- A robust process for an mGluR5 negative allosteric modulator: Difluoromethylation and sonogashira coupling on large scale
-
The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd and Cu in the final API. Due to the relative nonpolar nature of the intermediates, water-miscible solvents were employed in all four steps to allow for direct crystallizations upon reaction completion. In addition, several crystalline morphologies of the API were discovered, and the isolation of the desired form II will be discussed.
- Sperry, Jeffrey B.,Farr, Roger M.,Levent, Mahmut,Ghosh, Mousumi,Hoagland, Steven M.,Varsolona, Richard J.,Sutherland, Karen
-
p. 1854 - 1860
(2013/01/15)
-
- Inhibitors of dipeptidyl peptidase 8 and dipeptidyl peptidase 9. Part 2: Isoindoline containing inhibitors
-
To obtain selective and potent inhibitors of dipeptidyl peptidases 8 and 9, we synthesized a series of substituted isoindolines as modified analogs of allo-Ile-isoindoline, the reference DPP8/9 inhibitor. The influence of phenyl substituents and different P2 residues on the inhibitors' affinity toward other DPPs and more specifically, their potential to discriminate between DPP8 and DPP9 will be discussed. Within this series compound 8j was shown to be a potent and selective inhibitor of DPP8/9 with low activity toward DPP II.
- Van Goethem, Sebastiaan,Van der Veken, Pieter,Dubois, Veronique,Soroka, Anna,Lambeir, Anne-Marie,Chen, Xin,Haemers, Achiel,Scharpe, Simon,De Meester, Ingrid,Augustyns, Koen
-
scheme or table
p. 4159 - 4162
(2009/05/07)
-
- CARBOXYAMINE COMPOUNDS AND METHODS OF USE THEREOF
-
The invention relates to the use of carboxyamine compounds and salts thereof in the treatment of HDAC dependent diseases and for the manufacture of pharmaceutical preparations for the treatment of said diseases.
- -
-
Page/Page column 76
(2010/11/26)
-
- 1, 2, 4 -TRIAZOLE DERIVATIVES AS VASOPRESSIN ANTAGONISTS
-
Compounds of formula (I), or a pharmaceutically acceptable salt, solvate, ester or amide thereof, wherein R1 represents [CH2]n-R2; R2 represents H, C1-6 alkyloxy or Het; n represents a numb
- -
-
Page/Page column 40
(2010/11/25)
-