SID11111140

ID: ALA1458713

Cas Number: 66701-25-5

PubChem CID: 439487

Max Phase: Preclinical

Molecular Formula: C15H27N5O5

Molecular Weight: 357.41

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(C)C[C@H](NC(=O)[C@@H]1O[C@H]1C(=O)O)C(=O)NCCCCN=C(N)N

Standard InChI:  InChI=1S/C15H27N5O5/c1-8(2)7-9(20-13(22)10-11(25-10)14(23)24)12(21)18-5-3-4-6-19-15(16)17/h8-11H,3-7H2,1-2H3,(H,18,21)(H,20,22)(H,23,24)(H4,16,17,19)/t9-,10+,11+/m0/s1

Standard InChI Key:  LTLYEAJONXGNFG-HBNTYKKESA-N

Molfile:  

     RDKit          2D

 25 25  0  0  1  0  0  0  0  0999 V2000
   -4.8541   -0.1200    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4281   -2.3333    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -6.8279   -0.1923    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -6.5579   -1.5955    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7277   -1.0860    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3479   -1.3978    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4576   -2.4892    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.0529   -3.2688    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.4032   -3.7365    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.3230   -4.6720    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6982   -0.9301    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4777   -0.6601    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1581   -1.5538    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2879   -0.8160    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8079   -2.0215    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9977   -1.8656    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0779   -2.8010    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5378   -3.4247    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6475   -2.3333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7277   -3.2688    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8079   -4.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1074   -2.9569    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7027   -2.8010    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2428   -3.4247    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5930   -3.8924    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1 11  1  0
  1 12  1  0
  2 13  2  0
  3 14  2  0
  4 14  1  0
  5 16  2  0
  6 13  1  0
  6 15  1  0
  7 16  1  0
  7 19  1  0
  8 24  1  0
  8 25  2  0
  9 25  1  0
 10 25  1  0
 11 12  1  0
 11 13  1  1
 12 14  1  6
 15 16  1  0
 15 17  1  6
 17 18  1  0
 18 20  1  0
 18 21  1  0
 19 22  1  0
 22 23  1  0
 23 24  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1458713

   trans-Epoxysuccinyl-L-leucylamido(4-guanidino)butane

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

Calculated Properties

Molecular Weight: 357.41

Molecular Weight (Monoisotopic): 357.2012

AlogP: -1.46

#Rotatable Bonds: 11

Polar Surface Area: 172.43

Molecular Species: ZWITTERION

HBA: 5

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 3.67

CX Basic pKa: 11.27

CX LogP: -2.79

CX LogD: -2.79

Aromatic Rings: ┄

Heavy Atoms: 25

QED Weighted: 0.13

Np Likeness Score: 0.64

References

1. PubChem BioAssay data set, 

2. PubChem BioAssay data set, 

3. Borišek J, Vizovišek M, Sosnowski P, Turk B, Turk D, Mohar B, Novič M..  (2015)  Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors.,  58  (17): [PMID:26280490] [10.1021/acs.jmedchem.5b00746]

4. Parker EN, Song J, Kishore Kumar GD, Odutola SO, Chavarria GE, Charlton-Sevcik AK, Strecker TE, Barnes AL, Sudhan DR, Wittenborn TR, Siemann DW, Horsman MR, Chaplin DJ, Trawick ML, Pinney KG..  (2015)  Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L.,  23  (21): [PMID:26462052] [10.1016/j.bmc.2015.09.036]

5. Braga SF, Martins LC, da Silva EB, Sales Júnior PA, Murta SM, Romanha AJ, Soh WT, Brandstetter H, Ferreira RS, de Oliveira RB..  (2017)  Synthesis and biological evaluation of potential inhibitors of the cysteine proteases cruzain and rhodesain designed by molecular simplification.,  25  (6): [PMID:28215783] [10.1016/j.bmc.2017.02.009]

6. Vijayaraghavan S, Mahajan S..  (2017)  Docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives.,  27  (8): [PMID:28318947] [10.1016/j.bmcl.2017.03.005]

7. Chen W, Huang Z, Wang W, Mao F, Guan L, Tang Y, Jiang H, Li J, Huang J, Jiang L, Zhu J..  (2017)  Discovery of new antimalarial agents: Second-generation dual inhibitors against FP-2 and PfDHFR via fragments assembely.,  25  (24): [PMID:29111368] [10.1016/j.bmc.2017.10.017]

8. Wang Y, Xue S, Li R, Zheng Z, Yi H, Li Z..  (2018)  Synthesis and biological evaluation of novel synthetic chalcone derivatives as anti-tumor agents targeting Cat L and Cat K.,  26  (1): [PMID:29223717] [10.1016/j.bmc.2017.09.019]

9. Tber Z, Wartenberg M, Jacques JE, Roy V, Lecaille F, Warszycki D, Bojarski AJ, Lalmanach G, Agrofoglio LA..  (2018)  Selective inhibition of human cathepsin S by 2,4,6-trisubstituted 1,3,5-triazine analogs.,  26  (14): [PMID:30049585] [10.1016/j.bmc.2018.07.032]

10. Galibert M, Wartenberg M, Lecaille F, Saidi A, Mavel S, Joulin-Giet A, Korkmaz B, Brömme D, Aucagne V, Delmas AF, Lalmanach G..  (2018)  Substrate-derived triazolo- and azapeptides as inhibitors of cathepsins K and S.,  144  [PMID:29272750] [10.1016/j.ejmech.2017.12.012]

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. Stoye A, Juillard A, Tang AH, Legac J, Gut J, White KL, Charman SA, Rosenthal PJ, Grau GER, Hunt NH, Payne RJ..  (2019)  Falcipain Inhibitors Based on the Natural Product Gallinamide A Are Potent in Vitro and in Vivo Antimalarials.,  62  (11): [PMID:31062592] [10.1021/acs.jmedchem.9b00504]

13. Monteiro ME, Lechuga G, Lara LS, Souto BA, Viganó MG, Bourguignon SC, Calvet CM, Oliveira FOR, Alves CR, Souza-Silva F, Santos MS, Pereira MCS..  (2019)  Synthesis, structure-activity relationship and trypanocidal activity of pyrazole-imidazoline and new pyrazole-tetrahydropyrimidine hybrids as promising chemotherapeutic agents for Chagas disease.,  182  [PMID:31434040] [10.1016/j.ejmech.2019.111610]

14. 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]

15. 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]

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Source

Source(3):

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