DIMP (antiandrogen)

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DIMP
DIMP (antiandrogen).svg
Clinical data
SynonymsRo 7-8117; N-(3,5-Dimethyl-4-isoxazolylmethyl)phthalimide
Drug classNonsteroidal antiandrogen
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC14H12N2O3
Molar mass256.25668 g/mol g·mol−1
3D model (JSmol)

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 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[edit]

References[edit]

  1. ^ a b 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. ^ a b 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.
  3. ^ a b Hashimoto, Yuichi (2003). "Structural development of synthetic retinoids and thalidomide-related molecules". Cancer Chemotherapy and Pharmacology. 52 (0): 16–23. doi:10.1007/s00280-003-0590-3. ISSN 0344-5704.
  4. ^ a b c d 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.
  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.
  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.