2-{4-[(2,4-Diamino-furo[2,3-d]pyrimidin-5-ylmethyl)-amino]-benzoylamino}-pentanedioic acid

ID: ALA106628

Chembl Id: CHEMBL106628

Cas Number: 156595-84-5

PubChem CID: 158351

Max Phase: Preclinical

Molecular Formula: C19H20N6O6

Molecular Weight: 428.41

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Nc1nc(N)c2c(CNc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)coc2n1

Standard InChI:  InChI=1S/C19H20N6O6/c20-15-14-10(8-31-17(14)25-19(21)24-15)7-22-11-3-1-9(2-4-11)16(28)23-12(18(29)30)5-6-13(26)27/h1-4,8,12,22H,5-7H2,(H,23,28)(H,26,27)(H,29,30)(H4,20,21,24,25)/t12-/m0/s1

Standard InChI Key:  ACXZKUHGYNILFP-LBPRGKRZSA-N

Alternative Forms

1. Parent:

   

   ALA106628

   N-(4-(N-((2,4-Diaminofuro(2,3-d)pyrimidin-5-yl)methyl)amino)benzoyl)glutamic acid

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: 428.41

Molecular Weight (Monoisotopic): 428.1444

AlogP: 1.05

#Rotatable Bonds: 9

Polar Surface Area: 206.69

Molecular Species: ACID

HBA: 9

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 12

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.31

CX Basic pKa: 5.20

CX LogP: -1.89

CX LogD: -6.33

Aromatic Rings: 3

Heavy Atoms: 31

QED Weighted: 0.28

Np Likeness Score: -0.41

References

1. Gangjee A, Zeng Y, McGuire JJ, Kisliuk RL..  (2000)  Effect of C9-methyl substitution and C8-C9 conformational restriction on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines.,  43  (16): [PMID:10956221] [10.1021/jm000130i]

2. Gangjee A, Devraj R, McGuire JJ, Kisliuk RL..  (1995)  Effect of bridge region variation on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines.,  38  (19): [PMID:7562910] [10.1021/jm00019a009]

3. Gangjee A, Yu J, McGuire JJ, Cody V, Galitsky N, Kisliuk RL, Queener SF..  (2000)  Design, synthesis, and X-ray crystal structure of a potent dual inhibitor of thymidylate synthase and dihydrofolate reductase as an antitumor agent.,  43  (21): [PMID:11052789] [10.1021/jm000200l]

4. Gangjee A, Jain HD, Phan J, Guo X, Queener SF, Kisliuk RL..  (2010)  2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel classical and nonclassical antifolates as potential dual thymidylate synthase and dihydrofolate reductase inhibitors.,  18  (2): [PMID:20056546] [10.1016/j.bmc.2009.11.029]

Source

Source(1):

• Scientific Literature