4-Hydroxy-10,13-dimethyl-1,6,7,8,9,10,11,12,13,14,15,16-dodecahydro-2H-cyclopenta[a]phenanthrene-3,17-dione

ID: ALA132530

Chembl Id: CHEMBL132530

Max Phase: Approved

Molecular Formula: C19H26O3

Molecular Weight: 302.41

Molecule Type: Small molecule

Names and Identifiers

Synonyms: 4-oh-androstene-3,17-dione | CGP 32349 | CGP-32349 | NSC-282175

Trade Names(1): Lentaron

Canonical SMILES:  C[C@]12CCC(=O)C(O)=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12

Standard InChI:  InChI=1S/C19H26O3/c1-18-10-8-15(20)17(22)14(18)4-3-11-12-5-6-16(21)19(12,2)9-7-13(11)18/h11-13,22H,3-10H2,1-2H3/t11-,12-,13-,18+,19-/m0/s1

Standard InChI Key:  OSVMTWJCGUFAOD-KZQROQTASA-N

Alternative Forms

1. Parent:

   

   ALA132530

   FORMESTANE

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 302.41

Molecular Weight (Monoisotopic): 302.1882

AlogP: 3.97

#Rotatable Bonds: ┄

Polar Surface Area: 54.37

Molecular Species: NEUTRAL

HBA: 3

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 3

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 9.21

CX Basic pKa: ┄

CX LogP: 3.41

CX LogD: 3.40

Aromatic Rings: ┄

Heavy Atoms: 22

QED Weighted: 0.74

Np Likeness Score: 2.29

References

1. Lesuisse D, Gourvest JF, Hartmann C, Tric B, Benslimane O, Philibert D, Vevert JP..  (1992)  Synthesis and evaluation of a new series of mechanism-based aromatase inhibitors.,  35  (9): [PMID:1578485] [10.1021/jm00087a013]

2. Bednarski PJ, Nelson SD..  (1989)  Interactions of thiol-containing androgens with human placental aromatase.,  32  (1): [PMID:2909733] [10.1021/jm00121a037]

3. Numazawa M, Mutsumi A, Hoshi K, Oshibe M, Ishikawa E, Kigawa H..  (1991)  Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors.,  34  (8): [PMID:1875347] [10.1021/jm00112a028]

4. Cole PA, Robinson CH..  (1990)  Mechanism and inhibition of cytochrome P-450 aromatase.,  33  (11): [PMID:2231592] [10.1021/jm00173a001]

5. Li S, Parish EJ, Webb T, Brodie AM.  (1997)  The synthesis of N-aryl androsterone pyrazoles as aromatase inhibitors,  7  (4): [10.1016/S0960-894X(97)00033-4]

6. Jyrkkärinne J, Mäkinen J, Gynther J, Savolainen H, Poso A, Honkakoski P..  (2003)  Molecular determinants of steroid inhibition for the mouse constitutive androstane receptor.,  46  (22): [PMID:14561088] [10.1021/jm030861t]

7. Abul-Hajj YJ..  (1986)  Synthesis and evaluation of 4-(substituted thio)-4-androstene-3,17-dione derivatives as potential aromatase inhibitors.,  29  (4): [PMID:3959033] [10.1021/jm00154a025]

8. Lovett JA, Darby MV, Counsell RE..  (1984)  Synthesis and evaluation of 19-aza- and 19-aminoandrostenedione analogues as potential aromatase inhibitors.,  27  (6): [PMID:6547488] [10.1021/jm00372a005]

9. Marsh DA, Brodie HJ, Garrett W, Tsai-Morris CH, Brodie AM..  (1985)  Aromatase inhibitors. Synthesis and biological activity of androstenedione derivatives.,  28  (6): [PMID:4009601] [10.1021/jm00383a017]

10. Cepa MM, Tavares da Silva EJ, Correia-da-Silva G, Roleira FM, Teixeira NA..  (2005)  Structure-activity relationships of new A,D-ring modified steroids as aromatase inhibitors: design, synthesis, and biological activity evaluation.,  48  (20): [PMID:16190763] [10.1021/jm050129p]

11. Gnoatto SC, Dassonville-Klimpt A, Da Nascimento S, Galéra P, Boumediene K, Gosmann G, Sonnet P, Moslemi S..  (2008)  Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition.,  43  (9): [PMID:18192087] [10.1016/j.ejmech.2007.11.021]

12. Neves MA, Dinis TC, Colombo G, Sá e Melo ML..  (2009)  An efficient steroid pharmacophore-based strategy to identify new aromatase inhibitors.,  44  (10): [PMID:19500885] [10.1016/j.ejmech.2009.05.003]

13. Majetich G, Shimkus JM..  (2010)  The taiwaniaquinoids: a review.,  73  (2): [PMID:20102168] [10.1021/np9004695]

14. Bellavance E, Luu-The V, Poirier D..  (2009)  Potent and selective steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 7, an enzyme that catalyzes the reduction of the key hormones estrone and dihydrotestosterone.,  52  (23): [PMID:19772289] [10.1021/jm900921c]

15. Diamandis P, Wildenhain J, Clarke ID, Sacher AG, Graham J, Bellows DS, Ling EK, Ward RJ, Jamieson LG, Tyers M, Dirks PB..  (2007)  Chemical genetics reveals a complex functional ground state of neural stem cells.,  3  (5): [PMID:17417631] [10.1038/nchembio873]

16. Yuan J, Johnson RL, Huang R, Wichterman J, Jiang H, Hayton K, Fidock DA, Wellems TE, Inglese J, Austin CP, Su XZ..  (2009)  Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum.,  5  (10): [PMID:19734910] [10.1038/nchembio.215]

17. PubChem BioAssay data set, 

18. Dai Y, Wang Q, Zhang X, Jia S, Zheng H, Feng D, Yu P..  (2010)  Molecular docking and QSAR study on steroidal compounds as aromatase inhibitors.,  45  (12): [PMID:20926163] [10.1016/j.ejmech.2010.09.011]

19. PubChem BioAssay data set, 

20. PubChem BioAssay data set, 

21. PubChem BioAssay data set, 

22. Djurendić EA, Ajduković JJ, Sakač MN, Csanádi JJ, Kojić VV, Bogdanović GM, Penov Gaši KM..  (2012)  Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives.,  54  [PMID:22770744] [10.1016/j.ejmech.2012.06.030]

23. Varela C, Tavares da Silva EJ, Amaral C, Correia da Silva G, Baptista T, Alcaro S, Costa G, Carvalho RA, Teixeira NA, Roleira FM..  (2012)  New structure-activity relationships of A- and D-ring modified steroidal aromatase inhibitors: design, synthesis, and biochemical evaluation.,  55  (8): [PMID:22475216] [10.1021/jm300262w]

24. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

25. PubChem BioAssay data set, 

26. Ghosh D, Lo J, Morton D, Valette D, Xi J, Griswold J, Hubbell S, Egbuta C, Jiang W, An J, Davies HM..  (2012)  Novel aromatase inhibitors by structure-guided design.,  55  (19): [PMID:22951074] [10.1021/jm300930n]

27. PubChem BioAssay data set, 

28. Martin GD, Narvaez J, Marti A..  (2013)  Synthesis and bioconversions of formestane.,  76  (10): [PMID:24074257] [10.1021/np400585t]

29. De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP..  (2013)  Structure-based identification of OATP1B1/3 inhibitors.,  83  (6): [PMID:23571415] [10.1124/mol.112.084152]

30. Ajduković JJ, Djurendić EA, Petri ET, Klisurić OR, Celić AS, Sakač MN, Jakimov DS, Gaši KM..  (2013)  17(E)-picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: antiproliferative activity and molecular docking studies.,  21  (23): [PMID:24148837] [10.1016/j.bmc.2013.09.063]

31. PubChem BioAssay data set, 

32. PubChem BioAssay data set, 

33. Park MH, Kim IS, Kim SA, Na CS, Hong CY, Dong MS, Yoo HH..  (2014)  Inhibitory effect of Rhus verniciflua Stokes extract on human aromatase activity; butin is its major bioactive component.,  24  (7): [PMID:24630560] [10.1016/j.bmcl.2014.02.039]

34. Nikolić AR, Petri ET, Klisurić OR, Ćelić AS, Jakimov DS, Djurendić EA, Penov Gaši KM, Sakač MN..  (2015)  Synthesis and anticancer cell potential of steroidal 16,17-seco-16,17a-dinitriles: identification of a selective inhibitor of hormone-independent breast cancer cells.,  23  (4): [PMID:25619894] [10.1016/j.bmc.2014.12.069]

35. Ajduković JJ, Penov Gaši KM, Jakimov DS, Klisurić OR, Jovanović-Šanta SS, Sakač MN, Aleksić LD, Djurendić EA..  (2015)  Synthesis, structural analysis and antitumor activity of novel 17α-picolyl and 17(E)-picolinylidene A-modified androstane derivatives.,  23  (7): [PMID:25737400] [10.1016/j.bmc.2015.02.001]

36. Jakimov DS, Kojić VV, Aleksić LD, Bogdanović GM, Ajduković JJ, Djurendić EA, Penov Gaši KM, Sakač MN, Jovanović-Šanta SS..  (2015)  Androstane derivatives induce apoptotic death in MDA-MB-231 breast cancer cells.,  23  (22): [PMID:26494582] [10.1016/j.bmc.2015.10.015]

37. Yadav MR, Barmade MA, Tamboli RS, Murumkar PR..  (2015)  Developing steroidal aromatase inhibitors-an effective armament to win the battle against breast cancer.,  105  [PMID:26469743] [10.1016/j.ejmech.2015.09.038]

38. Varela CL, Amaral C, Correia-da-Silva G, Costa SC, Carvalho RA, Costa G, Alcaro S, Teixeira NA, Tavares-da-Silva EJ, Roleira FM..  (2016)  Exploring new chemical functionalities to improve aromatase inhibition of steroids.,  24  (12): [PMID:27160054] [10.1016/j.bmc.2016.04.056]

39. Ghosh D, Lo J, Egbuta C..  (2016)  Recent Progress in the Discovery of Next Generation Inhibitors of Aromatase from the Structure-Function Perspective.,  59  (11): [PMID:26689671] [10.1021/acs.jmedchem.5b01281]

40. WHO Anatomical Therapeutic Chemical Classification, 

41. British National Formulary (72nd edition), 

42. Savić MP, Ajduković JJ, Plavša JJ, Bekić SS, Ćelić AS, Klisurić OR, Jakimov DS, Petri ET, Djurendić EA..  (2018)  Evaluation of A-ring fused pyridine d-modified androstane derivatives for antiproliferative and aldo-keto reductase 1C3 inhibitory activity.,  9  (6): [PMID:30108986] [10.1039/C8MD00077H]

43. Franck Touret, Magali Gilles, Karine Barral, Antoine Nougairède, Etienne Decroly, Xavier de Lamballerie, Bruno Coutard.  (2020)  In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication,  [10.1101/2020.04.03.023846]

44. Roleira FMF, Varela C, Amaral C, Costa SC, Correia-da-Silva G, Moraca F, Costa G, Alcaro S, Teixeira NAA, Tavares da Silva EJ..  (2019)  C-6α- vs C-7α-Substituted Steroidal Aromatase Inhibitors: Which Is Better? Synthesis, Biochemical Evaluation, Docking Studies, and Structure-Activity Relationships.,  62  (7): [PMID:30852901] [10.1021/acs.jmedchem.9b00157]

45. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

46. Kuzminac IZ,Jakimov DS,Bekić SS,Ćelić AS,Marinović MA,Savić MP,Raičević VN,Kojić VV,Sakač MN.  (2021)  Synthesis and anticancer potential of novel 5,6-oxygenated and/or halogenated steroidal d-homo lactones.,  30  [PMID:33340938] [10.1016/j.bmc.2020.115935]

47. Khan MZI, Uzair M, Nazli A, Chen JZ..  (2022)  An overview on Estrogen receptors signaling and its ligands in breast cancer.,  241  [PMID:35964426] [10.1016/j.ejmech.2022.114658]

48. Adhikari N, Baidya SK, Jha T..  (2020)  Effective anti-aromatase therapy to battle against estrogen-mediated breast cancer: Comparative SAR/QSAR assessment on steroidal aromatase inhibitors.,  208  [PMID:33017749] [10.1016/j.ejmech.2020.112845]

49. Sutherland JJ, Yonchev D, Fekete A, Urban L..  (2023)  A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.,  14  (1): [PMID:37468498] [10.1038/s41467-023-40064-9]

Source

Source(7):

• Scientific Literature
• PubChem BioAssays
• USP Dictionary of USAN and International Drug Names
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data