Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors

Wenge Zhong; Hu Liu; Matthew R. Kaller; Charles Henley; Ella Magal; Thomas Nguyen; Timothy D. Osslund; David Powers; Robert M. Rzasa; Hui Ling Wang; Weiya Wang; Xiaoling Xiong; Jiandong Zhang; Mark H. Norman

doi:10.1016/j.bmcl.2007.07.045

Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors

Wenge Zhong
, Hu Liu
, Matthew R. Kaller
, Charles Henley
, Ella Magal
, Thomas Nguyen
, Timothy D. Osslund
, David Powers
, Robert M. Rzasa
, Hui Ling Wang
, Weiya Wang
, Xiaoling Xiong
, Jiandong Zhang
, Mark H. Norman

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Cyclin-dependent kinase 5 (CDK5) is a serine/threonine protein kinase and its deregulation is implicated in a number of neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Using active site homology modeling between CDK5 and CDK2, we explored several different chemical series of potent CDK5 inhibitors. In this report, we describe the design, synthesis, and CDK5 inhibitory activities of quinolin-2(1H)-one derivatives.

Original language	English
Pages (from-to)	5384-5389
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2007.07.045
State	Published - 1 Oct 2007
Externally published	Yes

Keywords

CDK5 inhibitor
Kinase
Neurodegenerative disorders
Quinolin-2(1H)-one

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10.1016/j.bmcl.2007.07.045

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title = "Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors",

abstract = "Cyclin-dependent kinase 5 (CDK5) is a serine/threonine protein kinase and its deregulation is implicated in a number of neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Using active site homology modeling between CDK5 and CDK2, we explored several different chemical series of potent CDK5 inhibitors. In this report, we describe the design, synthesis, and CDK5 inhibitory activities of quinolin-2(1H)-one derivatives.",

keywords = "CDK5 inhibitor, Kinase, Neurodegenerative disorders, Quinolin-2(1H)-one",

author = "Wenge Zhong and Hu Liu and Kaller, \{Matthew R.\} and Charles Henley and Ella Magal and Thomas Nguyen and Osslund, \{Timothy D.\} and David Powers and Rzasa, \{Robert M.\} and Wang, \{Hui Ling\} and Weiya Wang and Xiaoling Xiong and Jiandong Zhang and Norman, \{Mark H.\}",

year = "2007",

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doi = "10.1016/j.bmcl.2007.07.045",

language = "English",

volume = "17",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors

AU - Zhong, Wenge

AU - Liu, Hu

AU - Kaller, Matthew R.

AU - Henley, Charles

AU - Magal, Ella

AU - Nguyen, Thomas

AU - Osslund, Timothy D.

AU - Powers, David

AU - Rzasa, Robert M.

AU - Wang, Hui Ling

AU - Wang, Weiya

AU - Xiong, Xiaoling

AU - Zhang, Jiandong

AU - Norman, Mark H.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Cyclin-dependent kinase 5 (CDK5) is a serine/threonine protein kinase and its deregulation is implicated in a number of neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Using active site homology modeling between CDK5 and CDK2, we explored several different chemical series of potent CDK5 inhibitors. In this report, we describe the design, synthesis, and CDK5 inhibitory activities of quinolin-2(1H)-one derivatives.

AB - Cyclin-dependent kinase 5 (CDK5) is a serine/threonine protein kinase and its deregulation is implicated in a number of neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Using active site homology modeling between CDK5 and CDK2, we explored several different chemical series of potent CDK5 inhibitors. In this report, we describe the design, synthesis, and CDK5 inhibitory activities of quinolin-2(1H)-one derivatives.

KW - CDK5 inhibitor

KW - Kinase

KW - Neurodegenerative disorders

KW - Quinolin-2(1H)-one

UR - https://www.scopus.com/pages/publications/34548569914

U2 - 10.1016/j.bmcl.2007.07.045

DO - 10.1016/j.bmcl.2007.07.045

M3 - Article

C2 - 17709247

AN - SCOPUS:34548569914

SN - 0960-894X

VL - 17

SP - 5384

EP - 5389

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 19

ER -

Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors

Abstract

Keywords

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