65576-45-6 Usage
Description
Asenapine is an atypical antipsychotic medication that functions as a combined serotonin (5HT2) and dopamine (D2) receptor antagonist. It is structurally related to Mianserin and is used to treat schizophrenia and bipolar I disorder. Asenapine exhibits high affinity for a range of receptors, including dopamine D1-4, α-adrenergic, and histamine receptors, as well as various serotonin receptor subtypes. This medication is characterized by its ability to inhibit the suppression of neuron firing induced by specific receptor agonists and increase extracellular dopamine levels in certain brain regions.
Uses
Used in Pharmaceutical Industry:
Asenapine is used as an antipsychotic agent for the treatment of schizophrenia and bipolar I disorder. It modulates the activity of various neurotransmitter receptors, which helps in managing the symptoms of these conditions.
Used in Research and Development:
Asenapine is also utilized in research settings to study the interactions between different neurotransmitter systems and their roles in psychiatric disorders. Its diverse receptor binding profile makes it a valuable tool for understanding the complex mechanisms underlying these conditions.
Chemical Properties:
Asenapine is a yellow oil at room temperature, which is an important characteristic for its formulation and administration.
Biological Activity
Novel psychopharmacologic agent. Displays antagonist activity at 5-HT, dopamine, noradrenalin and histamine receptor subtypes (pK i values are 8.60, 8.40, 10.15, 9.75, 10.46, 8.84, 9.60, 9.94, 8.85, 8.90, 8.84, 9.38, 8.95, 8.93, 8.9, 9.49, 8.91, 9.00 and 8.21 for 5-HT 1A , 5-HT 1B , 5-HT 2A , 5-HT 2B , 5-HT 2C , 5-HT 5A , 5-HT 6 , 5-HT 7 , D 1 , D 2L , D 2S , D 3 , D 4 , α 1A , α 2A , α 2B , α 2C , H 1 and H 2 receptors respectively). Displays no appreciable affinity for muscarinic receptors. Exhibits potent activity in animal models predictive of antipsychotic efficacy.
Clinical Use
Atypical antipsychotic
Treatment of schizophrenia and bipolar disease
Enzyme inhibitor
This atypical antipsychotic agent (FW = 285.77 g/mol; CAS 65576-45-6), marketed under the trade names Saphris ?, and also known as Org 5222 and (3aRS,12bRS)-rel-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3: 6,7]-oxepino-[4,5-c]pyrrole, is multi-receptor antagonist with the following spectrum of binding interactions: serotonin 5-HT1A receptor, Ki = 2.5 nM; serotonin 5-HT1B receptor, Ki = 4.0 nM; serotonin 5-HT2A receptor, Ki = 0.06 nM; serotonin 5-HT2B receptor, Ki = 0.16 nM; serotonin 5-HT2C receptor, Ki = 0.03 nM; serotonin 5-HT5A receptor, Ki = 1.6 nM; serotonin 5-HT6 receptor, Ki = 1.5 nM; serotonin 5-HT7 receptor, Ki = 0.13 nM; a1- Adrenergic receptor, Ki = 1.2 nM; a2A-Adrenergic receptor, Ki = 1.2 nM; a2B-Adrenergic receptor, Ki = 0.25 nM; a2C-Adrenergic receptor, Ki = 1.2 nM; dopamine D1-receptor, Ki = 1.4 nM; dopamine D2-receptor, Ki = 1.3 nM; dopamine D3-receptor, Ki = 0.4 nM; dopamine D4-receptor, Ki = 1.1 nM; histamine H1-receptor, Ki = 1.0 nM; and histamine H2-receptor, Ki = 6 nM. Like other atypical antipsychotic drugs, asenapine preferentially enhances dopamine and acetylcholine efflux in the rat medial prefrontal cortex and hippocampus. See Reference-x for asenapine’s UV, IR, NMR, and mass spectra as well as X-ray analysis, thermal properties, solubilities and partition coefficient.
Drug interactions
Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: increased risk of convulsions with
tramadol; enhanced hypotensive and sedative effects
with opioids.
Anti-arrhythmics: increased risk of ventricular
arrhythmias with anti-arrhythmics that prolong the
QT interval; avoid with amiodarone, disopyramide
and procainamide (risk of ventricular arrhythmias).
Antidepressants: concentration possibly increased
by fluvoxamine; possibly increased paroxetine
concentration; concentration of tricyclics possibly
increased.
Antiepileptics: antagonises anticonvulsant effect.
Antimalarials: avoid with artemether/lumefantrine.
Antivirals: concentration possibly increased by
ritonavir.
Anxiolytics and hypnotics: increased sedative effects.
Metabolism
Metabolism is by direct glucuronidation by UGT1A4
and oxidative metabolism by cytochrome P450
isoenzymes (predominantly CYP1A2) are the primary
metabolic pathways for asenapine.
Excretion is 50% renal and 50% via the faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 65576-45-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,5,5,7 and 6 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 65576-45:
(7*6)+(6*5)+(5*5)+(4*7)+(3*6)+(2*4)+(1*5)=156
156 % 10 = 6
So 65576-45-6 is a valid CAS Registry Number.
InChI:InChI=1/C17H16ClNO/c1-19-9-14-12-4-2-3-5-16(12)20-17-7-6-11(18)8-13(17)15(14)10-19/h2-8,14-15H,9-10H2,1H3/t14-,15-/m0/s1
65576-45-6Relevant articles and documents
For the preparation of asenapine and used for preparing intermediates of asenapine
-
, (2019/01/22)
The invention relates to a method for preparing asenapine shown in a general formula (9) and an intermediate shown in a general formula (7) and used for preparing asenapine. The general formulas are shown in the specification. The method comprises the step that asenapine shown in the general formula (9) is obtained through ring-closure reaction of a compound shown in a general formula (8).
A process for the preparation of key intermediate asenapine
-
, (2017/01/31)
The invention provides a chemical synthesis method, in particular to a preparation method of a key intermediate [formula (III)] compound of asenapine capable of serving as a schizophrenia drug. In an anhydrous system, the intermediate [formula (III)] compound is obtained through dehydration of an intermediate [formula (II)] compound and anhydride under the action of a catalyst. The invention further provides a novel method for preparing asenapine by the intermediate [formula (III)]. The provided method has the advantages of simple operation, high yield, environment-friendliness, lower cost, stable technology and the like.
PROCESS FOR THE PREPARATION OF ASENAPINE INTERMEDIATE
-
Paragraph 0034, (2014/11/27)
The present invention provides a process for the preparation of the asenapine intermediate of Formula (III) using a magnesium-methanol-acetic acid mixture.