trans-6-((3S,4S)-3,4-Dihydroxypyrrolidin-1-yl)-2-((S)-3-hydroxy-3-methylpyrrolidin-1-yl)-4-(trifluoromethyl)nicotinonitrile

ID: ALA4070442

PubChem CID: 129900198

Max Phase: Preclinical

Molecular Formula: C16H19F3N4O3

Molecular Weight: 372.35

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C[C@]1(O)CCN(c2nc(N3C[C@H](O)[C@@H](O)C3)cc(C(F)(F)F)c2C#N)C1

Standard InChI:  InChI=1S/C16H19F3N4O3/c1-15(26)2-3-22(8-15)14-9(5-20)10(16(17,18)19)4-13(21-14)23-6-11(24)12(25)7-23/h4,11-12,24-26H,2-3,6-8H2,1H3/t11-,12-,15-/m0/s1

Standard InChI Key:  FAXXYODRCHXHTQ-HUBLWGQQSA-N

Molfile:  

     RDKit          2D

 26 28  0  0  0  0  0  0  0  0999 V2000
   35.7288   -9.5670    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.4465   -9.9777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.4454   -9.1502    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   36.1588  -12.4710    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.1577  -13.2990    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.8735  -13.7142    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5910  -13.2985    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5882  -12.4674    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.8717  -12.0601    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.3049  -13.7114    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.8677  -11.2401    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   35.4432  -12.0605    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.7270  -11.6452    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   35.4418  -13.7132    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.7266  -13.2979    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   35.4412  -14.5389    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   34.7206  -14.1181    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   37.5267  -10.7536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.2666   -9.9749    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.1985  -10.7601    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.3954  -14.5252    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.2009  -14.6947    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.6097  -13.9808    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0567  -13.3686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.5357  -15.4489    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   40.4306  -13.8941    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  2  3  1  1
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9  4  1  0
  7 10  1  0
  9 11  1  0
  4 12  1  0
 12 13  3  0
  5 14  1  0
 14 15  1  0
 14 16  1  0
 14 17  1  0
 11 18  1  0
 18 19  1  0
 19  2  1  0
  2 20  1  0
 20 11  1  0
 10 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  1  0
 24 10  1  0
 22 25  1  1
 23 26  1  6
M  END

Alternative Forms

1. Parent:

   

   ALA4070442

   ---

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: 372.35

Molecular Weight (Monoisotopic): 372.1409

AlogP: 0.47

#Rotatable Bonds: 2

Polar Surface Area: 103.85

Molecular Species: NEUTRAL

HBA: 7

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 13.45

CX Basic pKa: 3.71

CX LogP: 1.00

CX LogD: 1.00

Aromatic Rings: 1

Heavy Atoms: 26

QED Weighted: 0.69

Np Likeness Score: -0.60

References

1. Huard K, Ahn K, Amor P, Beebe DA, Borzilleri KA, Chrunyk BA, Coffey SB, Cong Y, Conn EL, Culp JS, Dowling MS, Gorgoglione MF, Gutierrez JA, Knafels JD, Lachapelle EA, Pandit J, Parris KD, Perez S, Pfefferkorn JA, Price DA, Raymer B, Ross TT, Shavnya A, Smith AC, Subashi TA, Tesz GJ, Thuma BA, Tu M, Weaver JD, Weng Y, Withka JM, Xing G, Magee TV..  (2017)  Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK).,  60  (18): [PMID:28853885] [10.1021/acs.jmedchem.7b00947]

2. Romero FA, Jones CT, Xu Y, Fenaux M, Halcomb RL..  (2020)  The Race to Bash NASH: Emerging Targets and Drug Development in a Complex Liver Disease.,  63  (10): [PMID:31930920] [10.1021/acs.jmedchem.9b01701]

3. Futatsugi K,Smith AC,Tu M,Raymer B,Ahn K,Coffey SB,Dowling MS,Fernando DP,Gutierrez JA,Huard K,Jasti J,Kalgutkar AS,Knafels JD,Pandit J,Parris KD,Perez S,Pfefferkorn JA,Price DA,Ryder T,Shavnya A,Stock IA,Tsai AS,Tesz GJ,Thuma BA,Weng Y,Wisniewska HM,Xing G,Zhou J,Magee TV.  (2020)  Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose.,  63  (22): [PMID:32910646] [10.1021/acs.jmedchem.0c00944]

Source

Source(1):

• Scientific Literature