Chemistry:Amtolmetin guacil

Short description: Chemical compound

Amtolmetin guacil

Clinical data
Other names	ST-679
ATC code	none
Identifiers
IUPAC name (2-methoxyphenyl) 2-[ [2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetyl]ami
CAS Number	87344-06-7 N
PubChem CID	65655
ChemSpider	59091 Y
UNII	323A00CRO9
KEGG	D07453 Y
ChEMBL	ChEMBL1766570 N
Chemical and physical data
Formula	C24H24N2O5
Molar mass	420.465 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(c1ccc(n1C)CC(=O)NCC(=O)Oc2ccccc2OC)c3ccc(cc3)C
InChI InChI=1S/C24H24N2O5/c1-16-8-10-17(11-9-16)24(29)19-13-12-18(26(19)2)14-22(27)25-15-23(28)31-21-7-5-4-6-20(21)30-3/h4-13H,14-15H2,1-3H3,(H,25,27) Y Key:CWJNMKKMGIAGDK-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Amtolmetin guacil is a non-steroidal anti-inflammatory drug (NSAID). It is a prodrug of tolmetin sodium.

Background

Tolmetin sodium is an approved NSAID, marketed for the treatment of rheumatoid arthritis, osteoarthritis and juvenile rheumatoid arthritis. In humans, tolmetin sodium is absorbed rapidly with peak plasma levels observed 30 minutes after administration. It is eliminated rapidly with a mean plasma elimination t_½ of approximately 1 hour. The preparation of slow release formulations or chemical modification of NSAIDs to form prodrugs has been suggested as a method to reduce the gastrotoxicity of these agents.

Amtolmetin guacil is a non-acidic prodrug of tolmetin, having NSAID properties similar to tolmetin with additional analgesic, antipyretic, and gastro protective properties. Amtolmetin is formed by amidation of tolmetin by glycine.

Pharmacology

• Most is absorbed on oral administration. It is concentrated in the gastric wall. Highest concentration is reached 2 hours after administration.
• Amtolmetin guacil can be hydrolysed to produce the metabolites Tolmetin, MED5 and Guiacol.
• Elimination completes in 24 hours. This happens mostly with urine in shape of gluconides products (77%), faecal (7.5%).
• It is advised to take the drug on empty stomach.
• Permanent anti-inflammatory action continues up to 72 hours, with single administration.

Mechanism of action

Amtolmetin guacil stimulates capsaicin receptors present on gastrointestinal walls, because of presence of vanillic moiety and also releases NO which is gastro protective. It also inhibits prostaglandin synthesis and cyclooxygenase (COX).