182349-12-8 Usage
Description
8-Chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridyl)methyl]-4-piperidylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine fumarate, also known as Rupatadine fumarate, is a novel antiallergic drug with a dual mechanism of action. It is a white or off-white color crystalline powder, odorless, and has a mildly bitter flavor. Rupatadine fumarate is a dual antagonist of histamine H1 and platelet-activating factor (PAF) receptors, making it effective in treating perennial and seasonal rhinitis.
Uses
Used in Pharmaceutical Industry:
8-Chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridyl)methyl]-4-piperidylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine fumarate is used as an antihistaminic for the treatment of perennial and seasonal rhinitis. It acts as a non-sedating histamine H1 receptor antagonist and PAF antagonist, providing rapid relief of symptoms within 2 hours and allowing for once-daily dosing due to its long duration of action (＞24 hours).
Used in Clinical Trials:
In comparative clinical trials, Rupatadine fumarate has demonstrated effectiveness similar to certizine and superior relief of rhinitis symptoms compared to ebastine and loratadine at the same dosage. It is well-tolerated and free of the sedative effects associated with first-generation antihistamines, making it a preferred choice for patients seeking relief from allergic symptoms without the risk of drowsiness.
Chemical Properties:
Rupatadine fumarate is slightly hygroscopic and dissolves in methanol. It is almost insoluble in water and slightly molten in a 0.1mol/L hydrochloric acid solution.
Brand Name:
The brand name for 8-Chloro-6,11-dihydro-11-[1-[(5-methyl-3-pyridyl)methyl]-4-piperidylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine fumarate is Rupafin.
Synthesis
One of the convergent
syntheses for rupatadine (XX) involved two key
intermediates, tricyclic ketone 162 and chloropiperidine
derivative 167. 3-Methylpicoline acid (157) was reacted with
p-chloroaniline in the presence of acid chloride and TEA to
provide amide 158 in 91% yield. Amide 158 was then treated with n-BuLi at -20°C for 1h, followed by addition of
3-chlorobenzyl chloride (159) to furnish amide 160 in 91%
yield after an aqueous workup. The cyclization of amide 160
was accomplished by treatment with 160 PCl5 first followed
by AlCl3 mediated Friedel-Crafts cyclization. The cyclic
intermediate 161 was directly subjected to hydrolysis
without isolation and tricyclic ketone 162 was obtained in
71% yield via a one-pot process. N-acylation of 5-
hydroxypiperidine (164) with 5-methylnictonic acid (163)
was accomplished by using HOBT, DCC to furnish amide
165. The carbonyl group in 165 was reduced by
chlorination/reduction sequence using POCl3 and NaBH4.
Alcohol 166 was then converted to the chloride 167 by
refluxing with SOCl2 in CHCl3. Coupling tricyclic ketone
162 and chloride 167 via a Grinard protocal followed by
dehydration furnished the rupatadine 168. Treatment of
rupatadine with fumaric acid in EtOH gave rupatadine
fumarate (XX) in 70% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 182349-12-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,2,3,4 and 9 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 182349-12:
(8*1)+(7*8)+(6*2)+(5*3)+(4*4)+(3*9)+(2*1)+(1*2)=138
138 % 10 = 8
So 182349-12-8 is a valid CAS Registry Number.
InChI:InChI=1/C26H26ClN3.C4H4O4/c1-18-13-19(16-28-15-18)17-30-11-8-20(9-12-30)25-24-7-6-23(27)14-22(24)5-4-21-3-2-10-29-26(21)25;5-3(6)1-2-4(7)8/h2-3,6-7,10,13-16H,4-5,8-9,11-12,17H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-
