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Details

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

SHOW SMILES / InChI
Structure of SERGOLEXOLE

SMILES

[H][C@@]12CC3=CN(C(C)C)C4=CC=CC(=C34)[C@@]1([H])C[C@H](CN2C)C(=O)O[C@H]5CC[C@@H](CC5)OC

InChI

InChIKey=RJBJIKXTJIZONR-HSWWXKJFSA-N
InChI=1S/C26H36N2O3/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/h5-7,15-16,18-20,22,24H,8-14H2,1-4H3/t18-,19-,20-,22-,24-/m1/s1

HIDE SMILES / InChI

Molecular Formula C26H36N2O3
Molecular Weight 424.5756
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Approval Year

PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

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: Other
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 Fri Dec 15 18:55:27 UTC 2023
Edited
by admin
on Fri Dec 15 18:55:27 UTC 2023
Record UNII
J6TGA89COP
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SERGOLEXOLE
INN  
INN  
Official Name English
TRANS-4-METHOXYCYCLOHEXYL 1-ISOPROPYL-6-METHYLERGOLINE-8.BETA.-CARBOXYLATE
Systematic Name English
sergolexole [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C66885
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL2110594
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
EPA CompTox
DTXSID10148700
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
INN
6330
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
PUBCHEM
60262
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
MESH
C054583
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
CAS
108674-86-8
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
EVMPD
SUB10493MIG
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
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WIKIPEDIA
Sergolexole
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
SMS_ID
100000084117
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
NCI_THESAURUS
C152343
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
FDA UNII
J6TGA89COP
Created by admin on Fri Dec 15 18:55:27 UTC 2023 , Edited by admin on Fri Dec 15 18:55:27 UTC 2023
PRIMARY
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SALT/SOLVATE -> PARENT
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ACTIVE MOIETY