DIMP (antiandrogen)

DIMP
Clinical data
Other names	Ro 7-8117; N-(3,5-Dimethyl-4-isoxazolylmethyl)phthalimide
Drug class	Nonsteroidal antiandrogen
Identifiers
	IUPAC name 2-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-2,3-dihydro-1H-isoindole-1,3-dione;
CAS Number	39962-28-2 ;
PubChem CID	135035;
ChemSpider	118991;
UNII	BW49C59ULP;
ChEMBL	ChEMBL1710671;
CompTox Dashboard (EPA)	DTXSID40193001 ;
Chemical and physical data
Formula	C14H12N2O3
Molar mass	256.261 g·mol−1
3D model (JSmol)	Interactive image;
	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 (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]

References

^ ^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.
^ ^a ^b Liu B, Su L, Geng J, Liu J, Zhao G (October 2010). "Developments in nonsteroidal antiandrogens targeting the androgen receptor". ChemMedChem. 5 (10): 1651–1661. doi:10.1002/cmdc.201000259. PMID 20853390. S2CID 23228778.
^ ^a ^b Hashimoto Y (July 2003). "Structural development of synthetic retinoids and thalidomide-related molecules". Cancer Chemotherapy and Pharmacology. 52 (Suppl 1): S16–S23. doi:10.1007/s00280-003-0590-3. PMID 12819930. S2CID 22663471.
^ ^a ^b ^c ^d Boris A, Scott JW, DeMartino L, Cox DC (March 1973). "Endocrine profile of a nonsteroidal antiandrogen N-(3,5-dimethyl-4-isoxazolylmethyl)phthalimide (DIMP)". Acta Endocrinologica. 72 (3): 604–614. doi:10.1530/acta.0.0720604. PMID 4739363.
^ Singhal RL, Thomas JA (1 January 1976). Cellular Mechanisms Modulating Gonadal Action. University Park Press. p. 239. ISBN 978-0-8391-0776-7.
^ 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". Archives d'Anatomie Microscopique et de Morphologie Expérimentale. 64 (1): 27–44. PMID 1217898.
^ Heyns W, Verhoeven G, De Moor P (May 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. PMID 180344.
^ Rasmusson GH (January 1986). "Chemical control of androgen action.". In Daily PM, Pawsen PA (eds.). Annual Reports in Medicinal Chemistry. Vol. 21. Academic Press. pp. 179-188 (182). ISBN 978-0-08-058365-5.
^ Wakeling AE, Furr BJ, Glen AT, Hughes LR (December 1981). "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens". Journal of Steroid Biochemistry. 15: 355–359. doi:10.1016/0022-4731(81)90297-1. PMID 7339263.
^ Gao W, Bohl CE, Dalton JT (September 2005). "Chemistry and structural biology of androgen receptor". Chemical Reviews. 105 (9): 3352–3370. doi:10.1021/cr020456u. PMC 2096617. PMID 16159155.
^ Kaur P, Khatik GL (2016). "Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer". Mini Reviews in Medicinal Chemistry. 16 (7): 531–546. doi:10.2174/1389557516666160118112448. PMID 26776222.

[HashimotoTanatani2004-1] 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.

[LiuSu2010-2] Liu B, Su L, Geng J, Liu J, Zhao G (October 2010). "Developments in nonsteroidal antiandrogens targeting the androgen receptor". ChemMedChem. 5 (10): 1651–1661. doi:10.1002/cmdc.201000259. PMID 20853390. S2CID 23228778.

[Hashimoto2003-3] Hashimoto Y (July 2003). "Structural development of synthetic retinoids and thalidomide-related molecules". Cancer Chemotherapy and Pharmacology. 52 (Suppl 1): S16–S23. doi:10.1007/s00280-003-0590-3. PMID 12819930. S2CID 22663471.

[BorisScott1973-4] Boris A, Scott JW, DeMartino L, Cox DC (March 1973). "Endocrine profile of a nonsteroidal antiandrogen N-(3,5-dimethyl-4-isoxazolylmethyl)phthalimide (DIMP)". Acta Endocrinologica. 72 (3): 604–614. doi:10.1530/acta.0.0720604. PMID 4739363.

[SinghalThomas1976-5] Singhal RL, Thomas JA (1 January 1976). Cellular Mechanisms Modulating Gonadal Action. University Park Press. p. 239. ISBN 978-0-8391-0776-7.

[pmid1217898-6] 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". Archives d'Anatomie Microscopique et de Morphologie Expérimentale. 64 (1): 27–44. PMID 1217898.

[HeynsG.1976-7] Heyns W, Verhoeven G, De Moor P (May 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. PMID 180344.

[8] Rasmusson GH (January 1986). "Chemical control of androgen action.". In Daily PM, Pawsen PA (eds.). Annual Reports in Medicinal Chemistry. Vol. 21. Academic Press. pp. 179-188 (182). ISBN 978-0-08-058365-5.

[pmid7339263-9] Wakeling AE, Furr BJ, Glen AT, Hughes LR (December 1981). "Receptor binding and biological activity of steroidal and nonsteroidal antiandrogens". Journal of Steroid Biochemistry. 15: 355–359. doi:10.1016/0022-4731(81)90297-1. PMID 7339263.

[GaoBohl2005-10] Gao W, Bohl CE, Dalton JT (September 2005). "Chemistry and structural biology of androgen receptor". Chemical Reviews. 105 (9): 3352–3370. doi:10.1021/cr020456u. PMC 2096617. PMID 16159155.

[pmid26776222-11] Kaur P, Khatik GL (2016). "Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer". Mini Reviews in Medicinal Chemistry. 16 (7): 531–546. doi:10.2174/1389557516666160118112448. PMID 26776222.

[1]

See also

References