190786-44-8 Usage
Description
Bepotastine besilate is a non-sedating, selective antagonist of the histamine H1 receptor with a pIC50 of 5.7. It is a structurally-related derivative of chlorpheniramine and ebastine, prepared by condensation of optically-resolved 4-[1-(4-chlorophenyl)-1-(2-pyridyl)-methoxy]piperidine with ethyl 4-bromobutyrate followed by ester hydrolysis. Bepotastine besilate is an organosulfonate salt obtained by combining equimolar amounts of bepotastine and benzenesulfonic acid. It is an off-white to light beige solid and is marketed under the brand name Talion.
Uses
Used in Pharmaceutical Industry:
Bepotastine besilate is used as an antihistamine for the treatment of allergic rhinitis, chronic urticaria, and pruritus associated with skin conditions such as eczema/dermatitis, prurigo, or pruritus cutaneus. It suppresses some allergic inflammatory processes by acting as a histamine H1 receptor antagonist.
Used in Respiratory Disorders:
Bepotastine besilate is used as a PAF antagonist and inhibits LTD4 in tracheal smooth muscle and ileum, IL-5 production by human peripheral blood mononuclear cells, and eosinophil infiltration in the airway and peripheral blood. It is currently being developed against other allergic and respiratory disorders.
Used in Ophthalmology:
Bepotastine besilate is used as a topical, selective, and non-sedating histamine (H1) receptor antagonist for the treatment of itching associated with allergic conjunctivitis. It prevents conjunctival vascular hyperpermeability in a guinea pig model of conjunctivitis in a dose-dependent manner.
Used in Allergy Treatment:
Bepotastine besilate is used as an anti-allergic agent due to its potent and long-acting activity in models of allergic rhinitis and its ability to reduce dye leakage from the nasal passages of rats acutely sensitized to an antigen. It also inhibits histamine-induced bronchoconstriction in anesthetized dogs.
Originator
UBE (Japan)
Manufacturing Process
Manufacturing process for BEPOTASTINE BESILATE includes these steps as follows: Step A: Synthesis of Methyl 2-endo-hydroxy-1-exo-hydroxymethyl-3a,8b-cis-2,3,3a,8b-tetrahydro-
1H-5-cyclopenta[b]benzofurancarboxylate,Step B: Synthesis of Methyl 3-methyl-trans-4a-cisoid-4a,5a-cis-5a-1,4a,5,5a,10b,10c-hexahydro-7-
dioxin o[5,4-a]cyclopenta[b]benzofurancarboxylate,Step C: Synthesis of 3-Methyl-trans-4a-cosoid-4a,5a-cis-5a-1,4a,5,5a,10b,10c-hexahydro-7-
dioxino[5,4-a]cyclopenta[b]benzofuranylmethanol,Step D: Synthesis of 7-Chloromethyl-3-methyl-trans-4a-cisoid-4a,5a-cis-5a-1,4a,5,5a,10b,10chexahydrodioxino[5,4-a]cyclopenta[b]benzofuran,Step E: Synthesis of 4-[3-Methyl-trans-4a-cisoid-4a,5a-cis-5a-1,4a,5,5a,10b,10c-hexahydro-7-
dioxino[5,4-a]cyclopenta[b]benzofuranyl]butyric acid, Step F: Synthesis of Methyl 4-[2-endo-hydroxy-1-exo-hydroxymethyl-3a,8b-cis-2,3,3a,8btetrahydro-1H-5- cyclopenta[b]benzofuranyl]butyrate, Step G: Synthesis of Methyl 4-[2-endo-acetoxy-1-exo-hydroxymethyl-3a,8b-cis-2,3,3a,8btetrahydro-1H-5-cyclopenta[b]benzofuranyl]butyrate, Step H: Synthesis of Methyl ester of 11,15-dideoxy-11-acetoxy-16-methyl-15-oxo-18,19-
tetradehydro-5,6,7-trinor-4,8-inter-m-phenylene PGI2,Step I: Synthesis of 11-Deoxy-11-acetoxy-16-methyl-18,19-tetradehydro-5,6,7-trinor-4,8-inter-mphenylene PGI2.To a solution of 54 mg of methyl ester of 11-deoxy-11-acetoxy-16-methyl-
18,19-tetradehydro-5,6,7-trinor-4,8-inter-m-phenylene PGI2 in 4.5 ml of
anhydrous methanol was added 0.001 ml of 4.8 N sodium methoxide under
argon, and the reaction mixture was stirred for 1.5 hours at room
temperature.
After addition of acetic acid to the reaction mixture and concentration of the
mixture, the residue was dissolved in 20 ml of ethyl acetate, and the solution
was washed with aqueous saturated solution of sodium hydrogen carbonate,
water and aqueous saturated solution of sodium chloride, dried and
concentrated to afford 55 mg of an oily material.
This oily material was purified by column chromatography using ethyl acetate
and cyclohexane (3:1) as eluent to give 48 mg of the methyl ester of 16-
methyl-18,19-tetradehydro-5,6,7-trinor-4,8-inter-m-phenylene PGI2.
Therapeutic Function
Antiallergic
Check Digit Verification of cas no
The CAS Registry Mumber 190786-44-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,9,0,7,8 and 6 respectively; the second part has 2 digits, 4 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 190786-44:
(8*1)+(7*9)+(6*0)+(5*7)+(4*8)+(3*6)+(2*4)+(1*4)=168
168 % 10 = 8
So 190786-44-8 is a valid CAS Registry Number.
InChI:InChI=1/C21H25ClN2O3.C6H6O3S/c22-17-8-6-16(7-9-17)21(19-4-1-2-12-23-19)27-18-10-14-24(15-11-18)13-3-5-20(25)26;7-10(8,9)6-4-2-1-3-5-6/h1-2,4,6-9,12,18,21H,3,5,10-11,13-15H2,(H,25,26);1-5H,(H,7,8,9)/t21-;/m1./s1
190786-44-8Relevant articles and documents
Improved Synthesis of Bepotastine Besilate
Han,Xia,Sun,Zou
, p. 206 - 210 (2021/03/15)
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IMPROVED PROCESS FOR THE MANUFACTURE OF BEPOTASTINE AND ITS BESILATE SALT
-
, (2019/05/02)
The present invention discloses a process for preparation of Bepotastine and its Besilate salt of formula I with good yield and purity. The invention also describes a process for recycle and reuse of the Ethyl-4-hydroxy piperidine-1-carboxylate from the aqueous medium after isolating the 2-[(S)-(4-Chlorophenyl)(piperidin-4- yloxy)methyl]pyridine, for subsequent batches in the production of Ethyl 4-[(4- Chlorophenyl)(pyridin-2-yl)methoxy]piperidine-1-carboxylate. The invention further discloses novel intermediates, viz., 2-[Chloro(4- chlorophenyl)methyl]pyridine hydrochloride and bis{2-[(S)-(4- Chlorophenyl)(piperidin-4-yloxy)methyl]pyridine} Dibenzoyl tartrate, useful in the preparation of Bepotastine and its Besilate salt.
Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N-Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent
Liu, Qixing,Wang, Chunqin,Zhou, Haifeng,Wang, Baigui,Lv, Jinliang,Cao, Lu,Fu, Yigang
, p. 971 - 974 (2018/02/23)
A highly enantioselective transfer hydrogenation of non-ortho-substituted aryl N-heteroaryl ketones, using readily available chiral diamine-derived iridium complex (S,S)-1f as a catalyst and sodium formate as a hydrogen source in a mixture of H2O/i-PrOH (v/v = 1:1) under ambient conditions, is described. The chiral aryl N-heteroaryl methanols were obtained with up to 98.2% ee by introducing an N-oxide as a removable ortho-substituent. In contrast, no more than 15.1% ee was observed in the absence of an N-oxide moiety. Furthermore, the practical utility of this protocol was also demonstrated by gram-scale asymmetric synthesis of bepotastine besilate in 51% total yield and 99.9% ee.