Cevimelinehydrochloride

Base Information

• Chemical Name: Cevimelinehydrochloride
• CAS No.: 153504-70-2
• Molecular Formula: 2(C10H17NOS)^.2(HCl)^.H2O
• Molecular Weight: 235.778
• European Community (EC) Number: 642-988-1
• DSSTox Substance ID: DTXSID001338113
• Mol file: 153504-70-2.mol

Synonyms:2-methyspiro(1,3-oxathiolane-5,3)quinuclidine;AF 102B;AF 102B, (cis-(+))-isomer;AF 102B, (trans)-isomer;AF-102B;AF102B;cevimeline;cevimeline hydrochloride;Evoxac;FKS 508;FKS-508;SNI 2011;SNI-2011

Chemical Property of Cevimelinehydrochloride

Chemical Property:

• Vapor Pressure: 0.000676mmHg at 25°C
• Boiling Point: 308.5°C at 760 mmHg
• Flash Point: 140.4°C
• PSA: 84.77000
• Density: 1.19g/cm3
• LogP: 4.53590
• Storage Temp.: ?20°C
• Solubility.: H2O: ≥25mg/mL
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 0
• Exact Mass: 488.1700908
• Heavy Atom Count: 29
• Complexity: 215

Purity/Quality:

99.9% ^*data from raw suppliers

Cevimeline hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25
• Safety Statements: 45

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1OC2(CN3CCC2CC3)CS1.CC1OC2(CN3CCC2CC3)CS1.O.Cl.Cl
• Description: Although it was initially developed as a cognition enhancer, cevimeline was launched in the US for the treatment of dry mouth symptoms (xerostomia) in patients with Sjogren’s syndrome. Cevimeline is a racemic mixture of cis-oxathiolanes that can be obtained with a three step synthesis starting from quinuclidin-3-one followed by separation from its 9-12- fold less potent trans-diastereomer, This conformationally rigid analog of acetylcholine is a dual muscarinic M1/M3 agonist, selective versus M2, M4 and M5 receptors. It is the fifth M, agonist that has failed in clinical trials against Alzheimer’s disease. On the contrary, the sialagogic effects of cevimeline caused by its stimulation of M3 receptors in salivary and lacrimal glands were demonstrated in randomized double-blind placebo-controlled clinical trials (30 mg t.i.d. oral dose). Cevimeline (l-3 mg/kg i.v.) was as potent in dogs as pilocarpine (0.1-0.3 mg/kg i.v.), the only prior drug efficacious against xerostomia associated with Sjogren’s syndrome, but the effects of cevimeline lasted around 2-fold longer. No cardiovascular side effects were reported with cevimeline, unlike pilocarpine which has a 40-fold higher affinrty for the M2 receptor. Cevimeline seems to bind extensively to tissues (volume of distribution 6 L/kg in man) since it was found to be less than 20% bound to human plasma proteins. It is metabolized into the cis and transsulfoxide, a glucuronide conjugate and the N-oxide.
• Uses: Cevimeline hydrochloride hemihydrate may be used in cell signaling studies. Treatment of cancer.
• Therapeutic Function: Salivation stimulant

Technology Process of Cevimelinehydrochloride

There total 6 articles about Cevimelinehydrochloride which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

2’-methylspiro{1-azabicyclo [2.2.2]octane-3,5'[1,3]oxathiolane} (107220-27-9,107233-08-9) → cevimeline hydrochloride (153504-70-2,107220-28-0)

Guidance literature:

With hydrogenchloride; In 1,4-dioxane; diethyl ether; water;

Reference yield:

3-hydroxy-3-(mercaptomethyl)quinuclidine (107220-26-8,158568-64-0) + acetaldehyde (75-07-0,9002-91-9) → trans-cevimeline hydrochloride (107220-28-0) + (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate (153504-70-2,107220-28-0)

Guidance literature:

3-hydroxy-3-(mercaptomethyl)quinuclidine; acetaldehyde; With boron trifluoride diethyl etherate; In dichloromethane; at 0 - 25 ℃;

With sodium hydroxide; In dichloromethane; water; pH=12 - 14;

Reference yield:

cis-cevimeline sulfate → (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate (153504-70-2,107220-28-0)

Guidance literature:

cis-cevimeline sulfate; With sodium hydroxide; In di-isopropyl ether; at 0 - 10 ℃; pH=12;

With hydrogenchloride; In isopropyl alcohol; at 0 - 10 ℃; Product distribution / selectivity;

upstream raw materials:

2’-methylspiro{1-azabicyclo [2.2.2]octane-3,5'[1,3]oxathiolane}

3-hydroxy-3-(mercaptomethyl)quinuclidine

acetaldehyde

trans-cevimeline

Refernces

• 1、 -. "PROCESS FOR THE PREPARATION OF CIS-2-METHYLSPIRO (1, 3-OXATHIOLANE 5-3') QUINUCLIDINE". Page/Page column 3. . Retrieved 2011/12/14.