ID: ALA323565

Max Phase: Preclinical

Molecular Formula: C20H21N5O6

Molecular Weight: 427.42

Molecule Type: Small molecule

Representations

Canonical SMILES:  Nc1nc(N)c2c(CCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)coc2n1

Standard InChI:  InChI=1S/C20H21N5O6/c21-16-15-12(9-31-18(15)25-20(22)24-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(29)30)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,29,30)(H4,21,22,24,25)/t13-/m0/s1

Standard InChI Key:  XMILWEOSKUGJJX-ZDUSSCGKSA-N

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

Properties

Molecular Weight: 427.42

Molecular Weight (Monoisotopic): 427.1492

AlogP: 1.22

#Rotatable Bonds: 9

Polar Surface Area: 194.66

Molecular Species: ACID

HBA: 8

HBD: 5

#RO5 Violations: 0

HBA (Lipinski): 11

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.34

CX Basic pKa: 5.33

CX LogP: -0.33

CX LogD: -4.98

Aromatic Rings: 3

Heavy Atoms: 31

QED Weighted: 0.33

Np Likeness Score: 0.02

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, Zeng Y, McGuire JJ, Kisliuk RL..  (2005)  Synthesis of classical, four-carbon bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.,  48  (16): [PMID:16078850] [10.1021/jm058213s]

5. Gangjee A, Zeng Y, McGuire JJ, Mehraein F, Kisliuk RL..  (2004)  Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.,  47  (27): [PMID:15615538] [10.1021/jm040123k]

6. 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