Atiprimod

Atiprimod

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Ball-and-stick model of the atiprimod molecule
Systematic (IUPAC) name
3-(8,8-dipropyl-3-azaspiro[4.5]decan-3-yl)-N,N- diethylpropan-1-amine
Identifiers
CAS Number	123018-47-3 N
ATC code	none
PubChem	CID: 129869
ChemSpider	114962 Y
UNII	MG7D3QD743 Y
ChEMBL	CHEMBL103735 Y
Chemical data
Formula	C22H44N2
Molecular mass	336.598 g/mol
SMILES N(CC)(CC)CCCN2CCC1(CCC(CC1)(CCC)CCC)C2
InChI InChI=1S/C22H44N2/c1-5-10-21(11-6-2)12-14-22(15-13-21)16-19-24(20-22)18-9-17-23(7-3)8-4/h5-20H2,1-4H3 Y Key:SERHTTSLBVGRBY-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

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. It was first developed by GlaxoSmithKline as a potential treatment for rheumatoid arthritis. The substance is also known as azaspirane, although this more properly refers to the class of chemicals to which atiprimod belongs.

History

Phase I trials have been successfully completed and Phase II multi-center trials have been approved by the FDA. The compound was discovered in a joint research and development program with SmithKline and French (now SmithKline Beecham, SB) but following acceptance of the Phase II protocol by the FDA, SB decided not to proceed with further development of atiprimod as a result of an internal restructuring program. All rights to atiprimod and other azaspiranes developed in this program have reverted to AnorMED. The compound was originally disclosed in European patent, EP-00310321, entitled 'Preparation of N-aminoalkyl-2-azaspiro[4.5]decanes and analogs as immunosuppressants', while a cost-effective, efficacious pilot plant synthesis has also been described. On January 7, 2008 Callisto Pharmaceuticals, Inc. announced that it has restructured its license agreement with Genzyme Corporation for Atiprimod. In August 2002, Callisto’s wholly owned subsidiary, Synergy, acquired from AnorMED Inc. worldwide exclusive rights to develop, manufacture and commercialize Atiprimod. AnorMED was acquired by Genzyme in November 2006.

The restructured agreement eliminates all milestone payments and reduces royalties owed to Genzyme to single digits. In return for the reduced future payments to Genzyme, Callisto is paying an upfront fee in 2008.

Synergy Pharmaceuticals, Inc. (a wholly owned subsidiary of Callisto) entered into a license agreement with AnorMED Inc. to license Atiprimod from AnorMED

Mechanism of action

Atiprimod is a cationic amphiphilic compound. It has been shown to inhibit angiogenesis in a developmental blood vessel model using chicken eggs, as well. It is thought to inhibit the secretion of VEGF - a growth factor that promotes such angiogenesis.

This compound has also been shown to kill mantle cell lymphoma cells in vitro.

Synthesis

File:Atiprimod.png

Atiprimod synthesis: Anormed Inc. Dagger, R. E.; Grady, C. W.; 1999, U.S. Patent 5,952,365.

External links

• Atiprimod entry in the public domain NCI Dictionary of Cancer Terms

 This article incorporates public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms".