107233-08-9

Basic information

• Product Name: CEVIMELINE, HYDROCHLORIDE SALT
• Synonyms: CevimelineHClSalt;(+/-)-cis-2-Methylspiro[1,3-oxathiolane-5,3quinuclidine;Spiro[1-azabicyclo[2.2.2]octane-3,5'-[1,3]oxathiolane], 2'-methyl-, (2'R,3R)-rel-;Spiro[1-azabicyclo[2.2.2]octane-3,5'-[1,3]oxathiolane], 2'-methyl-, cis-;2-methyspiro(1,3-oxathiolane-5,3)quinuclidine;AF-102B;Evoxac;SNI-2011
• CAS NO: 107233-08-9
• Molecular Formula: C10H18ClNOS
• Molecular Weight: 235.77
• Product Categories: Heterocycles;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals
• Mol File: 107233-08-9.mol

Chemical Properties

• Melting Point: 195-197°C
• Boiling Point: 308.5 °C at 760 mmHg
• Flash Point: 140.4 °C
• Appearance: Off-White Solid
• Density: 1.19
• Refractive Index: 1.586
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Soluble in DMSO
• PKA: 9.51±0.40(Predicted)
• CAS DataBase Reference: CEVIMELINE, HYDROCHLORIDE SALT(CAS DataBase Reference)
• NIST Chemistry Reference: CEVIMELINE, HYDROCHLORIDE SALT(107233-08-9)
• EPA Substance Registry System: CEVIMELINE, HYDROCHLORIDE SALT(107233-08-9)

Safety Data

• Hazardous Substances Data: 107233-08-9(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

A muscarinic M1 and M3 receptor agonist. Sialagogue

Biological Activity

cevimeline is a muscarinic receptor agonist especially on the m1 and m3 receptors. [1]cevimeline has been approved for use against symptoms of dry mouth by activating the m3 receptors of the parasympathetic nervous system. cevimeline is effective and safe in improving symptoms of dry eye with 20 mg three times per day [2]. cevimeline increased the intracellular ca+ level in parotid gland acinar cells over 1 μm and rat, enhanced the excitability via muscarinic receptors, thereby, cevimeline alleviates dry mouth symptoms by stimulating secretion by the salivary glands. cevimeline has a longer duration of salivation[3]. cevimeline plays a part in alzheimer’s disease. cevimeline decreased aβ (1–40) level in the cerebrospinal fluid (csf) at 1 mg/kg without changing α-apps in rabbit and significantly decreased csf aβ in ad patients.[4]

references

1. f. b. vivino, i. al-hashimi, z. khan, f. g. leveque, p. l. salisbury, 3rd, t. k. tran-johnson, c. c. muscoplat, m. trivedi, b. goldlust and s. c. gallagher, arch intern med 1999, 159, 174-181. 2. m. ono, e. takamura, k. shinozaki, t. tsumura, t. hamano, y. yagi and k. tsubota, am j ophthalmol 2004, 138, 6-17. 3. k. ono, t. inagaki, t. iida, r. hosokawa and k. inenaga, j med invest 2009, 56 suppl, 375. 4. a. fisher, z. pittel, r. haring, n. bar-ner, m. kliger-spatz, n. natan, i. egozi, h. sonego, i. marcovitch and r. brandeis, j mol neurosci 2003, 20, 349-356.

InChI:InChI=1/C10H17NOS/c1-8-12-10(7-13-8)6-11-4-2-9(10)3-5-11/h8-9H,2-7H2,1H3/t8?,10-/m1/s1

Upstream product

• 64168-68-9 Spiro- Hydrochlorid 
• 41353-91-7 1’-azaspiro[oxirane-2,3’-bicyclo[2.2.2]octane] 
• 1193-65-3 3-quinuclidinone hydrochloride 
• 107220-26-8 3-hydroxy-3-(mercaptomethyl)quinuclidine 
• 534-15-6 1,1-dimethoxyethane 
• 1435450-21-7 C₉H₁₃NO₂S 
• 1435450-13-7 C₈H₁₄BrNO*BrH 
• 1067881-02-0 3-hydroxy-3-acetoxymercaptomethylquiniclidine thiolacetate 
• 1467663-56-4 3-hydroxy-3-[(1-ethoxyethyl)mercaptomethyl]quinuclidine benzoic acid salt 
• 105-57-7 diethyl acetal 
• 75-07-0 acetaldehyde 

Downstream Products

• 107220-26-8 3-hydroxy-3-(mercaptomethyl)quinuclidine 

Relevant articles and documents

A new route to cevimeline

The present work demonstrates a new route for the synthesis of cevimeline in which safe and odorless thiourea is utilized as a thiolating reagent.

1,3-OXATHIOLANE DERIVATIVES, PROCESS FOR THE PREPARATION OF 1,3-OXATHIOLANE DERIVATIVES AND INTERMEDIATES THEREOF

This invention relates to 1,3-oxathiolane derivatives (I), processes for the preparation of 1,3-oxathiolane derivatives and intermediate compounds thereof.

Process for the preparation of 2-methylspiro(1,3-oxathiolane-5,3')quiniclidine

An industrially acceptable process for the preparation of 2-methylspiro(1,3-oxathiolane-5,3′)quiniclidine. The cis-isomer of 2-methylspiro(1,3-oxathiolane-5,3′)quiniclidine is known generally as Cevimeline.

OPHTHALMIC PERCUTANEOUSLY ABSORBED PREPARATION CONTAINING MUSCARINIC RECEPTOR AGONIST

A percutaneous absorption type ophthalmic preparation comprising muscarinic receptor agonist is prepared, which can promote lacrimal fluid secretion by administration to the skin surface of the eyelid, and which causes fewer side effects such as miosis, thereby to provide a percutaneous absorption type ophthalmic preparation capable of maintaining a therapeutically effective concentration of a muscarinic receptor agonist for promoting lacrimal fluid secretion, which is associated with fewer side effects such as miosis, and a method of promoting lacrimal fluid secretion by administering a percutaneous absorption type ophthalmic preparation containing a muscarinic receptor agonist to the skin surface of the eyelid.

Dry skin remedies

Novel dry skin remedies useful for treatment dry skin, containing as the active ingredient spiro [oxathiolane-quinuclidine] derivatives represented by general formula (I) or acid addition salts thereof, desirably cis-2-methylspiro [1,3-oxathiolane-5,3′-quinuclidine] hydrochloride. The remedies promote the secretion of sebaceous and sweat glands through oral or parenteral administration to treat dry skin, thus being useful as drugs.

Method for producing 2-methylspiro(1,3-oxathiolane-5,3')quinuclidine

A method for producing 2-methylspiro(1,3-oxathiolane-5,3')quinuclidine, which comprises reacting 3-hydroxy-3-mercaptomethylquinuclidine or a salt thereof and a carbonyl compound in the presence of a catalyst made of at least one member selected from the group consisting of tin halides, oxyacids of phosphorus, phosphorus oxyhalides and organic sulfonic acids, to produce cis-form 2-methylspiro(1,3-oxathiolane-5,3')quinuclidine or a salt thereof.

Method for the treatment of xerostomia

A method for the treatment of xerostomia not caused by Sjogren's syndrome comprising administering to an affected individual an effective amount of a derivative of spirooxathiolane-quinuclidine.

Composition and method for treating Sjoegren syndrome disease

A composition for treating a Sjoegren syndrome disease is disclosed. The composition comprising derivative of spirooxathiolane-quinuclidine of the following formula (I), STR1 wherein Z is CR 1 R 2, wherein R 1 and R 2 may be the same or different and each represents hydrogen, alkyl, cyclopentyl, cyclohexyl, aryl, diarylmethylol, or alkyl which may be substituted by one or more aryl groups, or an acid addition salt thereof, or an acid addition salt thereof, as an effective component. Especially effective is an administration of a hydrochloric acid addition salt of 2-methylspiro(1,3-oxathiolane-5,3'')quinuclidine.

Optical isomers

The (+)-cis-, (-)-cis-, (+)-trans- and (-)-trans- forms of 2-methylspiro(1,3-oxathiolan-5,3')quinuclidine are prepared by optical resolution of each of the (±)-cis- and (±)-trans-isomers. These compounds find application in treating diseases of the central nervous system in mammals, especially diseases due to a deficiency in the central cholinergic system. Biological tests indicate that the (-)-cis-form, as well as the (±)-cis-isomer, shows particular promise for treating senile dementia of Alzheimer's type.