Flibanserin

Bezeichnung:Flibanserin

CAS-Nr167933-07-5

Englisch Name:Flibanserin

CBNumberCB91178756

SummenformelC20H21F3N4O

Molgewicht390.4

MOL-Datei167933-07-5.mol

Flibanserin physikalisch-chemischer Eigenschaften

Dichte	1.292±0.06 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: soluble10mg/mL, clear
Aggregatzustand	powder
pka	12.12±0.30(Predicted)
Farbe	white to beige
InChI	InChI=1S/C20H21F3N4O/c21-20(22,23)15-4-3-5-16(14-15)26-11-8-25(9-12-26)10-13-27-18-7-2-1-6-17(18)24-19(27)28/h1-7,14H,8-13H2,(H,24,28)
InChIKey	PPRRDFIXUUSXRA-UHFFFAOYSA-N
SMILES	C1(=O)N(CCN2CCN(C3=CC=CC(C(F)(F)F)=C3)CC2)C2=CC=CC=C2N1

Sicherheit

Kennzeichnung gefährlicher	T
R-Sätze:	25-36/37/38
S-Sätze:	26-45
RIDADR	UN 2811 6.1 / PGIII
WGK Germany	3
Giftige Stoffe Daten	167933-07-5(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Flibanserin Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Flibanserin is a drug originally developed by Boehringer-Ingelheim and later Sprout Pharmaceuticals, which was approved in 2015 by the FDA for the treatment of premenopausal women with hypoactive sexual desire disorder (HSDD). The drug, which was originally developed for the treatment of depression by Boehringer- Ingelheim, is a full agonist of the 5-HT1A receptor, an antagonist of the 5-HT2A receptor, and a partial agonist of the dopamine-4 (D4) receptor, which triggers increased dopamine and norepinephrine levels along with decreased serotonin levels. In three randomized trials involving 2400 premenopausal women, the drug was found to increase the number of satisfying sexual events by 0.5-1.0 events per month and increased sexual desire on average by 10-12% over placebo. Side effects include decreased blood pressure and loss of consciousness, especially in subjects who consumed alcohol.
Verwenden
Antidepressant (5-HT1a agonist and 5-HT2 antagonist).
Definition
ChEBI: Flibanserin is an N-alkylpiperazine that is 1-[2-(1,3-dihydro-2-oxobenzimidazol-1-yl)ethyl]piperazine in which the remaining amino proton is replaced by a 3-(trifluoromethyl)phenyl group. A multifunctional serotonin agonist and antagonist which is used for the treatment of pre-menopausal women with hypoactive sexual desire disorder. It has a role as a serotonergic agonist, a serotonergic antagonist and an antidepressant. It is a member of benzimidazoles, a N-arylpiperazine, a N-alkylpiperazine and an organofluorine compound.
Biochem/physiol Actions
Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist. Flibanserin has high affinity for human 5-HT1A receptors (Ki = 1 nm) and lower affinity for 5-HT2A (Ki = 49 nm) and D4 (Ki = 4–24 nm) receptors, and negligible affinity for a variety of other neurotransmitter receptors and ion channels. Flibanserin was investigated as a novel, non-hormonal treatment for pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD). Flibanserin. Recently, Flibanserin was found to reduce L-DOPA-induced dyskinesia in a model of Parkinson′s Disease.
Synthese
The large-scale synthesis of flibanserin (X) mostly follows a patent from Symed Laboratories Limited which demonstrated hundred-gram-scale preparation of the drug as described in Scheme. Starting from commercially available 1-(prop-1- en-2-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (74), installation of an ethylene side chain was accomplished under conventional alkylation conditions with 1,2-dibromoethane and base, and this event was immediately followed by a second alkylation reaction involving piperazine to secure piperazinyl benzimidazolone 75. Interestingly, the enamine double bond within 74 was apparently reduced to the corresponding isopropyl group under these conditions. Although the authors do not comment about this reduction directly, similar examples of olefin reduction under non-hydrogenative alkylation conditions have been reported in the literature separately by both Pai and Ryu. Removal of the isopropyl group was facilitated by means of aqueous sodium hydroxide to afford 76, which underwent N-arylation under Buchwald conditions with 1-bromo-3-(trifluoromethyl)benzene 77 to furnish flibanserin (X) in 63% yield.
in vitro
previous study found that flibanserin was a 5-ht(1a) agonist, a very weak partial agonist on dopamine d(4) receptors, and a 5-ht(2a) antagonist. flibanserin could reduce neuronal firing rate and flibanserin-induced reduction in firing rate was likely mediated via stimulation of postsynaptic 5-ht(1a) receptors. moreover, flibanserin could quickly desensitize somatic 5-ht autoreceptors and enhance tonic activation of postsynaptic 5-ht(1a) receptors. in addition, flibanserin was able to reduce synthesis and extracellular levels of 5-ht in the cortex [1].
in vivo
previous animal study showd that flibanserin had antidepressant-like activity in most animal models sensitive to antidepressants, and such activity seemed different from that exerted by other antidepressants. in addition, flibanserin did not show consistent effects in animal models of anxiety and seemed to exert potential antipsychotic effects [1].
Einzelnachweise
[1] borsini f, evans k, jason k, rohde f, alexander b, pollentier s. pharmacology of flibanserin. cns drug rev. 2002 summer;8(2):117-42.
[2] katz m et al. efficacy of flibanserin in women with hypoactive sexual desire disorder: results from the begonia trial. j sex med. 2013 jul;10(7):1807-15.

Flibanserin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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