ORM-12741

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H23NO3
Molecular Weight	325.4015
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

OC1=CC=CC(=C1)[C@H]2CCCN(C[C@H]3COC4=CC=CC=C4O3)C2

InChI

InChIKey=FOESNAGBEJURCI-WMZOPIPTSA-N

InChI=1S/C20H23NO3/c22-17-7-3-5-15(11-17)16-6-4-10-21(12-16)13-18-14-23-19-8-1-2-9-20(19)24-18/h1-3,5,7-9,11,16,18,22H,4,6,10,12-14H2/t16-,18-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C20H23NO3
Molecular Weight	325.4015
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Juvantia Pharma and Orion developed ORM-12741, also known as ORM-10921, a novel selective antagonist of alpha-2C adrenoceptors for the treatment of depression and Alzheimer's disease. ORM-12741 participated in phase II clinical trial where was evaluated the safety and efficacy of the drug in patients with Alzheimer's disease. In spite of the successfully completed phase II, further study of the drug for this disease was discontinued. In addition, ORM-12741 participated in clinical trial phase II to prove the concept that this drug could prevent blood vessel spasms for Raynaud's phenomenon. Raynaud's phenomenon is a disorder of the digital blood vessels resulting in episodic impairment of blood flow. However, this study was terminated because of the recommendation by study Data and Safety Monitoring Committee to the sponsor following the interim analysis of 8 subjects.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor 75	Interacts 323
Nuclear factor NF-kappa-B complex 11	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Septic shock 21	Primary		Preclinical	Unknown
Rheumatoid arthritis 316	Primary		Phase I 428	Unknown

PubMed

Show entries

Title	Date	PubMed
The activity of pathway-selective estrogen receptor ligands in experimental septic shock.	2005 Dec	16317384
Estrogen receptor dependent inhibitors of NF-kappaB transcriptional activation-1 synthesis and biological evaluation of substituted 2-cyanopropanoic acid derivatives: pathway selective inhibitors of NF-kappaB, a potential treatment for rheumatoid arthritis.	2007 Nov 1	17902637
The α2C-adrenoceptor antagonist, ORM-10921, exerts antidepressant-like effects in the Flinders Sensitive Line rat.	2017 Feb	27749317

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Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical
Record UNII	D26C95A960
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ORM-12741

Code

English

DB-105

Code

English

Phenol, 3-[(3R)-1-[[(2S)-2,3-dihydro-1,4-benzodioxin-2-yl]methyl]-3-piperidinyl]-

Systematic Name

English

3-[(3R)-1-[[(2S)-2,3-Dihydro-1,4-benzodioxin-2-yl]methyl]-3-piperidinyl]phenol

Systematic Name

English

Showing 1 to 4 of 4 entries

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Code System

Code

Type

Description

SMS_ID

100000184092

PRIMARY

DRUG BANK

DB12057

PRIMARY

CAS

1106938-11-7

NON-SPECIFIC STEREOCHEMISTRY

PUBCHEM

25175001

PRIMARY

FDA UNII

D26C95A960

PRIMARY

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Related Record

Type

Details

D26C95A960

ORM-12741

ACTIVE MOIETY

Comments:

Standard in vitro receptor assays and antagonism of .ALPHA.2, and .ALPHA.1-AR agonist-evoked responses in vivo were used to demonstrate the .ALPHA.2C-AR selectivity for ORM-10921 which was tested in established behavioural models related to schizophrenia and cognitive dysfunction with an emphasis on pharmacologically induced hypoglutamatergic state by phencyclidine or MK-801. The Kb values of in vitro .ALPHA.2C-AR antagonism for ORM-10921 varied between 0.078-1.2 nM depending on the applied method. The selectivity ratios compared to .ALPHA.2A-AR subtype and other relevant receptors were 10-100 times in vitro. The in vivo experiments supported its potent .ALPHA.2C-antagonism combined with only a weak .ALPHA.2A-antagonism. In the pharmacodynamic microdialysis study, ORM-10921 was found to increase extracellular dopamine levels in prefrontal cortex in the baseline conditions.

Amount:

D26C95A960

ORM-12741

ACTIVE MOIETY

Comments:

Originator: Juvantia Pharma (CEASED), Orion; Class: Neuropsychotherapeutic; Mechanism of Action: Alpha 2c adrenergic receptor antagonist; Highest Development Phase: Discontinued for Major depressive disorder, Schizophrenia; Most Recent Events: 10 May 2006 Discontinued - Phase-I for Schizophrenia in Finland (unspecified route), 10 May 2006 Discontinued - Preclinical for Depression in Finland (unspecified route)

Amount:

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