- Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide
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Eletriptan hydrobromide (1) is a selective serotonin (5-HT1) agonist, used for the acute treatment of the headache phase of migraine attacks. During the manufacture of eletriptan hydrobromide the formation of various impurities were observed and identified by LC-MS. To control the formation of these impurities during the preparation of active pharmaceutical ingredients, the structure of the impurities must be known. Major impurities of the eletriptan hydrobromide synthesis were prepared and characterized by using various spectroscopic techniques, i.e., mass spectroscopy, FTIR , 1H NMR, 13C NMR/DEPT, and further confirmed by co-injection in HPLC. The present study will be of great help in the synthesis of highly pure eletriptan hydrobromide related compounds.
- Madasu, Suri Babu,Vekariya, Nagaji Ambabhai,Hari Kiran,Gupta, Badarinadh,Islam, Aminul,Douglas, Paul S.,Babu, Korupolu Raghu
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supporting information
p. 1400 - 1405
(2012/11/07)
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- Process for preparing 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole
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The invention encompasses a process for preparing 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole comprising reacting (R)-2-(5-bromo-1H-indole-3-carbonyl)-pyrrolidine-1-carboxylic acid benzyl ester with a reducing agent selected from the group consisting of sodium dihydro-bis(2-methoxyethoxy)aluminate, lithium tris[(3-ethyl-3-pentyl)oxy]aluminohydride, lithium tri-tert-butoxyaluminum hydride and diisobutylaluminium hydride. 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole is a key intermediate for preparing eletriptan and its salts thereof.
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Page/Page column 5
(2009/01/24)
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- Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists
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Several series of conformationally constrained N1- arylsulfonyltryptamine derivatives were prepared and tested for 5-HT6 receptor binding affinity and ability to modulate cAMP production in a cyclase assay. The 3-piperidin-3-yl-, 3-(1-methylpyrrolidin-2-ylmethyl)-, and 3-pyrrolidin-3-yl-1H-indole arrays (8-13) appear to be able to adopt a conformation that allows high affinity 5-HT6 receptor binding, while the β-carboline array 14 binds with a significantly weaker (10- to 100-fold) affinity. N1-Benzenesulfonyl-3-piperidin-3-yl-1H-indole 9a is a high affinity full agonist with EC50 = 24 nM. Several of the N1-arylsulfonyl-3-(1-methylpyrrolidin-2-ylmethyl)-1H-indole derivatives behave as very potent antagonists ((S)-11r, (S)-11t; IC50 = 0.8, 1.0 nM).
- Cole, Derek C.,Lennox, William J.,Stock, Joseph R.,Ellingboe, John W.,Mazandarani, Hossein,Smith, Deborah L.,Zhang, Guoming,Tawa, Gregory J.,Schechter, Lee E.
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p. 4780 - 4785
(2007/10/03)
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- Interaction of chiral MS-245 analogs at h5-HT6 receptors
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Optically active pyrrolidinylmethylindole analogs related in structure to the benzenesulfonyltryptamine 5-HT6 receptor antagonist MS-245 were evaluated and their R-isomers were found to bind with affinity higher than their S-enantiomers.
- Abate, Carmen,Kolanos, Renata,Dukat, Malgorzata,Setola, Vince,Roth, Bryan L.,Glennon, Richard A.
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p. 3510 - 3513
(2007/10/03)
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- Pyrrolidine-indole compounds having 5-HT6 affinity
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Described herein are compounds with affinity for the 5-HT 6 receptor, which have the general formula: STR1 wherein: R 1 is selected from the group consisting of H and C 1-4 alkyl;R 2 is selected from the group consisting of H, C 1-4 alkyl and benzyl;R 3 is selected from the group consisting of COR 5, SO 2 R 5, CONHC 1-4 alkyl and C(S)SR 6 ;R 4a is selected from the group consisting of H, OH, halo, C 1-4 alkyl and C 1-4 alkoxy;R 4b is selected from the group consisting of H, hydroxy, halo, C 3-7 cycloalkyloxy, C 1-4 alkoxy, C 1-4 alkyl, benzyloxy, phenoxy, trifluoromethyl, trifluoromethoxy and vinyl;R 4c is selected from the group consisting of H, OH, halo, C 1-4 alkyl and C 1-4 alkoxy;R 4d is selected from the group consisting of H, OH, halo, C 1-4 alkyl and C 1-4 alkoxy;R 5 is selected from the group consisting of phenyl, pyridyl, thienyl, quinolinyl and naphthyl which are optionally substituted with 1-4 substituents selected from C 1-4 alkoxy, C 1-4 alkyl, halo, nitro, trifluoromethyl, trifluoromethoxy, 1,2-methylenedioxy, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl and C 1-4 alkylS--; andR 6 is selected from C 1-4 alkyl, allyl, propargyl and optionally substituted benzyl wherein the benzyl group is optionally substituted with 1-4 substituents selected from cyano, C 1-4 alkyl and halo.Also described is the use of these compounds as pharmaceuticals to treat indications where inhibition of the 5-HT 6 receptor is implicated, such as schizophrenia.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein the substituents are as defined in the description and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of a dihalogenated intermediate.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein n is 0, 1, or 2; X is hydrogen, chlorine, bromine or iodine; R 1 is hydrogen; R 3 is selected from hydrogen and C 1 to C 6 linear or branched alkyl; and R 2 is as defined in the specification and the pharmaceutically acceptable salts thereof are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of a dihalogenated intermediate is also disclosed.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein R 1, R 2, R. sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein R 1, R 2, R. sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.
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- INDOLE DERIVATIVES
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Compounds of the formula STR1 wherein R 1, R 2, R. sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT 1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.
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