ID: ALA225180

Max Phase: Preclinical

Molecular Formula: C19H19N5O6S

Molecular Weight: 445.46

Molecule Type: Small molecule

Representations

Canonical SMILES:  Cc1[nH]c2nc(N)[nH]c(=O)c2c1Sc1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1

Standard InChI:  InChI=1S/C19H19N5O6S/c1-8-14(13-15(21-8)23-19(20)24-17(13)28)31-10-4-2-9(3-5-10)16(27)22-11(18(29)30)6-7-12(25)26/h2-5,11H,6-7H2,1H3,(H,22,27)(H,25,26)(H,29,30)(H4,20,21,23,24,28)/t11-/m0/s1

Standard InChI Key:  DSIACOJIIGFHHZ-NSHDSACASA-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: 445.46

Molecular Weight (Monoisotopic): 445.1056

AlogP: 1.34

#Rotatable Bonds: 8

Polar Surface Area: 191.26

Molecular Species: ACID

HBA: 7

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.05

CX Basic pKa: 2.58

CX LogP: 0.35

CX LogD: -5.87

Aromatic Rings: 3

Heavy Atoms: 31

QED Weighted: 0.30

Np Likeness Score: -0.42

References

1. Gangjee A, Jain HD, Phan J, Lin X, Song X, McGuire JJ, Kisliuk RL..  (2006)  Dual inhibitors of thymidylate synthase and dihydrofolate reductase as antitumor agents: design, synthesis, and biological evaluation of classical and nonclassical pyrrolo[2,3-d]pyrimidine antifolates(1).,  49  (3): [PMID:16451071] [10.1021/jm058276a]

2. Gangjee A, Jain HD, McGuire JJ, Kisliuk RL..  (2004)  Benzoyl ring halogenated classical 2-amino-6-methyl-3,4-dihydro-4-oxo-5-substituted thiobenzoyl-7H-pyrrolo[2,3-d]pyrimidine antifolates as inhibitors of thymidylate synthase and as antitumor agents.,  47  (27): [PMID:15615522] [10.1021/jm040144e]

3. Gangjee A, Li W, Yang J, Kisliuk RL..  (2008)  Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.,  51  (1): [PMID:18072727] [10.1021/jm701052u]

4. Gangjee A, Qiu Y, Li W, Kisliuk RL..  (2008)  Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates.,  51  (18): [PMID:18800768] [10.1021/jm8006933]

5. Zhang X, Zhou X, Kisliuk RL, Piraino J, Cody V, Gangjee A..  (2011)  Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.,  19  (11): [PMID:21550809] [10.1016/j.bmc.2011.03.067]

Source

Source(1):

• Scientific Literature