(1S,9aR,11aS)-9a,11a-Dimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid phenylamide

ID: ALA280155

Max Phase: Preclinical

Molecular Formula: C25H32N2O2

Molecular Weight: 392.54

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C[C@]12CCC(=O)C=C1NCC1C2CC[C@@]2(C)C1CC[C@@H]2C(=O)Nc1ccccc1

Standard InChI:  InChI=1S/C25H32N2O2/c1-24-13-11-20-18(15-26-22-14-17(28)10-12-25(20,22)2)19(24)8-9-21(24)23(29)27-16-6-4-3-5-7-16/h3-7,14,18-21,26H,8-13,15H2,1-2H3,(H,27,29)/t18?,19?,20?,21-,24+,25-/m1/s1

Standard InChI Key:  NEXQLYFTKBAWDD-KFFMOSLCSA-N

Molfile:  

     RDKit          2D

 29 33  0  0  1  0  0  0  0  0999 V2000
    3.4750   -6.0250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3250   -7.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3167   -8.0667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4667   -6.8500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0375   -6.8292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7417   -7.2542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4667   -4.9792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2542   -5.7792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0292   -8.4792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.6125   -8.4792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7667   -5.6042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7500   -8.0750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2625   -4.7542    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.0417   -6.0042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2417   -7.1125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6125   -6.8292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7292   -6.4500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0958   -8.0667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8792   -4.3917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8125   -8.4792    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0958   -7.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4750   -3.9625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4667   -5.2000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3167   -6.4167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2667   -3.7417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8875   -3.3875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.0917   -2.5875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4792   -2.9500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8917   -2.3667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  5  1  0
  3  2  1  0
  4  1  1  0
  5 14  1  0
  6  4  1  0
  8  7  1  1
  8  1  1  0
  9 12  1  0
 10  3  2  0
 11  1  1  0
 12  6  1  0
 13  7  1  0
 14 11  1  0
 15  4  1  0
 16  2  1  0
 17  8  1  0
 18 21  1  0
 19  7  2  0
 20 18  2  0
 21 16  1  0
 22 13  1  0
  1 23  1  1
  2 24  1  1
 25 22  2  0
 26 22  1  0
 27 26  2  0
 28 25  1  0
 29 27  1  0
 15 17  1  0
  6  5  1  0
  3  9  1  0
 10 18  1  0
 28 29  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA280155

   ---

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: 392.54

Molecular Weight (Monoisotopic): 392.2464

AlogP: 4.54

#Rotatable Bonds: 2

Polar Surface Area: 58.20

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 3.76

CX LogD: 3.76

Aromatic Rings: 1

Heavy Atoms: 29

QED Weighted: 0.78

Np Likeness Score: 0.90

References

1. Kenny B, Ballard S, Blagg J, Fox D..  (1997)  Pharmacological options in the treatment of benign prostatic hyperplasia.,  40  (9): [PMID:9135028] [10.1021/jm960697s]

2. Frye SV, Haffner CD, Maloney PR, Hiner RN, Dorsey GF, Noe RA, Unwalla RJ, Batchelor KW, Bramson HN, Stuart JD..  (1995)  Structure-activity relationships for inhibition of type 1 and 2 human 5 alpha-reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase by 6-azaandrost-4-en-3-ones: optimization of the C17 substituent.,  38  (14): [PMID:7629802] [10.1021/jm00014a015]

3. Guarna, A A and 8 more authors.  2000-10-05  Benzo[c]quinolizin-3-ones: a novel class of potent and selective nonsteroidal inhibitors of human steroid 5alpha-reductase 1.  [PMID:11020287]

4. 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]

5. Occhiato, Ernesto G EG and 11 more authors.  2004-07-01  Synthesis, biological activity, and three-dimensional quantitative structure-activity relationship model for a series of benzo[c]quinolizin-3-ones, nonsteroidal inhibitors of human steroid 5alpha-reductase 1.  [PMID:15214782]

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. Lao, Kejing K and 6 more authors.  2017-09-01  Design, synthesis and biological evaluation of novel 3-oxo-4-oxa-5α-androst-17β-amide derivatives as dual 5α-reductase inhibitors and androgen receptor antagonists.  [PMID:28757062]

Source

Source(1):

• Scientific Literature