4-Cyano-N-(4-(5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl)phenyl)benzenesulfonamide

ID: ALA4441357

PubChem CID: 155514963

Max Phase: Preclinical

Molecular Formula: C24H13F3N2O4S2

Molecular Weight: 514.51

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  N#Cc1ccc(S(=O)(=O)Nc2ccc(-c3ccc(C(=O)c4cc(F)c(F)c(O)c4F)s3)cc2)cc1

Standard InChI:  InChI=1S/C24H13F3N2O4S2/c25-18-11-17(21(26)24(31)22(18)27)23(30)20-10-9-19(34-20)14-3-5-15(6-4-14)29-35(32,33)16-7-1-13(12-28)2-8-16/h1-11,29,31H

Standard InChI Key:  JXUNVJWFIFYSLS-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

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   34.6894  -22.4274    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.6935  -21.6102    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   33.9837  -22.0152    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   32.2460  -21.6075    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.0614  -21.6086    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   27.7847  -22.7678    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   27.9592  -24.3930    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   29.4563  -25.0541    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   30.7775  -24.0823    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   34.2855  -20.9043    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   35.5111  -21.6123    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.9162  -22.3208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.7327  -22.3213    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.1422  -21.6132    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.7294  -20.9030    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.9143  -20.9060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.9594  -21.6123    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.7752  -21.6091    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
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 34 35  3  0
M  END

Alternative Forms

1. Parent:

   

   ALA4441357

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 514.51

Molecular Weight (Monoisotopic): 514.0269

AlogP: 5.44

#Rotatable Bonds: 6

Polar Surface Area: 107.26

Molecular Species: ACID

HBA: 6

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 6.16

CX Basic pKa: ┄

CX LogP: 5.46

CX LogD: 4.12

Aromatic Rings: 4

Heavy Atoms: 35

QED Weighted: 0.26

Np Likeness Score: -1.39

References

1. Abdelsamie AS, Salah M, Siebenbürger L, Merabet A, Scheuer C, Frotscher M, Müller ST, Zierau O, Vollmer G, Menger MD, Laschke MW, van Koppen CJ, Marchais-Oberwinkler S, Hartmann RW..  (2019)  Design, Synthesis, and Biological Characterization of Orally Active 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors Targeting the Prevention of Osteoporosis.,  62  (15): [PMID:31343176] [10.1021/acs.jmedchem.9b00932]

2. Frotscher, Martin M and 10 more authors.  2008-04-10  Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) for the treatment of estrogen-dependent diseases.  [PMID:18324762]

3. Bey, Emmanuel E and 8 more authors.  2008-06-15  Design, synthesis and biological evaluation of bis(hydroxyphenyl) azoles as potent and selective non-steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) for the treatment of estrogen-dependent diseases.  [PMID:18514529]

4. Schuster, Daniela D and 6 more authors.  2008-07-24  Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries.  [PMID:18533708]

5. Marchais-Oberwinkler, Sandrine S and 10 more authors.  2008-08-14  Substituted 6-phenyl-2-naphthols. Potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1): design, synthesis, biological evaluation, and pharmacokinetics.  [PMID:18630892]

6. Bey, Emmanuel E and 9 more authors.  2008-11-13  Design, synthesis, biological evaluation and pharmacokinetics of bis(hydroxyphenyl) substituted azoles, thiophenes, benzenes, and aza-benzenes as potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1).  [PMID:18855374]

7. Bey, Emmanuel E and 10 more authors.  2009-11-12  New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) inhibitory activity and selectivity.  [PMID:19831396]

8. Oster, Alexander A and 8 more authors.  2010-05-15  Novel estrone mimetics with high 17beta-HSD1 inhibitory activity.  [PMID:20413314]

9. Oster, Alexander A and 5 more authors.  2010-11-25  Bicyclic substituted hydroxyphenylmethanones as novel inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) for the treatment of estrogen-dependent diseases.  [PMID:20977238]

10. Marchais-Oberwinkler, Sandrine S and 7 more authors.  2011-01-27  New drug-like hydroxyphenylnaphthol steroidomimetics as potent and selective 17β-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of estrogen-dependent diseases.  [PMID:21189020]

11. Wetzel, Marie M, Marchais-Oberwinkler, Sandrine S and Hartmann, Rolf W RW.  2011-01-15  17β-HSD2 inhibitors for the treatment of osteoporosis: Identification of a promising scaffold.  [PMID:21211981]

12. Wetzel, Marie M, Gargano, Emanuele M EM, Hinsberger, Stefan S, Marchais-Oberwinkler, Sandrine S and Hartmann, Rolf W RW.  2012-01  Discovery of a new class of bicyclic substituted hydroxyphenylmethanones as 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors for the treatment of osteoporosis.  [PMID:21945251]

13. Wetzel, Marie M and 5 more authors.  2011-11-10  Introduction of an electron withdrawing group on the hydroxyphenylnaphthol scaffold improves the potency of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors.  [PMID:21972996]

14. Xu, Kuiying K, Al-Soud, Yaseen A YA, Wetzel, Marie M, Hartmann, Rolf W RW and Marchais-Oberwinkler, Sandrine S.  2011-12  Triazole ring-opening leads to the discovery of potent nonsteroidal 17β-hydroxysteroid dehydrogenase type 2 inhibitors.  [PMID:22037253]

15. Henn, Claudia C, Einspanier, Almuth A, Marchais-Oberwinkler, Sandrine S, Frotscher, Martin M and Hartmann, Rolf W RW.  2012-04-12  Lead optimization of 17β-HSD1 inhibitors of the (hydroxyphenyl)naphthol sulfonamide type for the treatment of endometriosis.  [PMID:22380653]

16. Marchais-Oberwinkler, Sandrine S and 9 more authors.  2013-01-10  Structural optimization of 2,5-thiophene amides as highly potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors for the treatment of osteoporosis.  [PMID:23145773]

17. Perspicace, Enrico E, Giorgio, Annalaura A, Carotti, Angelo A, Marchais-Oberwinkler, Sandrine S and Hartmann, Rolf W RW.  2013-11  Novel N-methylsulfonamide and retro-N-methylsulfonamide derivatives as 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors with good ADME-related physicochemical parameters.  [PMID:24036043]

18. Abdelsamie, Ahmed S AS and 5 more authors.  2014-07-23  Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker.  [PMID:24929290]

19. Vuorinen, Anna A and 6 more authors.  2014-07-24  Ligand-based pharmacophore modeling and virtual screening for the discovery of novel 17β-hydroxysteroid dehydrogenase 2 inhibitors.  [PMID:24960438]

20. Perspicace, Enrico E and 6 more authors.  2014-08-18  Novel, potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors as potential therapeutics for osteoporosis with dual human and mouse activities.  [PMID:24974351]

21. Gargano, Emanuele M EM and 5 more authors.  2014-11-24  Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors.  [PMID:25259513]

22. Abdelsamie, Ahmed S AS and 5 more authors.  2015-10-20  Towards the evaluation in an animal disease model: Fluorinated 17β-HSD1 inhibitors showing strong activity towards both the human and the rat enzyme.  [PMID:26322835]

23. Abdelsamie, Ahmed S AS and 8 more authors.  2017-02-15  Treatment of estrogen-dependent diseases: Design, synthesis and profiling of a selective 17β-HSD1 inhibitor with sub-nanomolar IC50 for a proof-of-principle study.  [PMID:27852458]

24. Vuorinen, Anna A and 14 more authors.  2017-04-28  Potential Antiosteoporotic Natural Product Lead Compounds That Inhibit 17β-Hydroxysteroid Dehydrogenase Type 2.  [PMID:28319389]

25. 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]

26. Vuorinen, Anna A and 6 more authors.  2017-07-01  Phenylbenzenesulfonates and -sulfonamides as 17β-hydroxysteroid dehydrogenase type 2 inhibitors: Synthesis and SAR-analysis.  [PMID:28506753]

27. Siebenbuerger, Lorenz L and 10 more authors.  2018-12-13  Highly Potent 17β-HSD2 Inhibitors with a Promising Pharmacokinetic Profile for Targeted Osteoporosis Therapy.  [PMID:30480443]

28. Abdelsamie, Ahmed S AS and 7 more authors.  2019-09-15  Development of potential preclinical candidates with promising in vitro ADME profile for the inhibition of type 1 and type 2 17β-Hydroxysteroid dehydrogenases: Design, synthesis, and biological evaluation.  [PMID:31176098]

29. Abdelsamie, Ahmed S AS and 13 more authors.  2019-08-08  Design, Synthesis, and Biological Characterization of Orally Active 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors Targeting the Prevention of Osteoporosis.  [PMID:31343176]

Source

Source(1):

• Scientific Literature