Alminoprofen

Alminoprofen

Clinical data
AHFS/Drugs.com	International Drug Names
ATC code	M01AE16 (WHO)
Identifiers
IUPAC name 2-{4-[(2-Methylprop-2-en-1-yl)amino]phenyl}propanoic acid
CAS Number	39718-89-3^N
PubChem CID	2097
ChemSpider	2013^Y
UNII	0255AHR9GJ
KEGG	D01513^Y
ChEBI	CHEBI:31190^N
ChEMBL	ChEMBL1765293^N
CompTox Dashboard (EPA)	DTXSID90865968
ECHA InfoCard	100.049.622
Chemical and physical data
Formula	C13H17NO2
Molar mass	219.284 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=C(O)C(c1ccc(NC/C(=C)C)cc1)C
InChI InChI=1S/C13H17NO2/c1-9(2)8-14-12-6-4-11(5-7-12)10(3)13(15)16/h4-7,10,14H,1,8H2,2-3H3,(H,15,16)^Y Key:FPHLBGOJWPEVME-UHFFFAOYSA-N^Y
^NY (what is this?)  (verify)

Alminoprofen is a non-steroidal anti-inflammatory drug.^[1][2] the non-proprietary name alminoprofen is derived from the compound's chemical name 2-(4-[{2-methylallyl}amino]phenyl)propanic acid.

Stereochemistry

Alminoprofen exists as two enantiomers; the stereocenter is located at the benzyl group.

Pharmacology

Although the pharmacology of non-steroidal anti-inflammatory drugs (non-steroidal anti-inflammatory drug) has been extensively studied, their mechanisms of action at the immunological level are not yet fully understood. Alminoprofen is a newer NSAID with a characteristic anti-inflammatory profile mediated through inhibition of cyclooxygenases and phospholipase A2 activity.^[3]

Comparison with ibuprofen

The effects of alminoprofen were examined in animal studies and compared with those of ibuprofen. At a dose of 30 mg/kg administered intraduodenally, alminoprofen significantly suppressed passive anaphylactic reaction-induced bronchoconstriction, whereas ibuprofen at the same dose did not. In vitro studies demonstrated that alminoprofen, unlike ibuprofen, inhibits arachidonate-5-lipoxygenase activity, which initiates the biosynthesis of leukotrienes. Alminoprofen inhibited arachidonic acid-induced ear edema in mice and homologous passive cutaneous anaphylaxis in rats at high doses, whereas ibuprofen showed no such effect at comparable doses.^[4]

Synthesis

The multistep synthesis of alminoprofen is shown in the following reaction sequence:^[5]

Synthesis of alminoprofen

Enantiomeric forms (R)-(-)-alminoprofen (top) and (S)-(+)-alminoprofen (bottom)

The synthesis begins with para-nitrophenylacetic acid as the starting material. The first step is a Mannich reaction with formaldehyde and dimethylamine. The second step is an elimination reaction forming a terminal alkene. In the third step, both the alkene and the nitro group are reduced using palladium on carbon as the catalyst and hydrogen as the reducing agent. The final step is a nucleophilic substitution in which the aryl group amine acts as the nucleophile. The product is a racemate.

Trade names

• Minalfen (J)^[5]

References

1. Raguenes-Nicol C, Russo-Marie F, Domage G, Diab N, Solito E, Dray F, Mace JL, Streichenberger G (February 1999). "Anti-inflammatory mechanism of alminoprofen: action on the phospholipid metabolism pathway". Biochemical Pharmacology. 57 (4): 433–43. doi:10.1016/s0006-2952(98)00312-8. PMID 9933032.
2. Céline Raguenes-Nicol, Françoise Russo-Marie, Gisèle Domage, Nadia Diab, Egle Solito (February 1999), "Anti-inflammatory mechanism of alminoprofen: action on the phospholipid metabolism pathway", Biochemical Pharmacology, vol. 57, no. 4, pp. 433–443, doi:10.1016/s0006-2952(98)00312-8
3. M. Shingu, T. Wada, I. Ezaki, M. Nobunaga (1992), "Pharmacologic modulation by alminoprofen of immunoglobulin and rheumatoid factor production by PWM-stimulated normal human mononuclear cells", Ensho, vol. 12, no. 4, pp. 327–331
4. Kojima E, Tamura N, Higashide Y, Lee B, Yamaura T, Ohnishi H (1990), "Effects of alminoprofen on the allergic reactions", Nihon Yakurigaku zasshi. Folia Pharmacologica Japonica, vol. 96, no. 6, pp. 315–321
5. A. Kleemann, J. Engel, B. Kutscher, D. Reichert (2014-05-14), Pharmaceutical Substances, 5th Edition: Syntheses, Patents and Applications of the most relevant APIs, Georg Thieme Verlag, p. 44, ISBN 978-3-13-179525-0