Synthesis and anticholinesterase activity of huperzine a analogues containing phenol and catechol replacements for the pyridone ring

Giuseppe Campiani; Alan P. Kozikowski; Shaomeng Wang; Liu Ming; Vito Nacci; Ashima Saxena; Bhupendra P. Doctor

doi:10.1016/S0960-894X(98)00229-7

Synthesis and anticholinesterase activity of huperzine a analogues containing phenol and catechol replacements for the pyridone ring

Giuseppe Campiani, Alan P. Kozikowski, Shaomeng Wang, Liu Ming, Vito Nacci, Ashima Saxena, Bhupendra P. Doctor

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

31 Scopus citations

Abstract

Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.

Original language	English (US)
Pages (from-to)	1413-1418
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	8
Issue number	11
DOIs	https://doi.org/10.1016/S0960-894X(98)00229-7
State	Published - Jun 2 1998
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0960-894X(98)00229-7

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title = "Synthesis and anticholinesterase activity of huperzine a analogues containing phenol and catechol replacements for the pyridone ring",

abstract = "Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.",

author = "Giuseppe Campiani and Kozikowski, {Alan P.} and Shaomeng Wang and Liu Ming and Vito Nacci and Ashima Saxena and Doctor, {Bhupendra P.}",

note = "Funding Information: Acknowledgment. We are indebted to the Dept. of Defense (DAMD17-93-V-3018) and MURST-Roma (Italy) for support of our research program. The authors also thank Sandra Gemma for her efforts.",

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T1 - Synthesis and anticholinesterase activity of huperzine a analogues containing phenol and catechol replacements for the pyridone ring

AU - Campiani, Giuseppe

AU - Kozikowski, Alan P.

AU - Wang, Shaomeng

AU - Ming, Liu

AU - Nacci, Vito

AU - Saxena, Ashima

AU - Doctor, Bhupendra P.

N1 - Funding Information: Acknowledgment. We are indebted to the Dept. of Defense (DAMD17-93-V-3018) and MURST-Roma (Italy) for support of our research program. The authors also thank Sandra Gemma for her efforts.

PY - 1998/6/2

Y1 - 1998/6/2

N2 - Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.

AB - Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.

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Synthesis and anticholinesterase activity of huperzine a analogues containing phenol and catechol replacements for the pyridone ring

Abstract

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