2-(6-(4-((6-aminopyridin-3-yl)sulfonyl)piperazin-1-yl)-5-chloropyridin-3-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol

ID: ALA3319523

PubChem CID: 118709613

Max Phase: Preclinical

Molecular Formula: C17H16ClF6N5O3S

Molecular Weight: 519.86

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1ccc(S(=O)(=O)N2CCN(c3ncc(C(O)(C(F)(F)F)C(F)(F)F)cc3Cl)CC2)cn1

Standard InChI:  InChI=1S/C17H16ClF6N5O3S/c18-12-7-10(15(30,16(19,20)21)17(22,23)24)8-27-14(12)28-3-5-29(6-4-28)33(31,32)11-1-2-13(25)26-9-11/h1-2,7-9,30H,3-6H2,(H2,25,26)

Standard InChI Key:  XBUBRXIUOXRHDZ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 33 35  0  0  0  0  0  0  0  0999 V2000
    6.2032   -3.5329    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.0204   -3.5370    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    6.6154   -2.8273    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.3215   -4.7669    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.3204   -5.5864    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.0284   -5.9954    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7381   -5.5860    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7352   -4.7633    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0266   -4.3581    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0282   -6.8126    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.7307   -3.1302    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.4438   -3.5366    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1482   -3.1293    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1499   -2.3118    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.4412   -1.9031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7306   -2.3120    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8552   -1.9063    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5629   -2.3171    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2704   -1.9098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2715   -1.0917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5592   -0.6827    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8545   -1.0924    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.9790   -0.6828    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6869   -1.0910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9786    0.1380    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6830   -0.2683    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.6874   -1.9082    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.3944   -0.6820    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.3887   -1.4982    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   12.6861    0.5462    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   11.2706    0.5469    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   11.9731    0.9534    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   10.5614   -3.1343    0.0000 Cl  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
 18 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3319523

   ---

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: 519.86

Molecular Weight (Monoisotopic): 519.0567

AlogP: 2.54

#Rotatable Bonds: 4

Polar Surface Area: 112.65

Molecular Species: NEUTRAL

HBA: 7

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 7.26

CX Basic pKa: 4.06

CX LogP: 2.42

CX LogD: 2.04

Aromatic Rings: 2

Heavy Atoms: 33

QED Weighted: 0.60

Np Likeness Score: -1.38

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