6-[(Azepan-1-ylmethylene)-amino]-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid

ID: ALA530

Chembl Id: CHEMBL530

Max Phase: Approved

First Approval: 1984

Molecular Formula: C15H23N3O3S

Molecular Weight: 325.43

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Amdinocillin | Mecillinam | FL 1060 | FL-1060 | RO 10-9070 | RO-10-9070

Trade Names(2): Coactin | Selexidin

Canonical SMILES:  CC1(C)S[C@@H]2[C@H](/N=C/N3CCCCCC3)C(=O)N2[C@H]1C(=O)O

Standard InChI:  InChI=1S/C15H23N3O3S/c1-15(2)11(14(20)21)18-12(19)10(13(18)22-15)16-9-17-7-5-3-4-6-8-17/h9-11,13H,3-8H2,1-2H3,(H,20,21)/b16-9+/t10-,11+,13-/m1/s1

Standard InChI Key:  BWWVAEOLVKTZFQ-ISVUSNJMSA-N

Alternative Forms

1. Parent:

   

   ALA530

   AMDINOCILLIN

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: Yes

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 325.43

Molecular Weight (Monoisotopic): 325.1460

AlogP: 1.41

#Rotatable Bonds: 3

Polar Surface Area: 73.21

Molecular Species: ACID

HBA: 4

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 3.30

CX Basic pKa: 7.92

CX LogP: -0.55

CX LogD: -0.66

Aromatic Rings: ┄

Heavy Atoms: 22

QED Weighted: 0.48

Np Likeness Score: 0.38

References

1. Jung F, Delvare C, Boucherot D, Hamon A, Ackerley N, Betts MJ..  (1991)  Synthesis and structure-activity relationship of new cephalosporins with amino heterocycles at C-7. Dependence of the antibacterial spectrum and beta-lactamase stability on the pKa of the C-7 heterocycle.,  34  (3): [PMID:2002452] [10.1021/jm00107a035]

2. Micetich RG, Maiti SN, Spevak P, Hall TW, Yamabe S, Ishida N, Tanaka M, Yamazaki T, Nakai A, Ogawa K..  (1987)  Synthesis and beta-lactamase inhibitory properties of 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide and related triazolyl derivatives.,  30  (8): [PMID:3039137] [10.1021/jm00391a032]

3. Tam KY, Avdeef A, Tsinman O, Sun N..  (2010)  The permeation of amphoteric drugs through artificial membranes--an in combo absorption model based on paracellular and transmembrane permeability.,  53  (1): [PMID:19947605] [10.1021/jm901421c]

4. Mendonça N, Manageiro V, Robin F, Salgado MJ, Ferreira E, Caniça M, Bonnet R..  (2008)  The Lys234Arg substitution in the enzyme SHV-72 is a determinant for resistance to clavulanic acid inhibition.,  52  (5): [PMID:18316518] [10.1128/aac.01381-07]

5. Obach RS, Lombardo F, Waters NJ..  (2008)  Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.,  36  (7): [PMID:18426954] [10.1124/dmd.108.020479]

6. Tängdén T, Cars O, Melhus A, Löwdin E..  (2010)  Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers.,  54  (9): [PMID:20547788] [10.1128/aac.00220-10]

7. Unpublished dataset, 

8. Sarkar A, Anderson KC, Kellogg GE..  (2012)  Computational analysis of structure-based interactions and ligand properties can predict efflux effects on antibiotics.,  52  [PMID:22483632] [10.1016/j.ejmech.2012.03.008]

9. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

10. PubChem BioAssay data set, 

11. PubChem BioAssay data set, 

12. WHO Anatomical Therapeutic Chemical Classification, 

13. British National Formulary (72nd edition), 

14. Unpublished dataset, 

15. 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]

16. 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]

17. 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]

18. 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 NIH (USA) - Clinical Collection,  [10.6019/CHEMBL4513141]

19. Unpublished dataset, 

20. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

21. Sutherland JJ, Yonchev D, Fekete A, Urban L..  (2023)  A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.,  14  (1): [PMID:37468498] [10.1038/s41467-023-40064-9]

Source

Source(11):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
• USP Dictionary of USAN and International Drug Names
• CO-ADD antimicrobial screening data
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• Active Ingredient of a Prodrug
• Fraunhofer HDAC6