Atiprimod (INN, codenamed SK&F106615) is a substance being studied in the treatment of certain multiple myelomas and other advanced cancers. It may block the growth of tumors and the growth of blood vessels from surrounding tissue to the tumor. This drug is also being researched as a potential treatment for various autoimmune diseases.
Atiprimod has been shown to inhibit angiogenesis (growth of blood vessels) in a blood vessel model using chicken eggs. It is thought to inhibit the secretion of vascular endothelial growth factor (VEGF), a growth factor that promotes angiogenesis.[citation needed]
The first part of the synthesis uses protocols that were used for Pramiverine and agents including SIR 117.
The second half of the synthesis shares features that are consonant with RS 86
The Johnson–Corey–Chaykovsky reaction on 4-Heptanone [123-19-3] (1) gives 2,2-dipropyloxirane [98560-25-9] (2). Treatment with Boron trifluoride etherate [109-63-7] gave 2-Propylpentanal [18295-59-5] (3). Upon acid treatment with Methyl vinyl ketone [78-94-4] (4) this led to 4,4-Dipropylcyclohex-2-enone [60729-41-1] (5). Catalytic hydrogenation of the enone olefin yielded 4,4-Dipropylcyclohexanone [123018-62-2] (7). The Knoevenagel condensation with ethyl 2-cyanoacetate [1187-46-8] (8) led to Cyano-(4,4-dipropyl-cyclohexylidene)-acetic acid ethyl ester [130065-93-9] (8).
Conjugate addition of cyanide anion led to ethyl 2-cyano-2-(1-cyano-4,4-dipropylcyclohexyl)acetate, PC45358714 (9). Acid hydrolysis of both the nitrile groups to acids, saponification of the ester, and decarboxylation of the geminal diacid gave 1-(carboxymethyl)-4,4-dipropylcyclohexane-1-carboxylic acid [130065-94-0] (10). Treatment with acetic anhydride gave 8,8-Dipropyl-2-oxaspiro[4.5]decane-1,3-dione [123018-64-4] (11). Condensation with 3-Diethylaminopropylamine [104-78-9] (12) gave the imide and hence, 2-[3-(diethylamino)propyl]-8,8-dipropyl-2-azaspiro[4.5]decane-1,3-dione, PC15634126 (13). Finally reduction of both carbonyl groups with lithium aluminium hydride completed the synthesis of Atiprimod (14).
^ abBadger, A. M., Schwartz, D. A., Picker, D. H., Dorman, J. W., Bradley, F. C., Cheeseman, E. N., DiMartino, M. J., Hanna, N., Mirabelli, C. K. (November 1990). "Antiarthritic and supressor cell inducing activity of azaspiranes: structure-function relationships of a novel class of immunomodulatory agents". Journal of Medicinal Chemistry. 33 (11): 2963–2970. doi:10.1021/jm00173a010.
^US4963557 idem Alison M. Badger, WO1989002889 (to Callisto Pharmaceuticals Inc).
^Alison Mary Badger, WO1994025024 (to SmithKline Beecham Corp).
^US4963557 idem Alison M. Badger, WO1989002889 (to Callisto Pharmaceuticals Inc).
^US 5952365, Dagger RE, Grady CW, "2-[2-(dimethylaminoehtyl]-8,8-diproply-2-azaspiro[4.5]decane dimaleate", issued 4 September 1999, assigned to Anormed Inc.
N
Y (what is this?) (verify)
This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.
