(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 (2-tert-butyl-5-trifluoromethyl-phenyl)-amide

ID: ALA277224

Max Phase: Preclinical

Molecular Formula: C30H39F3N2O2

Molecular Weight: 516.65

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)(C)c1ccc(C(F)(F)F)cc1NC(=O)[C@H]1CCC2C3CNC4=CC(=O)CC[C@]4(C)C3CC[C@@]21C

Standard InChI:  InChI=1S/C30H39F3N2O2/c1-27(2,3)22-7-6-17(30(31,32)33)14-24(22)35-26(37)23-9-8-20-19-16-34-25-15-18(36)10-12-29(25,5)21(19)11-13-28(20,23)4/h6-7,14-15,19-21,23,34H,8-13,16H2,1-5H3,(H,35,37)/t19?,20?,21?,23-,28+,29-/m1/s1

Standard InChI Key:  YBUBNNZIJZMUDV-WBDNBOLYSA-N

Molfile:  

     RDKit          2D

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    3.8542   -5.5250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8542   -6.3500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0000   -5.1292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5667   -5.1125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0000   -3.2542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    6.7917   -4.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    8.4875   -0.9000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    7.0792   -1.1542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4167   -2.6750    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.2667   -1.1792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8167   -1.7417    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    9.7125   -2.9542    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
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    6.0000   -3.4792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    6.9375   -0.3417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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  2  5  1  0
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  1 33  1  1
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 20 22  1  0
  7  5  1  0
  3 11  1  0
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M  END

Alternative Forms

1. Parent:

   

   ALA277224

   ---

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: 516.65

Molecular Weight (Monoisotopic): 516.2964

AlogP: 6.86

#Rotatable Bonds: 2

Polar Surface Area: 58.20

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 13.69

CX Basic pKa: ┄

CX LogP: 6.18

CX LogD: 6.18

Aromatic Rings: 1

Heavy Atoms: 37

QED Weighted: 0.45

Np Likeness Score: 0.44

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