eplerenone

ID: ALA1095097

Cas Number: 107724-20-9

PubChem CID: 443872

Product Number: E420533, Order Now?

Max Phase: Approved

First Approval: 2002

Molecular Formula: C24H30O6

Molecular Weight: 414.50

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Eplerenone | SC-66110 | SC-6611O | Eplerenone|Epoxymexrenone|Inspra|107724-20-9|Selara|SC-66110|Cgp 30083|CGP-30083|HSDB 7522|DTXSID2046094|UNII-6995V82D0B|CHEBI:31547|SC-6611O|6995V82D0B|SC 6110|CHEMBL1095097|DTXCID0026094|9,11alpha-Epoxy-17-hydroxy-3-oxo-17alpha-pregn-4-ene-7alpha,21-dicarboxylic acid, gamma-lactone, methyl ester|NCGC00159559-02|EPLERENONE (MART.)|EPLERENONE [MART.]|7alpha-methoxycarbonyl-3-oxo-9,11alpha-epoxy-17alpha-pregn-4-ene-21,17-carbolactone|EPLERENONE (USP-RS)|EPLERENOShow More⌵

Trade Names(2): Eplerenone | Inspra

Canonical SMILES:  COC(=O)[C@@H]1CC2=CC(=O)CC[C@]2(C)[C@@]23O[C@@H]2C[C@@]2(C)[C@@H](CC[C@@]24CCC(=O)O4)[C@H]13

Standard InChI:  InChI=1S/C24H30O6/c1-21-7-4-14(25)10-13(21)11-15(20(27)28-3)19-16-5-8-23(9-6-18(26)30-23)22(16,2)12-17-24(19,21)29-17/h10,15-17,19H,4-9,11-12H2,1-3H3/t15-,16+,17-,19+,21+,22+,23-,24-/m1/s1

Standard InChI Key:  JUKPWJGBANNWMW-VWBFHTRKSA-N

Molfile:  

     RDKit          2D

 33 38  0  0  1  0  0  0  0  0999 V2000
   -0.4458   -2.2750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0583   -1.9250    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4458   -1.5667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1750   -2.6250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0583   -2.6375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7792   -1.5625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0500   -3.3500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7792   -2.2625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1792   -3.3500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4542   -1.3417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1667   -1.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4375   -3.7000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1250   -1.1250    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6708   -3.7000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7917   -3.7000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1333   -0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4500   -2.4875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6708   -2.2792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8667   -1.9167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2833   -3.3500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0417   -0.7667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8042   -4.4042    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.7167   -0.0042    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9000   -3.7000    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4792   -0.1875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2833   -2.6375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7792   -0.8500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4042   -3.3375    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4458   -2.9917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0250   -3.6875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7792   -2.9750    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.1750   -1.9125    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4458   -0.8625    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  6
  3  1  1  0
  4  1  1  0
  5  1  1  0
  6  8  1  0
  7  5  1  0
  8  4  1  0
  9  4  1  0
 10  6  1  0
 11  3  1  0
 12  7  1  0
 10 13  1  1
 14  7  2  0
  9 15  1  6
 16 13  1  0
 17  8  1  0
 18  5  1  0
 19 17  1  0
 20 26  1  0
 21 10  1  0
 22 15  2  0
 23 16  2  0
 24 20  2  0
 25 21  1  0
 26 18  1  0
  6 27  1  1
 28 15  1  0
  5 29  1  1
 30 28  1  0
  8 31  1  6
  4 32  1  1
  3 33  1  1
  2  3  1  0
  6 11  1  0
 12  9  1  0
 20 14  1  0
 10 19  1  0
 16 25  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1095097

   Eplerenone

Molecule Features

Natural Product: Yes

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 414.50

Molecular Weight (Monoisotopic): 414.2042

AlogP: 3.12

#Rotatable Bonds: 1

Polar Surface Area: 82.20

Molecular Species: NEUTRAL

HBA: 6

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 2.33

CX LogD: 2.33

Aromatic Rings: ┄

Heavy Atoms: 30

QED Weighted: 0.48

Np Likeness Score: 2.30

References

1. Arhancet GB, Woodard SS, Dietz JD, Garland DJ, Wagner GM, Iyanar K, Collins JT, Blinn JR, Numann RE, Hu X, Huang HC..  (2010)  Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines.,  53  (10): [PMID:20408553] [10.1021/jm1002827]

2. Arhancet GB, Woodard SS, Iyanar K, Case BL, Woerndle R, Dietz JD, Garland DJ, Collins JT, Payne MA, Blinn JR, Pomposiello SI, Hu X, Heron MI, Huang HC, Lee LF..  (2010)  Discovery of novel cyanodihydropyridines as potent mineralocorticoid receptor antagonists.,  53  (16): [PMID:20672820] [10.1021/jm100506y]

3. Meyers MJ, Arhancet GB, Hockerman SL, Chen X, Long SA, Mahoney MW, Rico JR, Garland DJ, Blinn JR, Collins JT, Yang S, Huang HC, McGee KF, Wendling JM, Dietz JD, Payne MA, Homer BL, Heron MI, Reitz DB, Hu X..  (2010)  Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy.,  53  (16): [PMID:20672822] [10.1021/jm100505n]

4. Unpublished dataset, 

5.  (2008)  Casarett and Doull's Toxicology The Basic Science of Poisons, 7th edition, 

6. PubChem BioAssay data set, 

7. Liu Z, Shi Q, Ding D, Kelly R, Fang H, Tong W..  (2011)  Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).,  7  (12): [PMID:22194678] [10.1371/journal.pcbi.1002310]

8. Hasui T, Matsunaga N, Ora T, Ohyabu N, Nishigaki N, Imura Y, Igata Y, Matsui H, Motoyaji T, Tanaka T, Habuka N, Sogabe S, Ono M, Siedem CS, Tang TP, Gauthier C, De Meese LA, Boyd SA, Fukumoto S..  (2011)  Identification of benzoxazin-3-one derivatives as novel, potent, and selective nonsteroidal mineralocorticoid receptor antagonists.,  54  (24): [PMID:22074142] [10.1021/jm2011645]

9. Sun H..  (2012)  Capture hydrolysis signals in the microsomal stability assay: molecular mechanisms of the alkyl ester drug and prodrug metabolism.,  22  (2): [PMID:22197392] [10.1016/j.bmcl.2011.12.005]

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

11. Piotrowski DW..  (2012)  Mineralocorticoid receptor antagonists for the treatment of hypertension and diabetic nephropathy.,  55  (18): [PMID:22866979] [10.1021/jm300806c]

12. Yang C, Shen HC, Wu Z, Chu HD, Cox JM, Balsells J, Crespo A, Brown P, Zamlynny B, Wiltsie J, Clemas J, Gibson J, Contino L, Lisnock J, Zhou G, Garcia-Calvo M, Bateman T, Xu L, Tong X, Crook M, Sinclair P..  (2013)  Discovery of novel oxazolidinedione derivatives as potent and selective mineralocorticoid receptor antagonists.,  23  (15): [PMID:23777778] [10.1016/j.bmcl.2013.05.077]

13. PubChem BioAssay data set, 

14. PubChem BioAssay data set, 

15. Cox JM, Chu HD, Yang C, Shen HC, Wu Z, Balsells J, Crespo A, Brown P, Zamlynny B, Wiltsie J, Clemas J, Gibson J, Contino L, Lisnock J, Zhou G, Garcia-Calvo M, Bateman T, Xu L, Tong X, Crook M, Sinclair P..  (2014)  Mineralocorticoid receptor antagonists: identification of heterocyclic amide replacements in the oxazolidinedione series.,  24  (7): [PMID:24630411] [10.1016/j.bmcl.2014.02.057]

16. Casimiro-Garcia A, Piotrowski DW, Ambler C, Arhancet GB, Banker ME, Banks T, Boustany-Kari CM, Cai C, Chen X, Eudy R, Hepworth D, Hulford CA, Jennings SM, Loria PM, Meyers MJ, Petersen DN, Raheja NK, Sammons M, She L, Song K, Vrieze D, Wei L..  (2014)  Identification of (R)-6-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5-dihydro-1H-pyrazol-3-yl)-2-methoxynicotinic acid, a highly potent and selective nonsteroidal mineralocorticoid receptor antagonist.,  57  (10): [PMID:24738581] [10.1021/jm500206r]

17. Hu Q, Yin L, Hartmann RW..  (2014)  Aldosterone synthase inhibitors as promising treatments for mineralocorticoid dependent cardiovascular and renal diseases.,  57  (12): [PMID:24422519] [10.1021/jm401430e]

18. Hasui T, Ohyabu N, Ohra T, Fuji K, Sugimoto T, Fujimoto J, Asano K, Oosawa M, Shiotani S, Nishigaki N, Kusumoto K, Matsui H, Mizukami A, Habuka N, Sogabe S, Endo S, Ono M, Siedem CS, Tang TP, Gauthier C, De Meese LA, Boyd SA, Fukumoto S..  (2014)  Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists.,  22  (19): [PMID:25187277] [10.1016/j.bmc.2014.07.038]

19. Yang C, Balsells J, Chu HD, Cox JM, Crespo A, Ma X, Contino L, Brown P, Gao S, Zamlynny B, Wiltsie J, Clemas J, Lisnock J, Gibson J, Zhou G, Garcia-Calvo M, Bateman TJ, Tong V, Xu L, Crook M, Sinclair P, Shen HC..  (2015)  Discovery of benzimidazole oxazolidinediones as novel and selective nonsteroidal mineralocorticoid receptor antagonists.,  6  (4): [PMID:25941555] [10.1021/acsmedchemlett.5b00010]

20. Martin RE, Aebi JD, Hornsperger B, Krebs HJ, Kuhn B, Kuglstatter A, Alker AM, Märki HP, Müller S, Burger D, Ottaviani G, Riboulet W, Verry P, Tan X, Amrein K, Mayweg AV..  (2015)  Discovery of 4-Aryl-5,6,7,8-tetrahydroisoquinolines as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors: In Vivo Evaluation in Rodents and Cynomolgus Monkeys.,  58  (20): [PMID:26403853] [10.1021/acs.jmedchem.5b00851]

21. WHO Anatomical Therapeutic Chemical Classification, 

22. British National Formulary (72nd edition), 

23. Martín-Martínez M, Pérez-Gordillo FL, Álvarez de la Rosa D, Rodríguez Y, Gerona-Navarro G, González-Muñiz R, Zhou MM..  (2017)  Modulating Mineralocorticoid Receptor with Non-steroidal Antagonists. New Opportunities for the Development of Potent and Selective Ligands without Off-Target Side Effects.,  60  (7): [PMID:28051871] [10.1021/acs.jmedchem.6b01065]

24. Piotrowski DW, Futatsugi K, Casimiro-Garcia A, Wei L, Sammons MF, Herr M, Jiao W, Lavergne SY, Coffey SB, Wright SW, Song K, Loria PM, Banker ME, Petersen DN, Bauman J..  (2018)  Identification of Morpholino-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ones as Nonsteroidal Mineralocorticoid Antagonists.,  61  (3): [PMID:29300474] [10.1021/acs.jmedchem.7b01515]

25. Morgan RE, van Staden CJ, Chen Y, Kalyanaraman N, Kalanzi J, Dunn RT, Afshari CA, Hamadeh HK..  (2013)  A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.,  136  (1): [PMID:23956101] [10.1093/toxsci/kft176]

26. Chen M, Suzuki A, Thakkar S, Yu K, Hu C, Tong W..  (2016)  DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.,  21  (4): [PMID:26948801] [10.1016/j.drudis.2016.02.015]

27. Unpublished dataset, 

28. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

29. Katie Heiser, Peter F. McLean, Chadwick T. Davis, Ben Fogelson, Hannah B. Gordon, Pamela Jacobson, Brett Hurst, Ben Miller, Ronald W. Alfa, Berton A. Earnshaw, Mason L. Victors, Yolanda T. Chong, Imran S. Haque, Adeline S. Low, Christopher C. Gibson.  (2020)  Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2,  [10.1101/2020.04.21.054387]

30. Yu M, Ledeboer MW, Daniels M, Malojcic G, Tibbitts TT, Coeffet-Le Gal M, Pan-Zhou XR, Westerling-Bui A, Beconi M, Reilly JF, Mundel P, Harmange JC..  (2019)  Discovery of a Potent and Selective TRPC5 Inhibitor, Efficacious in a Focal Segmental Glomerulosclerosis Model.,  10  (11): [PMID:31749913] [10.1021/acsmedchemlett.9b00430]

31. Granberg KL, Yuan ZQ, Lindmark B, Edman K, Kajanus J, Hogner A, Malmgren M, O'Mahony G, Nordqvist A, Lindberg J, Tångefjord S, Kossenjans M, Löfberg C, Brånalt J, Liu D, Selmi N, Nikitidis G, Nordberg P, Hayen A, Aagaard A, Hansson E, Hermansson M, Ivarsson I, Jansson-Löfmark R, Karlsson U, Johansson U, William-Olsson L, Hartleib-Geschwindner J, Bamberg K..  (2019)  Identification of Mineralocorticoid Receptor Modulators with Low Impact on Electrolyte Homeostasis but Maintained Organ Protection.,  62  (3): [PMID:30596500] [10.1021/acs.jmedchem.8b01523]

32. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

33. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

34. Ogawa AK,Bunte EV,Mal R,Lan P,Sun Z,Crespo A,Wiltsie J,Clemas J,Gibson J,Contino L,Lisnock J,Zhou G,Garcia-Calvo M,Jochnowitz N,Ma X,Pan Y,Brown P,Zamlynny B,Bateman T,Leung D,Xu L,Tong X,Liu K,Crook M,Sinclair P.  (2016)  Discovery of novel non-steroidal reverse indole mineralocorticoid receptor antagonists.,  26  (12.0): [PMID:27161805] [10.1016/j.bmcl.2016.04.052]

35. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

36. Iijima T, Katoh M, Takedomi K, Yamamoto Y, Akatsuka H, Shirata N, Nishi A, Takakuwa M, Watanabe Y, Munakata H, Koyama N, Ikeda T, Iguchi T, Kato H, Kikkawa K, Kawaguchi T..  (2022)  Discovery of Apararenone (MT-3995) as a Highly Selective, Potent, and Novel Nonsteroidal Mineralocorticoid Receptor Antagonist.,  65  (12.0): [PMID:35652647] [10.1021/acs.jmedchem.2c00402]

37. 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(9):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
• USP Dictionary of USAN and International Drug Names
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6