2-[5-Amino-2-(4-fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-N-(3,3,3-trifluoro-1-isopropyl-2-oxo-propyl)-acetamide

ID: ALA428848

PubChem CID: 10024782

Max Phase: Preclinical

Molecular Formula: C18H18F4N4O3

Molecular Weight: 414.36

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)C(NC(=O)Cn1c(-c2ccc(F)cc2)ncc(N)c1=O)C(=O)C(F)(F)F

Standard InChI:  InChI=1S/C18H18F4N4O3/c1-9(2)14(15(28)18(20,21)22)25-13(27)8-26-16(24-7-12(23)17(26)29)10-3-5-11(19)6-4-10/h3-7,9,14H,8,23H2,1-2H3,(H,25,27)

Standard InChI Key:  YFKGOHSTGWLLKN-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 29 30  0  0  0  0  0  0  0  0999 V2000
    1.5792   -2.9750    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.5750   -2.1500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8667   -3.3875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8542   -1.7375    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.1500   -3.3750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1542   -2.9750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8625   -2.9625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4792   -3.0875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1500   -2.1542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2917   -3.3875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0042   -2.9750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7250   -3.3792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.1625   -1.5625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1542   -4.1917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.8625   -4.2125    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0042   -2.1500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5583   -3.3917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.5750   -3.3750    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    5.8625   -2.1375    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    6.0792   -3.7542    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.9625   -1.7667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9375   -0.7625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5000   -2.2625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3250   -0.3750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5042   -0.1750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5417   -1.1750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9000    0.2125    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    5.2167   -1.8667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7917   -1.8375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  1  1  0
  4  2  2  0
  5  8  1  0
  6  3  1  0
  7  5  1  0
  8 12  1  0
  9  6  2  0
 10  1  1  0
 11 10  1  0
 12 11  1  0
 13  2  1  0
 14  5  2  0
 15  3  2  0
 16 11  2  0
 17  6  1  0
 18  7  1  0
 19  7  1  0
 20  7  1  0
 21 13  2  0
 22 13  1  0
 23  8  1  0
 24 25  1  0
 25 22  2  0
 26 21  1  0
 27 24  1  0
 28 23  1  0
 29 23  1  0
  4  9  1  0
 26 24  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA428848

   2-[5-Amino-2-(4-fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-N-(3,3,3-trifluoro-1-isopropyl-2-oxo-propyl)-acetamide

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: 414.36

Molecular Weight (Monoisotopic): 414.1315

AlogP: 1.90

#Rotatable Bonds: 6

Polar Surface Area: 107.08

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.42

CX Basic pKa: 0.54

CX LogP: 2.12

CX LogD: 2.12

Aromatic Rings: 2

Heavy Atoms: 29

QED Weighted: 0.70

Np Likeness Score: -1.13

References

1. Veale CA, Bernstein PR, Bryant C, Ceccarelli C, Damewood JR, Earley R, Feeney SW, Gomes B, Kosmider BJ, Steelman GB..  (1995)  Nonpeptidic inhibitors of human leukocyte elastase. 5. Design, synthesis, and X-ray crystallography of a series of orally active 5-aminopyrimidin-6-one-containing trifluoromethyl ketones.,  38  (1): [PMID:7837246] [10.1021/jm00001a015]

2. Brown FJ, Andisik DW, Bernstein PR, Bryant CB, Ceccarelli C, Damewood JR, Edwards PD, Earley RA, Feeney S, Green RC..  (1994)  Design of orally active, non-peptidic inhibitors of human leukocyte elastase.,  37  (9): [PMID:8176703] [10.1021/jm00035a004]

3. Ohmoto K, Yamamoto T, Okuma M, Horiuchi T, Imanishi H, Odagaki Y, Kawabata K, Sekioka T, Hirota Y, Matsuoka S, Nakai H, Toda M, Cheronis JC, Spruce LW, Gyorkos A, Wieczorek M..  (2001)  Development of orally active nonpeptidic inhibitors of human neutrophil elastase.,  44  (8): [PMID:11312926] [10.1021/jm000410y]

4. Leung D, Abbenante G, Fairlie DP..  (2000)  Protease inhibitors: current status and future prospects.,  43  (3): [PMID:10669559] [10.1021/jm990412m]

5. Ohmoto K, Yamamoto T, Horiuchi T, Imanishi H, Odagaki Y, Kawabata K, Sekioka T, Hirota Y, Matsuoka S, Nakai H, Toda M, Cheronis JC, Spruce LW, Gyorkos A, Wieczorek M..  (2000)  Design and synthesis of new orally active nonpeptidic inhibitors of human neutrophil elastase.,  43  (26): [PMID:11150162] [10.1021/jm0004087]

6. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

7. Sun S, Jia Q, Zhang Z..  (2019)  Applications of amide isosteres in medicinal chemistry.,  29  (18): [PMID:31377035] [10.1016/j.bmcl.2019.07.033]

8. Zhang Y, Pike A..  (2021)  Pyridones in drug discovery: Recent advances.,  38  [PMID:33609656] [10.1016/j.bmcl.2021.127849]

Source

Source(2):

• Scientific Literature
• AstraZeneca Deposited Data