135729-61-2 Usage
Description
Palonosetron is a new generation 5-HT3 antagonist and It has hasgreater receptor-binding properties, which results in a much longer half-life than the previously described drugs. This selective and conformationally restricted 5-HT3 receptor antagonist was approved for the treatment of chemotherapy-induced nausea and vomiting. The drug was originally developed by Syntex Corp (now Roche Bioscience) and is currently being developed by Helsinn and MGI Pharm.
Uses
Palonosetron is a serotonin 5-HT3 receptor antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). Antiemetic.
Definition
ChEBI: An organic heterotricyclic compound that is an antiemetic used (as its hydrochloride salt) in combination with netupitant (under the trade name Akynzeo) to treat nausea and vomiting in patients undergoing cancer chemotherapy.
Clinical Use
Anti-emetic:
For use with cancer chemotherapy
Synthesis
(S)-3-Aminoquinuclidine was condensed with
inexpensive 1,8-naphthalic anhydride (138) to furnish imide
139 in 93% yield and isolated as its TFA salt. Imide
139 was hydrogenated at 5 psi to give intermediate 140 with
one of the reduced aromatic ring. The less hindered C-3
carbonyl group in 140 was selectively reduced to a hydroxy
group by using sodium borohydride in ethanol under
nitrogen at low temperature to give intermediate 141.
Intermediate 141 was not isolated because of the formation
of a tight boron complex. Subsequently, acid was added to
141 in i-PrOH to decompose the boron complex and
dehydrate intermediate 141 to 142, which was conveniently isolated as its HCl salt in 75% yield from 139. Palonosetron
(XVIII) was obtained in 57% yield by palladium-catalyzed
hydrogenation of 142.
Enzyme inhibitor
This serotonin 5-HT3 receptor antagonist and longlasting anti-emetic (FW = 296.41 g/mol; CAS 135729-61-2), known by code name RS 25259, RS 25259-197, trade name Aloxi?, and systematic name (3aS)-2-[(3S)-1- azabicyclo[2.2.2]oct-3-yl]-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin- 1-one, is used to treat chemotherapy-induced nausea/vomiting. Polonosetron affects both peripheral and central nervous systems, reducing vagus nerve activity, thereby deactivating the 5-HT3 receptor-dense vomiting center located in the medulla oblongata. It is without effect on dopamine receptors or muscarinic receptors. Primary Mode of Inhibitor Action: Intravenously administered palonosetron has a linear pharmacokinetic profile, with a long terminal elimination half-life of ~40 hours and moderate (62%) plasma protein binding. Its high affinity and long half-life most likely explains its persistent antiemetic effect. Similar 5- HT3 antagonists include tropisetron, ondansetron, dolasetron, and granisetron. The effectiveness of each depends on particular variants of 5- HT3 receptors expressed by the patient, including changes in promoters for the receptor genes
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Palonosetron is eliminated by a dual route, about 40%
eliminated through the kidney and approximately
50% metabolised by CYP2D6, and to a lesser extent,
CYP3A4 and CYP1A2 isoenzymes in the liver to form
two primary metabolites, which have less than 1% of
the 5HT3
receptor antagonist activity of palonosetron.
After a single intravenous dose of [14C]-palonosetron,
approximately 80% of the dose was recovered within
144 hours in the urine with unchanged palonosetron
representing approximately 40% of the administered dose.
Check Digit Verification of cas no
The CAS Registry Mumber 135729-61-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,5,7,2 and 9 respectively; the second part has 2 digits, 6 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 135729-61:
(8*1)+(7*3)+(6*5)+(5*7)+(4*2)+(3*9)+(2*6)+(1*1)=142
142 % 10 = 2
So 135729-61-2 is a valid CAS Registry Number.
InChI:InChI=1/C19H24N2O/c22-19-16-6-2-4-14-3-1-5-15(18(14)16)11-21(19)17-12-20-9-7-13(17)8-10-20/h2,4,6,13,15,17H,1,3,5,7-12H2/t15-,17+/m0/s1
135729-61-2Relevant articles and documents
A hydrochloric acid palonosetron production method
-
, (2017/08/25)
The invention belongs to the field of organic synthesis, and particularly relates to a production method of high-purity and high-yield palonosetron hydrochloride. Chiral compounds, namely, (S)-(-)-1,2,3,4-tetrahedro-naphthoic acid and S-3-aminoquinuclidine, are taken as raw materials, and an intermediate is obtained; the intermediate has a reduction reaction in the presence of NaBH4 and BF3*CH3OH, a product is added to a hydrochloric acid aqueous solution for a reflux reaction after the reaction, and a transparent oily substance is obtained through extraction after the reflux reaction; toluene is added to the substance, a toluene solution of triphosgene is dropwise added again at the temperature ranging from 10 DEG C to 15 DEG C, white solids are separated out, a reaction is performed under the condition of heating reflux, and the toluene solution of the triphosgene is dropwise added again under the reflux condition; then a system is cooled to the temperature ranging from 10 DEG C to 15 DEG C, BF3*CH3OH is added, the system is added to water and the hydrochloric acid aqueous solution at the reflux temperature after addition, then a reflux reaction is performed at the heating reflux temperature, and then a crude product is obtained through washing, extraction and crystallization; the crude product is dissolved in acetone, repeated crystallization is performed after dissolution, and the refined palonosetron hydrochloride is obtained. Steps are simple and convenient, reaction conditions are mild, and the production method is easy to operate and suitable for industrial production.
Process for the Preparation of Substantially Pure Palonosetron and its Acid Salts
-
Page/Page column 5, (2011/02/18)
This invention relates to an improved and scalable process for the preparation of substantially pure palonosetron and its acid addition salts, in particular hydrochloride (I) which comprises of, (a) converting intermediate (IIa) as such or as its freebase (II) to a crude mixture of diastereomeric palonosetrons (VIII) or (VIIIa) contaminated with varying amounts of unconverted intermediate (II) or (IIa) via hydrogenation under pressure with an appropriately chosen hydrogenation catalyst in an suitable organic solvent.(b) making the resulting crude mixture of diastereomeric palonosetrons (VIII) or (VIIIa) contaminated with varying amounts of unconverted intermediate (II) or (IIa) substantially free from (II) or (IIa) via halogenation reaction.(c) Finally, converting the resulting diastereomeric palonosetron (VIII) or its hydrochloride (VIIIa) substantially free from intermediate (II) or (IIa) to the desired palonosetron hydrochloride (I) in substantially pure form via selective crystallization from a suitable single or mixture of organic solvents.
PALONOSETRON FREE BASE AND PROCESS FOR ITS PREPARATION
-
Page/Page column 21-22, (2009/09/04)
The present invention provides novel palonosetron free base in an amorphous form and crystalline form-G and processes for their preparation. The present invention also provides a process for the preparation of palonosetron hydrochloride from the novel palonosetron free base in an amorphous form and/or in crystalline form-G.
