(14E,15S)-14-(hydroxyimino)-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-5-yl sulfamate

ID: ALA1627551

Max Phase: Preclinical

Molecular Formula: C18H24N2O4S

Molecular Weight: 364.47

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C[C@]12CC[C@@H]3c4ccc(OS(N)(=O)=O)cc4CC[C@H]3[C@@H]1CC/C2=N\O

Standard InChI:  InChI=1S/C18H24N2O4S/c1-18-9-8-14-13-5-3-12(24-25(19,22)23)10-11(13)2-4-15(14)16(18)6-7-17(18)20-21/h3,5,10,14-16,21H,2,4,6-9H2,1H3,(H2,19,22,23)/b20-17+/t14-,15-,16+,18+/m1/s1

Standard InChI Key:  KQYXFDNFKWDWLM-HMLLZFDZSA-N

Molfile:  

     RDKit          2D

 28 31  0  0  1  0  0  0  0  0999 V2000
    4.8173   -7.9547    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    9.8049   -5.0645    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7976   -5.8881    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0862   -6.3069    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3657   -5.8898    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6585   -6.3127    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6636   -7.1403    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5909   -4.8153    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0843   -4.6474    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3647   -5.0579    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5800   -6.1562    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0913   -7.1304    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5287   -7.5442    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.9421   -5.9038    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4110   -7.2351    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.2196   -8.6619    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.8507   -4.0371    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.9440   -7.5426    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3717   -7.5409    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1019   -8.3611    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.2359   -7.1337    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0758   -5.4894    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2349   -6.3143    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7957   -4.2452    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.6450   -3.8209    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.3667   -6.7167    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    9.0792   -5.4792    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    9.7917   -6.7208    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  2  9  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  6 14  2  0
  7 18  2  0
  8  2  1  0
  9 10  1  0
 10  5  1  0
 11  3  1  0
 12 19  1  0
 13  1  1  0
 14 23  1  0
 15  1  2  0
 16  1  2  0
 17  8  2  0
 18 21  1  0
 19  7  1  0
 20  1  1  0
 21 13  1  0
 22 11  1  0
 23 21  2  0
  2 24  1  1
 25 17  1  0
  6  7  1  0
 12  4  1  0
  2  3  1  0
 22  8  1  0
  5 26  1  6
  4 27  1  1
  3 28  1  6
M  END

Alternative Forms

1. Parent:

   

   ALA1627551

   ---

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: 364.47

Molecular Weight (Monoisotopic): 364.1457

AlogP: 2.96

#Rotatable Bonds: 2

Polar Surface Area: 101.98

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.70

CX Basic pKa: 1.79

CX LogP: 3.27

CX LogD: 3.27

Aromatic Rings: 1

Heavy Atoms: 25

QED Weighted: 0.62

Np Likeness Score: 1.01

References

1. Hejaz HA, Purohit A, Mahon MF, Reed MJ, Potter BV..  (1999)  Synthesis and biological activity of the superestrogen (E)-17-oximino-3-O-sulfamoyl-1,3,5(10)-estratriene: x-ray crystal structure of (E)-17-oximino-3-hydroxy-1,3,5(10)-estratriene.,  42  (16): [PMID:10447965] [10.1021/jm980717l]

2. Leese, Mathew P MP and 14 more authors.  2008-03-13  Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents.  [PMID:18260615]

3. Woo, L W Lawrence LW and 9 more authors.  2010-03-11  Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template.  [PMID:20148564]

4. Kajita, Daisuke; Nakamura, Masaharu; Matsumoto, Yotaro; Makishima, Makoto and Hashimoto, Yuichi.  2014-04-01  Design and synthesis of silicon-containing steroid sulfatase inhibitors possessing pro-estrogen antagonistic character.  [PMID:24630694]

5. Thomas, Mark P and Potter, Barry V L.  2015-10-08  Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women's Health.  [PMID:25992880]

6. Mostafa, Yaser A YA, Kralt, Braden B, Rao, Praveen P N PP and Taylor, Scott D SD.  2015-09-01  A-ring substituted 17β-arylsulfonamides of 17β-aminoestra-1,3,5(10)-trien-3-ol as highly potent reversible inhibitors of steroid sulfatase.  [PMID:26211459]

7. Salah, Mohamed M, Abdelsamie, Ahmed S AS and Frotscher, Martin M.  2017-05-11  First Dual Inhibitors of Steroid Sulfatase (STS) and 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1): Designed Multiple Ligands as Novel Potential Therapeutics for Estrogen-Dependent Diseases.  [PMID:28406629]

8. Saha, Tanmay T, Makar, Subhajit S, Swetha, Rayala R, Gutti, Gopichand G and Singh, Sushil K SK.  2019-09-01  Estrogen signaling: An emanating therapeutic target for breast cancer treatment.  [PMID:31129450]

9. Zaraei, Seyed-Omar SO and 6 more authors.  2019-06-22  Sulfamates in drug design and discovery: Pre-clinical and clinical investigations.  [PMID:31255926]

Source

Source(1):

• Scientific Literature