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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H36N2O3.C4H4O4
Molecular Weight 540.6478
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of SERGOLEXOLE MALEATE

SMILES

OC(=O)\C=C/C(O)=O.CO[C@H]1CC[C@@H](CC1)OC(=O)[C@@H]2C[C@H]3[C@@H](CC4=CN(C(C)C)C5=C4C3=CC=C5)N(C)C2

InChI

InChIKey=AWRYUNKJBYLYFR-RTFBGVDVSA-N
InChI=1S/C26H36N2O3.C4H4O4/c1-16(2)28-15-17-13-24-22(21-6-5-7-23(28)25(17)21)12-18(14-27(24)3)26(29)31-20-10-8-19(30-4)9-11-20;5-3(6)1-2-4(7)8/h5-7,15-16,18-20,22,24H,8-14H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t18-,19-,20-,22-,24-;/m1./s1

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C26H36N2O3
Molecular Weight 424.5756
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Sergolexole [LY 281067] is an ergoline ester similar in structure to amesergide [LY 237733], with potent and highly selective antagonist activity at serotonin 2. The preclinical pharmacologic activity of LY 281067 shows it to be a potent and highly selective serotonergic (5-HT2) receptor antagonist. Based upon binding studies with 5-HT2 receptors in brain cortical membranes and block of 5-HT-induced contractions in the rat jugular vein, LY 281067 showed high affinity at 5-HT2 receptors with a dissociation constant of approximately 1 nM. LY 281067 was a highly selective 5-HT2 receptor antagonist without appreciably binding to 5-HT1, D1 or D2 receptors or interacting with histamine (H1), cholinergic, beta adrenergic or alpha-1 adrenergic receptors in smooth muscle. LY 281067 had modest affinity at alpha-2 receptors with a dissociation constant of approximately 100 nM. Oral bioavailability of LY 281067 in spontaneously hypertensive rats was excellent with an oral to i.v. dose ratio approximating 4. Sergolexole was undergoing phase II clinical trials with Eli Lilly in the USA as a potential treatment for migraine and anxiety, but development of this compound, but development of this compound has been discontinued.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
5-Hydroxytryptamine2 receptor antagonist activity of the acid metabolite (1-isopropyl dihydrolysergic acid) of the ergoline ester, sergolexole (LY281067).
1989 Dec
Species variations in transmembrane region V of the 5-hydroxytryptamine type 2A receptor alter the structure-activity relationship of certain ergolines and tryptamines.
1994 Feb
Patents

Sample Use Guides

In Vivo Use Guide
Rats were each given a single dose of 0, 160 or 275 mg/kg of Sergolexole [LY 281067] by i.p. injection or 0, 300 or 500 mg/kg of LY 281067 by oral gavage. Five male and five female rats were used for each dose group. LY 281067 was prepared as a 50-mg/ml suspension in 10% aqueous acacia solution.
Route of Administration: i.p., p.o.
In Vitro Use Guide
Sergolexole (1 uM) blocked 5-HT-induced relaxation in endothelium denuded rings of canine coronary artery in an apparently competitive manner. In addition, the antagonist dissociation constant for sergolexole to antagonize 5-HT-induced relaxation was -log KB = 6.4. Sergolexole interacted with the cloned human 5-HT7 receptor with Ki value of 100.8 nM.
Substance Class Chemical
Created
by admin
on Tue Oct 22 06:09:08 UTC 2019
Edited
by admin
on Tue Oct 22 06:09:08 UTC 2019
Record UNII
XD5AHA648Y
Record Status Validated (UNII)
Record Version
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Name Type Language
SERGOLEXOLE MALEATE
USAN  
USAN  
Official Name English
LY-281067
Code English
ERGOLINE-8-CARBOXYLIC ACID, 6-METHYL-1-(1-METHYLETHYL)-, TRANS-4-METHOXYCYCLOHEXYL ESTER, (8.BETA.)-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
ERGOLINE-8-CARBOXYLIC ACID, 6-METHYL-1-(1-METHYLETHYL)-, 4-METHOXYCYCLOHEXYL ESTER, (8.BETA.(TRANS))-, (Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
SERGOLEXOLE MALEATE [USAN]
Common Name English
TRANS-4-METHOXYCYCLOHEXYL 6-METHYL-1-(1-METHYLETHYL)ERGOLINE-8.BETA.-CARBOXYLATE (Z)-2-BUTENEDIOATE (1:1)
Common Name English
LY281067
Code English
Classification Tree Code System Code
NCI_THESAURUS C66885
Created by admin on Tue Oct 22 06:09:09 UTC 2019 , Edited by admin on Tue Oct 22 06:09:09 UTC 2019
Code System Code Type Description
CAS
108674-87-9
Created by admin on Tue Oct 22 06:09:09 UTC 2019 , Edited by admin on Tue Oct 22 06:09:09 UTC 2019
PRIMARY
PUBCHEM
6435752
Created by admin on Tue Oct 22 06:09:09 UTC 2019 , Edited by admin on Tue Oct 22 06:09:09 UTC 2019
PRIMARY
NCI_THESAURUS
C152344
Created by admin on Tue Oct 22 06:09:09 UTC 2019 , Edited by admin on Tue Oct 22 06:09:09 UTC 2019
PRIMARY
ChEMBL
CHEMBL2110594
Created by admin on Tue Oct 22 06:09:09 UTC 2019 , Edited by admin on Tue Oct 22 06:09:09 UTC 2019
PRIMARY
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ACTIVE MOIETY