(1-Hydroxy-2-phenyl-1-phosphono-ethyl)-phosphonic acid

ID: ALA56556

PubChem CID: 405374

Max Phase: Preclinical

Molecular Formula: C8H12O7P2

Molecular Weight: 282.12

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=P(O)(O)C(O)(Cc1ccccc1)P(=O)(O)O

Standard InChI:  InChI=1S/C8H12O7P2/c9-8(16(10,11)12,17(13,14)15)6-7-4-2-1-3-5-7/h1-5,9H,6H2,(H2,10,11,12)(H2,13,14,15)

Standard InChI Key:  DNTYYKAZXNGNBX-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 17 17  0  0  0  0  0  0  0  0999 V2000
    2.5466    0.0046    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5454   -0.8230    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2582   -1.2358    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9776   -0.8224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9744    0.0086    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2562    0.4174    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6868    0.4247    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4032    0.0157    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8148    0.7307    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
    6.2192    1.4483    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.5316    0.3224    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.0986    1.1401    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.9818   -0.6921    0.0000 P   0  0  0  0  0  0  0  0  0  0  0  0
    6.1092   -0.3941    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.5647   -1.4024    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2717   -0.2721    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.6919   -1.1119    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  8  9  1  0
  4  5  1  0
  9 10  1  0
  2  3  1  0
  9 11  1  0
  5  6  2  0
  9 12  2  0
  6  1  1  0
  8 13  1  0
  1  2  2  0
  8 14  1  0
  5  7  1  0
 13 15  1  0
  3  4  2  0
 13 16  2  0
  7  8  1  0
 13 17  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA56556

   (1-Hydroxy-2-phenyl-1-phosphonoethyl)phosphonic 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: 282.12

Molecular Weight (Monoisotopic): 282.0058

AlogP: 0.23

#Rotatable Bonds: 4

Polar Surface Area: 135.29

Molecular Species: ACID

HBA: 3

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 5

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 0.69

CX Basic pKa: ┄

CX LogP: -0.56

CX LogD: -5.49

Aromatic Rings: 1

Heavy Atoms: 17

QED Weighted: 0.50

Np Likeness Score: 0.17

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, Matsumura Y, Fukura S, Martin MB, Sanders JM, Sengupta S, Cieslak JA, Loftus TC, Lea CR, Lee HJ, Koohang A, Coates RM, Sagami H, Oldfield E..  (2002)  Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents.,  45  (11): [PMID:12014956] [10.1021/jm010412y]

3. Martin MB, Sanders JM, Kendrick H, de Luca-Fradley K, Lewis JC, Grimley JS, Van Brussel EM, Olsen JR, Meints GA, Burzynska A, Kafarski P, Croft SL, Oldfield E..  (2002)  Activity of bisphosphonates against Trypanosoma brucei rhodesiense.,  45  (14): [PMID:12086478] [10.1021/jm0102809]

4. 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]

5. 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]

6. Fletcher S, Baker R, Leeson P, Teall M, Harley E, Ragan C.  (1992)  Inhibitors of myo-inositol monophosphatase unrelated to the enzyme substrate,  2  (6): [10.1016/S0960-894X(01)81212-9]

7. Martin MB, Grimley JS, Lewis JC, Heath HT, Bailey BN, Kendrick H, Yardley V, Caldera A, Lira R, Urbina JA, Moreno SN, Docampo R, Croft SL, Oldfield E..  (2001)  Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.,  44  (6): [PMID:11300872] [10.1021/jm0002578]

8. 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]

9. 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]

10. 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]

11. Guo RT, Cao R, Liang PH, Ko TP, Chang TH, Hudock MP, Jeng WY, Chen CK, Zhang Y, Song Y, Kuo CJ, Yin F, Oldfield E, Wang AH..  (2007)  Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.,  104  (24): [PMID:17535895] [10.1073/pnas.0702254104]

12. Mukkamala D, No JH, Cass LM, Chang TK, Oldfield E..  (2008)  Bisphosphonate inhibition of a Plasmodium farnesyl diphosphate synthase and a general method for predicting cell-based activity from enzyme data.,  51  (24): [PMID:19053772] [10.1021/jm8009074]

13. 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]

14. 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]

15. 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]

16. Agapkina J, Yanvarev D, Anisenko A, Korolev S, Vepsäläinen J, Kochetkov S, Gottikh M..  (2014)  Specific features of HIV-1 integrase inhibition by bisphosphonate derivatives.,  73  [PMID:24378711] [10.1016/j.ejmech.2013.11.028]

Source

Source(1):

• Scientific Literature