N-(3-((6-((3,5-bis(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)oxy)phenyl)-2-chloroacetamide

ID: ALA5283012

Max Phase: Preclinical

Molecular Formula: C21H15ClF6N4O2

Molecular Weight: 504.82

Names and Identifiers

Canonical SMILES:  O=C(CCl)Nc1cccc(Oc2cc(NCc3cc(C(F)(F)F)cc(C(F)(F)F)c3)ncn2)c1

Standard InChI:  InChI=1S/C21H15ClF6N4O2/c22-9-18(33)32-15-2-1-3-16(7-15)34-19-8-17(30-11-31-19)29-10-12-4-13(20(23,24)25)6-14(5-12)21(26,27)28/h1-8,11H,9-10H2,(H,32,33)(H,29,30,31)

Standard InChI Key:  SYFIOVQEHUOPSD-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 34 36  0  0  0  0  0  0  0  0999 V2000
   -3.1753    1.5568    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2064    0.7324    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5069    0.2952    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5383   -0.5334    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2654   -0.9186    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9686   -0.4792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9372    0.3493    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6993   -0.8622    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8387   -0.9706    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1102   -0.5832    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4107   -1.0204    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3166   -0.6310    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0198   -1.0704    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9958   -1.8993    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.2613   -2.2843    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4418   -1.8448    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7484   -0.6790    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.4480   -1.1162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1750   -0.7352    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8781   -1.1746    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8443   -2.0032    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1138   -2.3820    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4141   -1.9447    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6100   -0.7938    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.6461    0.0303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3779    0.4112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4139    1.2353    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    3.9464    0.4675    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8738    1.9961    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4606    1.9694    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1753    2.3820    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7330   -1.6868    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4139   -0.4496    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4139   -1.2748    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  3  2  1  0
  4  3  2  0
  4  5  1  0
  6  5  2  0
  2  7  2  0
  7  6  1  0
  8  6  1  0
  4  9  1  0
  9 10  1  0
 10 11  1  0
 12 11  2  0
 13 12  1  0
 14 13  2  0
 15 14  1  0
 16 15  2  0
 16 11  1  0
 13 17  1  0
 17 18  1  0
 19 18  1  0
 20 19  2  0
 20 21  1  0
 22 21  2  0
 18 23  2  0
 23 22  1  0
 20 24  1  0
 25 24  1  0
 25 26  1  0
 27 26  1  0
 25 28  2  0
  1 29  1  0
  1 30  1  0
  1 31  1  0
  8 32  1  0
  8 33  1  0
  8 34  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5283012

   ---

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: 504.82

Molecular Weight (Monoisotopic): 504.0788

AlogP: 6.10

#Rotatable Bonds: 7

Polar Surface Area: 76.14

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 13.08

CX Basic pKa: 4.71

CX LogP: 5.47

CX LogD: 5.47

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.30

Np Likeness Score: -1.60

References

1. Kim DR, Orr MJ, Kwong AJ, Deibler KK, Munshi HH, Bridges CS, Chen TJ, Zhang X, Lacorazza HD, Scheidt KA..  (2023)  Rational Design of Highly Potent and Selective Covalent MAP2K7 Inhibitors.,  14  (5): [PMID:37197477] [10.1021/acsmedchemlett.3c00029]

2. Patel, Snahel S and 19 more authors.  2015-10-22  Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12).  [PMID:26431428]

Source

Source(1):

• Scientific Literature