2-(6-(4-((6-Aminopyridin-3-yl)sulfonyl)piperazin-1-yl)-5-(3-methoxyprop-1-yn-1-yl)pyridin-3-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol

ID: ALA3319529

PubChem CID: 118709619

Max Phase: Preclinical

Molecular Formula: C21H21F6N5O4S

Molecular Weight: 553.49

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COCC#Cc1cc(C(O)(C(F)(F)F)C(F)(F)F)cnc1N1CCN(S(=O)(=O)c2ccc(N)nc2)CC1

Standard InChI:  InChI=1S/C21H21F6N5O4S/c1-36-10-2-3-14-11-15(19(33,20(22,23)24)21(25,26)27)12-30-18(14)31-6-8-32(9-7-31)37(34,35)16-4-5-17(28)29-13-16/h4-5,11-13,33H,6-10H2,1H3,(H2,28,29)

Standard InChI Key:  GBXLKJZAFUNCAL-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 37 39  0  0  0  0  0  0  0  0999 V2000
    9.4060  -12.0433    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.2231  -12.0474    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    9.8181  -11.3376    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.5242  -13.2773    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5231  -14.0968    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.2311  -14.5058    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9408  -14.0963    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9380  -13.2737    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2293  -12.8684    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2309  -15.3229    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.9334  -11.6405    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.6465  -12.0469    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3509  -11.6397    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3527  -10.8221    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.6439  -10.4135    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9333  -10.8224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0579  -10.4166    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   14.4731  -10.4201    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4742   -9.6021    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7619   -9.1931    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0572   -9.6028    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.1817   -9.1931    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8897   -9.6013    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1813   -8.3759    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8857   -8.7786    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   15.8901  -10.4185    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   16.5971   -9.1923    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   16.5915  -10.0085    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   15.8888   -7.9669    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   14.4734   -7.9677    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   15.1758   -7.5570    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.7661  -11.6404    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7646  -12.4575    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7631  -13.2747    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0546  -13.6820    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.0531  -14.4992    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  2  2  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9  4  1  0
  6 10  1  0
  9  2  1  0
  2 11  1  0
 11 12  1  0
 11 16  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 22 17  1  0
 14 17  1  0
 20 23  1  0
 23 24  1  0
 23 25  1  0
 23 26  1  0
 24 27  1  0
 24 28  1  0
 24 29  1  0
 25 30  1  0
 25 31  1  0
 25 32  1  0
 33 34  3  0
 18 33  1  0
 34 35  1  0
 35 36  1  0
 36 37  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3319529

   ---

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: 553.49

Molecular Weight (Monoisotopic): 553.1218

AlogP: 1.88

#Rotatable Bonds: 5

Polar Surface Area: 121.88

Molecular Species: NEUTRAL

HBA: 8

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 7.29

CX Basic pKa: 4.87

CX LogP: 2.17

CX LogD: 1.80

Aromatic Rings: 2

Heavy Atoms: 37

QED Weighted: 0.43

Np Likeness Score: -1.08

References

1. Hong FT, Norman MH, Ashton KS, Bartberger MD, Chen J, Chmait S, Cupples R, Fotsch C, Jordan SR, Lloyd DJ, Sivits G, Tadesse S, Hale C, St Jean DJ..  (2014)  Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 4. Exploration of a novel binding pocket.,  57  (14): [PMID:25001129] [10.1021/jm5001979]

2. Xu, Jiayi J and 25 more authors.  2017-05-01  Discovery of orally active hepatoselective glucokinase activators for treatment of Type II Diabetes Mellitus.  [PMID:28284809]

3. May-Dracka, Tricia L TL and 21 more authors.  2018-06-01  Investigating small molecules to inhibit germinal center kinase-like kinase (GLK/MAP4K3) upstream of PKCθ phosphorylation: Potential therapy to modulate T cell dependent immunity.  [PMID:29636220]

4. Narayan, Satya S and 7 more authors.  2019-01-01  ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.  [PMID:30384048]

5. Hinklin, Ronald J and 18 more authors.  2020-01-01  Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator.  [PMID:31818630]

Source

Source(1):

• Scientific Literature