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

ID: ALA169981

PubChem CID: 135543822

Max Phase: Preclinical

Molecular Formula: C25H23FN4O6

Molecular Weight: 494.48

Molecule Type: Small molecule

Names and Identifiers

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

Standard InChI:  InChI=1S/C25H23FN4O6/c1-3-10-30(13-15-4-7-20-18(11-15)24(34)28-14(2)27-20)16-5-6-17(19(26)12-16)23(33)29-21(25(35)36)8-9-22(31)32/h1,4-7,11-12,21H,8-10,13H2,2H3,(H,29,33)(H,31,32)(H,35,36)(H,27,28,34)/t21-/m0/s1

Standard InChI Key:  ZALTVGFCLRNRRP-NRFANRHFSA-N

Molfile:  

     RDKit          2D

 36 38  0  0  0  0  0  0  0  0999 V2000
   11.5333  -23.2875    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.5333  -24.1125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2454  -24.5208    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.2454  -22.8708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2454  -22.0458    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.9574  -23.2875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9558  -24.1107    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6667  -24.5219    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.3798  -24.1110    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.3774  -23.2847    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6658  -22.8772    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0905  -22.8699    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.8063  -23.2801    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.5195  -22.8653    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2366  -23.2780    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9493  -22.8639    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9471  -22.0380    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2263  -21.6280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.5166  -22.0444    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.6597  -21.6223    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.6560  -20.7973    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.3724  -22.0290    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.0848  -21.6129    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8014  -22.0217    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.0807  -20.7879    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.7928  -20.3713    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.3639  -20.3785    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   21.5137  -21.6056    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.2303  -22.0145    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.2354  -22.8408    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.9436  -21.5997    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   15.8090  -24.1051    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.5247  -24.5153    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2333  -24.9250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2207  -20.8030    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   10.8195  -24.5260    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  3  7  1  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
 18 35  1  0
 16 17  2  0
  2 36  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA169981

   ---

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: 494.48

Molecular Weight (Monoisotopic): 494.1602

AlogP: 2.06

#Rotatable Bonds: 10

Polar Surface Area: 152.69

Molecular Species: ACID

HBA: 6

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 3.14

CX Basic pKa: 6.10

CX LogP: 0.52

CX LogD: -3.54

Aromatic Rings: 3

Heavy Atoms: 36

QED Weighted: 0.31

Np Likeness Score: -1.20

References

1. Thornton TJ, Jackman AL, Marsham PR, O'Connor BM, Bishop JA, Calvert AH..  (1992)  Quinazoline antifolate thymidylate synthase inhibitors: difluoro-substituted benzene ring analogues.,  35  (12): [PMID:1613755] [10.1021/jm00090a024]

2. 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]

3. Marsham PR, Jackman AL, Oldfield J, Hughes LR, Thornton TJ, Bisset GM, O'Connor BM, Bishop JA, Calvert AH..  (1990)  Quinazoline antifolate thymidylate synthase inhibitors: benzoyl ring modifications in the C2-methyl series.,  33  (11): [PMID:2231608] [10.1021/jm00173a026]

4. Bisset GM, Pawelczak K, Jackman AL, Calvert AH, Hughes LR..  (1992)  Syntheses and thymidylate synthase inhibitory activity of the poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino ]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates.,  35  (5): [PMID:1372358] [10.1021/jm00083a008]

5. 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