Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12

S F Nielsen; Ole Thastrup; R Pedersen; C E Olsen; S B Christensen

Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12

S F Nielsen, Ole Thastrup, R Pedersen, C E Olsen, S B Christensen

31 Citations (Scopus)

Abstract

A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	38
Issue number	2
Pages (from-to)	272-6
Number of pages	5
ISSN	0022-2623
Publication status	Published - 1995

Keywords

Animals
Calcium-Transporting ATPases
Muscles
Rabbits
Structure-Activity Relationship
Terpenes
Thapsigargin

Cite this

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title = "Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12",

abstract = "A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme.",

keywords = "Animals, Calcium-Transporting ATPases, Muscles, Rabbits, Structure-Activity Relationship, Terpenes, Thapsigargin",

author = "Nielsen, {S F} and Ole Thastrup and R Pedersen and Olsen, {C E} and Christensen, {S B}",

year = "1995",

language = "English",

volume = "38",

pages = "272--6",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "2",

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TY - JOUR

T1 - Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12

AU - Nielsen, S F

AU - Thastrup, Ole

AU - Pedersen, R

AU - Olsen, C E

AU - Christensen, S B

PY - 1995

Y1 - 1995

N2 - A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme.

AB - A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme.

KW - Animals

KW - Calcium-Transporting ATPases

KW - Muscles

KW - Rabbits

KW - Structure-Activity Relationship

KW - Terpenes

KW - Thapsigargin

M3 - Journal article

C2 - 7830270

SN - 0022-2623

VL - 38

SP - 272

EP - 276

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 2

ER -

Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12

Abstract

Keywords

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