Vestipitant

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 203130

CAS#: 334476-46-9

Description: Vestipitant, also known as GW597599, is one of the most potent and selective NK(1) receptor antagonists ever discovered, showing appropriate pharmacokinetic properties and in vivo activity. Its actions support the utility of NK(1) receptor blockade in the alleviation of anxiety and, possibly, depression. It is under development as a potential antiemetic and anxiolytic drug, and as a treatment for tinnitusand insomnia.


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10mg
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1g
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2g
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5g
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Vestipitant is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 203130
Name: Vestipitant
CAS#: 334476-46-9
Chemical Formula: C23H24F7N3O
Exact Mass: 491.18076
Molecular Weight: 491.44
Elemental Analysis: C, 56.21; H, 4.92; F, 27.06; N, 8.55; O, 3.26


Related CAS #: 334476-46-9 (free)   334476-64-1 (Mesylate)  

Synonym: GW597599; GW 597599; GW-597599; Vestipitant

IUPAC/Chemical Name: (2S)-N-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-N-methylpiperazine-1-carboxamide

InChi Key: SBBYBXSFWOLDDG-JLTOFOAXSA-N

InChi Code: InChI=1S/C23H24F7N3O/c1-13-8-18(24)4-5-19(13)20-12-31-6-7-33(20)21(34)32(3)14(2)15-9-16(22(25,26)27)11-17(10-15)23(28,29)30/h4-5,8-11,14,20,31H,6-7,12H2,1-3H3/t14-,20-/m1/s1

SMILES Code: O=C(N1[C@@H](C2=CC=C(F)C=C2C)CNCC1)N([C@@H](C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)C)C


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Vestipitant is a drug developed by GlaxoSmithKline which acts as a selective antagonist for the NK1 receptor. It is under development as a potential antiemetic and anxiolytic drug, and as a treatment for tinnitus.
 
Vestipitant has anxiolytic properties and a good safety profile. Vestipitant was investigated for potential effect against chronic tinnitus as a stand-alone treatment and in conjunction with a selective serotonin reuptake inhibitor, paroxetine. No statistically significant treatment benefit effect was detected for tinnitus (intensity, pitch, and distress) VAS scores, arousal-anxiety VAS scores, Tinnitus Handicap Inventory, or tinnitus aggravation scores assessed on Days 1 and 14. However, a statistically significant worsening of tinnitus intensity and distress scores was observed after vestipitant compared with placebo for the mean data collected over the treatment period. No relevant differences in vestipitant plasma concentrations were observed between the subjects given the combination with paroxetine and those receiving vestipitant alone. No specific relationships were observed between tinnitus intensity and vestipitant plasma concentrations. CONCLUSION: Although well-tolerated vestipitant, alone or in combination with paroxetine, was not effective in ameliorating tinnitus in this patient group. (source: Otol Neurotol. 2011 Jul;32(5):721-7. )
   
 
 
Synthetic Process of Vestipitant
Synthetic Process of Vestipitant
T he following synthetic route was reported by Giuseppe Guercio et al from GlaxoSmithKline:
T he following synthetic route was reported by
et al from
The initial chemical development synthetic route, derived from the one used by medicinal chemistry, involved several hazardous reagents, gave low yields and produced high levels of waste. Through a targeted process of research and development, application of novel techniques and extensive route scouting, a new synthetic route for GW597599 was developed. This paper reports the optimisation work of the third and last stage in the chemical synthesis of GW597599 and the development of a pilot-plant-suitable process for the manufacturing of optically pure arylpiperazine derivative 1 . In particular, the process eliminated the use of triphosgene in the synthesis of an intermediate carbamoyl chloride, substantially enhancing safety, overall yield, and throughput.
source:
 Org. Process Res. Dev., 2009, 13 (6), pp 1100–1110. 
Org. Process Res. Dev., 2009, 13 (3), pp 489–493.
Org. Process Res. Dev., 2008, 12 (6), pp 1188–1194.
  
  
  
  


References

1: Ratti E, Carpenter DJ, Zamuner S, Fernandes S, Squassante L, Danker-Hopfe H, Archer G, Robertson J, Alexander R, Trist DG, Merlo-Pich E. Efficacy of vestipitant, a neurokinin-1 receptor antagonist, in primary insomnia. Sleep. 2013 Dec 1;36(12):1823-30. doi: 10.5665/http://52.6.152.39:3000/admins/products/5948/edit#tabs-pricingsleep.3208. PubMed PMID: 24293756; PubMed Central PMCID: PMC3825431.

2: Poma SZ, Merlo-Pich E, Bettica P, Bani M, Fina P, Ziviani L, Milleri S. Anxiolytic effects of vestipitant in a sub-group of healthy volunteers known to be sensitive to CO2 challenge. J Psychopharmacol. 2014 May;28(5):491-7. doi: 10.1177/0269881113507641. Epub 2013 Oct 9. PubMed PMID: 24108409.

3: Trist DG, Ratti E, Bye A. Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists. J Recept Signal Transduct Res. 2013 Dec;33(6):333-7. doi: 10.3109/10799893.2013.843194. Epub 2013 Oct 9. Review. PubMed PMID: 24106886.

4: Roberts C, Inamdar A, Koch A, Kitchiner P, Dewit O, Merlo-Pich E, Fina P, McFerran DJ, Baguley DM. A randomized, controlled study comparing the effects of vestipitant or vestipitant and paroxetine combination in subjects with tinnitus. Otol Neurotol. 2011 Jul;32(5):721-7. doi: 10.1097/MAO.0b013e318218a086. PubMed PMID: 21646935.

5: Di Fabio R, Alvaro G, Griffante C, Pizzi DA, Donati D, Mattioli M, Cimarosti Z, Guercio G, Marchioro C, Provera S, Zonzini L, Montanari D, Melotto S, Gerrard PA, Trist DG, Ratti E, Corsi M. Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2- methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clinical candidate. J Med Chem. 2011 Feb 24;54(4):1071-9. doi: 10.1021/jm1013264. Epub 2011 Jan 13. PubMed PMID: 21229983.

6: Gannon RL, Lungwitz E, Batista N, Hester I, Huntley C, Peacock A, Delagrange P, Millan MJ. The benzodiazepine diazepam demonstrates the usefulness of Syrian hamsters as a model for anxiety testing: evaluation of other classes of anxiolytics in comparison to diazepam. Behav Brain Res. 2011 Mar 17;218(1):8-14. doi: 10.1016/j.bbr.2010.11.029. Epub 2010 Nov 20. PubMed PMID: 21094664.

7: Provera S, Guercio G, Turco L, Curcuruto O, Alvaro G, Rossi T, Marchioro C. Application of LC-NMR to the identification of bulk drug impurities in NK1 antagonist GW597599 (vestipitant). Magn Reson Chem. 2010 Jul;48(7):523-30. doi: 10.1002/mrc.2611. PubMed PMID: 20535779.

8: Provera S, Martini L, Guercio G, Turco L, Costa L, Marchioro C. Application of LC-NMR and HR-NMR to the characterization of biphenyl impurities in the synthetic route development for vestipitant, a novel NK1 antagonist. J Pharm Biomed Anal. 2010 Nov 2;53(3):389-95. doi: 10.1016/j.jpba.2010.04.027. Epub 2010 Apr 29. PubMed PMID: 20478677.

9: Sabbatini FM, Di Fabio R, Griffante C, Pentassuglia G, Zonzini L, Melotto S, Alvaro G, Capelli AM, Pippo L, Perdona' E, St Denis Y, Costa S, Corsi M. Synthesis and pharmacological characterization of constrained analogues of Vestipitant as in vitro potent and orally active NK(1) receptor antagonists. Bioorg Med Chem Lett. 2010 Jan 15;20(2):623-7. doi: 10.1016/j.bmcl.2009.11.078. Epub 2009 Nov 20. PubMed PMID: 19963378.

10: Di Fabio R, Griffante C, Alvaro G, Pentassuglia G, Pizzi DA, Donati D, Rossi T, Guercio G, Mattioli M, Cimarosti Z, Marchioro C, Provera S, Zonzini L, Montanari D, Melotto S, Gerrard PA, Trist DG, Ratti E, Corsi M. Discovery process and pharmacological characterization of 2-(S)-(4-fluoro-2-methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethylphenyl)ethyl]methylamide (vestipitant) as a potent, selective, and orally active NK1 receptor antagonist. J Med Chem. 2009 May 28;52(10):3238-47. doi: 10.1021/jm900023b. PubMed PMID: 19388677.