ID: ALA129841

Max Phase: Preclinical

Molecular Formula: C11H17N5O9P2

Molecular Weight: 425.23

Molecule Type: Small molecule

Representations

Synonyms (1): MRS-2179
Synonyms from Alternative Forms(1):

Canonical SMILES:  CNc1ncnc2c1ncn2[C@H]1C[C@H](OP(=O)(O)O)[C@@H](COP(=O)(O)O)O1

Standard InChI:  InChI=1S/C11H17N5O9P2/c1-12-10-9-11(14-4-13-10)16(5-15-9)8-2-6(25-27(20,21)22)7(24-8)3-23-26(17,18)19/h4-8H,2-3H2,1H3,(H,12,13,14)(H2,17,18,19)(H2,20,21,22)/t6-,7+,8+/m0/s1

Standard InChI Key:  CCPLITQNIFLYQB-XLPZGREQSA-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: 425.23

Molecular Weight (Monoisotopic): 425.0502

AlogP: -0.26

#Rotatable Bonds: 7

Polar Surface Area: 198.38

Molecular Species: ACID

HBA: 10

HBD: 5

#RO5 Violations: 0

HBA (Lipinski): 14

HBD (Lipinski): 5

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 0.85

CX Basic pKa: 4.72

CX LogP: -3.84

CX LogD: -8.31

Aromatic Rings: 2

Heavy Atoms: 27

QED Weighted: 0.36

Np Likeness Score: 0.63

References

1. Moro S, Guo D, Camaioni E, Boyer JL, Harden TK, Jacobson KA..  (1998)  Human P2Y1 receptor: molecular modeling and site-directed mutagenesis as tools to identify agonist and antagonist recognition sites.,  41  (9): [PMID:9554879] [10.1021/jm970684u]

2. Nandanan E, Camaioni E, Jang SY, Kim YC, Cristalli G, Herdewijn P, Secrist JA, Tiwari KN, Mohanram A, Harden TK, Boyer JL, Jacobson KA..  (1999)  Structure-activity relationships of bisphosphate nucleotide derivatives as P2Y1 receptor antagonists and partial agonists.,  42  (9): [PMID:10229631] [10.1021/jm980657j]

3. Camaioni E, Boyer JL, Mohanram A, Harden TK, Jacobson KA..  (1998)  Deoxyadenosine bisphosphate derivatives as potent antagonists at P2Y1 receptors.,  41  (2): [PMID:9457242] [10.1021/jm970433l]

4. Kim YC, Brown SG, Harden TK, Boyer JL, Dubyak G, King BF, Burnstock G, Jacobson KA..  (2001)  Structure-activity relationships of pyridoxal phosphate derivatives as potent and selective antagonists of P2X1 receptors.,  44  (3): [PMID:11462975] [10.1021/jm9904203]

5. Jacobson KA, Jarvis MF, Williams M..  (2002)  Purine and pyrimidine (P2) receptors as drug targets.,  45  (19): [PMID:12213051] [10.1021/jm020046y]

6. Xu B, Stephens A, Kirschenheuter G, Greslin AF, Cheng X, Sennelo J, Cattaneo M, Zighetti ML, Chen A, Kim SA, Kim HS, Bischofberger N, Cook G, Jacobson KA..  (2002)  Acyclic analogues of adenosine bisphosphates as P2Y receptor antagonists: phosphate substitution leads to multiple pathways of inhibition of platelet aggregation.,  45  (26): [PMID:12477353] [10.1021/jm020173u]

7. Kim YC, Gallo-Rodriguez C, Jang SY, Nandanan E, Adams M, Harden TK, Boyer JL, Jacobson KA..  (2000)  Acyclic analogues of deoxyadenosine 3',5'-bisphosphates as P2Y(1) receptor antagonists.,  43  (4): [PMID:10691699] [10.1021/jm9905211]

8. Nandanan E, Jang SY, Moro S, Kim HO, Siddiqui MA, Russ P, Marquez VE, Busson R, Herdewijn P, Harden TK, Boyer JL, Jacobson KA..  (2000)  Synthesis, biological activity, and molecular modeling of ribose-modified deoxyadenosine bisphosphate analogues as P2Y(1) receptor ligands.,  43  (5): [PMID:10715151] [10.1021/jm990249v]

9. Raboisson P, Baurand A, Cazenave JP, Gachet C, Retat M, Spiess B, Bourguignon JJ..  (2002)  Novel antagonists acting at the P2Y(1) purinergic receptor: synthesis and conformational analysis using potentiometric and nuclear magnetic resonance titration techniques.,  45  (4): [PMID:11831909] [10.1021/jm0104062]

10. Costanzi S, Mamedova L, Gao ZG, Jacobson KA..  (2004)  Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling.,  47  (22): [PMID:15481977] [10.1021/jm049914c]

11. Pfefferkorn JA, Choi C, Winters T, Kennedy R, Chi L, Perrin LA, Lu G, Ping YW, McClanahan T, Schroeder R, Leininger MT, Geyer A, Schefzick S, Atherton J..  (2008)  P2Y1 receptor antagonists as novel antithrombotic agents.,  18  (11): [PMID:18445527] [10.1016/j.bmcl.2008.04.028]

12. PubChem BioAssay data set, 

13. PubChem BioAssay data set, 

14. Yanachkov IB, Chang H, Yanachkova MI, Dix EJ, Berny-Lang MA, Gremmel T, Michelson AD, Wright GE, Frelinger AL..  (2016)  New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors.,  107  [PMID:26588064] [10.1016/j.ejmech.2015.10.055]

15. Xu P, Feng X, Luan H, Wang J, Ge R, Li Z, Bian J..  (2018)  Current knowledge on the nucleotide agonists for the P2Y2 receptor.,  26  (2): [PMID:29254895] [10.1016/j.bmc.2017.11.043]

16. Li X, Guo T, Feng Q, Bai T, Wu L, Liu Y, Zheng X, Jia J, Pei J, Wu S, Song Y, Zhang Y..  (2022)  Progress of thrombus formation and research on the structure-activity relationship for antithrombotic drugs.,  228  [PMID:34902735] [10.1016/j.ejmech.2021.114035]

17. Conroy S, Kindon N, Kellam B, Stocks MJ..  (2016)  Drug-like Antagonists of P2Y Receptors-From Lead Identification to Drug Development.,  59  (22): [PMID:27413802] [10.1021/acs.jmedchem.5b01972]

Source

Source(2):

• Scientific Literature
• PubChem BioAssays