- CONFORMATIONALLY CONSTRAINED CARBOXYLIC ACID DERIVATIVES USEFUL FOR TREATING METABOLIC DISORDERS
-
The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I or the general formula III: where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.
- -
-
-
- Dual aromatase-steroid sulfatase inhibitors
-
By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in'vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC 50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.
- Woo, L. W. Lawrence,Bubert, Christian,Sutcliffe, Oliver-B.,Smith, Andrew,Chander, Surinder K.,Mahon, Mary F.,Purohit, Atul,Reed, Michael J.,Potter, Barry V. L.
-
p. 3540 - 3560
(2008/02/09)
-
- SULFAMIC ACID ESTER COMPOUNDS USEFUL IN THE INHIBITION OF SEROID SULPHATASE ACTIVITY AND AROMATASE ACTIVITY
-
There is provided a compound of Formula (III) or Formula (IV), wherein A is selected from H, OH, halogen and hydrocarbyl D, E and F are each independently of each other an optional linker group; P, Q and R are independently of each other a ring system, wherein R4 and R5 are independently selected from H, alkyl, cycloalkyl, alkenyl, acyl and aryl, or combinations thereof, or together represent alkylene, wherein the or each alkyl or cycloalkyl or alkenyl or optionally contain one or more hetero atoms or groups
- -
-
Page/Page column 66-67
(2010/02/14)
-