1N-(2-naphthyl)-5-amino(imino)methylamino-2-[1-amino-2-phenyl-(1S)-ethylcarboxamido]-(2S)-pentanamide

ID: ALA56252

Chembl Id: CHEMBL56252

Cas Number: 115871-02-8

PubChem CID: 443301

Max Phase: Preclinical

Molecular Formula: C25H30N6O2

Molecular Weight: 446.56

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Phenylalanine Arginine Beta-Naphthylamide | Phenylalanine Arginine-Beta-Naphthylamide | 115871-02-8|N2-(L-PHENYLALANYL)-N1-(NAPHTHALENYL)-L-ARIGNINAMIDE|MC-207,110|Phenylalanine Arginine Beta-naphthylamide|CHEMBL56252|CHEBI:6611|(S)-2-((S)-2-Amino-3-phenylpropanamido)-5-guanidino-N-(naphthalen-2-yl)pentanamide|AC1L9EE8|L-Argininamide, L-phenylalanyl-N-2-naphthalenyl-|SCHEMBL1738816|mc207110|ZNHUFUZDUQRKBB-VXKWHMMOSA-N|BDBM50102053|phenylalanyl-arginine beta-naphthylamide|Phenylalanine Arginine-BShow More⌵

Canonical SMILES:  N=C(N)NCCC[C@H](NC(=O)[C@@H](N)Cc1ccccc1)C(=O)Nc1ccc2ccccc2c1

Standard InChI:  InChI=1S/C25H30N6O2/c26-21(15-17-7-2-1-3-8-17)23(32)31-22(11-6-14-29-25(27)28)24(33)30-20-13-12-18-9-4-5-10-19(18)16-20/h1-5,7-10,12-13,16,21-22H,6,11,14-15,26H2,(H,30,33)(H,31,32)(H4,27,28,29)/t21-,22-/m0/s1

Standard InChI Key:  ZNHUFUZDUQRKBB-VXKWHMMOSA-N

Alternative Forms

1. Parent:

   

   ALA56252

   PABETAN

2. Alternative Forms:

   

   ALA56252

   PAβN dihydrochloride

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: 446.56

Molecular Weight (Monoisotopic): 446.2430

AlogP: 2.10

#Rotatable Bonds: 10

Polar Surface Area: 146.12

Molecular Species: BASE

HBA: 4

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 12.60

CX Basic pKa: 11.89

CX LogP: 1.73

CX LogD: -0.82

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.16

Np Likeness Score: -0.24

References

1. Thorarensen A, Presley-Bodnar AL, Marotti KR, Boyle TP, Heckaman CL, Bohanon MJ, Tomich PK, Zurenko GE, Sweeney MT, Yagi BH..  (2001)  3-Arylpiperidines as potentiators of existing antibacterial agents.,  11  (14): [PMID:11459657] [10.1016/s0960-894x(01)00330-4]

2. Renau TE, Léger R, Filonova L, Flamme EM, Wang M, Yen R, Madsen D, Griffith D, Chamberland S, Dudley MN, Lee VJ, Lomovskaya O, Watkins WJ, Ohta T, Nakayama K, Ishida Y..  (2003)  Conformationally-restricted analogues of efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa.,  13  (16): [PMID:12873508] [10.1016/s0960-894x(03)00556-0]

3. Renau TE, Léger R, Flamme EM, Sangalang J, She MW, Yen R, Gannon CL, Griffith D, Chamberland S, Lomovskaya O, Hecker SJ, Lee VJ, Ohta T, Nakayama K..  (1999)  Inhibitors of efflux pumps in Pseudomonas aeruginosa potentiate the activity of the fluoroquinolone antibacterial levofloxacin.,  42  (24): [PMID:10585202] [10.1021/jm9904598]

4. Renau TE, Léger R, Flamme EM, She MW, Gannon CL, Mathias KM, Lomovskaya O, Chamberland S, Lee VJ, Ohta T, Nakayama K, Ishida Y..  (2001)  Addressing the stability of C-capped dipeptide efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa.,  11  (5): [PMID:11266165] [10.1016/s0960-894x(01)00033-6]

5. Gibreel A, Wetsch NM, Taylor DE..  (2007)  Contribution of the CmeABC efflux pump to macrolide and tetracycline resistance in Campylobacter jejuni.,  51  (9): [PMID:17606685] [10.1128/aac.01592-06]

6. Kehrenberg C, Friederichs S, de Jong A, Schwarz S..  (2008)  Novel variant of the qnrB gene, qnrB12, in Citrobacter werkmanii.,  52  (3): [PMID:18086833] [10.1128/aac.01042-07]

7. Kuete V, Ngameni B, Tangmouo JG, Bolla JM, Alibert-Franco S, Ngadjui BT, Pagès JM..  (2010)  Efflux pumps are involved in the defense of Gram-negative bacteria against the natural products isobavachalcone and diospyrone.,  54  (5): [PMID:20160051] [10.1128/aac.01533-09]

8. O'Regan E, Quinn T, Pagès JM, McCusker M, Piddock L, Fanning S..  (2009)  Multiple regulatory pathways associated with high-level ciprofloxacin and multidrug resistance in Salmonella enterica serovar enteritidis: involvement of RamA and other global regulators.,  53  (3): [PMID:19104017] [10.1128/aac.01005-08]

9. Vecchione JJ, Alexander B, Sello JK..  (2009)  Two distinct major facilitator superfamily drug efflux pumps mediate chloramphenicol resistance in Streptomyces coelicolor.,  53  (11): [PMID:19687245] [10.1128/aac.00853-09]

10. Tran QT, Dupont M, Lavigne JP, Chevalier J, Pagès JM, Sotto A, Davin-Regli A..  (2009)  Occurrence of efflux mechanism and cephalosporinase variant in a population of Enterobacter aerogenes and Klebsiella pneumoniae isolates producing extended-spectrum beta-lactamases.,  53  (4): [PMID:19164140] [10.1128/aac.00822-08]

11. Bohnert JA, Karamian B, Nikaido H..  (2010)  Optimized Nile Red efflux assay of AcrAB-TolC multidrug efflux system shows competition between substrates.,  54  (9): [PMID:20606071] [10.1128/aac.00620-10]

12. Okandeji BO, Greenwald DM, Wroten J, Sello JK..  (2011)  Synthesis and evaluation of inhibitors of bacterial drug efflux pumps of the major facilitator superfamily.,  19  (24): [PMID:22055717] [10.1016/j.bmc.2011.10.011]

13. Handzlik J, Szymańska E, Alibert S, Chevalier J, Otrębska E, Pękala E, Pagès JM, Kieć-Kononowicz K..  (2013)  Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin.,  21  (1): [PMID:23218781] [10.1016/j.bmc.2012.10.053]

14. Brunel JM, Lieutaud A, Lome V, Pagès JM, Bolla JM..  (2013)  Polyamino geranic derivatives as new chemosensitizers to combat antibiotic resistant gram-negative bacteria.,  21  (5): [PMID:23352753] [10.1016/j.bmc.2012.12.030]

15. Whalen KE, Poulson-Ellestad KL, Deering RW, Rowley DC, Mincer TJ..  (2015)  Enhancement of antibiotic activity against multidrug-resistant bacteria by the efflux pump inhibitor 3,4-dibromopyrrole-2,5-dione isolated from a Pseudoalteromonas sp.,  78  (3): [PMID:25646964] [10.1021/np500775e]

16. Rajamuthiah R, Jayamani E, Majed H, Conery AL, Kim W, Kwon B, Fuchs BB, Kelso MJ, Ausubel FM, Mylonakis E..  (2015)  Antibacterial properties of 3-(phenylsulfonyl)-2-pyrazinecarbonitrile.,  25  (22): [PMID:26459212] [10.1016/j.bmcl.2015.09.066]

17. Allam A, Maigre L, Alves de Sousa R, Dumont E, Vergalli J, Pagès JM, Artaud I..  (2017)  New amphiphilic neamine conjugates bearing a metal binding motif active against MDR E. aerogenes Gram-negative bacteria.,  127  [PMID:27823890] [10.1016/j.ejmech.2016.10.054]

18. Wang Y, Mowla R, Guo L, Ogunniyi AD, Rahman T, De Barros Lopes MA, Ma S, Venter H..  (2017)  Evaluation of a series of 2-napthamide derivatives as inhibitors of the drug efflux pump AcrB for the reversal of antimicrobial resistance.,  27  (4): [PMID:28129976] [10.1016/j.bmcl.2017.01.042]

19. Schillaci D, Spanò V, Parrino B, Carbone A, Montalbano A, Barraja P, Diana P, Cirrincione G, Cascioferro S..  (2017)  Pharmaceutical Approaches to Target Antibiotic Resistance Mechanisms.,  60  (20): [PMID:28594170] [10.1021/acs.jmedchem.7b00215]

20. Blankson G, Parhi AK, Kaul M, Pilch DS, LaVoie EJ..  (2019)  Structure-activity relationships of potentiators of the antibiotic activity of clarithromycin against Escherichia coli.,  178  [PMID:31173969] [10.1016/j.ejmech.2019.05.075]

21. Blankson GA, Parhi AK, Kaul M, Pilch DS, LaVoie EJ..  (2019)  Advances in the structural studies of antibiotic potentiators against Escherichia coli.,  27  (15): [PMID:31235265] [10.1016/j.bmc.2019.06.003]

22. Lieutaud A, Pieri C, Bolla JM, Brunel JM..  (2020)  New Polyaminoisoprenyl Antibiotics Enhancers against Two Multidrug-Resistant Gram-Negative Bacteria from Enterobacter and Salmonella Species.,  63  (18): [PMID:32840108] [10.1021/acs.jmedchem.0c01335]

23. Wang Y,Mowla R,Ji S,Guo L,De Barros Lopes MA,Jin C,Song D,Ma S,Venter H.  (2018)  Design, synthesis and biological activity evaluation of novel 4-subtituted 2-naphthamide derivatives as AcrB inhibitors.,  143  [PMID:29220791] [10.1016/j.ejmech.2017.11.102]

Source

Source(1):

• Scientific Literature