2-[(1S,5R)-3-[2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid

ID: ALA4549658

Cas Number: 2102501-84-6

PubChem CID: 129278694

Product Number: K669283, Order Now?

Max Phase: Phase

Molecular Formula: C16H19F3N4O2

Molecular Weight: 356.35

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Pf-06835919

Canonical SMILES:  C[C@H]1CCN1c1nc(N2C[C@@H]3[C@@H](CC(=O)O)[C@@H]3C2)cc(C(F)(F)F)n1

Standard InChI:  InChI=1S/C16H19F3N4O2/c1-8-2-3-23(8)15-20-12(16(17,18)19)5-13(21-15)22-6-10-9(4-14(24)25)11(10)7-22/h5,8-11H,2-4,6-7H2,1H3,(H,24,25)/t8-,9-,10-,11+/m0/s1

Standard InChI Key:  MDUYWDNWFXSMJJ-XWLWVQCSSA-N

Molfile:  

     RDKit          2D

 27 30  0  0  1  0  0  0  0  0999 V2000
   25.8341  -11.8606    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.5725  -10.9439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.0543   -9.4609    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.6135   -9.4609    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0953  -10.9439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.2562  -12.4920    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.6074  -13.2719    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9582  -12.4920    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.3092  -13.2719    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   24.2743   -8.1099    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.9378   -6.7617    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7141   -8.1095    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7181   -5.4103    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   25.0577   -6.7532    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.2701   -5.4073    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.9582  -10.9320    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   24.7307  -12.9635    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   28.4465  -10.1641    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   25.0503   -4.0565    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.6396   -2.5238    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.5575   -3.6526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.1466   -2.1201    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0643   -4.0563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.3776   -6.7617    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.9739   -5.2551    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   19.0268   -7.5419    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   19.0268   -5.9818    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  5  1  1  0
  4  5  1  0
  3  4  1  0
  1  2  1  0
  2  3  1  0
  5  6  1  0
  1  6  1  0
  6  7  1  1
  7  8  1  0
  8  9  1  0
  3 10  1  0
 15 13  1  0
 14 15  2  0
 11 12  1  0
 13 11  2  0
 12 10  2  0
 10 14  1  0
  8 16  2  0
  1 17  1  1
  5 18  1  1
 15 19  1  0
 22 20  1  0
 22 21  1  0
 20 19  1  0
 21 19  1  0
 21 23  1  6
 11 24  1  0
 24 25  1  0
 24 26  1  0
 24 27  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4549658

   Ketohexokinase inhibitor 1

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: 356.35

Molecular Weight (Monoisotopic): 356.1460

AlogP: 2.25

#Rotatable Bonds: 4

Polar Surface Area: 69.56

Molecular Species: ACID

HBA: 5

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 3.45

CX Basic pKa: 4.49

CX LogP: 1.25

CX LogD: -0.60

Aromatic Rings: 1

Heavy Atoms: 25

QED Weighted: 0.89

Np Likeness Score: -0.60

References

1. 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]

2. 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]

3. Xie Z, Yang X, Duan Y, Han J, Liao C..  (2021)  Small-Molecule Kinase Inhibitors for the Treatment of Nononcologic Diseases.,  64  (3.0): [PMID:33481605] [10.1021/acs.jmedchem.0c01511]

4. Unpublished dataset, 

Source

Source(2):

• Scientific Literature
• Clinical Candidates