211427-08-6

Basic information

• Product Name: INS 365
• Synonyms: INS 365;D03864;Diquafosol sodium;Diquafosol sodium (jan);Diquafosol tetrasodium;Diquafosol tetrasodium (usan)
• CAS NO: 211427-08-6
• Molecular Formula: C18H22N4Na4O23P4
• Molecular Weight: 878.234404
• Mol File: 211427-08-6.mol
• Article Data: 0

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: g/cm³
• CAS DataBase Reference: INS 365(CAS DataBase Reference)
• NIST Chemistry Reference: INS 365(211427-08-6)
• EPA Substance Registry System: INS 365(211427-08-6)

Safety Data

• Hazardous Substances Data: 211427-08-6(Hazardous Substances Data)

Usage

Description

Diquafosol (INS 365) is a P2Y2 purinergic receptor agonist that was approved in Japan in 2010 as a 3% ophthalmic solution for the treatment of dry eye disease. It is a unique agent that acts on the ocular surface to stimulate water, lipid, and mucin secretion, enhancing mucosal hydration and providing relief from the symptoms of chronic dry eye. Diquafosol is metabolized by phosphodiesterases to UTP, UDP, UMP, and uridine, and has been well tolerated in clinical trials with minimal side effects.

Uses

Used in Ophthalmology:
INS 365 is used as a P2Y2 receptor antagonist for the treatment of chronic dry eye. It enhances mucosal hydration by stimulating water, lipid, and mucin secretion on the ocular surface, providing relief from the symptoms of dry eye disease.
Used in Pharmaceutical Industry:
Diquafosol (INS 365) is used as an active pharmaceutical ingredient in the development of ophthalmic solutions for the treatment of dry eye disease. It is marketed under the brand name Diquas and has been well-tolerated in clinical trials, with minimal side effects and no serious ocular or systemic adverse drug reactions reported.

Originator

Inspire Pharmaceuticals (United States)

Clinical Use

Diquafosol tetrasodium was approved in April 2010 as Diquas ? ophthalmic solution 3% for the treatment of dry eye syndrome and launched in Japan by Santen Pharmaceuticals. Diquafosol tetrasodium was originally discovered by Inspire Pharmaceuticals. In 2001, it was licensed to Santen for co-development and commercialization in Asian countries, and co-developed in collaboration with Allergan for the countries outside of Asia. In the U.S., diquafosol tetrasodium was submitted for a New Drug Application (NDA) as Prolacria ?(2% ophthalmic formulation) in June 2003. However, it is still in Phase III clinical development for dry eye syndrome. Diquafosol tetrasodium, also known as INS- 365, is a P2Y2 receptor agonist, which activates P2Y2 receptor on the ocular surface, leading to rehydration through activation of the fluid pump mechanism of the accessory lacrimal glands on the conjunctival surface.

Synthesis

The large-scale synthesis route of diquafosol tetrasodium is described in Scheme 4. Commercially available uridine 5’-diphosphate disodium salt (21) was transformed into the corresponding tributylamine salt by ion exchange chromatography on Dowex 50 using Bu3NH+ phase, and then dimerized by means of CDI in DMF at 50 oC. The crude product was purified by Sephadex DEAE column followed by ion exchange using a Dowex 50W resin in Na+ mode. The onepot process provided diquafosol tetrasodium (IV) in 25% yield.

InChI:InChI=1/C18H26N4O23P4.4Na/c23-9-1-3-21(17(29)19-9)15-13(27)11(25)7(41-15)5-39-46(31,32)43-48(35,36)45-49(37,38)44-47(33,34)40-6-8-12(26)14(28)16(42-8)22-4-2-10(24)20-18(22)30;;;;/h1-4,7-8,11-16,25-28H,5-6H2,(H,31,32)(H,33,34)(H,35,36)(H,37,38)(H,19,23,29)(H,20,24,30);;;;/q;4*+1/p-4/t7-,8-,11-,12-,13-,14-,15-,16-;;;;/m1..../s1