Roxatidine acetate

Roxatidine acetate is a specific and competitive histamine H₂ receptor antagonist drug that is used to treat gastric ulcers, Zollinger–Ellison syndrome, erosive esophagitis, gastro-oesophageal reflux disease, and gastritis.^[1][2]

Roxatidine acetate

Clinical data
Routes of administration	Oral
ATC code	A02BA06 (WHO)
Pharmacokinetic data
Bioavailability	80–90%
Protein binding	5–7%
Metabolism	Hepatic deacetylation Minor involvement of CYP2D6 and CYP2A6
Elimination half-life	5–7 hours
Excretion	Renal
Identifiers
IUPAC name 2-oxo-2-(3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino)ethyl acetate
CAS Number	78628-28-1 Y roxatidine: 78273-80-0 Y
PubChem CID	5105
DrugBank	DB08806 Y
ChemSpider	4926 Y
UNII	ZUP3LSD0DO roxatidine: IV9VHT3YUM Y
KEGG	D08495 Y
ChEMBL	ChEMBL46102 Y
CompTox Dashboard (EPA)	DTXSID2048325
Chemical and physical data
Formula	C19H28N2O4
Molar mass	348.443 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(C)OCC(=O)NCCCOc1cccc(c1)CN2CCCCC2
InChI InChI=1S/C19H28N2O4/c1-16(22)25-15-19(23)20-9-6-12-24-18-8-5-7-17(13-18)14-21-10-3-2-4-11-21/h5,7-8,13H,2-4,6,9-12,14-15H2,1H3,(H,20,23) Y Key:SMTZFNFIKUPEJC-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Pharmacodynamic studies showed that 150 mg of roxatidine acetate were optimal in suppressing gastric acid secretion, and that a single bedtime dose of 150 mg was more effective than a dose of 75 mg twice daily in terms of inhibiting nocturnal acid secretion.^[1]

It was patented in 1979 and approved for medical use in 1986.^[3] It is available in countries including China, Japan, Korea, Germany, Italy, the Netherlands, Greece, and South Africa.^[2]

Synthesis

ThiemeChemDrug Synthesis:^[4] Patent:^[5] Sino revised protocols:^[6][7][8][9]

The reductive amination between piperidine (1) and 3-hydroxybenzaldehyde (2) gives 3-(1-piperidinylmethyl)phenol (3). Williamson ether synthesis with N-(3-bromopropyl)phthalimide (4) gives the intermediate 5. Deprotection with hydrazine yields (3-(1-piperidinylmethyl)phenoxy)propylamine (6). Heating with glycolic acid (7) provides roxatidine (8) which is then converted to its acetate ester, roxatidine acetate (9), by acetylation with acetic anhydride.