6-(cyclopropanecarbonylamino)-4-[2-methoxy-3-[(4-pyrazol-1-ylphenyl)carbamoyl]anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide

ID: ALA5278999

Max Phase: Preclinical

Molecular Formula: C27H26N8O4

Molecular Weight: 526.56

Names and Identifiers

Canonical SMILES:  [2H]C([2H])([2H])NC(=O)c1nnc(NC(=O)C2CC2)cc1Nc1cccc(C(=O)Nc2ccc(-n3cccn3)cc2)c1OC

Standard InChI:  InChI=1S/C27H26N8O4/c1-28-27(38)23-21(15-22(33-34-23)32-25(36)16-7-8-16)31-20-6-3-5-19(24(20)39-2)26(37)30-17-9-11-18(12-10-17)35-14-4-13-29-35/h3-6,9-16H,7-8H2,1-2H3,(H,28,38)(H,30,37)(H2,31,32,33,36)/i1D3

Standard InChI Key:  ZKVTWPITXACVMU-FIBGUPNXSA-N

Molfile:  

 
     RDKit          2D

 42 46  0  0  0  0  0  0  0  0999 V2000
   -0.6632    1.3959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3752    1.8126    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0921    1.4043    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6632    0.5709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3897    0.1626    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3897   -0.6623    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6825   -1.0790    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6825   -1.9040    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0295   -2.3206    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.7464   -1.9123    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4584   -2.3289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2834   -2.3289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.8668   -3.0459    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7464   -1.0873    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3993   -2.3122    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1066   -1.8956    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1066   -1.0706    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8186   -0.6539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8186    0.1710    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5355   -1.0623    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2476   -0.6456    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9596   -0.2290    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2476    0.1793    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9644   -1.0539    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.0440    0.1543    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7608    0.5626    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7608    1.3876    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0536    1.8042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0536    2.6292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7753    3.0376    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.4873    2.6209    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4873    1.7959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1946    1.3793    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9163    1.7875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9163    2.6125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2042    3.0292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6535    3.0459    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.6310    1.3749    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.3456    1.7875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9644    1.2161    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6337    0.4816    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8094    0.5739    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  1  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 13 11  1  0
 13 12  1  0
 14 10  2  0
  8 15  1  0
 15 16  2  0
 17  6  2  0
 16 17  1  0
 17 18  1  0
 18 19  2  0
 18 20  1  0
 20 21  1  0
 21 22  1  0
 21 23  1  0
 21 24  1  0
  4 25  2  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28  1  2  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  2  0
 33 34  1  0
 34 35  2  0
 36 31  2  0
 35 36  1  0
 29 37  2  0
 34 38  1  0
 39 38  1  0
 39 40  2  0
 40 41  1  0
 42 41  2  0
 38 42  1  0
M  ISO  3  22   2  23   2  24   2
M  END

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 526.56

Molecular Weight (Monoisotopic): 526.2077

AlogP: 3.37

#Rotatable Bonds: 9

Polar Surface Area: 152.16

Molecular Species: NEUTRAL

HBA: 9

HBD: 4

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 11.09

CX Basic pKa: 3.35

CX LogP: 3.61

CX LogD: 3.61

Aromatic Rings: 4

Heavy Atoms: 39

QED Weighted: 0.26

Np Likeness Score: -1.85

References

1. Liu F, Wang B, Liu Y, Shi W, Hu Z, Chang X, Tang X, Zhang Y, Xu H, He Y..  (2023)  Design, synthesis and biological evaluation of novel N-(methyl-d₃) pyridazine-3-carboxamide derivatives as TYK2 inhibitors.,  86  [PMID:36907336] [10.1016/j.bmcl.2023.129235]

Source

Source(1):

• Scientific Literature