2-(dimethylamino)-2-phenyl-1,1-di(pyridin-3-yl)ethanol

ID: ALA1090817

PubChem CID: 11638319

Max Phase: Preclinical

Molecular Formula: C20H21N3O

Molecular Weight: 319.41

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CN(C)C(c1ccccc1)C(O)(c1cccnc1)c1cccnc1

Standard InChI:  InChI=1S/C20H21N3O/c1-23(2)19(16-8-4-3-5-9-16)20(24,17-10-6-12-21-14-17)18-11-7-13-22-15-18/h3-15,19,24H,1-2H3

Standard InChI Key:  JPKILPNLNPLMOZ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 24 26  0  0  0  0  0  0  0  0999 V2000
    8.3152  -17.8166    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3141  -18.6440    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0289  -19.0569    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7453  -18.6435    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7425  -17.8130    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0271  -17.4039    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.4605  -19.0549    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4617  -19.8799    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1743  -18.6413    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7466  -20.2919    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7475  -21.1162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4632  -21.5284    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1794  -21.1103    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.1749  -20.2875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8894  -19.0527    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8860  -19.8761    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6003  -20.2874    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3151  -19.8737    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3111  -19.0444    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5963  -18.6369    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7417  -19.4625    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.1730  -17.8163    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.8868  -17.4027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4579  -17.4049    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 11 12  2  0
  6  1  1  0
 12 13  1  0
  1  2  2  0
 13 14  2  0
 14  8  1  0
  4  7  1  0
  9 15  1  0
  3  4  2  0
 15 16  2  0
  7  8  1  0
 16 17  1  0
 17 18  2  0
  7  9  1  0
 18 19  1  0
  4  5  1  0
 19 20  2  0
 20 15  1  0
  8 10  2  0
  7 21  1  0
  2  3  1  0
  9 22  1  0
 10 11  1  0
 22 23  1  0
  5  6  2  0
 22 24  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1090817

   2-(Dimethylamino)-2-phenyl-1,1-di(pyridin-3-yl)ethanol

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: 319.41

Molecular Weight (Monoisotopic): 319.1685

AlogP: 3.02

#Rotatable Bonds: 5

Polar Surface Area: 49.25

Molecular Species: BASE

HBA: 4

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.37

CX Basic pKa: 8.55

CX LogP: 2.14

CX LogD: 0.96

Aromatic Rings: 3

Heavy Atoms: 24

QED Weighted: 0.79

Np Likeness Score: -0.41

References

1. Beshore DC, Liverton NJ, McIntyre CJ, Claiborne CF, Libby B, Culberson JC, Salata JJ, Regan CP, Lynch JJ, Kiss L, Spencer RH, Kane SA, White RB, Yeh S, Hartman GD, Dinsmore CJ..  (2010)  Discovery of triarylethanolamine inhibitors of the Kv1.5 potassium channel.,  20  (8): [PMID:20304642] [10.1016/j.bmcl.2010.03.005]

2. Harvey, Andrew J AJ, Baell, Jonathan B JB, Toovey, Nathan N, Homerick, Daniel D and Wulff, Heike H.  2006-02-23  A new class of blockers of the voltage-gated potassium channel Kv1.3 via modification of the 4- or 7-position of khellinone.  [PMID:16480279]

3. Blass, Benjamin E BE and 17 more authors.  2006-09-01  Synthesis and evaluation of (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones as Kv1.5 channel blockers for the treatment of atrial fibrillation.  [PMID:16793267]

4. Jackson, Chris M CM and 11 more authors.  2007-01-01  Evolution of thiazolidine-based blockers of human Kv1.5 for the treatment of atrial arrhythmias.  [PMID:17095219]

5. Trotter, B Wesley BW and 17 more authors.  2006-11-30  Design and synthesis of novel isoquinoline-3-nitriles as orally bioavailable Kv1.5 antagonists for the treatment of atrial fibrillation.  [PMID:17125248]

6. Gross, Michael F MF and 7 more authors.  2007-05-15  Aryl sulfonamido indane inhibitors of the Kv1.5 ion channel.  [PMID:17350840]

7. Lloyd, John J and 11 more authors.  2007-06-15  Benzopyran sulfonamides as KV1.5 potassium channel blockers.  [PMID:17462888]

8. Gross, Michael F MF and 5 more authors.  2009-06-01  Aryl sulfonamido tetralin inhibitors of the Kv1.5 ion channel.  [PMID:19398199]

9. Blass, Benjamin E BE and 13 more authors.  2009-11-12  Selective Kv1.5 blockers: development of (R)-1-(methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone (KVI-020/WYE-160020) as a potential treatment for atrial arrhythmia.  [PMID:19888755]

10. Olsson, Roine I RI and 22 more authors.  2013-02-01  Synthesis and evaluation of diphenylphosphinic amides and diphenylphosphine oxides as inhibitors of Kv1.5.  [PMID:23260347]

11. Guo, Xiaoke X and 13 more authors.  2013-11-01  Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors.  [PMID:24071446]

12. Olsson, Roine I RI and 25 more authors.  2014-03-01  Lactam sulfonamides as potent inhibitors of the Kv1.5 potassium ion channel.  [PMID:24513046]

13. Guo, Xiaoke X and 14 more authors.  2014-06-23  Discovery of 1-aryloxyethyl piperazine derivatives as Kv1.5 potassium channel inhibitors (part I).  [PMID:24824064]

14. Johnson, James A JA and 12 more authors.  2014-07-15  Design, synthesis and evaluation of phenethylaminoheterocycles as K(v)1.5 inhibitors.  [PMID:24881565]

15. and Boström, Jonas J.  2012-09-13  Symmetric kv1.5 blockers discovered by focused screening.  [PMID:24900546]

16. Wolkenberg, Scott E SE and 21 more authors.  2017-02-15  Discovery of MK-1832, a Kv1.5 inhibitor with improved selectivity and pharmacokinetics.  [PMID:28131713]

17. Gunaga, Prashantha P and 30 more authors.  2017-05-11  Selective IKur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide.  [PMID:28418664]

18. Kajanus, Johan J and 6 more authors.  2019-05-15  Potassium channel blocking 1,2-bis(aryl)ethane-1,2-diamines active as antiarrhythmic agents.  [PMID:30879840]

Source

Source(1):

• Scientific Literature