[(Biphenyl-3-ylamino)-phosphono-methyl]-phosphonic acid

ID: ALA55371

PubChem CID: 5277466

Max Phase: Preclinical

Molecular Formula: C13H15NO6P2

Molecular Weight: 343.21

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=P(O)(O)C(Nc1cccc(-c2ccccc2)c1)P(=O)(O)O

Standard InChI:  InChI=1S/C13H15NO6P2/c15-21(16,17)13(22(18,19)20)14-12-8-4-7-11(9-12)10-5-2-1-3-6-10/h1-9,13-14H,(H2,15,16,17)(H2,18,19,20)

Standard InChI Key:  IXFMBXNLOHKCPT-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 22 23  0  0  0  0  0  0  0  0999 V2000
   12.6591  -19.6577    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6579  -20.4827    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3708  -20.8944    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0852  -20.4823    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0823  -19.6540    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3690  -19.2460    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8015  -19.2360    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.7986  -18.4092    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.0840  -17.9958    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
   15.5091  -17.9959    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
   16.2290  -17.5829    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.3664  -17.5830    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   14.4992  -17.2769    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.6676  -18.7146    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   15.9233  -18.7146    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.9445  -19.2424    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9456  -18.4186    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2339  -18.0076    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5164  -18.4191    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5150  -19.2461    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.2274  -19.6576    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5026  -17.1729    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 10 11  2  0
  5  6  2  0
  9 12  2  0
  6  1  1  0
  9 13  1  0
  1  2  2  0
  9 14  1  0
  5  7  1  0
 10 15  1  0
  3  4  2  0
  7  8  1  0
 16 17  2  0
 17 18  1  0
  8  9  1  0
 18 19  2  0
  4  5  1  0
 19 20  1  0
  8 10  1  0
 20 21  2  0
 21 16  1  0
  1 16  1  0
  2  3  1  0
 10 22  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA55371

   (Biphenyl-3-ylamino)methylenediphosphonic acid

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: 343.21

Molecular Weight (Monoisotopic): 343.0375

AlogP: 2.40

#Rotatable Bonds: 5

Polar Surface Area: 127.09

Molecular Species: ACID

HBA: 3

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 5

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 0.95

CX Basic pKa: ┄

CX LogP: 1.72

CX LogD: -3.10

Aromatic Rings: 2

Heavy Atoms: 22

QED Weighted: 0.53

Np Likeness Score: -0.48

References

1. Ghosh S, Chan JM, Lea CR, Meints GA, Lewis JC, Tovian ZS, Flessner RM, Loftus TC, Bruchhaus I, Kendrick H, Croft SL, Kemp RG, Kobayashi S, Nozaki T, Oldfield E..  (2004)  Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.,  47  (1): [PMID:14695831] [10.1021/jm030084x]

2. Kotsikorou E, Song Y, Chan JM, Faelens S, Tovian Z, Broderick E, Bakalara N, Docampo R, Oldfield E..  (2005)  Bisphosphonate inhibition of the exopolyphosphatase activity of the Trypanosoma brucei soluble vacuolar pyrophosphatase.,  48  (19): [PMID:16162013] [10.1021/jm058220g]

3. Hudock MP, Sanz-Rodríguez CE, Song Y, Chan JM, Zhang Y, Odeh S, Kosztowski T, Leon-Rossell A, Concepción JL, Yardley V, Croft SL, Urbina JA, Oldfield E..  (2006)  Inhibition of Trypanosoma cruzi hexokinase by bisphosphonates.,  49  (1): [PMID:16392806] [10.1021/jm0582625]

4. Leon A, Liu L, Yang Y, Hudock MP, Hall P, Yin F, Studer D, Puan KJ, Morita CT, Oldfield E..  (2006)  Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin.,  49  (25): [PMID:17149863] [10.1021/jm060492b]

5. Sanz-Rodríguez CE, Concepción JL, Pekerar S, Oldfield E, Urbina JA..  (2007)  Bisphosphonates as inhibitors of Trypanosoma cruzi hexokinase: kinetic and metabolic studies.,  282  (17): [PMID:17329254] [10.1074/jbc.m607286200]

6. Song Y, Chan JM, Tovian Z, Secrest A, Nagy E, Krysiak K, Bergan K, Parniak MA, Oldfield E..  (2008)  Bisphosphonate inhibitors of ATP-mediated HIV-1 reverse transcriptase catalyzed excision of chain-terminating 3'-azido, 3'-deoxythymidine: a QSAR investigation.,  16  (19): [PMID:18789701] [10.1016/j.bmc.2008.08.047]

7. Prado-Prado FJ, García-Mera X, González-Díaz H..  (2010)  Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.,  18  (6): [PMID:20185316] [10.1016/j.bmc.2010.01.068]

8. Lin YS, Park J, De Schutter JW, Huang XF, Berghuis AM, Sebag M, Tsantrizos YS..  (2012)  Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.,  55  (7): [PMID:22390415] [10.1021/jm201657x]

9. Tauro M, Laghezza A, Loiodice F, Agamennone M, Campestre C, Tortorella P..  (2013)  Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors.,  21  (21): [PMID:24071448] [10.1016/j.bmc.2013.08.054]

10. Tauro M, Loiodice F, Ceruso M, Supuran CT, Tortorella P..  (2014)  Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.,  24  (8): [PMID:24650641] [10.1016/j.bmcl.2014.03.001]

Source

Source(1):

• Scientific Literature