Linomide

Linomide

Clinical data
ATC code	L03AX02 ( WHO )
Pharmacokinetic data
Elimination half-life	26-42 hours
Identifiers
IUPAC name 4-hydroxy-N,1-dimethyl-2-oxo-N- phenyl-1,2-dihydroquinoline-3-carboxamide
CAS Number	84088-42-6  Y
PubChem CID	54676478
DrugBank	DB11366
ChemSpider	10619239  N
UNII	372T2944C0
KEGG	D05756
ChEBI	CHEBI:92056
ChEMBL	ChEMBL11672
CompTox Dashboard (EPA)	DTXSID4045680
ECHA InfoCard	100.163.758
Chemical and physical data
Formula	C18H16N2O3
Molar mass	308.337 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN1C2=CC=CC=C2C(=C(C1=O)C(=O)N(C)C3=CC=CC=C3)O
InChI InChI=1S/C18H16N2O3/c1-19(12-8-4-3-5-9-12)17(22)15-16(21)13-10-6-7-11-14(13)20(2)18(15)23/h3-11,21H,1-2H3 N Key:SGOOQMRIPALTEL-UHFFFAOYSA-N N
NY  (what is this?)    (verify)

Linomide (Roquinimex) is a quinoline derivative immunostimulant which increases NK cell activity and macrophage cytotoxicity. It also inhibits angiogenesis and reduces the secretion of TNF alpha.

Linomide has been investigated as a treatment for some cancers (including as adjuvant therapy after bone marrow transplantation in acute leukemia) and autoimmune diseases, such as multiple sclerosis ^{[1] [2]} and recent-onset type I diabetes. ^[3] Several trials have been terminated due to serious cardiovascular toxicity.

Synthesis

Linomide synthesis:

Ethyl 2-(methylamino)benzoate is condensed with ethyl malonate. Amine-ester interchange of that compound with N-methylaniline results in formation of the amide linomide.

References

1. Weilbach EX, Hartung HP (August 1996). "[Immune modulation in multiple sclerosis: linomide]". Der Nervenarzt (in German). 67 (8): 701–5. doi:10.1007/s001150050044. PMID   8805117. S2CID   31845910.
2. Hedlund G, Link H, Zhu J, Xiao BG (June 2001). "Effects of Linomide on immune cells and cytokines inhibit autoimmune pathologies of the central and peripheral nervous system". International Immunopharmacology. 1 (6): 1123–30. doi:10.1016/s1567-5769(01)00041-8. PMID   11407306.
3. Gross DJ, Weiss L, Reibstein I, Hedlund G, Dahlén E, Rapoport MJ, Slavin S (June 2001). "The immunomodulator Linomide: role in treatment and prevention of autoimmune diabetes mellitus". International Immunopharmacology. 1 (6): 1131–9. doi:10.1016/s1567-5769(01)00042-x. PMID   11407307.
4. EP 59698,Eriksoo, Edgar; Sandberg, Eva Britt-Marie& Stalhandsk, Lars Johan Torbjörn,"Heterocyclic carboxamides, compositions containing such compounds, processes for their preparation and methods of treatment therewith",published 1982-09-08, assigned to AB Leo ; E. Eriksoo et al., U.S. patent 4,738,971 (1988 to AB Leo).