1262197-81-8Relevant articles and documents
1-CYANO-PYRROLIDINE DERIVATIVES AS DUB INHIBITORS
-
Paragraph 0889; 0894, (2020/11/30)
The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R1a, R1b, R1c, R1d, R1e and R1f each independently represent hydrogen, optionally substituted C1-C6 alkyl or optionally substituted C3-C4 cycloalkyl, or R1b and R1c together form an optionally substituted C3-C6 cycloalkyl ring, or R1d and R1e together form an optionally substituted C3-C6 cycloalkyl ring; R2 represents hydrogen or optionally substituted C1-C6 alkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.
NOVEL BICYCLIC PYRIDINONES AS GAMMA-SECRETASE MODULATORS
-
Page/Page column 46, (2015/04/22)
Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I I as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis,
Design and synthesis of dihydrobenzofuran amides as orally bioavailable, centrally active γ-secretase modulators
Pettersson, Martin,Johnson, Douglas S.,Subramanyam, Chakrapani,Bales, Kelly R.,Am Ende, Christopher W.,Fish, Benjamin A.,Green, Michael E.,Kauffman, Gregory W.,Lira, Ricardo,Mullins, Patrick B.,Navaratnam, Thayalan,Sakya, Subas M.,Stiff, Cory M.,Tran, Tuan P.,Vetelino, Beth C.,Xie, Longfei,Zhang, Liming,Pustilnik, Leslie R.,Wood, Kathleen M.,O'Donnell, Christopher J.
scheme or table, p. 2906 - 2911 (2012/06/04)
We report the discovery and optimization of a novel series of dihydrobenzofuran amides as γ-secretase modulators (GSMs). Strategies for aligning in vitro potency with drug-like physicochemical properties and good microsomal stability while avoiding P-gp mediated efflux are discussed. Lead compounds such as 35 and 43 have moderate to good in vitro potency and excellent selectivity against Notch. Good oral bioavailability was achieved as well as robust brain Aβ42 lowering activity at 100 mg/kg po dose.
