Novel and potent 5-piperazinyl methyl- N1-aryl sulfonyl indole derivatives as 5-HT6 receptor ligands

ACS Medicinal Chemistry Letters

Volumn 1, Issue 7, 2010, Pages 340-344

  Nirogi, Ramakrishna V S ^a   Kothmirkar, Prabhakar ^a   Kambhampati, Ramasastri ^a   Konda, Jagadish Babu ^a   Arepalli, Sobhanadri ^a   Pamuleti, Narasimhareddy G ^a   Deshpande, Amol D ^a   Bandyala, Trinathreddy ^a   Shinde, Anil K ^a   Dubey, P K ^b  

^a SUVEN LIFE SCIENCES LTD   (India)

^b JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY   (India)

Author keywords

5 HT6R; 5 Piperazinyl methyl N1 aryl sulfonyl indole; Morris water mazes; NORT; PK profile; SAR

Indexed keywords

1 BENZENESULFONYL 5 METHOXY N,N DIMETHYLTRYPTAMINE; 3 CHLORO 5 PIPERAZINYL METHYL N 1 ARYL SULFONYL INDOLE DERIVATIVE; 3 PHENYLSULFONYL 8 (1 PIPERAZINYL)QUINOLINE; 5 PIPERAZINYL METHYL N 1 ARYL BENZYL INDOLE DERIVATIVE; 5 PIPERAZINYL METHYL N 1 ARYL CARBONYL INDOLE DERIVATIVE; 5 PIPERAZINYL METHYL N 1 ARYL SULFONYL INDOLE DERIVATIVE; AE 58054; CYTOCHROME P450 1A2; CYTOCHROME P450 2A6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; INDOLE DERIVATIVE; LIGAND; RADIOLIGAND; SAM 531; SEROTONIN 6 RECEPTOR; UNCLASSIFIED DRUG;

AREA UNDER THE CURVE; ARTICLE; CELL STRAIN HEK293; COGNITION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG COMPETITION; DRUG DESIGN; DRUG HALF LIFE; DRUG METABOLISM; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; IN VITRO STUDY; LIGAND BINDING; LIVER MICROSOME; MAXIMUM PLASMA CONCENTRATION; MAZE TEST; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

ANIMALIA;

EID: 77958107921     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml100101u     Document Type: Article

References (28)

1. 6 receptors Curr. Drug Targets CNS Neurol. Disord. 2004, 3, 59-79
2. 6 receptors: A novel target for cognitive enhancement Pharmacol. Ther. 2005, 108, 320-333
3. 6 receptor in cognitive function Neuropharmacology 2008, 55, 1015-1022
4. 6 receptors Br. J. Pharmacol. 1998, 124, 556-562
5. 6 receptor-selective radioligand [3H] Ro63-0563 labels 5-HT receptor-binding sites in rat and porcine striatum Mol. Pharmacol. 1998, 54, 577-583
6. 6 receptor antagonist J. Med. Chem. 1999, 42, 202-205
7. 6R antagonist SB-742457 as a novel cognitive enhancing agent for Alzheimer's disease. Alzheimer's Dementia 2006, 3, S631 - S632 (abstract).
8. Bruton, G.; Orlek, B. S.; Stemp, G. PCT Int. Appl. WO 2008113818, 2008; Chem. Abstr. 149, 394689.
9. 6 antagonist for the treatment of cognitive dysfunction associated with schizophrenia and Alzheimer's disease. ACS 239th National Meeting and Exposition, San Francisco, CA, MEDI 34, March 21-25th, 2010.
10. 6 receptor: A viable drug target for treating cognitive deficits in Alzheimer's disease Expert Rev. Neurother. 2009, 9, 1073-1085
11. 6 antagonists as potential treatment for cognitive dysfunction Drug Dev Res. 2009, 70, 145-168
12. 6 antagonist, reverses subchronic PCP-induced cognitive impairment in a rat novel object recognition test. 2nd Biennial Schizophrenia International Research Conference (SIRS), Florence, Italy April 10-14th, 2010.
13. 6 serotonin receptors: Receptor modeling studies J. Med. Chem. 2008, 51, 603-611
14. 6 serotonin receptors J. Med. Chem. 2006, 49, 5217-5225
15. 6 receptor Pharmacol. Ther. 2008, 117, 207-231
16. Epix Pharmaceuticals, Inc. October 29, 2007, press release; http://www.epixpharma.com.
17. 6 receptor antagonist, first in human phase-1 Single Ascending Dose (SAD) study Alzheimer's Dementia 2009, 5 (4 Suppl.) P250
18. 7 J. Med. Chem. 2003, 46, 2795-2812
19. 6 receptor agonists and antagonists J. Med. Chem. 2005, 48, 353-356 (Pubitemid 40139779)
20. 6 receptor antagonists Biol. Med. Chem. Lett. 2005, 15, 379-383 (Pubitemid 39647154)
21. 6 antagonists Biol. Med. Chem. Lett. 2000, 10, 2295-2299
22. 6 receptor ligands J. Med. Chem. 2001, 44, 3881-3895
23. 6 Receptor Antagonist; ACS, Atlanta, GA, 2006; MEDI-142.
24. Clark, R. D.; Repke, D. H. Heterocycles 1984, 22, 195 - 222.
25. Batcho, A. D.; Leimgruber, W. Org. Synth. 1984, 63, 214 - 224.
26. Lewis, D. F. V. Cytochromes P450: Structure, Function and Mechanism; Taylor and Francis Publishing: London, 1996.
27. Ennaceur, A.; Aggleton, J. P. The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat Behav. Brain. Res. 1997, 88, 181-193
28. 6 receptor antagonists in rodent models of learning. Society for neuroscience 35th annual meeting, Washington, DC, Nov 12-16, 2005.