Macrocyclic BACE-1 inhibitors acutely reduce Aβ in brain after po application
摘要:
A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDRI-MDCK assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while P-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Ab in human APP-wildtype transgenic (APP51/16) mice after oral administration. (C) 2009 Elsevier Ltd. All rights reserved.
[EN] COT MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE COT ET LEURS PROCÉDÉS D'UTILISATION
申请人:GILEAD SCIENCES INC
公开号:WO2020252151A1
公开(公告)日:2020-12-17
The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) of generic Formula (I) and methods of use and manufacture thereof.
本公开涉及一般性地与Cot(癌症大阪甲状腺)的通用化学式(I)的调节剂,以及其使用和制造方法。
MACROCYCLIC COMPOUNDS USEFUL AS BASE INHIBITORS
申请人:Betschart Claudia
公开号:US20090029960A1
公开(公告)日:2009-01-29
The invention relates to novel macrocyclic compounds of the formula
in which all of the variables are as defined in the specification, in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.
ETHANOLAMINE DERIVATIVES USEFUL AS BACE INHIBITORS
申请人:Frederiksen Mathias
公开号:US20100144741A1
公开(公告)日:2010-06-10
The invention relates to novel cyclic compounds of the formula (I), in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.
The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.
The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.