公开(公告)号：EP0991636B1

公开(公告)日：2005-03-02

申请号：EP98932821.6

申请日：1998-06-24

申请人： ALLERGAN, INC.

发明人： KLEIN, Elliott, S. ,  JOHNSON, Alan, T. ,  STANDEVEN, Andrew, M. ,  BEARD, Richard, L. ,  GILLETT, Samuel, J. ,  DUONG, Tien, T. ,  NAGPAL, Sunil ,  VULIGONDA, Vidyasagar ,  TENG, Min ,  CHANDRARATNA, Roshantha, A.

IPC分类号： C07D311/58 ,  C07C233/81 ,  C07F7/18 ,  A61K31/215 ,  A61K31/335

CPC分类号： C07C57/50 ,  C07C63/33 ,  C07C63/49 ,  C07C63/66 ,  C07C63/72 ,  C07C63/74 ,  C07C65/19 ,  C07C65/28 ,  C07C65/38 ,  C07C69/618 ,  C07C69/76 ,  C07C69/90 ,  C07C69/94 ,  C07C233/81 ,  C07C233/87 ,  C07C245/10 ,  C07C327/48 ,  C07C2602/10 ,  C07C2602/28 ,  C07D213/55 ,  C07D277/30 ,  C07D307/54 ,  C07D311/58 ,  C07D333/24 ,  C07D335/06 ,  C07F7/0818

摘要： Aryl-substituted and aryl and (3-oxo-1-propenyl)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.

公开(公告)号：EP1042313B1

公开(公告)日：2004-04-28

申请号：EP98964231.9

申请日：1998-12-21

申请人： Allergan, Inc.

发明人： KLEIN, Elliott, S. ,  JOHNSON, Alan, T. ,  STANDEVEN, Andrew, M. ,  BEARD, Richard, L. ,  GILLETT, Samuel, J. ,  DUONG, Tien, T. ,  NAGPAL, Sunil ,  VULIGONDA, Vidyasagar ,  TENG, Min ,  CHANDRARATNA, Roshantha, A.

IPC分类号： C07D335/06 ,  C07D311/58 ,  C07D213/55 ,  C07D277/30 ,  C07D333/24 ,  C07D307/54 ,  C07D409/04 ,  C07D409/06 ,  C07C69/78 ,  C07C233/65 ,  C07C327/48 ,  A61K31/44 ,  A61K31/335 ,  A61K31/38 ,  A61K31/425

CPC分类号： C07D335/06 ,  C07D213/55 ,  C07D277/30 ,  C07D307/54 ,  C07D311/58 ,  C07D333/24 ,  C07D409/04 ,  C07D417/04

摘要： 2,2-Dialkyl- 4-aryl-substituted benzopyran and benzothiopyran derivatives of formula (I) where the symbols have the meaning described in the specification, have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action or RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists.