ID: ALA2335419

Max Phase: Preclinical

Molecular Formula: C22H23N5O

Molecular Weight: 373.46

Molecule Type: Small molecule

Representations

Canonical SMILES:  CCc1nc(N)nc(N)c1C#CC(C)c1cc(OC)cc(-c2ccncc2)c1

Standard InChI:  InChI=1S/C22H23N5O/c1-4-20-19(21(23)27-22(24)26-20)6-5-14(2)16-11-17(13-18(12-16)28-3)15-7-9-25-10-8-15/h7-14H,4H2,1-3H3,(H4,23,24,26,27)

Standard InChI Key:  KEPLBUUTAQCZOE-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: 373.46

Molecular Weight (Monoisotopic): 373.1903

AlogP: 3.43

#Rotatable Bonds: 4

Polar Surface Area: 99.94

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 7.12

CX LogP: 3.62

CX LogD: 3.43

Aromatic Rings: 3

Heavy Atoms: 28

QED Weighted: 0.68

Np Likeness Score: -0.58

References

1. Paulsen JL, Viswanathan K, Wright DL, Anderson AC..  (2013)  Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species.,  23  (5): [PMID:23375226] [10.1016/j.bmcl.2013.01.008]

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

3. 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]

4. 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]

5.  (2014)  Heterocyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase, 

6. Reeve SM, Scocchera E, Ferreira JJ, G-Dayanandan N, Keshipeddy S, Wright DL, Anderson AC..  (2016)  Charged Propargyl-Linked Antifolates Reveal Mechanisms of Antifolate Resistance and Inhibit Trimethoprim-Resistant MRSA Strains Possessing Clinically Relevant Mutations.,  59  (13): [PMID:27308944] [10.1021/acs.jmedchem.6b00688]

7. Johannes Zuegg, Alysha Elliott, Maite Amado, Emma Cowie, Ali Hinton, Geraldine Kaeslin, Angela Kavanagh, Anne Kunert, Gabriell Lowe, Soumya Ramu, Janet Reid, Robin Trauer, Mathilde Desselle, Ruth Neale, Karl Hansford, Mark Blascovich, Matthew Cooper. CO-ADD screening of MMV (CH) - Pandemic Response Box,  [10.6019/CHEMBL4513161]

Source

Source(3):

• Scientific Literature
• BindingDB Database
• CO-ADD antimicrobial screening data