ID: ALA394429

Max Phase: Preclinical

Molecular Formula: C10H15N2O8P

Molecular Weight: 322.21

Molecule Type: Small molecule

Representations

Synonyms (3): 2'-Deoxythymidine Monophosphate | Thymidine Monophosphate | Thymidine-5'-Phosphate
Synonyms from Alternative Forms(3):

Canonical SMILES:  Cc1cn([C@H]2C[C@H](O)[C@@H](COP(=O)(O)O)O2)c(=O)[nH]c1=O

Standard InChI:  InChI=1S/C10H15N2O8P/c1-5-3-12(10(15)11-9(5)14)8-2-6(13)7(20-8)4-19-21(16,17)18/h3,6-8,13H,2,4H2,1H3,(H,11,14,15)(H2,16,17,18)/t6-,7+,8+/m0/s1

Standard InChI Key:  GYOZYWVXFNDGLU-XLPZGREQSA-N

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

Properties

Molecular Weight: 322.21

Molecular Weight (Monoisotopic): 322.0566

AlogP: -1.40

#Rotatable Bonds: 4

Polar Surface Area: 151.08

Molecular Species: ACID

HBA: 7

HBD: 4

#RO5 Violations: 0

HBA (Lipinski): 10

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 1.23

CX Basic pKa:

CX LogP: -1.24

CX LogD: -4.77

Aromatic Rings: 1

Heavy Atoms: 21

QED Weighted: 0.49

Np Likeness Score: 1.00

References

1. Kim CU, Luh BY, Misco PF, Bronson JJ, Hitchcock MJ, Ghazzouli I, Martin JC..  (1990)  Acyclic purine phosphonate analogues as antiviral agents. Synthesis and structure-activity relationships.,  33  (4): [PMID:2157012] [10.1021/jm00166a019]

2. Goldstein S, Pogolotti AL, Garvey EP, Santi DV..  (1984)  Interaction of N4-hydroxy-2'-deoxycytidylic acid with thymidylate synthetase.,  27  (10): [PMID:6434741] [10.1021/jm00376a004]

3. Vanheusden V, Munier-Lehmann H, Pochet S, Herdewijn P, Van Calenbergh S..  (2002)  Synthesis and evaluation of thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.,  12  (19): [PMID:12217356] [10.1016/s0960-894x(02)00551-6]

4. Traynor AJ, Hall ET, Walker G, Miller WH, Melançon P, Kuchta RD..  (1996)  Inhibition of UDP-N-acetylglucosamine import into Golgi membranes by nucleoside monophosphates.,  39  (15): [PMID:8709123] [10.1021/jm960175c]

5. Vanheusden V, Van Rompaey P, Munier-Lehmann H, Pochet S, Herdewijn P, Van Calenbergh S..  (2003)  Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.,  13  (18): [PMID:12941330] [10.1016/s0960-894x(03)00643-7]

6. Vanheusden V, Munier-Lehmann H, Froeyen M, Dugué L, Heyerick A, De Keukeleire D, Pochet S, Busson R, Herdewijn P, Van Calenbergh S..  (2003)  3'-C-branched-chain-substituted nucleosides and nucleotides as potent inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.,  46  (18): [PMID:12930144] [10.1021/jm021108n]

7. Chawla RR, Freed JJ, Kappler F, Hampton A..  (1986)  Zwitterionic 3'-O-acyl derivatives of thymidine 5'-phosphate as potential sources of intracellular thymidine 5'-phosphate in cells in culture.,  29  (5): [PMID:3701790] [10.1021/jm00155a033]

8. Douguet D, Munier-Lehmann H, Labesse G, Pochet S..  (2005)  LEA3D: a computer-aided ligand design for structure-based drug design.,  48  (7): [PMID:15801836] [10.1021/jm0492296]

9. Vanheusden V, Munier-Lehmann H, Froeyen M, Busson R, Rozenski J, Herdewijn P, Van Calenbergh S..  (2004)  Discovery of bicyclic thymidine analogues as selective and high-affinity inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.,  47  (25): [PMID:15566289] [10.1021/jm040847w]

10. Van Daele I, Munier-Lehmann H, Froeyen M, Balzarini J, Van Calenbergh S..  (2007)  Rational design of 5'-thiourea-substituted alpha-thymidine analogues as thymidine monophosphate kinase inhibitors capable of inhibiting mycobacterial growth.,  50  (22): [PMID:17910427] [10.1021/jm0706158]

11. Hsu CH, Hu R, Dutschman GE, Yang G, Krishnan P, Tanaka H, Baba M, Cheng YC..  (2007)  Comparison of the phosphorylation of 4'-ethynyl 2',3'-dihydro-3'-deoxythymidine with that of other anti-human immunodeficiency virus thymidine analogs.,  51  (5): [PMID:17353236] [10.1128/aac.01432-06]

12. Familiar O, Munier-Lehmann H, Aínsa JA, Camarasa MJ, Pérez-Pérez MJ..  (2010)  Design, synthesis and inhibitory activity against Mycobacterium tuberculosis thymidine monophosphate kinase of acyclic nucleoside analogues with a distal imidazoquinolinone.,  45  (12): [PMID:20951473] [10.1016/j.ejmech.2010.09.056]

13. Topalis D, Pradère U, Roy V, Caillat C, Azzouzi A, Broggi J, Snoeck R, Andrei G, Lin J, Eriksson S, Alexandre JA, El-Amri C, Deville-Bonne D, Meyer P, Balzarini J, Agrofoglio LA..  (2011)  Novel antiviral C5-substituted pyrimidine acyclic nucleoside phosphonates selected as human thymidylate kinase substrates.,  54  (1): [PMID:21128666] [10.1021/jm1011462]

14. Wataya Y, Santi DV, Hansch C..  (1977)  Inhibition of Lactobacillus casei thymidylate synthetase by 5-substituted 2'-deoxyuridylates. Preliminary quantitative structure-activity relationship.,  20  (11): [PMID:410930] [10.1021/jm00221a021]

15. Singh VK, Doharey PK, Kumar V, Saxena JK, Siddiqi MI, Rathaur S, Narender T..  (2015)  Synthesis, molecular docking and Brugia malayi thymidylate kinase (BmTMK) enzyme inhibition study of novel derivatives of [6]-shogaol.,  93  [PMID:25659753] [10.1016/j.ejmech.2015.01.035]

16. Fang Z,Jiang X,Zhang Q,Zhang L,Zhang W,Yang C,Zhang H,Zhu Y,Zhang C.  (2020)  S-Bridged Thioether and Structure-Diversified Angucyclinone Derivatives from the South China Sea-Derived Micromonospora echinospora SCSIO 04089.,  83  (10): [PMID:32970433] [10.1021/acs.jnatprod.0c00719]

Source

Source(1):

• Scientific Literature