2-{2-Fluoro-4-[(2-methoxy-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-pentanedioic acid

ID: ALA105026

PubChem CID: 136056572

Max Phase: Preclinical

Molecular Formula: C25H23FN4O7

Molecular Weight: 510.48

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C#CCN(Cc1ccc2nc(OC)[nH]c(=O)c2c1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)c(F)c1

Standard InChI:  InChI=1S/C25H23FN4O7/c1-3-10-30(13-14-4-7-19-17(11-14)23(34)29-25(28-19)37-2)15-5-6-16(18(26)12-15)22(33)27-20(24(35)36)8-9-21(31)32/h1,4-7,11-12,20H,8-10,13H2,2H3,(H,27,33)(H,31,32)(H,35,36)(H,28,29,34)/t20-/m0/s1

Standard InChI Key:  CHQUJBYQQDSTOJ-FQEVSTJZSA-N

Molfile:  

     RDKit          2D

 37 39  0  0  0  0  0  0  0  0999 V2000
   10.5958   -8.7625    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.5958   -9.5875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3079   -9.9958    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.3079   -8.3458    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.3079   -7.5208    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.0199   -8.7625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.0183   -9.5857    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7292   -9.9969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4423   -9.5860    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4399   -8.7597    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7283   -8.3522    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1530   -8.3449    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8688   -8.7551    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.5820   -8.3403    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2991   -8.7530    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.0118   -8.3389    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.0096   -7.5130    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2888   -7.1030    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5791   -7.5194    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7222   -7.0973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7185   -6.2723    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   18.4349   -7.5040    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.1473   -7.0879    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.8639   -7.4967    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.1432   -6.2629    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.8553   -5.8463    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   18.4264   -5.8535    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   20.5762   -7.0806    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2928   -7.4895    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2979   -8.3158    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.0061   -7.0747    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   14.8715   -9.5801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5872   -9.9903    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2958  -10.4000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8831  -10.0025    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.8843  -10.8275    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2832   -6.2780    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
 17 18  1  0
  8  9  2  0
 18 19  2  0
 19 14  1  0
  6  4  1  0
 17 20  1  0
  9 10  1  0
 20 21  2  0
 20 22  1  0
 10 11  2  0
 22 23  1  0
 11  6  1  0
 23 24  1  6
  4  5  2  0
 23 25  1  0
 10 12  1  0
  1  2  1  0
 25 26  1  0
 25 27  2  0
 12 13  1  0
 24 28  1  0
  1  4  1  0
 28 29  1  0
 13 14  1  0
  6  7  2  0
 29 30  1  0
 29 31  2  0
 14 15  2  0
 13 32  1  0
  2  3  2  0
 32 33  1  0
 15 16  1  0
 33 34  3  0
  7  8  1  0
 16 17  2  0
 35 36  1  0
  2 35  1  0
  3  7  1  0
 18 37  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA105026

   ---

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: 510.48

Molecular Weight (Monoisotopic): 510.1551

AlogP: 1.76

#Rotatable Bonds: 11

Polar Surface Area: 161.92

Molecular Species: ACID

HBA: 7

HBD: 4

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.11

CX Basic pKa: 4.39

CX LogP: 1.32

CX LogD: -3.92

Aromatic Rings: 3

Heavy Atoms: 37

QED Weighted: 0.28

Np Likeness Score: -0.97

References

1. Jackman AL, Marsham PR, Thornton TJ, Bishop JA, O'Connor BM, Hughes LR, Calvert AH, Jones TR..  (1990)  Quinazoline antifolate thymidylate synthase inhibitors: 2'-fluoro-N10-propargyl-5,8-dideazafolic acid and derivatives with modifications in the C2 position.,  33  (11): [PMID:2231607] [10.1021/jm00173a025]

2. Srivastava V, Gupta SP, Siddiqi MI, Mishra BN..  (2010)  3D-QSAR studies on quinazoline antifolate thymidylate synthase inhibitors by CoMFA and CoMSIA models.,  45  (4): [PMID:20153089] [10.1016/j.ejmech.2009.12.065]

Source

Source(1):

• Scientific Literature