公开(公告)号：US20050037953A1

公开(公告)日：2005-02-17

申请号：US10471655

申请日：2002-03-15

Applicant: Ernesto Freire ,  Azia Nezami ,  Yoshiaki Kiso

Inventor： Ernesto Freire ,  Azia Nezami ,  Yoshiaki Kiso

IPC: A61K31/198 ,  A61K31/366 ,  A61K31/426 ,  A61K38/05 ,  A61K38/06 ,  C07C237/20 ,  A61K38/00

CPC classification number: C07C237/20 ,  A61K31/198 ,  A61K31/366 ,  A61K31/426 ,  A61K38/05 ,  A61K38/06 ,  Y02A50/411

Abstract: Compounds and methods for the inhibition of anti-malarial target aspartyl protease plasmepsins (e.g. Plasmepsin I, Plasmepsin II, Plasmepsin IV and HAP) are provided. The compounds are based on allophenylnorstatine substituted at positions R1-R4, such that R1 is isoquinoline, carboxyl, naphtalene, phenyl, phenol, benzene, an amino acid, and derivatives thereof; R2 and R3 are aliphatic groups; and R4 is indan, naphthalene, benzylamine, phenyl, phenol, cyclopentane, tert-butylamine, or derivatives thereof. The compounds may be used to inhibit Plasmepsin II, to kill malarial parasites, and to treat malaria in a patient. Certain of the substituted allophenylnorstatine-based compounds also exhibit inhibitory activity against Cathepsin D.

Abstract translation: 提供了用于抑制抗疟疾靶标天冬氨酰蛋白酶plasmepsin（例如Plasmepsin I，Plasmepsin II，Plasmepsin IV和HAP）的化合物和方法。 这些化合物基于在R1-R4位置被取代的异氰酸酯基，其中R 1是异喹啉，羧基，萘，苯基，苯酚，苯，氨基酸及其衍生物; R2和R3是脂族基团; R4为茚满，萘，苄胺，苯基，苯酚，环戊烷，叔丁胺或其衍生物。 该化合物可用于抑制Plasmepsin II，杀死疟疾寄生虫，并治疗患者的疟疾。 某些取代的基于异氰酸酯基的化合物也表现出对组织蛋白酶D的抑制活性。