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
| Molecular Formula | C20H23NO3 |
| Molecular Weight | 325.4015 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionSources: http://adisinsight.springer.com/drugs/800022078https://www.ncbi.nlm.nih.gov/pubmed/29067315 | https://www.ncbi.nlm.nih.gov/pubmed/24489014 | https://adisinsight.springer.com/drugs/800029247Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/16317384 | https://www.ncbi.nlm.nih.gov/pubmed/17902637
Sources: http://adisinsight.springer.com/drugs/800022078https://www.ncbi.nlm.nih.gov/pubmed/29067315 | https://www.ncbi.nlm.nih.gov/pubmed/24489014 | https://adisinsight.springer.com/drugs/800029247
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/16317384 | https://www.ncbi.nlm.nih.gov/pubmed/17902637
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.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| The activity of pathway-selective estrogen receptor ligands in experimental septic shock. | 2005 Dec |
|
| 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 |
|
| A double-blind, randomized, placebo-controlled crossover trial of the α2C-adrenoceptor antagonist ORM-12741 for prevention of cold-induced vasospasm in patients with systemic sclerosis. | 2014 May |
|
| The α2C-adrenoceptor antagonist, ORM-10921, has antipsychotic-like effects in social isolation reared rats and bolsters the response to haloperidol. | 2016 Nov 3 |
|
| Therapeutic Potential of Selectively Targeting the α(2C)-Adrenoceptor in Cognition, Depression, and Schizophrenia-New Developments and Future Perspective. | 2017 |
|
| The α2C-adrenoceptor antagonist, ORM-10921, exerts antidepressant-like effects in the Flinders Sensitive Line rat. | 2017 Feb |
|
| Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer's disease. | 2017 Jan |
Patents
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 10:35:02 GMT 2023
by
admin
on
Sat Dec 16 10:35:02 GMT 2023
|
| Record UNII |
D26C95A960
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Code | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
100000184092
Created by
admin on Sat Dec 16 10:35:02 GMT 2023 , Edited by admin on Sat Dec 16 10:35:02 GMT 2023
|
PRIMARY | |||
|
DB12057
Created by
admin on Sat Dec 16 10:35:02 GMT 2023 , Edited by admin on Sat Dec 16 10:35:02 GMT 2023
|
PRIMARY | |||
|
1106938-11-7
Created by
admin on Sat Dec 16 10:35:02 GMT 2023 , Edited by admin on Sat Dec 16 10:35:02 GMT 2023
|
NON-SPECIFIC STEREOCHEMISTRY | |||
|
25175001
Created by
admin on Sat Dec 16 10:35:02 GMT 2023 , Edited by admin on Sat Dec 16 10:35:02 GMT 2023
|
PRIMARY | |||
|
D26C95A960
Created by
admin on Sat Dec 16 10:35:02 GMT 2023 , Edited by admin on Sat Dec 16 10:35:02 GMT 2023
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
ACTIVE MOIETY |
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.
|
||
|
ACTIVE MOIETY |
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)
|
