2-(1,1-Difluoroethyl)-5-methyl-N-[4-(trifluoromethyl)phenyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine

ID: ALA1738786

Cas Number: 1281861-06-0

PubChem CID: 51349276

Max Phase: Preclinical

Molecular Formula: C15H12F5N5

Molecular Weight: 357.29

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cc(Nc2ccc(C(F)(F)F)cc2)n2nc(C(C)(F)F)nc2n1

Standard InChI:  InChI=1S/C15H12F5N5/c1-8-7-11(22-10-5-3-9(4-6-10)15(18,19)20)25-13(21-8)23-12(24-25)14(2,16)17/h3-7,22H,1-2H3

Standard InChI Key:  CUCVTDOXQYMYKL-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 25 27  0  0  0  0  0  0  0  0999 V2000
    2.3383   -1.3500    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
    0.0031    3.0008    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.3039    3.7494    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3092    5.2494    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6108    5.9949    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9072    5.2405    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9020    3.7405    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6004    2.9949    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2096    5.9864    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2145    7.1864    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    6.2465    5.3825    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    6.2511    6.5823    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990    0.7500    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7248    1.2135    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6065    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7248   -1.2135    0.0000 N   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 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1047    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7044   -1.0395    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7054    1.0388    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -6.3047   -0.0006    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11  6  1  0
  9 12  1  0
 12 13  1  0
 12 14  1  0
 12 15  1  0
  4 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 16  1  0
 20 21  1  0
 21  2  2  0
 18 22  1  0
 22 23  1  0
 22 24  1  0
 22 25  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1738786

   2-(1,1-Difluoroethyl)-5-Methyl-N-[4-(Trifluoromethyl)phenyl][1,2,4]triazolo[1,5-A]pyrimidin-7-Amine

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: 357.29

Molecular Weight (Monoisotopic): 357.1013

AlogP: 4.31

#Rotatable Bonds: 3

Polar Surface Area: 55.11

Molecular Species: NEUTRAL

HBA: 5

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 4.18

CX LogD: 4.18

Aromatic Rings: 3

Heavy Atoms: 25

QED Weighted: 0.71

Np Likeness Score: -1.93

References

1. Coteron JM, Marco M, Esquivias J, Deng X, White KL, White J, Koltun M, El Mazouni F, Kokkonda S, Katneni K, Bhamidipati R, Shackleford DM, Angulo-Barturen I, Ferrer SB, Jiménez-Díaz MB, Gamo FJ, Goldsmith EJ, Charman WN, Bathurst I, Floyd D, Matthews D, Burrows JN, Rathod PK, Charman SA, Phillips MA..  (2011)  Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential.,  54  (15): [PMID:21696174] [10.1021/jm200592f]

2. Deng X, Kokkonda S, El Mazouni F, White J, Burrows JN, Kaminsky W, Charman SA, Matthews D, Rathod PK, Phillips MA..  (2014)  Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors.,  57  (12): [PMID:24801997] [10.1021/jm500481t]

3.  (2016)  Antimalarial agents that are inhibitors of dihydroorotate dehydrogenase, 

4. Boschi D, Pippione AC, Sainas S, Lolli ML..  (2019)  Dihydroorotate dehydrogenase inhibitors in anti-infective drug research.,  183  [PMID:31557612] [10.1016/j.ejmech.2019.111681]

Source

Source(2):

• Scientific Literature
• BindingDB Database