2-{4-[(2,4-Diamino-quinazolin-6-ylmethyl)-amino]-benzoylamino}-pentanedioic acid

ID: ALA305177

Chembl Id: CHEMBL305177

PubChem CID: 353015

Max Phase: Preclinical

Molecular Formula: C21H22N6O5

Molecular Weight: 438.44

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

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

Associated Targets(Human)

DHFR Tclin Dihydrofolate reductase (3072 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Tyms Thymidylate synthase (842 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Dhfr Dihydrofolate reductase (2343 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Dhfr Dihydrofolate reductase (711 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
L1210 (27553 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
L1210 ( R81) (43 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
thyA Thymidylate synthase (501 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
folA Dihydrofolate reductase (93 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 438.44Molecular Weight (Monoisotopic): 438.1652AlogP: 1.45#Rotatable Bonds: 9
Polar Surface Area: 193.55Molecular Species: ACIDHBA: 8HBD: 6
#RO5 Violations: 1HBA (Lipinski): 11HBD (Lipinski): 8#RO5 Violations (Lipinski): 2
CX Acidic pKa: 3.53CX Basic pKa: 7.05CX LogP: -1.52CX LogD: -4.67
Aromatic Rings: 3Heavy Atoms: 32QED Weighted: 0.28Np 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