Literature DB >> 24900182

Discovery of WAY-260022, a Potent and Selective Inhibitor of the Norepinephrine Transporter.

Lori K Gavrin1, Paige E Mahaney2, Douglas Jenkins2, Lisa M Nogle2, Cheryl A Mugford3, Christine Huselton3, Jennifer Leiter4, Grace H Johnston4, Jenifer A Bray4, Kevin D Burroughs4, Scott A Cosmi4, Peter Alfinito4, Douglas M Ho5, Darlene C Deecher4, Eugene J Trybulski2.   

Abstract

The potency and selectivity of a series of 1-{(1S)-2-[amino]-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol analogues are described. These compounds were prepared to improve in vitro metabolic stability and achieve brain penetration. Compound 13 (WAY-260022, NRI-022) was found to be a potent inhibitor of norepinephrine reuptake and demonstrated excellent selectivity over the serotonin and dopamine transporters. Additionally, 13 exhibited oral efficacy in a rat model of thermoregulatory dysfunction.

Entities:  

Keywords:  WAY-260022; brain penetration, vasomotor symptoms; dopamine transporter; norepinephrine reuptake inhibitor; serotonin transporter

Year:  2010        PMID： 24900182      PMCID： PMC4007968          DOI： 10.1021/ml100009p

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  16 in total

1.  Breast cancer and hormone replacement therapy.

Authors:  A Z LaCroix; W Burke
Journal:  Lancet       Date:  1997-10-11       Impact factor: 79.321

2.  The role of the selective serotonin reuptake inhibitor fluoxetine in temperature regulation in ovariectomized rat models.

Authors:  Navin Maswood; Scott Cosmi; Peter D Alfinito; Liza Leventhal; Darlene C Deecher
Journal:  Neuroendocrinology       Date:  2006-12-28       Impact factor: 4.914

3.  Effect of continuous intraventricular estrogen or catechol estrogen treatment on catecholamine turnover in various brain regions.

Authors:  D U Panek; W R Dixon
Journal:  J Pharmacol Exp Ther       Date:  1986-03       Impact factor: 4.030

4.  High throughput artificial membrane permeability assay for blood-brain barrier.

Authors:  Li Di; Edward H Kerns; Kristi Fan; Oliver J McConnell; Guy T Carter
Journal:  Eur J Med Chem       Date:  2003-03       Impact factor: 6.514

Review 5.  Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis.

Authors:  Heidi D Nelson; Kimberly K Vesco; Elizabeth Haney; Rongwei Fu; Anne Nedrow; Jill Miller; Christina Nicolaidis; Miranda Walker; Linda Humphrey
Journal:  JAMA       Date:  2006-05-03       Impact factor: 56.272

6.  Effect of tibolone and raloxifene on the tail temperature of oestrogen-deficient rats.

Authors:  H H Berendsen; A H Weekers; H J Kloosterboer
Journal:  Eur J Pharmacol       Date:  2001-05-04       Impact factor: 4.432

7.  Alleviation of thermoregulatory dysfunction with the new serotonin and norepinephrine reuptake inhibitor desvenlafaxine succinate in ovariectomized rodent models.

Authors:  Darlene C Deecher; Peter D Alfinito; Liza Leventhal; Scott Cosmi; Grace H Johnston; Istvan Merchenthaler; Richard Winneker
Journal:  Endocrinology       Date:  2006-11-22       Impact factor: 4.736

8.  Phase III evaluation of fluoxetine for treatment of hot flashes.

Authors:  Charles L Loprinzi; Jeff A Sloan; Edith A Perez; Susan K Quella; Phillip J Stella; James A Mailliard; Michele Y Halyard; Sandhya Pruthi; Paul J Novotny; Teresa A Rummans
Journal:  J Clin Oncol       Date:  2002-03-15       Impact factor: 44.544

9.  Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial.

Authors:  Vered Stearns; Katherine L Beebe; Malini Iyengar; Eric Dube
Journal:  JAMA       Date:  2003-06-04       Impact factor: 56.272

10.  Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors.

Authors:  Paige E Mahaney; Lori K Gavrin; Eugene J Trybulski; Gary P Stack; T An Vu; Stephen T Cohn; Fei Ye; Justin K Belardi; Arthur A Santilli; Joseph P Sabatucci; Jennifer Leiter; Grace H Johnston; Jenifer A Bray; Kevin D Burroughs; Scott A Cosmi; Liza Leventhal; Elizabeth J Koury; Yingru Zhang; Cheryl A Mugford; Douglas M Ho; Sharon J Rosenzweig-Lipson; Brian Platt; Valerie A Smith; Darlene C Deecher
Journal:  J Med Chem       Date:  2008-06-17       Impact factor: 7.446
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