DIMP (antiandrogen)

DIMP (developmental code name Ro 7-8117), or N-(3,5-dimethyl-4-isoxazolylmethyl)phthalimide, is a nonsteroidal antiandrogen (NSAA) structurally related to thalidomide (which also binds to and antagonizes the androgen receptor (AR))[1][2][3] that was first described in 1973 and was never marketed.[4] Along with flutamide, it was one of the earliest NSAAs to be discovered,[5] and for this reason, has been described as a "classical" NSAA.[1][2][3] The drug is a selective, competitive, silent antagonist of the AR,[4][6] although it is described as an "only relatively weak competitor".[7][8] Its relative binding affinity for the androgen receptor is about 2.6% of that of metribolone.[9] DIMP possesses no androgenic, estrogenic, progestogenic, or antigonadotropic activity,[4] but it does reverse the antigonadotropic effects of testosterone, indicating that, like other pure AR antagonists, it is progonadotropic.[4]

DIMP
Clinical data
Other namesRo 7-8117; N-(3,5-Dimethyl-4-isoxazolylmethyl)phthalimide
Drug classNonsteroidal antiandrogen
Identifiers
IUPAC name
  • 2-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-2,3-dihydro-1H-isoindole-1,3-dione
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H12N2O3
Molar mass256.261 g·mol−1
3D model (JSmol)
SMILES
  • CC1=C(C(=NO1)C)CN2C(=O)C3=CC=CC=C3C2=O
InChI
  • InChI=1S/C14H12N2O3/c1-8-12(9(2)19-15-8)7-16-13(17)10-5-3-4-6-11(10)14(16)18/h3-6H,7H2,1-2H3
  • Key:SHPRUADECKZSMQ-UHFFFAOYSA-N

DIMP is the lead antiandrogen of the phthalimide group of nonsteroidal AR ligands, and a variety of AR ligands with higher affinity for the AR have been derived from DIMP and thalidomide.[10][11]

See also

References
  1. Hashimoto, Y.; Tanatani, A.; Nagasawa, K.; Miyachi, H. (2004). "Thalidomide as a multitarget drug and its application as a template for drug design". Drugs of the Future. 29 (4): 383. doi:10.1358/dof.2004.029.04.792298. ISSN 0377-8282.
  2. Liu, Bo; Su, Lei; Geng, Jingkun; Liu, Junjie; Zhao, Guisen (2010). "Developments in Nonsteroidal Antiandrogens Targeting the Androgen Receptor". ChemMedChem. 5 (10): 1651–1661. doi:10.1002/cmdc.201000259. ISSN 1860-7179. PMID 20853390. S2CID 23228778.
  3. Hashimoto, Yuichi (2003). "Structural development of synthetic retinoids and thalidomide-related molecules". Cancer Chemotherapy and Pharmacology. 52: 16–23. doi:10.1007/s00280-003-0590-3. ISSN 0344-5704. PMID 12819930. S2CID 22663471.
  4. Boris, A.; Scott, J. W.; DeMartino, L.; Cox, D. C. (1973). "Endocrine Profile of a Nonsteroidal Antiandrogen N-(3,5-Dimethyl-4-Isoxazolylmethyl)Phthalimide (Dimp)". European Journal of Endocrinology. 72 (3): 604–614. doi:10.1530/acta.0.0720604. ISSN 0804-4643. PMID 4739363.
  5. Radhey Lal Singhal; John A. Thomas (1 January 1976). Cellular Mechanisms Modulating Gonadal Action. University Park Press. p. 239. ISBN 978-0-8391-0776-7.
  6. Ahlin K, Forsberg JG, Jacobsohn D, Thore-Berger B (1975). "The male genital tract and the nipples of male and female offspring of rats given the non-steroidal antiandrogens DIMP and Sch 13521, during pregnancy". Arch Anat Microsc Morphol Exp. 64 (1): 27–44. PMID 1217898.
  7. Heyns, W.; G., Verhoeven; De Moor, P. (1976). "Androgen binding in rat uterus cytosol. Study of the specificity". Journal of Steroid Biochemistry. 7 (5): 335–343. doi:10.1016/0022-4731(76)90092-3. ISSN 0022-4731. PMID 180344.
  8. Annual Reports in Medicinal Chemistry. Academic Press. 16 September 1986. pp. 182–. ISBN 978-0-08-058365-5.
  9. Wakeling AE, Furr BJ, Glen AT, Hughes LR (December 1981). "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens". J. Steroid Biochem. 15: 355–9. doi:10.1016/0022-4731(81)90297-1. PMID 7339263.
  10. Gao, Wenqing; Bohl, Casey E.; Dalton, James T. (2005). "Chemistry and Structural Biology of Androgen Receptor". Chemical Reviews. 105 (9): 3352–3370. doi:10.1021/cr020456u. ISSN 0009-2665. PMC 2096617. PMID 16159155.
  11. Kaur P, Khatik GL (2016). "Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer". Mini Rev Med Chem. 16 (7): 531–46. doi:10.2174/1389557516666160118112448. PMID 26776222.
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