5HT6 receptor antagonists: A patent update. Part 1. Sulfonyl derivatives

Expert Opinion on Therapeutic Patents

Volumn 22, Issue 8, 2012, Pages 917-964

  Ivachtchenko, Alexandre V ^a,b   Ivanenkov, Yan A ^a,b  

^a CHEMDIV INC   (United States)

^b Chemical Diversity Research Institute   (Russian Federation)

Author keywords

5HT6R; Alzheimer's disease; Antagonists; Depression; Huntington's disease; Ligands; Obesity; Schizophrenia; Serotonin receptors

Indexed keywords

1 (ARYLSULFONYL) 4 (PIPERAZIN 1 YL)1H BENZIMIDAZOLE DERIVATIVE; 2 METHYL N (3 FLUOROPHENYL) 2,3,4,5 TATRAHYDRO 1H PYRIDO[4,3 B]INDOLE 8 SULFON AMIDE; 3 (NAPHTHALEN 1 YLSULFONYL) 5 (PIPERAZIN 1 YL) 1H INDAZOL; 3 (NAPHTHALEN 1 YLSULFONYL) 5 (PIPERAZIN 1 YL) 1H INDAZOL DERIVATIVE; 3 (PHENYLSULFONYL)THIENO[2,3 E][1,2,3]TRIAZOLO[1,5 A]PYRIMIDINE DERIVATIVE; 3 [(3 CHLOROPHENYL)SULFONYL] N (TETRAHYDROFURAN 2 YLMETHYL)THIENO[2,3 E][1,2,3]TRIAZOLO[1,5 A]PYRIMIDIN 5 AMINE DERIVATIVE; 3 PHENYLSULFONYL PYRAZOLO[1,5 A]PYRIMIDINE DERIVATIVE; 5 CHLORO N [4 METHOXY 3 (1 PIPERAZINYL)PHENYL] 3 METHYL 2 BENZOTHIOPHENESULFONAMIDE; 5 FHLORONAPHTHALENE 2 SULFONIC ACID [3 (2 DIMETHYLAMINO ETHYL)1H INDOL 5 YL]AMIDE; 5 METHOXYTRYPTAMINE; 5,7 DIMETHYL 3 PHENYLSULFONYL PYRAZOLO[1,5 A]PYRIMIDIN 2 YL METHYL AMINE; AVN 101; DIMEBON; IMIDAZO[2,1 B]THIAZOLE 5 SULFONAMIDE DERIVATIVE; MEBHYDROLIN; MEBHYDROLIN NAPADISILATE; METHYL [7 METHYL 3 PHENYLSULFONYL 6,7,8,9 TETRAHYDRO PYRAZOLO(1,5 A)]PYRIDO[(4,3 E)PYRIMIDIN 2 YL] AMINE; N ARYLSULFONYL INDOLE DERIVATIVE; N PHENYL 2,3 DIHYDROIMIDAZO[2,1 B]THIAZOLE 5 SULFONAMIDE DERIVATIVE; OLANZAPINE; PYRROLO[3,2 B]PYRIDINE DERIVATIVE; PYRROLO[3,2 B]PYRIDINE PIPERAZINE DERIVATIVE; SEROTONIN 6 ANTAGONIST; SEROTONIN 6 RECEPTOR; SEROTONIN 7 RECEPTOR; SULFONAMIDE; SULFONYL PYRAZOLE CARBOXIMIDAMIDE; TRYPTAMINE SULFONAMIDE DERIVATIVE; UNCLASSIFIED DRUG; CENTRAL NERVOUS SYSTEM AGENTS; LIGAND; SEROTONIN ANTAGONIST; SEROTONIN RECEPTOR; SULFONE;

ANXIETY; BINDING AFFINITY; BINDING ASSAY; BRAIN DISEASE; DEMENTIA; DEPRESSION; DRUG EFFECT; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; IC 50; NONHUMAN; OBESITY; PATENT; REVIEW; SCHIZOPHRENIA; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG LEGISLATION; METABOLISM; PROTEIN CONFORMATION; STRUCTURE ACTIVITY RELATION;

ANIMALS; CENTRAL NERVOUS SYSTEM AGENTS; DRUG DESIGN; HUMANS; LEGISLATION, DRUG; LIGANDS; MOLECULAR STRUCTURE; PATENTS AS TOPIC; PROTEIN CONFORMATION; RECEPTORS, SEROTONIN; SEROTONIN ANTAGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; SULFONES;

EID: 84864242444     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2012.709236     Document Type: Review

References (173)

1. Monsma FJ, Shen Y, Ward RP, et al. Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 1993;43:320-7 (Pubitemid 23081986)
2. Unsworth CD, Molinoff PB. Characterization of a 5-Hydroxytryptamine receptor in mouse neuroblastoma N18TG2 cells. J Pharmacol Exp Ther 1994;269:246-55 (Pubitemid 24143261)
3. Kohen R, Metcalf MA, Khan N, et al. Cloning, characterization, and chromosomal localization of a human 5HT6 serotonin receptor. J Neurochem 1996;66:47-56 (Pubitemid 26010763)
4. Sebben M, Ansanay H, Bockaert J, Dumuis A. 5HT6 receptors positively coupled to adenylyl cyclase in striatal neurones in culture. Neuroreport 1994;5:2553-7
5. Roberts JC, Reavill C, East SZ, et al. The distribution of 5HT(6) receptors in rat brain: An autoradiographic binding study using the radiolabelled 5HT(6) receptor antagonist [(125)I]SB-258585. Brain Res 2002;934:49-57 (Pubitemid 34286567)
6. Gerard C, Mestikawy S, Lebrand C, et al. Quantitative RT-PCR distribution of serotonin 5HT6 receptor mRNA in the central nervous system of control or 5,7-dihydroxytryptamine-treated rats. Synapse 1996;23:164-73 (Pubitemid 26230563)
7. Dawson LA, Nguyen HQ, Li P. The 5HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus. Neuropsychopharmacology 2001;25:662-8 (Pubitemid 32995948)
8. Ivachtchenko AV, Ivanenkov YA, Tkachenko SE. 5HT6 receptor modulators: A patent survey. Expert Opin Ther Patents 2010;20:1247-57
9. Borsini EdF. Pharmacology of 5HT6 receptors; Part II, Intern. Rev Neurobiol Acad Press 2011;96:242
10. Marazziti D, Baroni S, Dell'Osso MC, et al. Serotonin receptors of type 6 (5HT6): What can we expect from them. Curr Med Chem 2011;18:2783-90
11. Marsden CA, King MV, Fone KC. Influence of social isolation in the rat on serotonergic function and memory-relevance to models of schizophrenia and the role of 5HT6 receptors. Neuropharmacology 2011;61:400-7
12. Codony X, Vela JM, Ramirez MJ. 5HT(6) receptor and cognition. Curr Opin Pharmacol 2011;11:94-100
13. Meneses A, Perez-Garcia G, Ponce-Lopez T, Castillo C. 5HT6 receptor memory and amnesia: Behavioral pharmacology-learning and memory processes. Int Rev Neurobiol 2011;96:27-47
14. Borsini F, Bordi F, Riccioni T. 5HT6 pharmacology inconsistencies. Pharmacol Biochem Behav 2011;98:169-72
15. Borsini EDF. Pharmacology of 5HT6 receptors. Part I, Intern. Rev Neurobiol Acad Press 2010;95:2411
16. Wesolowska A. Potential role of the 5HT6 receptor in depression and anxiety: An overview of preclinical data. Pharmacol Rep 2010;62:564-77
17. Fukuo Y, Kishi T, Yoshimura R, et al. Serotonin 6 receptor gene and mood disorders: Case-control study and meta-analysis. Neurosci Res 2010;67:250-5
18. Rosse G, Schaffhauser H. 5HT6 receptor antagonists as potential therapeutics for cognitive impairment. Curr Top Med Chem 2010;10:207-21
19. Glennon RA, Siripurapu U, Roth BL, et al. The medicinal chemistry of 5HT6 receptor ligands with a focus on arylsulfonyltryptamine analogs. Curr Top Med Chem 2010;10:579-95
20. Liu KG, Robichaud AJ. 5HT6 antagonists as potential treatment for cognitive dysfunction. Drug Dev Res 2009;70:145-68
21. Geldenhuys WJ, Van Der Schyf CJ. The serotonin 5HT6 receptor: A viable drug target for treating cognitive deficits in Alzheimer's disease. Expert Rev Neurother 2009;9:1073-85
22. Witty D, Ahmed M, Chuang TT. Advances in the design of 5HT6 receptor ligands with therapeutic potential. Prog Med Chem 2009;48:163-224
23. Garfield AS, Heisler LK. Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol 2009;587:49-60
24. King MV, Marsden CA, Fone KC. A role for the 5HT(1A), 5HT4 and 5HT6 receptors in learning and memory. Trends Pharmacol Sci 2008;29:482-92
25. Johnson CN, Ahmed M, Miller ND. 5HT6 receptor antagonists: Prospects for the treatment of cognitive disorders including dementia. Curr Opin Drug Discov Devel 2008;11:642-54
26. Geldenhuys WJ, Van Der Schyf CJ. Serotonin 5HT6 receptor antagonists for the treatment of Alzheimer's disease. Curr Top Med Chem 2008;8:1035-408
27. Fone KC. An update on the role of the 5-Hydroxytryptamine6 receptor in cognitive function. Neuropharmacology 2008;55:1015-22
28. Upton N, Chuang TT, Hunter AJ, Virley DJ. 5HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease. Neurotherapeutics 2008;5:458-69 (Pubitemid 351952494)
29. Heal DJ, Smith SL, Fisas A, et al. Selective 5HT6 receptor ligands: Progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders. Pharmacol Ther 2008;117:207-31
30. Halford JC, Harrold JA, Boyland EJ, et al. Serotonergic drugs : Effects on appetite expression and use for the treatment of obesity. Drugs 2007;67:27-55 (Pubitemid 46105086)
31. Holenz J, Pauwels PJ, Diaz JL, et al. Medicinal chemistry strategies to 5HT(6) receptor ligands as potential cognitive enhancers and antiobesity agents. Drug Discov Today 2006;11:283-99
32. Ramage AG. The role of central 5-Hydroxytryptamine (5HT, serotonin) receptors in the control of micturition. Br J Pharmacol 2006;147:120-31
33. Van Der Schyf CJ, Geldenhuys WJ. Multimodal drugs and their future for Alzheimer's and Parkinson's disease. Int Rev 2011;100:107-5
34. Van Der Schyf CJ. The use of multi-target drugs in the treatment of neurodegenerative diseases. Expert Rev Clin Pharmacol 2011;4:293-8
35. Bang-Andersen B, Ruhland T, Jorgensen M, et al. Discovery of 1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): A novel multimodal compound for the treatment of major depressive disorder. J Med Chem 2011;54: 3206-21
36. Van Der Schyf CJ, Geldenhuys WJ. Multimodal drugs and their future for Alzheimer's and Parkinson's disease. Int Rev c 2011;100:107-105
37. Van Der Schyf CJ. The use of multitarget drugs in the treatment of neurodegenerative diseases. Expert Rev Clin Pharmacol 2011;4:293-298
38. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, et al. Discovery of 1-[2- (2,4-Dimethylphenylsulfanyl)phenyl] piperazine (Lu AA21004): A Novel Multimodal Compound for the Treatment of Major Depressive Disorder. J Med Chem 2011;54:3206-3221
39. U.S. National Library of Medicine. Available from: Www.pubmed.com
40. Marazziti D, Baroni S, Catena Dell'Osso M, et al. Serotonin receptors of type 6 (5HT6): What can we expect from them? Curr Med Chem 2011;18(18):2783-90
41. Heal D, Gosden J, Smith S. The 5HT6 receptor as a target for developing novel antiobesity drugs. Int Rev Neurobiol 2011;96:73-109
42. Di Chiara G, Valentini V, Fenu S. Behavioral and neurochemical pharmacology of 5HT6 receptors related to reward and reinforcement. Int Rev Neurobiol 2011;96:111-39
43. Borsini F, Bordi F, Riccioni T. 5HT6 pharmacology inconsistencies. Pharmacol Biochem Behav 2011;98(2):169-72
44. Liu KG, Robichaud AJ. 5HT6 medicinal chemistry. Int Rev Neurobiol 2010; 94:1-34
45. Borsini F. Other 5HT6 receptor-mediated effects. Int Rev Neurobiol 2011;96:189-91
46. Mitchell ES. 5HT6 receptor ligands as antidementia drugs. Int Rev Neurobiol 2011;96:163-87
47. Arnt J, Olsen CK. 5HT6 receptor ligands and their antipsychotic potential. Int Rev Neurobiol 2011;96:141-61
48. Glennon RA, Siripurapu U, Roth BL, et al. The medicinal chemistry of 5HT6 receptor ligands with a focus on arylsulfonyltryptamine analogs. Curr Top Med Chem 2010;10(5):579-95
49. Henderson AJ, Guzzo PR, Ghosh A, et al. Epiminocyclohepta[b]indole analogs as 5HT6 antagonists. Bioorg. Med. Chem. Lett. 2012;22(4):1494-8
50. Nirogi R, Dwarampudi A, Kambhampati R, Bhatta V, et al. Rigidized 1-aryl sulfonyl tryptamines: Synthesis and pharmacological evaluation as 5HT6 receptor ligands. Bioorg. Med. Chem. Lett. 2011;21(15):4577-80
51. Nirogi R, Dwarampudi A, Kambhampati R, et al. 5HT6 receptor ligands, EMD386088 and SB258585, differentially regulate 5HT6 receptor-independent events. Toxicol In Vitro 2011;25(8):2035-40
52. Da Silva Costa-Aze V, Quiedeville A, Boulouard M, Dauphin F. 5HT6 receptor blockade differentially affects scopolamineinduced deficits of working memory, recognition memory and aversive learning in mice. Psychopharmacology (Berl) 2012;222(1):99-115
53. Slassi A. Recent advances in 5HT1B/1D receptor antagonists and agonists and their potential therapeutic applications. Curr Top Med Chem 2002;2(6):559-74
54. Unsworth CD, Molinoff PB. Characterization of a 5-hydroxytryptamine receptor in mouse neuroblastoma N18TG2 cells. J Pharmacol Exp Ther 1994;269(1):246-55 (Pubitemid 24143261)
55. Holenz J, Merce R, Diaz JL, et al. Medicinal chemistry driven approaches toward novel and selective serotonin 5HT6 receptor ligands. J Med Chem 2005;48(6):1781-95 (Pubitemid 40396311)
56. Trani G, Baddeley SM, Briggs MA, et al. Tricyclic azepine derivatives as selective brain penetrant 5HT6 receptor antagonists. Bioorg. Med. Chem. Lett. 2008;18(20):5698-700
57. Several databases including Prous Integrity Database. Available from: http://www.prous.com/integrity WIPO http://www.wipo.int Thomson Delphion http://www.delphion.com EPO http://www.epo.org; etc
58. Suven Life Sciences Ltd, India. !ryl sulfonamide amine compounds and their use as 5HT6 ligands. WO032258; 2010
59. Abbott Gmbh & Co. KG, Germany; Abbott Laboratories. N-phenyl-(piperazinyl or homopiperazinyl)-benzenesulfonamide or benzenesulfonyl-phenyl-(piperazine or homopiperazine) compounds suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor.WO125134; 2010
60. Abbott GmbH & Co. KG, Germany. Benzenesulfonanilide compounds suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor. WO056632; 2009
61. Abbott Gmbh & Co. KG, Germany; Abbott Laboratories. Benzenesulfonanilide compounds suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor. WO125135; 2010
62. Abbott Gmbh & Co. KG, Germany; Abbott Laboratories. Benzenesulfonanilide compounds suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor. WO125136; 2011
63. Laboratorios del Dr. Esteve, S. A, Spain. Naphthyl-substituted sulfonamides as 5HT6 receptor modulators. ES2344243B1; 2011
64. Laboratorios del Dr. Esteve, S. A, Spain. 5HT6-Ligands such as sulfonamide derivatives in drug-induced weight-gain. ES2360164B1; 2012
65. Korea Research Institute of Chemical Technology, S. Korea. Piperazine derivatives for preventing and treating central nervous system diseases. KR111508; 2010
66. Laboratorios del Dr. Esteve, S. A, Spain. Substituted tetrahydro-quinolinesulfonamide compounds, their preparation and use as medicament. US7964603B2; 2011
67. Korea Research Institute of Chemical Technology, S. Korea. Preparation of piperazine-quinoline derivatives for prevention or treatment of central nervous system diseases. KR124020; 2010
68. Laboratorios del Dr. Esteve, S. A, Spain. Substituted N-phenyl-2,3-dihydroimidazo [2,1-b]thiazole-5-sulfonamide derivatives as 5HT6 ligands. EP2116546; 2009
69. Laboratorios del Dr. Esteve, S. A, Spain. Substituted N-phenyl-2,3-dihydroimidazo [2,1-b]thiazole-5-sulfonamide derivatives as 5HT6 ligands. WO135927; 2009
70. Laboratorios del Dr. Esteve, S. A, Spain. N-Substituted imidazo[2,1-b]thiazole- 5-sulfonamide derivatives as 5HT6 ligands. WO135925; 2009
71. Laboratorios del Dr. Esteve, S. A, Spain. N-Substituted imidazo[2,1-b]thiazole-5- sulfonamide derivatives as 5HT6 ligands. EP2116547; 2009
72. Laboratorios del Dr. Esteve, S. A, Spain. Combination of at least two 5HT6-Ligands. EP2020230; 2009
73. Solvay Pharmaceuticals B. V, Netherlands. Arylsulfonyl pyrazoline carboxamidine derivatives as 5HT6 antagonists. WO115515; 2009
74. Roche Palo Alto LLC, USA. Tetralin and indane derivatives as selective 5HT6 and 5HT2A receptor antagonists. US7671235; 2010
75. Cephalon, Inc, USA. Tricyclic derivatives and their pharmaceutical serotonin receptors. WO087712; 2011
76. Cephalon, Inc, USA. Tricyclic derivatives and their pharmaceutical use and compositions. WO087713; 2011
77. Wyeth, John, and Brother Ltd. 1-Substituted-3-(naphthalen-1- ylsulfonyl)-5-(piperazin-1-yl)-1H-indazole compounds as 5-hydroxytryptamine- 6 ligands. WO155399; 2009
78. Suven Life Sciences Ltd. Substituted indolyl compounds and their use as 5HT6 ligands. WO034581; 2009
79. Suven Life Sciences Ltd. Aminoarylsulfonamide compounds and their use as 5HT6 ligands. WO053997; 2009
80. Suven Life Sciences Ltd. Aminoarylsulfonamide compounds and their use as 5HT6 ligands. EP2200980; 2010
81. Suven Life Sciences Ltd. Novel sulfone compounds as 5HT6 receptor ligands. INCH00018; 2011
82. Suven Life Sciences Ltd, India. Arylindolyl sulfonamide compounds and their use as 5HT6 ligands. WO032257; 2010
83. Merck & Co, Inc. Tryptaminesulfonamides as serotonin 5HT6 antagonists. WO073118; 2009
84. Laboratorios del Dr. Esteve, S.A. Substituted indole sulfonamide compounds, their preparation and use as medicaments. WO012806; 2010
85. Laboratorios del. Dr. Esteve, S.A. Substituted indole sulfonamide compounds their preparation and use as medicaments. EP2149573; 2010
86. Memory Pharmaceuticals Corp. 3-Substituted compounds having 5HT6 receptor affinity. WO023844; 2009
87. Memory Pharmaceuticals Corp. 4'-Amino cyclic compounds having 5HT6 receptor affinity. WO024980; 2010
88. Memory Pharmaceuticals Corp. 4'-Amino cyclic compounds having 5HT6 receptor affinity. US0056491; 2010
89. Memory Pharmaceuticals Corp. Pyrrolo-pyridine-3-yl piperazine derivatives having 5HT6 receptor affinity. WO008832; 2010
90. Memory Pharmaceuticals Corp. Pyrrolo-pyridine-3-yl piperazine derivatives having 5HT6 receptor affinity. US0016297; 2010
91. Memory Pharmaceuticals Corp. Condensed heterocyclic compounds having 5HT6 receptor affinity. WO021797; 2010
92. Memory Pharmaceuticals Corp. Pyrrolidine-substituted azaindole compounds having 5HT6 receptor affinity. WO002802; 2010
93. Memory Pharmaceuticals Corp. Pyrrolidine-substituted azaindole compounds having 5HT6 receptor affinity. US0022581; 2010
94. Memory Pharmaceuticals Corp. Acyclic compounds having 5HT6 receptor affinity. WO011546; 2010
95. Memory Pharmaceuticals Corp. Acyclic compounds having 5HT6 receptor affinity. US0029629; 2010
96. Wyeth, John, and Brother Ltd. 1-(Arylsulfonyl)-4-(piperazin-1-yl)- 1H-benzimidazole as 5- hydroxytryptamine-6 ligands. US0120779; 2010
97. H. Lundbeck A/S. Novel 4-(aryl-4- sulfonyl)-6,6a,7,8,9,10-hexahydro-4H- 4,8,10a-triazaacephenanthrylene and 3- arylsulfonyl-6,6a,7,8,9,10-hexahydro-3H- 3,8,10a-triazacyclo-penta[c]fluorene derivatives as serotonin 5HT6 ligands. WO088836; 2011
98. Ivachtchenko AA, Savchuk NP, Ivachtchenko AV. 3-Sulfonyl-pyrazolo [1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. WO093206; 2009
99. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. Substituted 4-sulfonylpyrazoles and 3-sulfonyl-pyrazolo[1,5-a] pyrimidines, antagonists of serotonin 5HT6 receptors, active component, pharmaceutical composition, drag and methods for the production. RU2369600; 2009
100. Ivachtchenko AA, Ivachtchenko AV, Savchuk NP. Substituted 2-amino-3- sulfonyl-pyrazolo[1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. WO093208; 2009
101. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. Substituted 3,5- diamino-4-sulfonyl-pyrazoles and 2- amino-3-sulfonyl-pyrazolo[1,5-a] pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2376291; 2009
102. Ivachtchenko AA, Ivachtchenko AV, Savchuk NP. Substituted 2-alkylsulfanyl- 3-sulfonyl-cycloalkano[e or d]pyrazolo [1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. WO093209; 2009
103. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. 2-alkylamino- 3-sulfonyl-cycloalkano[e or d]pyrazolo [1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2377244; 2009
104. Ivachtchenko AA, Ivachtchenko AV, Savchuk NP. Substituted cycloalkano[e or d]pyrazolo[1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. WO093210; 2009
105. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. Substituted cycloalkano[e or d]pyrazolo[1,5-a] pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2374249; 2009
106. Ivachtchenko AA, Kysil VM, Savchuk NP, Ivachtchenko AV. 2-Aamino-3-sulfonyl-pyrazolo[1,5-a] pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. WO136813; 2009
107. Ivachtchenko AV, Ivachtchenko AA, Savchuk, NP, Kysil VM. Substituted 2-amino-3-sulfonyl-pyrazolo[1,5-a] pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2384581; 2010
108. Ivachtchenko AV, Kysil VM, Ivachtchenko AA, Savchuk NP. Tetrahydro-pyrazolo[1,5-a]pyridopyrimidines as antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU239134; 2010
109. Ivachtchenko AA, Ivachtchenko AV, Savchuk NP, et al. Substituted 3-arylsulfonyl-cycloalkano[e or d]pyrazolo [1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. WO041983; 2010
110. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. 3-Alkylamino- 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2393157; 2010
111. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. Substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2393158; 2010
112. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. Substituted 2-alkylsulfanyl-3-sulfonyl-pyrazolo[1,5-a] pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2393159; 2010
113. Ivachtchenko AV, Savchuk NP, Ivachtchenko AA. Substituted 2-alkylamino-3-sulfonyl-pyrazolo[1,5-a] pyrimidines, antagonists of serotonin 5HT6 receptors, methods for the production and use thereof. RU2399621; 2010
114. Bayer Pharmaceuticals Corp. 4-Sulfide/ sulfoxide/sulfonyl-1h-pyrazolyl derivative compounds, for use in diseases associated with the 5HT2C receptor. WOA12003057674; 2003
115. Hoffmann La Roche. Pyrazolopyrimidines and pyrazolotriazines with 5HT6 receptor affinity. EPA1941994; 1999
116. Alla Chem, LLC. 3-Sulfonyl-pyrazolo [1,5-a]pyrimidines as antagonists of serotonin 5HT6 receptors and methods for their production and use thereof. WO093206; 2009
117. Alla Chem, LLC. Substituted 4-sulfonylpyrazoles and 3-sulfonylpyrazolo[1, 5-a]pyrimidines - antagonists of serotonin 5HT6 receptors, active component, pharmaceutical composition, medicinal agent and method of obtaining them. RU2369600; 2009
118. Alla Chem, LLC. 3-Sulfonyl-pyrazolo [1,5-a]pyrimidines as antagonists of serotonin 5HT6 receptors and methods for their production and use thereof. US331347; 2010
119. Alla Chem, LLC. 2-Alkylamino- 3-arylsulfonyl-cycloalkano [e or d] pyrazolo[1,5-a]pyrimidines/ antagonists of serotonin 5HT6 receptors methods for the production and the use in thereof. WO093209; 2009
120. Alla Chem, LLC. Substituted cycloalkano [e and d]pyrazolo[1,5-a] pyrimidines/ antagonists of serotonin 5HT6 receptors and methods for their production and use thereof. WO093210; 2009
121. Ivachtchenko AV, Golovina ES, Kadieva MG, et al. The antagonists of serotonin 5HT6 receptors. Substituted 3-benzenesulfonyl-pyrazolo[1,5-a]pyrido [4,3-e]pyrimidines and 3- benzenesulfonyl-pyrazolo[1,5-a]pyrido [4,3-d]pyrimidines - synthesis and "Structure-Activity" relationship. J Med Chem 2012. [in press]
122. Alla Chem, LLC. Substituted 2-amino- 3-(arylsulfonyl)pyrazolo[1,5-a] pyrimidines as antagonists of serotonin 5HT6 receptors, methods for the production and thereof. WO093208; 2009
123. Alla Chem, LLC. Substituted 3- arylsulfonylpyrazolo[1,5-a]pyrimidines, serotonin 5HT6 receptors antagonists, and methods for the production and their use thereof. WO041983; 2010
124. Alla Chem, LLC. Substituted 2-(alkylamino)-3-(arylsulfonyl)pyrazolo [1,5-a]pyrimidines serotonin 5HT6 receptors antagonists, and methods for the production and their use thereof. RU2393157; 2010
125. Alla Chem, LLC. Substituted 3- (arylsulfonyl)pyrazolo[1,5-a]pyrimidines as antagonists of serotonin 5HT6 receptors, and methods for the production and their use thereof. RU2393158; 2010
126. Alla Chem, LLC. Tetrahydropyrazolo [1,5-a]pyrido-pyrimidines as antagonists of serotonin 5HT6 receptors, methods for their production and use thereof. WO136814; 2009
127. Alla Chem, LLC. 2-Amino-3-sulfonyl- 6,7,8,9-tetrahydropyrazolo[1,5-a] pyrido [4,3-e]pyrimidines - antagonists serotonin 5HT6, methods for the production and use thereof. WO136813; 2009
128. Alla Chem, LLC. Substituted 2-amino- 3-sulfonyl-6,7,8,9- tetrahydropyrazolo[1,5- a]pyrido[4,3-e]pyrimidines - serotonin 5HT6 receptor antagonists and methods for the production and their use thereof. RU2384581; 2010
129. Ivachtchenko AV, Golovina ES, Kadieva MG, et al. 2-Substituted 5,6- dimethyl-3-phenylsulfonyl-pyrazolo[1,5- a]pyrimidines: new series of highly potent and specific serotonin 5-HT6 receptor antagonists. Eur J Med Chem 2011;46(4):1189-97
130. Alla Chem, LLC. Substituted 3-sulfonyl [1,2,3]triazolo[1,5-a]pyrimidines - antagonists of serotonin 5HT6 receptors, medicinal substance, pharmaceutical compositions, medicinal preparation and methods for the production thereof. WO093934; 2009
131. Ivachtchenko AV, Golovina ES, Kadieva MG, et al. Synthesis and biological study of 3-(phenylsulfonyl) thieno[2,3-e][1,2,3]triazolo[1,5-a] pyrimidines as potent and selective serotonin 5HT6 receptor antagonists. Bioorg Med Chem 2010;18(14):5282-90
132. Kost AN, Vinogradova EV, Daut Kh, et al.. Alkaloids and alkaloid-like structures. Khim 1962;32:2050
133. Hung D. Hydrogenated pyrido[4,3-b] indoles such as Dimebon for treating canine cognitive dysfunction syndrome. WO036400; 2008. [Chem. Abstr. 2008, 148, 369989]
134. Grigorev VV, Dranyi OA, Bachurin SO. Comparative study of action mechanisms of dimebon and memantine on AMPAand NMDA-subtypes glutamate receptors in rat cerebral neurons Bull Exp Biol Med 2003;136:474
135. Lermontova NN, Lukoyanov NV, Serkova TP, et al. Dimebon improves learning in animals with experimental Alzheimer's disease Bull Exp Biol Med 2000;129:544
136. Bachurin SO, Shevtsova EP, Kireeva EG, et al. Mitochondria as a target for neurotoxins and neuroprotective agents Ann NY Acad Sci 2003;993:334
137. 2+ channels Bull Exp Biol Med 2001;132:1079
138. Hung D. Dimebon, 11th Int. Conf. Alzheimer's Dis. Relat. Disord. (ICAD); 26 - 31 July 2008; Chicago
139. Tkachenko SE, Ivachtchenko AV, Khvat A, et al. 1st International Conference on Drug Design and Discovery; 2 - 6 February 2008; Dubai
140. Tkachenko SE, Ivachtchenko AV, Khvat A, et al. 11th Int. Conf. Alzheimer's Dis. Relat. Disord. (ICAD); 26-31 July 2008; Chicago
141. Tkachenko SE, Khvat A, Lavrovsky Y, et al. XXth International Symposium on Medicinal Chemistry
142. Lavrovsky Y, Ivachtchenko A, Morozova M, et al. Preclinical and early clinical studies of AVN-101, a novel balanced molecule for the treatment of Alzheimer's disease. Alzheimer's Association International Conference on Alzheimer's Disease; 2010. p. 3-442
143. Ivashchenko AV, Lavrovsky Y, Mitkin O, et al. Discovery and Preclinical Studies of AVN-101, a Novel "Balanced" Molecule for Treatment of Alzheimer Disease (AD)
144. Dimebon Disappoints in Phase 3 Trial of Huntington's Disease. Medscape. Available from: http://www.medscape. com/viewarticle/740692 [Last accessed 12 April 2011]
145. Medivation, Pfizer End Work on Alzheimer's Drug. WSJ Blogs. Available from: http://online.wsj.com/article/SB1000142405297020 4555904577166522162859292.html [Last accessed 18 January 2012]
146. A.M. Vitals: Pfizer, Medivation End Dimebon Development. WSJ Blogs. Available from: http://blogs.wsj.com/ health/2012/01/18/a-m-vitals- pfizermedivation- end-dimebon-development/ [Last accessed 18 January 2012]
147. Ivachtchenko AV, Kisil' VM, Mit'kin OD, et al. Substituted 8-sulfonyl-2,3,4,5-tetrahydro-1h-gammacarbolines, ligands and pharmaceutical composition; method for the production and use of same. RU2404180; 2010
148. Alla Chem, LLC. Substituted 8-sulfonyl- 2,3,4,5-tetrahydro-1H-gamma- carbolines, ligands and pharmaceutical composition; method for their production and use of same. WO134846; 2010
149. Alla Chem, LLC. Substituted 8-sulfonyl- 2,3,4,5-tetrahydro-1H-gamma- carbolines as ligands towards a wide range of receptors, and their preparation and use in the treatment and prophylaxis of CNS diseases. RU2404180; 2010
150. Alla Chem, LLC. Substituted 8-sulfonyl- 2,3,4,5-tetrahydro-1H-gamma- carbolines, ligands and pharmaceutical composition; method for their production and use of same. WO134846; 2010
151. Alla Chem, LLC. Substituted 8-sulfonyl- 2,3,4,5-tetrahydro-1H-gamma- carbolines as ligands towards a wide range of receptors, and their preparation and use in the treatment and prophylaxis of CNS diseases. RU2404180; 2010
152. Kohen R, Fashingbauer LA, Heidmann DE, et al. Cloning of the mouse 5HT6 serotonin receptor and mutagenesis studies of the third cytoplasmic loop. Brain Res Mol Brain Res 2001;90:110-17 (Pubitemid 32537632)
153. Teitler M, Herrick-Davis K, Purohit A. Constitutive activity of G-protein coupled receptors: Emphasis on serotonin receptors. Curr Top Med Chem 2002;2:529-38
154. Romero G, Sanchez E, Pujol M, et al. Efficacy of selective 5HT6 receptor ligands determined by monitoring 5HT6 receptor-mediated cAMP signaling pathways. Br J Pharmacol 2006;148:1133-43 (Pubitemid 44223019)
155. Riemer C, Borroni E, Levet-Trat B, et al. Influence of the 5HT6 receptor on acetylcholine release in the cortex: Pharmacological characterization of 4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine, a potent and selective 5HT6 receptor antagonist. Med Chem 2003;46:1273-6 (Pubitemid 36428233)
156. Meneses A. Role of 5HT6 receptors in memory formation. Drug News Perspect 2001;14:396-400 (Pubitemid 33140705)
157. Hirst WD, Stean TO, Rogers DC, et al. SB-399885 is a potent, selective 5HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models. Eur J Pharmacol 2006; 553:109-19 (Pubitemid 44779592)
158. Lieben CK, Blokland A, Sik A, et al. The selective 5HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat. Neuropsychopharmacology 2005;30:2169-79 (Pubitemid 41643968)
159. Marcos B, Gil-Bea FJ, Hirst WD, et al. Lack of localization of 5HT6 receptors on cholinergic neurons: Implication of multiple neurotransmitter systems in 5HT6 receptor-mediated acetylcholine release. Eur J Neurosci 2006;24:1299-306 (Pubitemid 44401652)
160. Dawson LA, Nguyen HQ, Li P. In vivo effects of the 5HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5HT, glutamate and aspartate. Br J Pharmacol 2000;130:23-6 (Pubitemid 30248421)
161. Schechter LE, Lin Q, Smith DL, et al. Neuropharmacological profile of novel and selective 5HT6 receptor agonists: WAY-181187 and WAY-208466. Neuropsychopharmacology 2008;33:1323-35 (Pubitemid 351521711)
162. Mitchell ES, Neumaier JF. 5HT6 receptors: A novel target for cognitive enhancement. Pharmacol Ther 2005;108:320-33 (Pubitemid 41691871)
163. Ballaz SJ, Akil H, Watson SJ. Analysis of 5HT6 and 5HT7 receptor gene expression in rats showing differences in novelty-seeking behavior. Neuroscience 2007;147:428-38 (Pubitemid 46907454)
164. Svenningsson P, Tzavara ET, Qi H, et al. Biochemical and behavioral evidence for antidepressant-like effects of 5HT6 receptor stimulation. Neuroscience 2007;27:4201-9 (Pubitemid 46597167)
165. Wesolowska A, Nikiforuk A. Effects of the brain-penetrant and selective 5HT6 receptor antagonist SB-399885 in animal models of anxiety and depression. Neuropharmacology 2007;52:1274-83
166. Fisas A, Codony X, Romero G, et al. Chronic 5HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats. Br J Pharmacol 2006;148:973-83 (Pubitemid 44543615)
167. De Foubert G, O'Neill MJ, Zetterstrom TS. Acute onset by 5HT6-receptor activation on rat brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression. Neuroscience 2007;147:778-85 (Pubitemid 46990655)
168. Cole DC, Stock JR, Lennox WJ, et al. Discovery of N1-(6-chloroimidazo[2, 1-b] [1,3]-thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5HT6 receptor agonist. J Med Chem 2007;50:5535-8 (Pubitemid 350106003)
169. Ivachtchenko AV, Golovina EV, Kadieva MD, et al. Synthesis and Structure 5-HG6 receptor antagonistic activity relationship of substituted bis-phenylsulfones. Chem Biol Drug Des 2012;80(3):[in press] compared with serotonin analogs.
170. Ivachtchenko A.V.,Kadieva M.D.,Mitkin O.D. Synthesis and pharmacological activity of methyl-(3-piperazin-1-yl-6-fenylsulfonylfenyl)-amine [abstracts]. In Second Scientific Conference with international participation"The successes and the synthesis of complex" on the 95th anniversary of the birth of Professor N. Prostakov, Peoples' Friendship University of Russia (RUDN); 23 - 27 April 2012; Moscow, Russia
171. Ivachtchenko AV, Kadieva MD, Mitkin OD. Substituted methyl-amines, antagonists, serotonin 5HT6 receptor, methods for the production and use thereof. RU152052; 2010
172. Ivachtchenko AV, Kadieva MD, Mitkin OD. Synthesis and pharmacological activity of methyl-(8-piperazin-1-yl)-3-phenylsulfonyl-quinolin-4-yl)-amine [abstracts]. In Organic Synthesis: Chemistry and Technology. The Ural Federal University; 4 - 8 June 2012; Russia, Ekaterinburg
173. Harris RN III, Stabler RS, Repke DB, et al. Highly potent, non-basic 5HT6 ligands. Site mutagenesis evidence for a second binding mode at 5HT6 for antagonism. Bioorg. Med. Chem. Lett. 2010;20:3436-40.