- CHEMICAL SUBSTANCES WHICH INHIBIT THE ENZYMATIC ACTIVITY OF HUMAN KALLIKREIN-RELATED PEPTIDASE 6 (KLK6)
-
The invention relates to compounds which are suitable for the treatment of a disease associated with kallikrein-like peptidase 6 overexpression and to pharmaceutical compositions containing such compounds. The invention further relates to a kit of parts comprising such compounds or pharmaceutical compositions.
- -
-
Paragraph 0453; 0454
(2018/04/19)
-
- Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure-Activity Relationships and Membrane Targeting Properties
-
Antibacterials that disrupt cell membrane function have the potential to eradicate “persister” organisms and delay the emergence of resistance. Here we report the antimycobacterial activities of 4-fluoro and 6-methoxyindoles bearing a cationic amphiphilic motif represented by a lipophilic n-octyl side chain at position 1 and a positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]decane moiety at position 3. These analogues exhibited balanced profiles of potency (Mycobacterium bovis BCG, M tuberculosis H37Rv), selective activity, solubility, and metabolic stability. Bacteriological mechanism of action investigations on a representative analogue revealed cell membrane permeabilization and depolarization in M bovis BCG. These membrane-related changes preceded cell death indicating that the loss in membrane integrity was not an epiphenomenon. Bactericidal activity was observed against both growing and nongrowing mycobacterial cultures. The analogue also upregulated cell envelope stress-inducible promoters piniBAC and pclgR, implicating the involvement of envelope-related targets in its mode of action.
- Yang, Tianming,Moreira, Wilfried,Nyantakyi, Samuel Agyei,Chen, Huan,Aziz, Dinah binte,Go, Mei-Lin,Dick, Thomas
-
p. 2745 - 2763
(2017/04/21)
-
- Indolyl and dihydroindolyl N-glycinamides as potent and in vivo active NPY5 antagonists
-
A novel series of indolyl and dihydroindolyl glycinamides were identified as potent NPY5 antagonists with in vivo activity from screen hit 1. The dihydroindolyl glycinamide 10a significantly inhibits NPY5 agonist induced feeding at a dose of 0.1 mg/kg. The indolyl glycinamide 12c also inhibits NPY5 agonist induced feeding at a dose of 1 mg/kg. Both compounds 10a and 12c represent potential tools for further investigation into the biology of the NPY5 receptor.
- Wu, Lingyun,Lu, Kai,Packiarajan, Mathivanan,Jubian, Vrej,Chandrasena, Gamini,Wolinsky, Toni C.,Walker, Mary W.
-
scheme or table
p. 2167 - 2171
(2012/04/18)
-
- Synthesis and evaluation of indole aspartyl ketones as novel caspase-3 inhibitors
-
Synthesis, biological evaluation and structure-activity relationships for a series of novel nonpeptide small molecule inhibitors of caspase-3 are described. Among the synthesized compounds, 2,3,5,6-tetrafluorophenoxymethyl ketone derivatives of indole-N-a
- Sengupta,Rao, G.Venkateshwar,Dubey
-
scheme or table
p. 5517 - 5520
(2012/07/27)
-
- SUBSTITUTED AMINO CARBOXYLIC ACIDS
-
Disclosed are compounds and pharmaceutically acceptable salts of formula (I): which are useful in the treatment of metabolic disorders related to insulin resistance, leptin resistance, or hyperglycemia. Compounds of the invention include inhibitors of Protein tyrosine phosphatases, in particular Protein tyrosine phosphatase-1B (PTP-1B), that are useful in the treatment of diabetes and other PTP mediated diseases, such as cancer, neurodegenerative diseases and the like. Also disclosed are pharmaceutical compositions comprising compounds of the invention and methods of treating the aforementioned conditions using such compounds.
- -
-
Page/Page column 189
(2008/06/13)
-