ID: ALA520358

Max Phase: Preclinical

Molecular Formula: C22H22N4O

Molecular Weight: 358.45

Molecule Type: Small molecule

Representations

Canonical SMILES:  COc1cc(-c2ccccc2)cc(C(C)C#Cc2c(C)nc(N)nc2N)c1

Standard InChI:  InChI=1S/C22H22N4O/c1-14(9-10-20-15(2)25-22(24)26-21(20)23)17-11-18(13-19(12-17)27-3)16-7-5-4-6-8-16/h4-8,11-14H,1-3H3,(H4,23,24,25,26)

Standard InChI Key:  JPENSYBRTSIYGO-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: 358.45

Molecular Weight (Monoisotopic): 358.1794

AlogP: 3.78

#Rotatable Bonds: 3

Polar Surface Area: 87.05

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 7.29

CX LogP: 4.14

CX LogD: 3.89

Aromatic Rings: 3

Heavy Atoms: 27

QED Weighted: 0.70

Np Likeness Score: -0.49

References

1. Bolstad DB, Bolstad ES, Frey KM, Wright DL, Anderson AC..  (2008)  Structure-based approach to the development of potent and selective inhibitors of dihydrofolate reductase from cryptosporidium.,  51  (21): [PMID:18834108] [10.1021/jm8009124]

2. Paulsen JL, Liu J, Bolstad DB, Smith AE, Priestley ND, Wright DL, Anderson AC..  (2009)  In vitro biological activity and structural analysis of 2,4-diamino-5-(2'-arylpropargyl)pyrimidine inhibitors of Candida albicans.,  17  (14): [PMID:19560363] [10.1016/j.bmc.2009.06.021]

3. Beierlein JM, Karri NG, Anderson AC..  (2010)  Targeted mutations of Bacillus anthracis dihydrofolate reductase condense complex structure−activity relationships.,  53  (20): [PMID:20882962] [10.1021/jm100727t]

4. Zhou W, Scocchera EW, Wright DL, Anderson AC.  (2013)  Antifolates as effective antimicrobial agents: new generations of trimethoprim analogs,  4  (6): [10.1039/C3MD00104K]

5. G-Dayanandan N, Paulsen JL, Viswanathan K, Keshipeddy S, Lombardo MN, Zhou W, Lamb KM, Sochia AE, Alverson JB, Priestley ND, Wright DL, Anderson AC..  (2014)  Propargyl-linked antifolates are dual inhibitors of Candida albicans and Candida glabrata.,  57  (6): [PMID:24568657] [10.1021/jm401916j]

6. Zhou W, Viswanathan K, Hill D, Anderson AC, Wright DL..  (2012)  Acetylenic linkers in lead compounds: a study of the stability of the propargyl-linked antifolates.,  40  (10): [PMID:22815313] [10.1124/dmd.112.046870]

7.  (2014)  Heterocyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase, 

Source

Source(2):

• Scientific Literature
• BindingDB Database