[Phosphono-(pyridin-2-ylamino)-methyl]-phosphonic acid

ID: ALA291736

PubChem CID: 5276533

Max Phase: Preclinical

Molecular Formula: C6H10N2O6P2

Molecular Weight: 268.10

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=P(O)(O)C(Nc1ccccn1)P(=O)(O)O

Standard InChI:  InChI=1S/C6H10N2O6P2/c9-15(10,11)6(16(12,13)14)8-5-3-1-2-4-7-5/h1-4,6H,(H,7,8)(H2,9,10,11)(H2,12,13,14)

Standard InChI Key:  OEAFYMDEEMRBOS-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 16 16  0  0  0  0  0  0  0  0999 V2000
   -5.1919  -14.6501    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1931  -15.4772    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4806  -15.8900    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7615  -15.4768    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.7647  -14.6460    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4826  -14.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0471  -15.8884    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3334  -15.4755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6188  -15.8871    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3341  -14.6509    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3409  -13.8255    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5095  -14.6470    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1587  -14.6554    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9117  -16.2993    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2054  -15.1737    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0270  -16.6035    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  7  8  1  0
  8  9  1  0
  4  5  1  0
  8 10  1  0
  2  3  1  0
 10 11  1  0
  5  6  2  0
 10 12  1  0
  6  1  1  0
 10 13  2  0
  1  2  2  0
  9 14  1  0
  4  7  1  0
  9 15  2  0
  3  4  2  0
  9 16  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA291736

   2-[(Bis-phosphono-methyl)-amino]-pyridinium

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: 268.10

Molecular Weight (Monoisotopic): 268.0014

AlogP: 0.13

#Rotatable Bonds: 4

Polar Surface Area: 139.98

Molecular Species: ACID

HBA: 4

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 5

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 0.87

CX Basic pKa: 6.47

CX LogP: -2.59

CX LogD: -5.40

Aromatic Rings: 1

Heavy Atoms: 16

QED Weighted: 0.49

Np Likeness Score: -0.58

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. Szabo CM, Martin MB, Oldfield E..  (2002)  An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs.,  45  (14): [PMID:12086477] [10.1021/jm010279+]

3. Sanders JM, Ghosh S, Chan JM, Meints G, Wang H, Raker AM, Song Y, Colantino A, Burzynska A, Kafarski P, Morita CT, Oldfield E..  (2004)  Quantitative structure-activity relationships for gammadelta T cell activation by bisphosphonates.,  47  (2): [PMID:14711309] [10.1021/jm0303709]

4. Sanders JM, Gómez AO, Mao J, Meints GA, Van Brussel EM, Burzynska A, Kafarski P, González-Pacanowska D, Oldfield E..  (2003)  3-D QSAR investigations of the inhibition of Leishmania major farnesyl pyrophosphate synthase by bisphosphonates.,  46  (24): [PMID:14613320] [10.1021/jm0302344]

5. Ling Y, Sahota G, Odeh S, Chan JM, Araujo FG, Moreno SN, Oldfield E..  (2005)  Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.,  48  (9): [PMID:15857119] [10.1021/jm040132t]

6. 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]

7. Dunford JE, Kwaasi AA, Rogers MJ, Barnett BL, Ebetino FH, Russell RG, Oppermann U, Kavanagh KL..  (2008)  Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.,  51  (7): [PMID:18327899] [10.1021/jm7015733]

8. Hounslow AM, Carran J, Brown RJ, Rejman D, Blackburn GM, Watts DJ..  (2008)  Determination of the microscopic equilibrium dissociation constants for risedronate and its analogues reveals two distinct roles for the nitrogen atom in nitrogen-containing bisphosphonate drugs.,  51  (14): [PMID:18590315] [10.1021/jm7015792]

9. 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]

10. 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]

11. De Schutter JW, Shaw J, Lin YS, Tsantrizos YS..  (2012)  Design of potent bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase via targeted interactions with the active site 'capping' phenyls.,  20  (18): [PMID:22884353] [10.1016/j.bmc.2012.07.019]

12. Forlani G, Giberti S, Berlicki L, Petrollino D, Kafarski P..  (2007)  Plant P5C reductase as a new target for aminomethylenebisphosphonates.,  55  (11): [PMID:17474756] [10.1021/jf0701032]

13. Obojska A, Berlicki L, Kafarski P, Lejczak B, Chicca M, Forlani G..  (2004)  Herbicidal pyridyl derivatives of aminomethylene-bisphosphonic acid inhibit plant glutamine synthetase.,  52  (11): [PMID:15161194] [10.1021/jf049843q]

Source

Source(1):

• Scientific Literature