- KETONES AND REDUCED KETONES AS THERAPEUTIC AGENTS FOR THE TREATMENT OF BONE CONDITIONS
-
The present invention pertains to certain ketones and reduced ketones and derivatives thereof which, inter alia, inhibit osteoclast survival, formation, and/or activity; and/or inhibit bone resorption, and more particularly to compounds of the formulae: (1) (2) wherein: Ar1 is independently a biphenyl, phenanthryl, fluorenyl, or carbazolyl, and is optionally substituted; Ralk is independently a C2-10alkylene group, and is optionally substituted; -ORO, if present, is independently -OH or -ORK; -ORK, if present, is independently selected from: -O-RK1; -O-C(=O)RK2; -O-C(=O)ORK3; -O-S(=O)2ORK4; Q is independently -OH or -OROT; wherein: -OROT, if present, is independently selected from: -O-RE1; -O-C(=O)-RE2; -O-C(=O)-O-RE3; -O-C(=O)-O-SO3RE4; -O-C(=O)-O-(CH2)n-COORE5; -O-C(=O)-(CH2)n-NRN1RN2; -O-C(=O)-(CH2)n-NH-C(=O)RE6; -O-C(=O)-(CH2)n-C(=O)-NRN3RN4; -O-P(=O)(ORE7)(ORE8); -O-RPA; RPA, if present, is an organic group which incorporates a phosphonic acid group; with the proviso that if -OROT is -O-RE1, then RE1 is not a phenyl group substituted with a sulfonyl group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, or prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit osteoclast survival, formation, and/or activity, and to inhibit conditions mediated by osteoclasts and/or characterised by bone resorption, in the treatment of bone disorders such as osteoporosis, rheumatoid arthritis, cancer associated bone disease, Paget's disease, aseptic loosening of prosthetic implants, and the like; and/or in the treatment of conditions associated with inflammation or activation of the immune system.
- -
-
-
- Phenanthryl piperazinyl dicarboxylic acids as selective nmda receptor modulating agents
-
Disclosed are compounds of formula (I) wherein: L is (a) optionally substituted by replacement of one or more of the hydrogen atoms on the phenanthrene ring system by one or more groups other than hydrogen; A is CH2, SO2 or C=O; X is CO2H, PO3H2, PO2H2, PO2HR5, PO2HOR5, SO3H, SO2H, or tetrazole; and R1, R2, R3, R4 and R5 are independently selected from H, alkyl, alkenyl, alkynyl, aryl and aralkyl; or a pharmaceutically acceptable acid salt or base addition salt or an in vivo hydrolysable ester or amide thereof. Compounds of formula (I) are selective NMDA receptor modulating agents and, therefore, may be used to advantage in vitro in neuroassays and in vivo in the treatment of disorders of the CNS.
- -
-
-
- Glucocorticoid receptor modulators
-
The present invention provides non-steroidal compounds of formula I which are selective modulators (i.e., agonists and antagonists) of a steroid receptor, specifically, the glucocorticoid receptor. The present invention also provides pharmaceutical compositions containing these compounds and methods for using these compounds to treat animals requiring glucocorticoid receptor agonist or antagonist therapy. Glucocorticoid receptor modulators are useful to treat diseases, such as obesity, diabetes, inflammation and others as described below. The present invention also provides intermediates and processes for preparing these compounds. STR1
- -
-
-
- Preparation and biological activity of tricyclic non-steroidal inhibitors of human steroid 5α-reductase
-
The synthesis and in vitro inhibitory studies against human types 1 and 2 steroid 5α-reductase of a series of 9,10-dihydrophenanthrene-2-carboxylic acids is reported. A (4-carboxy)phenyl substituent at C-7 provides a compound with activity against both is
- Abell, Andrew D.,Brandt, Martin,Levy, Mark A.,Holt, Dennis A.
-
p. 1663 - 1667
(2007/10/03)
-
- Properties of the Liquid Crystals formed by Certain 4-Alkoxy-N-(2-phenanthrylmethylene)anilines
-
The liquid crystal transition temperatures of twelve 4-alkoxy-N-(2-phenanthrylmethylene)anilines are reported and compared with those of corresponding members of similar homologous series of azomethines.Differences in liquid crytal thermal stability between comparable azomethines in which the -CH=N- linkage is reversed are discussed.
- Brown, John W.,Byron, David J.,Fawcett, Linda A.,Wilson, Robert C.,Gillyon, Andrew M.,et al.
-
p. 1593 - 1596
(2007/10/02)
-