4-(6-fluoroindolin-1-yl)-N-(5-(2-hydroxyethyl)thiazol-2-yl)piperidine-1-carboxamide

ID: ALA3093874

PubChem CID: 71657441

Max Phase: Preclinical

Molecular Formula: C19H23FN4O2S

Molecular Weight: 390.48

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(Nc1ncc(CCO)s1)N1CCC(N2CCc3ccc(F)cc32)CC1

Standard InChI:  InChI=1S/C19H23FN4O2S/c20-14-2-1-13-3-9-24(17(13)11-14)15-4-7-23(8-5-15)19(26)22-18-21-12-16(27-18)6-10-25/h1-2,11-12,15,25H,3-10H2,(H,21,22,26)

Standard InChI Key:  HUKKGZZMIRBZOE-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 27 30  0  0  0  0  0  0  0  0999 V2000
   -6.9457  -13.5397    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -6.7331  -12.3586    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.8788  -11.3891    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.6134   -9.9146    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.6493   -8.8297    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.9376   -7.5093    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -6.4777   -7.7931    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.3902   -6.7589    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9504   -7.1827    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6687   -8.3492    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8628   -6.1485    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4233   -6.5700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3384   -5.5341    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6928   -4.0817    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1327   -3.6551    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2175   -4.6910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3114   -2.9665    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.8032   -3.1233    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4133   -1.7530    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
    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
   -2.3383    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
    0.0000   -1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2615   -9.2646    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  1  0
  9 10  2  0
  9 11  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 11  1  0
 14 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 23 25  1  0
 25 26  2  0
 26 17  1  0
 26 20  1  0
  7 27  1  0
 27  4  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3093874

   4-(6-fluoroindolin-1-yl)-N-(5-(2-hydroxyethyl)thiazol-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: 390.48

Molecular Weight (Monoisotopic): 390.1526

AlogP: 2.88

#Rotatable Bonds: 4

Polar Surface Area: 68.70

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 7.86

CX Basic pKa: 2.68

CX LogP: 2.42

CX LogD: 2.30

Aromatic Rings: 2

Heavy Atoms: 27

QED Weighted: 0.84

Np Likeness Score: -1.70

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