ID: ALA32113

Max Phase: Preclinical

Molecular Formula: C17H20N6O2

Molecular Weight: 340.39

Molecule Type: Small molecule

Representations

Canonical SMILES:  COc1ccc(OC)c(CN(C)c2cnc3nc(N)nc(N)c3c2)c1

Standard InChI:  InChI=1S/C17H20N6O2/c1-23(9-10-6-12(24-2)4-5-14(10)25-3)11-7-13-15(18)21-17(19)22-16(13)20-8-11/h4-8H,9H2,1-3H3,(H4,18,19,20,21,22)

Standard InChI Key:  HZTFNSCZLJLPEO-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: 340.39

Molecular Weight (Monoisotopic): 340.1648

AlogP: 1.84

#Rotatable Bonds: 5

Polar Surface Area: 112.41

Molecular Species: NEUTRAL

HBA: 8

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 8

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 3.05

CX LogP: 1.66

CX LogD: 1.66

Aromatic Rings: 3

Heavy Atoms: 25

QED Weighted: 0.72

Np Likeness Score: -0.87

References

1. Gangjee A, Vasudevan A, Queener SF, Kisliuk RL..  (1996)  2,4-diamino-5-deaza-6-substituted pyrido[2,3-d]pyrimidine antifolates as potent and selective nonclassical inhibitors of dihydrofolate reductases.,  39  (7): [PMID:8691474] [10.1021/jm950786p]

2. Rosowsky A, Forsch RA, Queener SF..  (2003)  Further studies on 2,4-diamino-5-(2',5'-disubstituted benzyl)pyrimidines as potent and selective inhibitors of dihydrofolate reductases from three major opportunistic pathogens of AIDS.,  46  (9): [PMID:12699390] [10.1021/jm020466n]

3. Gangjee A, Vidwans AP, Vasudevan A, Queener SF, Kisliuk RL, Cody V, Li R, Galitsky N, Luft JR, Pangborn W..  (1998)  Structure-based design and synthesis of lipophilic 2,4-diamino-6-substituted quinazolines and their evaluation as inhibitors of dihydrofolate reductases and potential antitumor agents.,  41  (18): [PMID:9719595] [10.1021/jm980081y]

4. Gangjee A, Adair OO, Queener SF..  (2003)  Synthesis and biological evaluation of 2,4-diamino-6-(arylaminomethyl)pyrido[2,3-d]pyrimidines as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase and as antiopportunistic infection and antitumor agents.,  46  (23): [PMID:14584957] [10.1021/jm030312n]

5. Gangjee A, Lin X..  (2005)  CoMFA and CoMSIA analyses of Pneumocystis carinii dihydrofolate reductase, Toxoplasma gondii dihydrofolate reductase, and rat liver dihydrofolate reductase.,  48  (5): [PMID:15743188] [10.1021/jm040153n]

6. Gangjee A, Adair OO, Pagley M, Queener SF..  (2008)  N9-substituted 2,4-diaminoquinazolines: synthesis and biological evaluation of lipophilic inhibitors of pneumocystis carinii and toxoplasma gondii dihydrofolate reductase.,  51  (19): [PMID:18771252] [10.1021/jm800694g]

7. Gangjee A, Namjoshi OA, Raghavan S, Queener SF, Kisliuk RL, Cody V..  (2013)  Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; application of Buchwald-Hartwig aminations of heterocycles.,  56  (11): [PMID:23627352] [10.1021/jm400086g]

8. Wu RZ, Zhou HY, Song JF, Xia QH, Hu W, Mou XD, Li X..  (2021)  Chemotherapeutics for Toxoplasma gondii: Molecular Biotargets, Binding Modes, and Structure-Activity Relationship Investigations.,  64  (24.0): [PMID:34894691] [10.1021/acs.jmedchem.1c01569]

Source

Source(1):

• Scientific Literature