ID: ALA286534

Max Phase: Preclinical

Molecular Formula: C9H14N5O5P

Molecular Weight: 303.21

Molecule Type: Small molecule

Representations

Canonical SMILES:  Nc1ncnc2c1ncn2C[C@@H](CO)OCP(=O)(O)O

Standard InChI:  InChI=1S/C9H14N5O5P/c10-8-7-9(12-3-11-8)14(4-13-7)1-6(2-15)19-5-20(16,17)18/h3-4,6,15H,1-2,5H2,(H2,10,11,12)(H2,16,17,18)/t6-/m0/s1

Standard InChI Key:  FRPXSOOHWNMLPH-LURJTMIESA-N

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

Properties

Molecular Weight: 303.21

Molecular Weight (Monoisotopic): 303.0733

AlogP: -1.08

#Rotatable Bonds: 6

Polar Surface Area: 156.61

Molecular Species: ACID

HBA: 8

HBD: 4

#RO5 Violations: 0

HBA (Lipinski): 10

HBD (Lipinski): 5

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 1.35

CX Basic pKa: 4.71

CX LogP: -4.48

CX LogD: -4.59

Aromatic Rings: 2

Heavy Atoms: 20

QED Weighted: 0.49

Np Likeness Score: 0.09

References

1. Bronson JJ, Ghazzouli I, Hitchcock MJ, Webb RR, Martin JC..  (1989)  Synthesis and antiviral activity of the nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine.,  32  (7): [PMID:2544723] [10.1021/jm00127a010]

2. Holý A, Votruba I, Masojídková M, Andrei G, Snoeck R, Naesens L, De Clercq E, Balzarini J..  (2002)  6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity.,  45  (9): [PMID:11960502] [10.1021/jm011095y]

3. Legraverend M, Boumchita H, Zerial A, Huel C, Lemaitre M, Bisagni E..  (1990)  Synthesis of new (+-)-3,5-dihydroxypentyl nucleoside analogues from 1-amino-5-(benzyloxy)pentan-3-ol and their antiviral evaluation.,  33  (9): [PMID:2391689] [10.1021/jm00171a022]

4. Dvoráková H, Masojídková M, Holý A, Balzarini J, Andrei G, Snoeck R, De Clercq E..  (1996)  Synthesis of 2'-aminomethyl derivatives of N-(2-(phosphonomethoxy)ethyl) nucleotide analogues as potential antiviral agents.,  39  (17): [PMID:8765509] [10.1021/jm9601314]

5. Verheggen I, Van Aerschot A, Van Meervelt L, Rozenski J, Wiebe L, Snoeck R, Andrei G, Balzarini J, Claes P, De Clercq E..  (1995)  Synthesis, biological evaluation, and structure analysis of a series of new 1,5-anhydrohexitol nucleosides.,  38  (5): [PMID:7877148] [10.1021/jm00005a010]

6. Beadle JR, Wan WB, Ciesla SL, Keith KA, Hartline C, Kern ER, Hostetler KY..  (2006)  Synthesis and antiviral evaluation of alkoxyalkyl derivatives of 9-(S)-(3-hydroxy-2-phosphonomethoxypropyl)adenine against cytomegalovirus and orthopoxviruses.,  49  (6): [PMID:16539388] [10.1021/jm050473m]

7. Lebeau I, Andrei G, Krecmerová M, De Clercq E, Holy A, Snoeck R..  (2007)  Inhibitory activities of three classes of acyclic nucleoside phosphonates against murine polyomavirus and primate simian virus 40 strains.,  51  (6): [PMID:17420214] [10.1128/aac.01422-06]

8. de Castro S, Peromingo MT, Naesens L, Andrei G, Snoeck R, Balzarini J, Velázquez S, Camarasa MJ..  (2008)  4"-Benzoylureido-TSAO derivatives as potent and selective non-nucleoside HCMV inhibitors. Structure-activity relationship and mechanism of antiviral action.,  51  (18): [PMID:18707089] [10.1021/jm800050t]

9. Quenelle DC, Collins DJ, Herrod BP, Keith KA, Trahan J, Beadle JR, Hostetler KY, Kern ER..  (2007)  Effect of oral treatment with hexadecyloxypropyl-[(S)-9-(3-hydroxy-2- phosphonylmethoxypropyl)adenine] [(S)-HPMPA] or octadecyloxyethyl-(S)-HPMPA on cowpox or vaccinia virus infections in mice.,  51  (11): [PMID:17846137] [10.1128/aac.00184-07]

10. Duraffour S, Snoeck R, Krecmerová M, van Den Oord J, De Vos R, Holy A, Crance JM, Garin D, De Clercq E, Andrei G..  (2007)  Activities of several classes of acyclic nucleoside phosphonates against camelpox virus replication in different cell culture models.,  51  (12): [PMID:17893157] [10.1128/aac.00838-07]

11. De Castro S, García-Aparicio C, Andrei G, Snoeck R, Balzarini J, Camarasa MJ, Velázquez S..  (2009)  4-Benzyloxy-gamma-sultone derivatives: discovery of a novel family of non-nucleoside inhibitors of human cytomegalovirus and varicella zoster virus.,  52  (6): [PMID:19226140] [10.1021/jm8014662]

12. Prado-Prado FJ, Martinez de la Vega O, Uriarte E, Ubeira FM, Chou KC, González-Díaz H..  (2009)  Unified QSAR approach to antimicrobials. 4. Multi-target QSAR modeling and comparative multi-distance study of the giant components of antiviral drug-drug complex networks.,  17  (2): [PMID:19112024] [10.1016/j.bmc.2008.11.075]

13. Botros SS, William S, Beadle JR, Valiaeva N, Hostetler KY..  (2009)  Antischistosomal activity of hexadecyloxypropyl cyclic 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine and other alkoxyalkyl esters of acyclic nucleoside phosphonates assessed by schistosome worm killing in vitro.,  53  (12): [PMID:19704122] [10.1128/aac.00840-09]

14. Wyles DL, Kaihara KA, Korba BE, Schooley RT, Beadle JR, Hostetler KY..  (2009)  The octadecyloxyethyl ester of (S)-9-[3-hydroxy-2-(phosphonomethoxy) propyl]adenine is a potent and selective inhibitor of hepatitis C virus replication in genotype 1A, 1B, and 2A replicons.,  53  (6): [PMID:19289518] [10.1128/aac.01546-08]

15. Morrey JD, Korba BE, Beadle JR, Wyles DL, Hostetler KY..  (2009)  Alkoxyalkyl esters of 9-(s)-(3-hydroxy-2-phosphonomethoxypropyl) adenine are potent and selective inhibitors of hepatitis B virus (HBV) replication in vitro and in HBV transgenic mice in vivo.,  53  (7): [PMID:19398648] [10.1128/aac.00114-09]

16. Zakharova VM, Serpi M, Krylov IS, Peterson LW, Breitenbach JM, Borysko KZ, Drach JC, Collins M, Hilfinger JM, Kashemirov BA, McKenna CE..  (2011)  Tyrosine-based 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) prodrugs: synthesis, stability, antiviral activity, and in vivo transport studies.,  54  (16): [PMID:21812420] [10.1021/jm2001426]

17. Cheviet T, Lefebvre-Tournier I, Wein S, Peyrottes S..  (2019)  Plasmodium Purine Metabolism and Its Inhibition by Nucleoside and Nucleotide Analogues.,  62  (18): [PMID:30964283] [10.1021/acs.jmedchem.9b00182]

18. Tan, Shuai, Groaz, Elisabetta, Prichard, Mark N., Kalkeri, Raj, Ptak, Roger, Herdewijn, Piet.  (2021)  Introduction of a cyano group at the 2-position of an (R,S)-3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) derivative of thymine elicits selective anti-HBV activity,  12  (5.0): [PMID:34124679] [10.1039/d1md00086a]

Source

Source(1):

• Scientific Literature