ID: ALA298827

Max Phase: Preclinical

Molecular Formula: C12H15NO3S

Molecular Weight: 253.32

Molecule Type: Small molecule

Representations

Canonical SMILES:  O=C(O)CNC(=O)[C@@H](CS)Cc1ccccc1

Standard InChI:  InChI=1S/C12H15NO3S/c14-11(15)7-13-12(16)10(8-17)6-9-4-2-1-3-5-9/h1-5,10,17H,6-8H2,(H,13,16)(H,14,15)/t10-/m1/s1

Standard InChI Key:  LJJKNPQAGWVLDQ-SNVBAGLBSA-N

Molecule Features

Natural Product: Yes

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: 253.32

Molecular Weight (Monoisotopic): 253.0773

AlogP: 0.98

#Rotatable Bonds: 6

Polar Surface Area: 66.40

Molecular Species: ACID

HBA: 3

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 4.02

CX Basic pKa:

CX LogP: 1.46

CX LogD: -1.69

Aromatic Rings: 1

Heavy Atoms: 17

QED Weighted: 0.66

Np Likeness Score: -0.18

References

1. Gomez-Monterrey I, Beaumont A, Nemecek P, Roques BP, Fournie-Zaluski MC..  (1994)  New thiol inhibitors of neutral endopeptidase EC 3.4.24.11: synthesis and enzyme active-site recognition.,  37  (12): [PMID:8021926] [10.1021/jm00038a016]

2. Beight DW, Mehdi S, Koehl JR, Flynn GA.  (1996)  Synthesis of constrained thiorphan analogs as inhibitors of neutral endopeptidase,  6  (17): [10.1016/0960-894X(96)00367-8]

3. Fillion E, Gravel D.  (1996)  Design and synthesis of a new class of conformationally constrained inhibitors to probe the active sites of thermolysine and neutral endopeptidase 24.11,  6  (17): [10.1016/0960-894X(96)00375-7]

4. Danvy D, Monteil T, Plaquevent J, Duhamel L, Duhamel P, Gros C, Noel N, Schwartz J, Lecomte J.  (1996)  Studies on the structural feature of S'1 subsite of neprilysin (EC.3.4.24.11): Stereochemical requirement for the enzyme-inhibitor docking process,  6  (20): [10.1016/0960-894X(96)00448-9]

5. Leung D, Abbenante G, Fairlie DP..  (2000)  Protease inhibitors: current status and future prospects.,  43  (3): [PMID:10669559] [10.1021/jm990412m]

6. Fournié-Zaluski MC, Lucas-Soroca E, Devin J, Roques BP..  (1986)  1H NMR configurational correlation for retro-inverso dipeptides: application to the determination of the absolute configuration of "enkephalinase" inhibitors. Relationships between stereochemistry and enzyme recognition.,  29  (5): [PMID:3517331] [10.1021/jm00155a027]

7. PubChem BioAssay data set, 

8. PubChem BioAssay data set, 

9. Poras H, Bonnard E, Dangé E, Fournié-Zaluski MC, Roques BP..  (2014)  New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment.,  57  (13): [PMID:24927250] [10.1021/jm500602h]

10. Poras H, Bonnard E, Fournié-Zaluski MC, Roques BP..  (2015)  Modulation of disulfide dual ENKephalinase inhibitors (DENKIs) activity by a transient N-protection for pain alleviation by oral route.,  102  [PMID:26241877] [10.1016/j.ejmech.2015.07.027]

11. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

12. Sharma U, Cozier GE, Sturrock ED, Acharya KR..  (2020)  Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin-Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme.,  63  (10): [PMID:32337993] [10.1021/acs.jmedchem.0c00441]

13. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

14. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

15. Van der Poorten O, Knuhtsen A, Sejer Pedersen D, Ballet S, Tourwé D..  (2016)  Side Chain Cyclized Aromatic Amino Acids: Great Tools as Local Constraints in Peptide and Peptidomimetic Design.,  59  (24): [PMID:27690430] [10.1021/acs.jmedchem.6b01029]

Source

Source(3):

• Scientific Literature
• PubChem BioAssays
• SARS-CoV-2 Screening Data 2020-21