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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	38
Udgave nummer	2
Sider (fra-til)	272-6
Antal sider	5
ISSN	0022-2623
Status	Udgivet - 1995

Citationsformater

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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

Fingeraftryk

Citationsformater