BMY-7378

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H31N3O3.2ClH
Molecular Weight	458.422
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.COC1=CC=CC=C1N2CCN(CCN3C(=O)CC4(CCCC4)CC3=O)CC2

InChI

InChIKey=NIBOMXUDFLRHRV-UHFFFAOYSA-N

InChI=1S/C22H31N3O3.2ClH/c1-28-19-7-3-2-6-18(19)24-13-10-23(11-14-24)12-15-25-20(26)16-22(17-21(25)27)8-4-5-9-22;;/h2-3,6-7H,4-5,8-17H2,1H3;2*1H

HIDE SMILES / InChI

Molecular Formula	C22H31N3O3
Molecular Weight	385.4998
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16176444 | https://www.ncbi.nlm.nih.gov/pubmed/7713154
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1970304

BMY-7378 is a multi-targeted inhibitor of α2C-adrenoceptor and α1D-adrenoceptor with pKi of 6.54 and 8.2, respectively, and acts as a mixed agonist and antagonist for 5-HT1A receptor with pKi of 8.3. BMY-7378 was at the preclinical stage of development for the treatment of anxiety disorders, but later was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Alpha-2c adrenergic receptor 37 Target ID: CHEMBL1916 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16176444	Antagonist 2778	6.54 null [pKi]
Alpha-1d adrenergic receptor 36 Target ID: CHEMBL223 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7713154 \| https://www.ncbi.nlm.nih.gov/pubmed/21514979	Antagonist 2778	8.2 null [pKi]
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7713154	Partial Agonist 290	8.3 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 267 Sources: http://adisinsight.springer.com/drugs/800001317	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Pharmacological characterization of recombinant human 5-hydroxytryptamine1A receptors using a novel antagonist radioligand, [3H]WAY-100635.	1997	9048968
Molecular cloning and functional expression of the guinea pig alpha(1a)-adrenoceptor.	2001 Aug 31	11527538
Alpha1-adrenoceptor subtypes on rat afferent arterioles assessed by radioligand binding and RT-PCR.	2001 Jul	11399658
Characterization of alpha1-adrenoceptor-mediated contraction in the mouse thoracic aorta.	2001 Jul 20	11476759
Affinity of serotonin receptor antagonists and agonists to recombinant and native alpha1-adrenoceptor subtypes.	2001 Jun	11459121
Failure of AH11110A to functionally discriminate between alpha(1)-adrenoceptor subtypes A, B and D or between alpha(1)- and alpha(2)-adrenoceptors.	2001 Mar	11275009
Use of antisense oligonucleotides to verify the role of the alpha(1A)-adrenergic receptor in the contractility of the rat uterus post partum.	2001 May	11306708
Two novel and potent 3-[(o-methoxyphenyl)piperazinylethyl]-5-phenylthien.	2001 May 7	11354357
Functional characterization of alpha1-adrenoceptor subtypes in human subcutaneous resistance arteries.	2001 Nov	11602687
Pharmacological characterization of alpha1-adrenoceptor in mouse iliac artery.	2002 Dec 5	12450572
alpha(1A)-adrenoceptors mediate sympathetically evoked pupillary dilation in rats.	2002 Feb	11805212
Evidence for the role of alpha1D- and alpha1A-adrenoceptors in contraction of the rat mesenteric artery.	2003 Feb	12646397
Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats.	2003 Jun 20	12818701
Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to alpha1D subtypes overexpressed in cell membrane.	2004 Aug	15493479
Evidence that alpha(1B)-adrenoceptors are involved in noradrenaline-induced contractions of rat tail artery.	2004 Mar 19	15044047
The hypotensive effect of BMY 7378 involves central 5-HT1A receptor stimulation in the adult but not in the young rat.	2004 Nov-Dec	15631873
Cloned human 5-HT1A receptor pharmacology determined using agonist binding and measurement of cAMP accumulation.	2004 Oct	15482641
Pharmacological characterization of alpha1-adrenoceptors in mouse isolated femoral small arteries.	2004 Oct 25	15496310
Differential distribution of functional alph}1-adrenergic receptor subtypes along the rat tail artery.	2005 Aug	15872040
Correlation between mRNA levels and functional role of alpha1-adrenoceptor subtypes in arteries: evidence of alpha1L as a functional isoform of the alpha1A-adrenoceptor.	2005 Nov	15951348
Heterodimers of alpha1B- and alpha1D-adrenergic receptors form a single functional entity.	2006 Jan	16195468
Selective agonists reveal alpha(1A)- and alpha(1B)-adrenoceptor subtypes in caudal artery of the young rat.	2006 Oct	16968476
Alpha(1A/L)-adrenoceptors mediate contraction of the circular smooth muscle of the pig urethra.	2006 Oct	16968473
Mechanical function and gene expression of alpha(1)-adrenoceptor subtypes in dog intravesical ureter.	2009 Aug	19371927
Adventitia removal does not modify the alphaID-adrenoceptors response in aorta during hypertension and ageing.	2009 Jul	19566752
Phenylephrine contracts porcine pulmonary veins via alpha(1B)-, alpha(1D)-, and alpha(2)-adrenoceptors.	2009 Jun 24	19376108
Inhibitory effect of fentanyl on phenylephrine-induced contraction of the rat aorta.	2009 Jun 30	19568605

Patents

Sample Use Guides

In Vivo Use Guide

Rats: BMY-7378 dose dependently (0.25-5 mg/kg s.c.) reduces the undetectable levels forepaw treading and head weaving induced by 8-OH-DPAT (0.75 mg/kg s.c.) in rats.

Route of Administration: Other

In Vitro Use Guide

BMY-7378 at concentration of 1 nM to 30 nM elicits inhibitory effects in a concentration-dependent manner in the rat dorsal raphe nucleus.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:57:48 GMT 2023` Edited by `admin` on `Sat Dec 16 09:57:48 GMT 2023`
Record UNII	KC07KV8T5O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BMY-7378

Common Name

English

8-AZASPIRO(4.5)DECANE-7,9-DIONE, 8-(2-(4-(2-METHOXYPHENYL)-1-PIPERAZINYL)ETHYL)-, DIHYDROCHLORIDE

Systematic Name

English

1,1-CYCLOPENTANEDIACETIMIDE, N-(2-(4-(O-METHOXYPHENYL)-1-PIPERAZINYL)ETHYL)-, DIHYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID10175334