Novel ligands of steroid hormone receptors

被引:13
作者
Coghlan, MJ [1 ]
Kort, ME [1 ]
机构
[1] Abbott Labs, Dept 47C, Abbott Pk, IL 60064 USA
关键词
androgen; glucocorticoid; hormone receptor; intracellular receptor; mineralocorticoid; oestrogen; progesterone; selective oestrogen receptor modulator (SERM); steroid receptor;
D O I
10.1517/13543776.9.11.1523
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The development of novel ligands for steroid hormone receptors has become a burgeoning field with tremendous potential in numerous human therapies. Novel structures offer the advantage of greatly improved proprietary position, as well as the potential for highly selective compounds with fewer side effects and reduced metabolic liabilities. This opinion details the recent progress in the area of non-steroidal ligands of the principal steroid receptors. Published intellectual property associated with established areas such as oestrogen and androgen receptors have been updated, and new patents detailing ligands for progesterone, glucocorticoid and mineralocorticoid receptors are also discussed. A wide variety of structures are disclosed along with data in comparison with steroidal references. These novel structural families have strong potential, and these compounds will likely grow into complementary pharmacophores of defined function and enhanced therapeutic utility.
引用
收藏
页码:1523 / 1536
页数:14
相关论文
共 108 条
[1]   Progesterone receptor agonists and antagonists [J].
Allan, G ;
Macielag, M .
EXPERT OPINION ON THERAPEUTIC PATENTS, 1999, 9 (07) :955-962
[2]   RETRACTED: Synergistic activation of estrogen receptor with combinations of environmental chemicals (Retracted Article) [J].
Arnold, SF ;
Klotz, DM ;
Collins, BM ;
Vonier, PM ;
Guillette, LJ ;
McLachlan, JA .
SCIENCE, 1996, 272 (5267) :1489-1492
[3]   CLONING OF HUMAN MINERALOCORTICOID RECEPTOR COMPLEMENTARY-DNA - STRUCTURAL AND FUNCTIONAL KINSHIP WITH THE GLUCOCORTICOID RECEPTOR [J].
ARRIZA, JL ;
WEINBERGER, C ;
CERELLI, G ;
GLASER, TM ;
HANDELIN, BL ;
HOUSMAN, DE ;
EVANS, RM .
SCIENCE, 1987, 237 (4812) :268-275
[4]   Pharmacological profile of RU 58642, a potent systemic antiandrogen for the treatment of androgen-dependent disorders [J].
Battmann, T ;
Branche, C ;
Bouchoux, F ;
Cerede, E ;
Philibert, D ;
Goubet, F ;
Teutsch, G ;
Gaillard-Kelly, M .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1998, 64 (1-2) :103-111
[5]   BIS(4-HYDROXYPHENYL)[2-(PHENOXYSULFONYL)PHENYL]METHANE - ISOLATION AND STRUCTURE ELUCIDATION OF A NOVEL ESTROGEN FROM COMMERCIAL PREPARATIONS OF PHENOL RED (PHENOLSULFONPHTHALEIN) [J].
BINDAL, RD ;
KATZENELLENBOGEN, JA .
JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (10) :1978-1983
[6]   ESTROGENIC ACTIVITY OF DDT ANALOGS AND POLYCHLORINATED BIPHENYLS [J].
BITMAN, J ;
CECIL, HC .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 1970, 18 (06) :1108-&
[7]  
Bittar N, 1997, PRINCIPLES MED BIOL, V8, P427
[8]   Cytokine modulation by glucocorticoids: Mechanisms and actions in cellular studies [J].
Brattsand, R ;
Linden, M .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 1996, 10 :81-90
[9]   Molecular basis of agonism and antagonism in the oestrogen receptor [J].
Brzozowski, AM ;
Pike, ACW ;
Dauter, Z ;
Hubbard, RE ;
Bonn, T ;
Engstrom, O ;
Ohman, L ;
Greene, GL ;
Gustafsson, JA ;
Carlquist, M .
NATURE, 1997, 389 (6652) :753-758
[10]   The antibiotic rifampicin is a nonsteroidal ligand and activator of the human glucocorticoid receptor [J].
Calleja, C ;
Pascussi, JM ;
Mani, JC ;
Maurel, P ;
Vilarem, MJ .
NATURE MEDICINE, 1998, 4 (01) :92-96