ID: ALA3917415

Max Phase: Preclinical

Molecular Formula: C25H23ClF3N3O4

Molecular Weight: 521.92

Molecule Type: Small molecule

Associated Items:

Representations

Canonical SMILES:  N#CC1(NC(=O)[C@@H]2Cc3ccc(c(Cl)c3)OCCCCOc3cc(C(F)(F)F)ccc3C(=O)N2)CC1

Standard InChI:  InChI=1S/C25H23ClF3N3O4/c26-18-11-15-3-6-20(18)35-9-1-2-10-36-21-13-16(25(27,28)29)4-5-17(21)22(33)31-19(12-15)23(34)32-24(14-30)7-8-24/h3-6,11,13,19H,1-2,7-10,12H2,(H,31,33)(H,32,34)/t19-/m0/s1

Standard InChI Key:  XAPRSGPLBWSEHV-IBGZPJMESA-N

Associated Targets(Human)

Cathepsin L 3852 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cytochrome P450 3A4 53859 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cytochrome P450 2D6 33882 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cytochrome P450 2C9 32119 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Liver 3974 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cathepsin B 3822 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cathepsin K 3011 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cathepsin S 3285 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cathepsin L2 273 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Rhodesain 1463 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Mus musculus 284745 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Trypanosoma brucei rhodesiense 7991 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Plasma 10718 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Brain 4256 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cerebrospinal fluid 288 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Liver 4264 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Blood 1764 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Trypanosoma brucei brucei 13300 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

Properties

Molecular Weight: 521.92Molecular Weight (Monoisotopic): 521.1329AlogP: 4.42#Rotatable Bonds: 2
Polar Surface Area: 100.45Molecular Species: NEUTRALHBA: 5HBD: 2
#RO5 Violations: 1HBA (Lipinski): 7HBD (Lipinski): 2#RO5 Violations (Lipinski): 1
CX Acidic pKa: 10.56CX Basic pKa: CX LogP: 3.97CX LogD: 3.97
Aromatic Rings: 2Heavy Atoms: 36QED Weighted: 0.61Np Likeness Score: -0.39

References

1.  (2016)  Cyclic amides, 
2. Giroud M, Dietzel U, Anselm L, Banner D, Kuglstatter A, Benz J, Blanc JB, Gaufreteau D, Liu H, Lin X, Stich A, Kuhn B, Schuler F, Kaiser M, Brun R, Schirmeister T, Kisker C, Diederich F, Haap W..  (2018)  Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.,  61  (8): [PMID:29590750] [10.1021/acs.jmedchem.7b01869]
3. Giroud M, Kuhn B, Saint-Auret S, Kuratli C, Martin RE, Schuler F, Diederich F, Kaiser M, Brun R, Schirmeister T, Haap W..  (2018)  2 H-1,2,3-Triazole-Based Dipeptidyl Nitriles: Potent, Selective, and Trypanocidal Rhodesain Inhibitors by Structure-Based Design.,  61  (8): [PMID:29590751] [10.1021/acs.jmedchem.7b01870]