ID: ALA305177

Max Phase: Preclinical

Molecular Formula: C21H22N6O5

Molecular Weight: 438.44

Molecule Type: Small molecule

Representations

Canonical SMILES:  Nc1nc(N)c2cc(CNc3ccc(C(=O)NC(CCC(=O)O)C(=O)O)cc3)ccc2n1

Standard InChI:  InChI=1S/C21H22N6O5/c22-18-14-9-11(1-6-15(14)26-21(23)27-18)10-24-13-4-2-12(3-5-13)19(30)25-16(20(31)32)7-8-17(28)29/h1-6,9,16,24H,7-8,10H2,(H,25,30)(H,28,29)(H,31,32)(H4,22,23,26,27)

Standard InChI Key:  IOLLERXPKZGYRA-UHFFFAOYSA-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: 438.44

Molecular Weight (Monoisotopic): 438.1652

AlogP: 1.45

#Rotatable Bonds: 9

Polar Surface Area: 193.55

Molecular Species: ACID

HBA: 8

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.53

CX Basic pKa: 7.05

CX LogP: -1.52

CX LogD: -4.67

Aromatic Rings: 3

Heavy Atoms: 32

QED Weighted: 0.28

Np Likeness Score: -0.59

References

1. Hynes JB, Harmon SJ, Floyd GG, Farrington M, Hart LD, Gale GR, Washtien WL, Susten SS, Freisheim JH..  (1985)  Chemistry and antitumor evaluation of selected classical 2,4-diaminoquinazoline analogues of folic acid.,  28  (2): [PMID:3968685] [10.1021/jm00380a011]

2. Hynes JB, Patil SA, Tomazic A, Kumar A, Pathak A, Tan XH, Li XQ, Ratnam M, Delcamp TJ, Freisheim JH..  (1988)  Inhibition of murine thymidylate synthase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin.,  31  (2): [PMID:3339615] [10.1021/jm00397a031]

3. Crippen GM..  (1980)  Quantitative structure-activity relationships by distance geometry: systematic analysis of dihydrofolate reductase inhibitors.,  23  (6): [PMID:7392027] [10.1021/jm00180a004]

4. Rosowsky A, Mota CE, Queener SF, Waltham M, Ercikan-Abali E, Bertino JR..  (1995)  2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.,  38  (5): [PMID:7877140] [10.1021/jm00005a002]

5. Ghose AK, Crippen GM..  (1982)  Quantitative structure-activity relationship by distance geometry: quinazolines as dihydrofolate reductase inhibitors.,  25  (8): [PMID:7120278] [10.1021/jm00350a003]

6. Chen BK, Horváth C, Bertino JR..  (1979)  Multivariate analysis and quantitative structure-activity relationships. Inhibition of dihydrofolate reductase and thymidylate synthetase by quinazolines.,  22  (5): [PMID:110930] [10.1021/jm00191a005]

7. Hansch C, Fukunaga JY, Jow PY..  (1977)  Quantitative structure-activity relationships of antimalarial and dihydrofolate reductase inhibition by quinazolines and 5-substituted benzyl-2,4-diaminopyrimidines.,  20  (1): [PMID:319234] [10.1021/jm00211a020]

Source

Source(1):

• Scientific Literature