Dextraze, Pierre,Qian-Cutrone, Jingfang,Gao, Qi,Ma, Baoqing,Beno, Brett R.,Mattson, Gail K.,Molski, Thaddeus F.,Krause, Rudolph G.,Taber, Matthew T.,Lodge, Nicholas J.,Mattson, Ronald J.
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p. 3099 - 3104
(2008/02/13)
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- 5-CYCLO INDOLE COMPOUNDS AS 5-HT1D RECEPTOR LIGANDS
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Described herein are compounds selective for a 5-HT1D-like receptor, which have general formula (I), wherein A is selected from a six-membered, non-aromatic, optionally substituted carbocycle and a six-membered, non-aromatic, optionally substituted heterocycle having one or two heteroatoms selected from O, S, SO, SO2 and NR; R is selected from H and OH; n is 0 or 1 as permitted by chemical structure; R is selected from CRRCH2NRR or a group of formula (II), (III) or (IV); R is selected from H and benzoyl; R is selected from H, loweralkyl, benzyl, loweralkylcarbonyl, loweralkylaminocarbonyl; loweralkylaminothiocarbonyl, loweralkanoyl, loweralkylaminoimide and loweralkoxy-substituted loweralkylene; R and R are independently selected from H, loweralkoxy and hydroxy; R and R are independently selected from H and loweralkyl or R and R form an alkylene bridge which, together with the nitrogen atom to which they are attached, creates an optionally substituted 3- to 6-membered ring; ----- denotes a single or double bond; and R, R and R are independently selected from H and loweralkyl. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of a 5-HT1D-like receptor is implicated, such as migraine.
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Page/Page column 20
(2008/06/13)
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- 5-HT1F agonists
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The present invention relates to a compound of formula (I): or a pharmaceutical acid addition salt thereof; which is useful for activating 5-HT1freceptors and inhibiting protein extravasation in a mammal.
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- Indazole derivatives as 5-HT1F agonists
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The present invention relates to a compound of formula or a pharmaceutical acid addition salt thereof; which are useful for activating 5-HT1F receptors and inhibiting neuronal protein extravasation in a mammal.
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- Piperidine-indole compounds having 5-HT6 affinity
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Described herein are compounds with affinity for the 5-HT6 receptor, which have the general formula: wherein: R1 is selected from the group consisting of H and C1-4alkyl; R2 is selected from the group consisting of H, C1-4alkyl and benzyl; - - - represents a single or double bond; R3 is selected from the group consisting of COR5 and SO2R5; R4a is selected from the group consisting of H, OH, halo, C1-4alkyl and C1-4alkoxy; R4b is selected from the group consisting of H, hydroxy, halo, C3-7cycloalkyloxy, C1-4alkoxy, C1-4alkyl, benzyloxy, phenoxy, trifluoromethyl, trifluoromethoxy and vinyl; R4c is selected from the group consisting of H, OH, halo, C1-4alkyl and C1-4alkoxy; R4d is selected from the group consisting of H, OH, halo, C1-4alkyl and C1-4alkoxy; and R5 is selected from the group consisting of phenyl, pyridyl, thienyl, quinolinyl and naphthyl which are optionally substituted with 1-4 substituents selected from C1-4alkoxy, C1-4alkyl, halo, nitro, trifluoromethyl, trifluoromethoxy, 1,2-methylenedioxy, C1-4alkylcarbonyl, C1-4alkoxycarbonyl and C1-4alkylS-. Also described is the use of these compounds as pharmaceuticals to treat indications where inhibition of the 5-HT6 receptor is implicated, such as schizophrenia.
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- Conformationally constrained 5-(thienyl)tryptamine derivatives as serotonin 5-HT(1B/1D) receptor agonists: Potential treatments for migraine
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In the search for human 5-HT(1D) selective agonists, a series of conformationally constrained 5-(2- or 3-thienyl)tryptamine derivatives 7, 10, and 12 have been synthesized. In vitro binding experiments at the cloned human 5-HT(1D) and 5-HT(1B) receptors h
- Slassi, Abdelmalik,Meng, Charles Q.,Dyne, Kerry,Wang, Xin,Lee, David K. H.,Kamboj, Rajender,McCallum, Kirk L.,Mazzocco, Lucy,Rakhit, Suman
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p. 668 - 674
(2007/10/03)
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- 5-CYCLO INDOLE COMPOUNDS
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Described herein are compounds selective for a 5-HT 1D-like receptor, which have the general formula: STR1 wherein A is selected from a six-membered, non-aromatic, optionally substituted carbocycle and a six-membered, non-aromatic, optionally substituted heterocycle having one or two heteroatoms selected from O, S, SO, SO 2 and N 4 ; R 1 is selected from H and OH;n is 0 or 1 as permited by chemical structure;R 2 is selected from CR 5 CR 6 CH. sub.2 NR 7 R 8 or a group of formula II, III or IV: STR2 R. sup.3 is selected from H and benzoyl; R 4 is selected from H, loweralkyl, benzyl, loweralkylcarbonyl, loweralkylaminocarbonyl, loweralkylaminothiocarbonyl, loweralkanoyl, loweralkylaminoimide and loweralkoxy-substituted loweralkylene; R 5 and R. sup.6 are independently selected from H, loweralkoxy and hydroxy;R 7 and R. sup.8 are independently selected from H and loweralkyl or R 7 and R. sup.8 form an alkylene bridge which, together with the nitrogen atom to which they are attached, creates an optionally substituted 3-to 6-membered ring; denotes a single or double bond; andR. sup.9, R. sup.10 and R. sup.11 are independently selected from H and loweralkyl. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of a 5-HT 1D-like receptor is implicated, such as migraine.
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- Use of a serotonin 5-HTlf agonist in the manufacture of a medicament for treating or ameliorating the symptoms of common cold or allergic rhinitis
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This invention provides methods for the treatment or amelioration of the symptoms of the common cold or allergic rhinitis which comprises administering to a mammal in need thereof a serotonin 5-HT1F agonist.
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- 5-SUBSTITUTED-3-(1,2,3,6-TETRAHYDROPYRIDIN-4-YL)-AND 3-(PIPERIDIN-4-YL)-1H-INDOLES: NEW 5-HT1F AGONISTS
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This invention provides novel 5-HT 1F agonists of Formula I STR1 where A--B, R, R 1 and X are as defined in the specification, which are useful for the treatment of migraine and associated disorders.
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- Use of serotonin 5-HT1F agonists for the prevention of migraine
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This invention provides methods for the prevention of migraine which comprises administering to a mammal in need thereof a serotonin 5-HT1F agonist.
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- 1H-indole and benzo(b)thiophene derivatives with 4-(1,2,3,6-tetra:hydro:pyridinyl)- and 4-piperidinyl-groups bound to the heterocyclic ring as inhibitors of serotonin reuptake
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The pharmaceutical use of novel compounds of formula I: where Z is a structure of formula A-B is -C=CH- or -C(R5)-CH2-; X is S or NR4; R1is H, halo, formyl, C1-C4alkyl, C1-C4alkoxy, thienylmethyloxy, 4,5-dihydrothiazol-2-yl, cyano, nitro, carboxamido, trifluoromethyl or hydroxy; R2is H or halo; R3is H, C1-C4alkyl, (C1-C4alkylene)-aryl, or -CH2-Y-NR7R8; R4is H, C1-C4alkyl, C1-C5acyl, or phenylsulfonyl; R5is H or OH; R6is H or methyl; Y is -CH2- or -C(O)-; R7is pyridinyl; and R8is H or -C(O)-(C3-C6cycloalkyl); and pharmaceutically acceptable salts thereof.
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