162359-56-0 Usage
Description
Fingolimod hydrochloride, also known as Gilenya, is a white solid compound and a derivative of ISP-1 (myriocin), a fungal metabolite of the Chinese herb Iscaria sinclarii. It is a structural analogue of Sphingosine and was approved by the U.S. FDA in September 2010 as the first oral therapy for the relapsing-remitting form of multiple sclerosis (RRMS). Fingolimod is a novel immune modulator that affects sphingolipid metabolism in cells and mediates multiple biological processes by binding to novel GPCR's referred to as sphingosine-1-phosphate (S1P) receptors.
Uses
Used in Pharmaceutical Industry:
Fingolimod hydrochloride is used as an oral medicine for the treatment of multiple sclerosis (RRMS) due to its immune-modulating properties and ability to prolong allograft transplant survival in numerous models by inhibiting lymphocyte emigration from lymphoid organs.
Used in Immunosuppressive Applications:
Fingolimod hydrochloride is used as a cell-permeable aminopropanediol immunosuppressive agent that displays lymphocyte sequestration properties, making it a valuable compound in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells.
Used in Transplant Medicine:
Fingolimod hydrochloride is used as an immune modulator to prolong allograft transplant survival in various models by inhibiting lymphocyte emigration from lymphoid organs, thus improving the success rate of transplants and reducing the risk of rejection.
Used in Research and Development:
Fingolimod hydrochloride is used as a research compound to study the effects of S1P receptors and their role in various biological processes, including endothelial barrier function, maintaining vascular tone, regulating heart rate, and natural killer cell trafficking.
Oral drug for the treatment of multiple sclerosis
Fingolimod hydrochloride is the first oral drug for the treatment of multiple sclerosis. It is successfully developed by the pharmaceutical company Novartis, and it has been approved for marketing by the US Food and Drug Administration (FDA). The recommended dose is 0.5mg once a day for oral administration.
Multiple sclerosis is a debilitating neurological disease that can cause the patient to lose a sense of balance, appear muscle spasms and other movement disorders. The disease has been treated with injectable drugs. This kind of medication brought great inconvenience to patients.
Fingolimod is a sphingosine-l-phosphate (S1PR) receptor modulator. After phosphorylation, It is bound to s1P receptor that is on the surface of lymphocyte, which will change lymphocyte migration, and promote cells into the lymphatic tissue, and prevent lymphocytes from leaving the lymphoid tissue and get into the graft. Thereby, it will prevent these cells from infiltrating the central nervous system (CNS), which achieves the effect of immunosuppression. According to the drug's introduction, drugmaker Novartis said that this process of pharmacological effects is reversible. If medication is stopped, the level of lymphocytes in circulating system will return to normal.
The above information is edited by the lookchem of Kui Ming.
Originator
Yoshitomi Pharmaceutical Industries
(now Mitsubishi Tanabe Pharma) (United States)
Biochem/physiol Actions
FTY720 is an immunomodulating drug and sphingosine 1-phosphate (S1P) receptor modulator. Phosphorylation of FTY270 by sphingosine kinase causes S1P1R internalization, which sequesters lymphocytes in lymph nodes, preventing them from taking part in an autoimmune response. Clinically, it has been approved for the treatment of multiple sclerosis (MS). It has also been shown to block and reverse paclitaxel-induced chemotherapy induced peripheral neuropathy (CIPN) through S1PR inhibition as well as inhibit the activity of histone deacetylases in the hippocampus of mouse brains, thereby modulating memory.
Clinical Use
Fingolimod hydrochloride is an immunosuppressive drug developed by Novartis and approved in the
U.S., Europe, and Australia in 2010 for the treatment of multiple sclerosis. The structure of
fingolimod derives from the naturally-occurring myriocin (ISP-1) metabolite of the fungus I. sinclairii
and the aminoalcohol functionality within the drug possesses structural similarity to the sphingosine
family of natural products.
Synthesis
Although several convenient preparations of fingolimod (FTY720)
have been reported in the literature, the route most closely resembling the process-scale
approach is described in the scheme. Friedel-Crafts acylation of commercial toluene derivative 89
with bromoacetyl chloride followed by ethoxide-mediated N-acylated aminomalonate (91) attack onto
the resulting -bromoketone 90 gave rise to ketoamide 92 in good overall yield. Next, separate hydride
reduction protocols were employed to furnish diol 93. Presumably, triethylsilyl hydride reduced the
ketone and both ethyl esters within 92 to the corresponding diacid, which then underwent lithium
aluminum hydride treatment to arrive at diol 93. Careful attention to stoichiometry was required to
avoid over reduction of amide 93, which was critical to achieve high-yielding (76%) salt formation of
fingolimod HCl (VI) through the use of 6 N ethanolic hydrochloric acid.
References
1) Brinkmann et al. (2002), The immune modulator FTY720 targets spingosine-1-phosphate receptors; J. Biol. Chem., 277 21453
2) Wolf et al. (2009), The sphingosine 1-phosphate receptor agonist FTY720 potently inhibits regulatory T cell proliferation in vitro and in vivo; J. Immunol., 183 3751
3) Awojoodu et al. (2013), Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis; Proc. Natl. Acad. Sci. USA, 110 13785
4) Chiba (2005), FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors; Pharmacol. Ther., 108 308
Check Digit Verification of cas no
The CAS Registry Mumber 162359-56-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,2,3,5 and 9 respectively; the second part has 2 digits, 5 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 162359-56:
(8*1)+(7*6)+(6*2)+(5*3)+(4*5)+(3*9)+(2*5)+(1*6)=140
140 % 10 = 0
So 162359-56-0 is a valid CAS Registry Number.
InChI:InChI=1/C19H33NO2/c1-2-3-4-5-6-7-8-17-9-11-18(12-10-17)13-14-19(20,15-21)16-22/h9-12,21-22H,2-8,13-16,20H2,1H3
