(R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide

ID: ALA2170943

Chembl Id: CHEMBL2170943

PubChem CID: 53362052

Max Phase: Preclinical

Molecular Formula: C23H24FN3O2S

Molecular Weight: 425.53

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CCN1CCC[C@@H]1CNC(=O)c1ccc2c(c1)NC(=O)/C(=C/c1ccccc1F)S2

Standard InChI:  InChI=1S/C23H24FN3O2S/c1-2-27-11-5-7-17(27)14-25-22(28)16-9-10-20-19(12-16)26-23(29)21(30-20)13-15-6-3-4-8-18(15)24/h3-4,6,8-10,12-13,17H,2,5,7,11,14H2,1H3,(H,25,28)(H,26,29)/b21-13-/t17-/m1/s1

Standard InChI Key:  SPCVDRWAFFUROT-OJSPLJLUSA-N

Alternative Forms

1. Parent:

   

   ALA2170943

   (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide

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

Calculated Properties

Molecular Weight: 425.53

Molecular Weight (Monoisotopic): 425.1573

AlogP: 4.13

#Rotatable Bonds: 5

Polar Surface Area: 61.44

Molecular Species: BASE

HBA: 4

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.54

CX Basic pKa: 8.58

CX LogP: 3.29

CX LogD: 2.20

Aromatic Rings: 2

Heavy Atoms: 30

QED Weighted: 0.71

Np Likeness Score: -1.82

References

1. Preuss J, Maloney P, Peddibhotla S, Hedrick MP, Hershberger P, Gosalia P, Milewski M, Li YL, Sugarman E, Hood B, Suyama E, Nguyen K, Vasile S, Sergienko E, Mangravita-Novo A, Vicchiarelli M, McAnally D, Smith LH, Roth GP, Diwan J, Chung TD, Jortzik E, Rahlfs S, Becker K, Pinkerton AB, Bode L..  (2012)  Discovery of a Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase inhibitor (R,Z)-N-((1-ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (ML276) that reduces parasite growth in vitro.,  55  (16): [PMID:22813531] [10.1021/jm300833h]

2. Alencar N, Sola I, Linares M, Juárez-Jiménez J, Pont C, Viayna A, Vílchez D, Sampedro C, Abad P, Pérez-Benavente S, Lameira J, Bautista JM, Muñoz-Torrero D, Luque FJ..  (2018)  First homology model of Plasmodium falciparum glucose-6-phosphate dehydrogenase: Discovery of selective substrate analog-based inhibitors as novel antimalarial agents.,  146  [PMID:29407943] [10.1016/j.ejmech.2018.01.044]

3. Koperniku A, Garcia AA, Mochly-Rosen D..  (2022)  Boosting the Discovery of Small Molecule Inhibitors of Glucose-6-Phosphate Dehydrogenase for the Treatment of Cancer, Infectious Diseases, and Inflammation.,  65  (6.0): [PMID:35239352] [10.1021/acs.jmedchem.1c01577]

Source

Source(1):

• Scientific Literature