121679-13-8 Usage
Originator
Amerge,Glaxo Wellcome,UK
Uses
Different sources of media describe the Uses of 121679-13-8 differently. You can refer to the following data:
1. Antimigraine.
2. Naratriptan is a triptan drug that is used for the treatment of migraine headaches.
Manufacturing Process
N-Methyl-3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indole-5-
ethanesulphonamide oxalateA solution of N-methyl-1H-indole-5-ethanesulphonamide (1.0 g) in methanol
(50 ml) containing potassium hydroxide (5.6 g) and N-methyl-4-piperidone
(1.0 ml) was heated at reflux for 24 h, cooled, and the resulting solid filtered
off (1.0 g). A sample of the solid (0.2 g) was dissolved in a hot methanolic
solution of oxalic acid (0.06 g), the solution cooled, and the salt precipitated
by adding ethyl acetate (20 ml) and dry ether (50 ml). The salt was filtered
off, and dried in vacuo to give the title compound as a solid (0.12 g), m.p.
87°-90°C (shrinks).Analysis Found: C,52.2; H,5.6; N,9.5. C17H23N3O2S · C2H2O4 · 0.6H2O
requires C,52.5; H,6.0; N,9.7%.N-Methyl-3-(1-methyl-4 -piperidinyl)-1H-indole-5-ethansulphonamideN-Methyl-3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indole-5-
ethanesulphonamide oxalate (as the free base) (0.36 g, 0.001 mol) in
absolute alcohol (70 ml) and anhydrous dimethylformamide (5 ml) was
hydrogenated, in the presence of 5% palladium on activated carbon (0.36 g)
at ambient temperature and atmospheric pressure. After 20 h, hydrogen
absorption (25 cm3, theoretical = 24 cm3) ceased. The catalyst was filtered
off and the solvent removed in vacuo to given an opaque gum which solidified
as a soft white solid (0.3 g). Purification by flash chromatography (Sorbsil C60
silica gel, CH2Cl2/EtOH/0.88 ammonia; 50:80:1) gave a colorless oil (0.21 g)
that was triturated with ether to give the title compound (0.17 g) m.p. 156°-
158°C. TLC SiO2(CH2Cl2/EtOH/0.88 ammonia; 50:8:1) Rf 0.4.N-Methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulphonamide may be
prepared the another way.A solution of 4-hydrazino-N-methyl-benzenethanesulphonamide (0.5 g) and 1-
methyl-4-piperidineacetaldehyde (0.35 g) in a mixture of water (10 ml) of 2 N
hydrochloric acid (1.0 ml, 2.00 mmol) was stirred for 2 days at room
temperature. A further quantity of the aldehyde (0.35 g) was added and
stirring continued for a further 30 min. The solution was then basified with
8% sodium bicarbonate to pH 8 and extracted with chloroform (3 times 50
ml). The combined organic extracts were dried (Na2SO4) and evaporated in
vacuo to give the crude hydrazone as an oil (1.0 g). A solution of the
hydrazone (1.0 g) in chloroform (20 ml) containing polyphosphate ester (10
g) was heated at reflux for 8 min. The solution was poured onto ice (200 g),
stirred for 2 h treated with 2 M sodium carbonate (20 ml) and extracted with
chloroform (3 times 50 ml). The combined organic extracts were dried
(Na2SO4), evaporated in vacuo and the residue purified by flash
chromatography (silica 9385, 100 g) eluting with CH2Cl2/EtOH/NH3(75:8:1) to
give impure material as a yellow oil. Further flash chromatography (silica
9385, 100 g) eluting with CH2Cl2/EtOH/NH3 (100:8:1) gave the product as an
oil (0.05 g). This was crystallised from ethyl acetate to give the title compound
solid m.p. 156°-157°C. TLC SiO2(CH2Cl2/EtOH/NH3(50:8:1)) Rf 0.6.
Brand name
Amerge (GlaxoSmithKline).
Therapeutic Function
Serotonin antagonist, Migraine therapy
General Description
Naratriptan, the third triptan approved in 1998, is one of themost lipophilic triptans marketed to date. It has a much improvedbioavailability (63% in men and 74% in women), agreater affinity for 5-HT1B/1D receptors (3–6 times), and alower recurrence rate than sumatriptan because of its muchlonger elimination half-life. Naratritan also has a favorableCNS side effect profile when compared with sumatriptanor zolmitriptan because of its metabolic stability,thereby lacking a N-demethylated active metabolite and asignificant renal excretion ( 70% of naratriptan is excretedunchanged and the rest of the administered dose is degradedvia several CYP isozymes).
Clinical Use
5HT1
receptor agonist:
Acute treatment of migraine
Drug interactions
Potentially hazardous interactions with other drugs
Antidepressants: increased CNS toxicity with
citalopram - avoid; possibly increased serotonergic
effects with duloxetine, SSRIs and venlafaxine;
increased serotonergic effects with St John’s wort -
avoid.
Dapoxetine: possible increased risk of serotonergic
effects - avoid for 2 weeks after stopping 5HT1
agonists.
Ergot alkaloids: increased risk of vasospasm - avoid.
Metabolism
Naratriptan undergoes some hepatic metabolism via
a wide range of cytochrome P450 isoenzymes to form
inactive metabolites.
Naratriptan is excreted by glomerular filtration and active
secretion into the renal tubules. It is mainly excreted
in the urine with 50% of a dose being recovered as
unchanged drug and 30% as inactive metabolites.
Check Digit Verification of cas no
The CAS Registry Mumber 121679-13-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,1,6,7 and 9 respectively; the second part has 2 digits, 1 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 121679-13:
(8*1)+(7*2)+(6*1)+(5*6)+(4*7)+(3*9)+(2*1)+(1*3)=118
118 % 10 = 8
So 121679-13-8 is a valid CAS Registry Number.
InChI:InChI=1/C17H25N3O2S/c1-18-23(21,22)10-7-13-3-4-17-15(11-13)16(12-19-17)14-5-8-20(2)9-6-14/h3-4,11-12,14,18-19H,5-10H2,1-2H3
121679-13-8Relevant articles and documents
Preparation, characterization and buccal permeation of naratriptan
Sattar, Mohammed,Hadgraft, Jonathan,Lane, Majella E.
, p. 146 - 151 (2015)
Abstract Naratriptan (NAR) is currently used for the management of migraine as the hydrochloride salt (NAR.HCl) and is administered as an oral tablet. This work evaluates the feasibility of buccal delivery of NAR in order to ensure faster onset of action and avoid the side-effects associated with conventional oral formulations. We hypothesized that the unionized form of NAR would permeate buccal tissue to a greater extent than the salt. Therefore the first stage of this work required preparation of the free base from NAR.HCl. Characterisation of the base with thermal and elemental analyses confirmed its purity; log P and log D values were also determined. The pH permeation profile of NAR was also determined in the range 7.4-10. Solubility studies in non-aqueous solvents indicated that Transcutol (TC) and dipropylene glycol (DPG) were suitable vehicles for the free base. Maximum amounts of NAR which permeated after 6 h were ～130 μg/cm2. Based on the pH permeation results and studies conducted at two different doses NAR appears to permeate porcine buccal tissue via the transcellular route. Finally, estimates of likely systemic values suggest that optimised formulations should be taken forward for in vivo evaluation.
New synthesis of naratriptan
Poszavacz, Laszlo,Simig, Gyula,Fetter, Jozsef,Bertha, Ferenc
, p. 713 - 719 (2006)
A new synthesis of N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide (naratriptan, 1a) has been elaborated starting from 1-benzyl-1H-indole-5-carbaldehyde (14b). The 1-benzyl group proved to be an advantageous protecting group in the course of the construction of the ethanesulfonamide and methylpipieridinyl side-chains and it was removed in the last step of the synthesis.{A figure is presented}.
An efficient synthetic protocol for the synthesis of 2-(1H-Indol-5-yl)-ethanesulfonic acid methylamide: A potential synthetic precursor for naratriptan and its novel 3-substituted derivatives
Behera, Ajaya Kumar,Majumdar, Poulomi,Mohanta, Prajna Parimita,Mishra, Sushanta Kumar
, p. 265 - 269 (2018/04/20)
Background: The 3-Substituted indoles are found to possess a wide range of biological and pharmacological activities. The efficient and impurity free scalable preparation of 2-(1H-Indol-5-yl)-ethanesulfonic acid methylamide has been successfully achieved
PROCESS FOR PREPARING INDOLE DERIVATIVES
-
Page/Page column 20, (2010/04/03)
The present invention provides a process for the preparation of indole derivatives, specifically N- methyl-1H-indole-5-ethanesulfonamide of formula (I), involving novel intermediate, which is used as key intermediate for the synthesis of naratriptan of formula (II), and its pharmaceutically acceptable salts thereof high yield and purity.
