3-((5S,8R,9S,10S,13S,14S)-3-methoxy-10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-5-methylpyridine

ID: ALA3965562

PubChem CID: 89882605

Max Phase: Preclinical

Molecular Formula: C26H37NO

Molecular Weight: 379.59

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COC1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)C(c4cncc(C)c4)=CC[C@@H]32)C1

Standard InChI:  InChI=1S/C26H37NO/c1-17-13-18(16-27-15-17)22-7-8-23-21-6-5-19-14-20(28-4)9-11-25(19,2)24(21)10-12-26(22,23)3/h7,13,15-16,19-21,23-24H,5-6,8-12,14H2,1-4H3/t19-,20?,21-,23-,24-,25-,26+/m0/s1

Standard InChI Key:  WWOFVBIUARGLJR-WDIXAJRSSA-N

Molfile:  

     RDKit          2D

 32 36  0  0  0  0  0  0  0  0999 V2000
   38.2130   -2.8242    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.9460   -3.6042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.4232   -4.2749    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.9288   -4.9369    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.1477   -4.6730    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.4290   -5.0760    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.4151   -5.9017    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.6953   -6.3036    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.9852   -5.8838    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.2665   -6.2867    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.5564   -5.8628    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.5703   -5.0371    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.2889   -4.6382    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.9991   -5.0580    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.7189   -4.6521    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.7328   -3.8304    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.4514   -3.4275    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.1615   -3.8514    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.1615   -3.0257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.7189   -5.4778    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   34.9991   -4.2323    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.8366   -6.2646    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   32.1318   -5.8418    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.9852   -6.7095    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   36.4290   -4.2502    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   37.1477   -5.4988    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   37.6696   -2.2025    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.9335   -1.4270    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   38.7456   -1.2648    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.2869   -1.8845    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0255   -2.6654    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.0850   -1.6708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  3  2  2  0
  4  3  1  0
  5  4  1  0
  6  5  1  0
  7  6  1  0
  8  7  1  0
  9  8  1  0
 10  9  1  0
 11 10  1  0
 12 11  1  0
 13 12  1  0
 13 14  1  0
 15 14  1  0
 16 15  1  0
 17 16  1  0
 18 17  1  0
  2 18  1  0
  5 18  1  0
 18 19  1  1
  6 15  1  0
 15 20  1  6
  9 14  1  0
 14 21  1  1
 11 22  1  0
 22 23  1  0
  9 24  1  6
  6 25  1  1
  5 26  1  6
 27  1  2  0
 28 27  1  0
 29 28  2  0
 30 29  1  0
 31 30  2  0
  1 31  1  0
 30 32  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3965562

   3-[(5S,8R,9S,10S,13S,14S)-3-methoxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-5-methylpyridine

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 379.59

Molecular Weight (Monoisotopic): 379.2875

AlogP: 6.44

#Rotatable Bonds: 2

Polar Surface Area: 22.12

Molecular Species: NEUTRAL

HBA: 2

HBD: ┄

#RO5 Violations: 1

HBA (Lipinski): 2

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 5.32

CX LogP: 5.53

CX LogD: 5.52

Aromatic Rings: 1

Heavy Atoms: 28

QED Weighted: 0.59

Np Likeness Score: 1.69

References

1.  (2013)  C-17-heteroaryl steroidal compounds as inhibitors of CYP11B, CYP17, and/or CYP21, 

2. Ling, Y Z YZ and 5 more authors.  1997-09-26  17-Imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives. Novel steroidal inhibitors of human cytochrome C17,20-lyase (P450(17 alpha).  [PMID:9379450]

3. Hartmann, R W RW and 5 more authors.  2000-11-02  Synthesis and evaluation of novel steroidal oxime inhibitors of P450 17 (17 alpha-hydroxylase/C17-20-lyase) and 5 alpha-reductase types 1 and 2.  [PMID:11063622]

4. Recanatini, M M and 9 more authors.  2001-03-01  A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17,20-lyase.  [PMID:11262078]

5. Clement, Omoshile O OO and 6 more authors.  2003-06-05  Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy.  [PMID:12773039]

6. Handratta, Venkatesh D VD and 10 more authors.  2005-04-21  Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model.  [PMID:15828836]

7. Voets, Marieke M and 7 more authors.  2005-10-20  Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis.  [PMID:16220979]

8. Pinto-Bazurco Mendieta, Mariano A E MA and 5 more authors.  2008-08-28  Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer.  [PMID:18672868]

9. Hu, Qingzhong Q and 8 more authors.  2008-08-15  Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge.  [PMID:18674917]

10. Hille, Ulrike E UE and 7 more authors.  2009-07  Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls.  [PMID:19211174]

11. Hu, Qingzhong Q, Yin, Lina L, Jagusch, Carsten C, Hille, Ulrike E UE and Hartmann, Rolf W RW.  2010-07-08  Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors.  [PMID:20550118]

12. Hu, Qingzhong Q, Jagusch, Carsten C, Hille, Ulrike E UE, Haupenthal, Jörg J and Hartmann, Rolf W RW.  2010-08-12  Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer.  [PMID:20684610]

13. Yin, Lina L and 5 more authors.  2012-07-26  Novel imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij]quinolin-4-ones as potent and selective CYP11B1 inhibitors for the treatment of Cushing's syndrome.  [PMID:22788843]

14. Purushottamachar, Puranik P and 8 more authors.  2013-06-27  Systematic structure modifications of multitarget prostate cancer drug candidate galeterone to produce novel androgen receptor down-regulating agents as an approach to treatment of advanced prostate cancer.  [PMID:23713567]

15. Pinto-Bazurco Mendieta, Mariano A E MA, Hu, Qingzhong Q, Engel, Matthias M and Hartmann, Rolf W RW.  2013-08-08  Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the treatment of prostate cancer to reduce risks of cardiovascular diseases.  [PMID:23859149]

16. Rafferty, Stephen W SW, Eisner, Joel R JR, Moore, William R WR, Schotzinger, Robert J RJ and Hoekstra, William J WJ.  2014-06-01  Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors.  [PMID:24775307]

17. Njar, Vincent C O VC and Brodie, Angela M H AM.  2015-03-12  Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer.  [PMID:25591066]

18. Huang, Audris A and 21 more authors.  2016-01-14  Discovery of the Selective CYP17A1 Lyase Inhibitor BMS-351 for the Treatment of Prostate Cancer.  [PMID:26819663]

19. Blass, Benjamin E BE and 18 more authors.  2016-12-01  Design, synthesis, and evaluation of (2S,4R)-Ketoconazole sulfonamide analogs as potential treatments for Metabolic Syndrome.  [PMID:27789139]

20. Wang, Mingliang M and 6 more authors.  2017-05-26  Discovery of novel 1,2,3,4-tetrahydrobenzo[4, 5]thieno[2, 3-c]pyridine derivatives as potent and selective CYP17 inhibitors.  [PMID:28350999]

21. Fehl, Charlie C and 5 more authors.  2018-06-14  Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2.  [PMID:29792703]

22. Blass, Benjamin E BE and 20 more authors.  2018-07-15  Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17).  [PMID:29803730]

23. Child, Stella A and Guengerich, F Peter.  2020-06-25  Multistep Binding of the Non-Steroidal Inhibitors Orteronel and Seviteronel to Human Cytochrome P450 17A1 and Relevance to Inhibition of Enzyme Activity.  [PMID:32223238]

Source

Source(1):

• Patent Bioactivity Data