4-(6-fluoroindolin-1-yl)-N-(4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)piperidine-1-carboxamide

ID: ALA3093863

PubChem CID: 71657549

Max Phase: Preclinical

Molecular Formula: C20H23FN6O2

Molecular Weight: 398.44

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C1NCCn2nc(NC(=O)N3CCC(N4CCc5ccc(F)cc54)CC3)cc21

Standard InChI:  InChI=1S/C20H23FN6O2/c21-14-2-1-13-3-9-26(16(13)11-14)15-4-7-25(8-5-15)20(29)23-18-12-17-19(28)22-6-10-27(17)24-18/h1-2,11-12,15H,3-10H2,(H,22,28)(H,23,24,29)

Standard InChI Key:  RJNFVDPBBUNVSC-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 29 33  0  0  0  0  0  0  0  0999 V2000
    2.3383   -1.3500    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7248    1.2135    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6065    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7248   -1.2135    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1884   -2.6409    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6234   -3.0602    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9781   -4.5176    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8933   -5.5536    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4537   -5.1320    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0990   -3.6745    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2452   -7.0125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.3962   -7.3518    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1582   -8.0475    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5101   -9.5065    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5343  -10.6289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3218  -11.9046    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9003  -13.3441    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7343  -13.6279    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9362  -14.4290    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.3936  -14.0743    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.8152  -12.6347    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7793  -11.5499    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8926  -10.0550    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  2  0
  3  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14  9  1  0
 12 15  1  0
 15 16  2  0
 15 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 21 23  1  0
 23 24  1  0
 24 25  1  0
 25 26  1  0
 26 20  1  0
 26 27  1  0
 27 18  2  0
  8 28  1  0
 28  5  1  0
 28 29  2  0
 29  2  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3093863

   4-(6-fluoroindolin-1-yl)-N-(4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)piperidine-1-carboxamide

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: 398.44

Molecular Weight (Monoisotopic): 398.1867

AlogP: 1.82

#Rotatable Bonds: 2

Polar Surface Area: 82.50

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.02

CX Basic pKa: 2.69

CX LogP: 1.27

CX LogD: 1.27

Aromatic Rings: 2

Heavy Atoms: 29

QED Weighted: 0.81

Np Likeness Score: -1.36

References

1. Yang SM, Tang Y, Zhang R, Lu H, Kuo GH, Gaul MD, Li Y, Ho G, Conway JG, Liang Y, Lenhard JM, Demarest KT, Murray WV..  (2013)  4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs.,  23  (24): [PMID:24153205] [10.1016/j.bmcl.2013.09.096]

2.  (2016)  Substituted piperidinyl-carboxamide derivatives useful as SCD 1 inhibitors, 

3. Koltun, Dmitry O DO and 16 more authors.  2009-06-01  Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors.  [PMID:19394219]

4. Li, Chun Sing CS and 7 more authors.  2009-09-01  Thiazole analog as stearoyl-CoA desaturase 1 inhibitor.  [PMID:19632834]

5. Ramtohul, Yeeman K YK and 10 more authors.  2010-03-01  SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors.  [PMID:20137926]

6. Oballa, Renata M RM and 30 more authors.  2011-07-28  Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia.  [PMID:21661758]

7. Lachance, Nicolas N and 9 more authors.  2012-01-01  Discovery of potent and liver-selective stearoyl-CoA desaturase (SCD) inhibitors in an acyclic linker series.  [PMID:22101133]

8. Lachance, Nicolas N and 16 more authors.  2012-01-15  Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series.  [PMID:22209206]

9. Zhang, Zaihui Z and 15 more authors.  2013-01-24  Discovery of piperazin-1-ylpyridazine-based potent and selective stearoyl-CoA desaturase-1 inhibitors for the treatment of obesity and metabolic syndrome.  [PMID:23245208]

10. Sun, Shaoyi S and 14 more authors.  2014-01-15  Discovery of thiazolylpyridinone SCD1 inhibitors with preferential liver distribution and reduced mechanism-based adverse effects.  [PMID:24370012]

11. Sun, Shaoyi S and 15 more authors.  2014-01-15  Systematic evaluation of amide bioisosteres leading to the discovery of novel and potent thiazolylimidazolidinone inhibitors of SCD1 for the treatment of metabolic diseases.  [PMID:24374272]

Source

Source(2):

• Scientific Literature
• BindingDB Database