190786-44-8

Basic information

• Product Name: BEPOTASTINE BESILATE
• Synonyms: BEPOTASTINE BESILATE;1-Piperidinebutanoic acid, 4-[(4-chlorophenyl)-2-pyridinylmethoxy]-, (S)-, monobenzenesulfonate;1-Piperidinebutanoic acid, 4-[(S)-(4-chlorophenyl)-2-pyridinylmethoxy]-, monobenzenesulfonate;4-[4-[(R)-(4-chlorophenyl)-pyridin-2-yl-methoxy]-1-piperidyl]butanoic acid;(+)-(S)-4-[4-[1-(4-Chlorophenyl)-1-(2-pyridyl)methoxy]piperidin-1-yl]butyric acid benzenesulfonate;(+)-(S)-4-(4-((4-Chlorophenyl)(2-pyridyl)methoxy)piperidino)butyric acid monobenzenesulfonate;4-((4-Chlorophenyl)-2-pyridinylmethoxy)- (S)-1-piperidinebutanoic acid monobenzenesulfonate;Talion (TN)
• CAS NO: 190786-44-8
• Molecular Formula: C27H31ClN2O6S
• Molecular Weight: 547.07
• EINECS: 1806241-263-5
• Product Categories: API;Amino Acids & Derivatives;Aromatics;Drug Analogues;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Other APIs;Inhibitors
• Mol File: 190786-44-8.mol
• Article Data: 17

Chemical Properties

• Melting Point: 161-163°
• Boiling Point: 546.8 °C at 760 mmHg
• Flash Point: 284.5 °C
• Appearance: Brown Viscous liquid
• Vapor Pressure: 8.63E-13mmHg at 25°C
• Storage Temp.: -196°C
• Solubility: DMSO (Slightly, Heated), Methanol (Slightly, Heated)
• Stability: Hygroscopic
• CAS DataBase Reference: BEPOTASTINE BESILATE(CAS DataBase Reference)
• NIST Chemistry Reference: BEPOTASTINE BESILATE(190786-44-8)
• EPA Substance Registry System: BEPOTASTINE BESILATE(190786-44-8)

Safety Data

• Hazardous Substances Data: 190786-44-8(Hazardous Substances Data)

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

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

Upstream product

• 98-11-3 benzenesulfonic acid 
• 125602-71-3 Bepotastine 
• 1415692-17-9 bepotastine besilate 
• 122368-54-1 4-[(4-chlorophenyl)(pyridin-2-yl)methoxy]piperidine 
• 1560797-65-0 (RS)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butyric acid D-menthyl ester 
• 1560797-70-7 (S)-4-{4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino}butyric acid D-menthyl ester L-tartrate 
• 1560797-69-4 (S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino] butyric acid D-menthyl ester 
• 4045-22-1 N-acetyl-4-hydroxypiperidine 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 26158-00-9 benzene-sulfonic acid monohydrate 
• 210095-55-9 (S)-(-)-2-((4-chlorophenyl)(piperidin-4-yloxy)methyl)pyridine 
• 2969-81-5 Ethyl 4-bromobutyrate 
• 176022-47-2 (S)-(+)-(4-chlorophenyl)-(2-pyridyl)methanol 
• 6318-51-0 2-(4-chlorobenzoyl)pyridine 

Downstream Products

• 125602-71-3 [14C]-Bepotastine besilate 

Relevant articles and documents

Total synthesis method of bestatin

The method comprises the following steps: (4 - chlorophenyl) (2 - pyridyl) - methanol as a starting raw material, and sequential addition reaction. Examples of the etherification reaction include a deprotection reaction, a chiral resolution, a condensation reaction, a hydrolysis reaction, and the like. The synthesis method has the advantages of cheap and easily available raw materials, no need of expensive chiral catalysts, simpler synthesis method, mild conditions, less side reactions and low cost.

IMPROVED PROCESS FOR THE MANUFACTURE OF BEPOTASTINE AND ITS BESILATE SALT

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.

A stable besylate bepotastine crystal and its preparation method

The invention discloses a stable bepotastine besilate crystal in novel crystal form through a recrystallization method. The obtained bepotastine besilate crystal is confirmed through X-ray powder diffraction and infrared spectrum. Stability contrast experiments prove that the provided bepotastine besilate crystal has extremely high stability, and both bulk drug and preparation of the bepotastine besilate crystal have stability obviously better than that of existing bepotastine besilate crystals.