2-[6-(3-Chloro-phenylamino)-purin-9-yl]-5-hydroxymethyl-tetrahydro-furan-3,4-diol

ID: ALA607682

PubChem CID: 46877184

Max Phase: Preclinical

Molecular Formula: C16H16ClN5O4

Molecular Weight: 377.79

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  OC[C@H]1OC(n2cnc3c(Nc4cccc(Cl)c4)ncnc32)[C@H](O)[C@@H]1O

Standard InChI:  InChI=1S/C16H16ClN5O4/c17-8-2-1-3-9(4-8)21-14-11-15(19-6-18-14)22(7-20-11)16-13(25)12(24)10(5-23)26-16/h1-4,6-7,10,12-13,16,23-25H,5H2,(H,18,19,21)/t10-,12-,13-,16?/m1/s1

Standard InChI Key:  TZNHRMFCCGYSTQ-AARXTDBFSA-N

Molfile:  

     RDKit          2D

 26 29  0  0  0  0  0  0  0  0999 V2000
    5.2292   -5.1667    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2167   -6.5542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6542   -4.9875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6542   -4.3792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2292   -4.1917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.0292   -7.1292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5875   -4.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7292   -6.2042    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.1292   -4.0792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4292   -7.1292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2417   -6.5542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1292   -5.2875    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.6167   -4.3792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.1292   -3.4792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.6167   -4.9875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6042   -3.1917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6042   -2.5917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3917   -7.6292    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.0542   -7.6375    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0875   -2.2917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6750   -6.3667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0792   -1.6917    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    3.2292   -6.7667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.5750   -3.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1000   -3.4917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5667   -2.6000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  1  1  0
  4  3  1  0
  5  7  2  0
  6  2  1  0
  7  1  1  0
  8  2  1  0
  9  4  2  0
 10  6  1  0
 11  8  1  0
 12  3  2  0
 13 15  2  0
 14  9  1  0
 15 12  1  0
 16 14  1  0
 17 16  2  0
  6 18  1  6
 10 19  1  6
 20 17  1  0
 11 21  1  1
 22 20  1  0
 23 21  1  0
 24 25  2  0
 25 16  1  0
 26 24  1  0
  4  5  1  0
 10 11  1  0
 13  9  1  0
 26 20  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA607682

   (3R,4S,5R)-2-[6-(3-chloroanilino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol

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: 377.79

Molecular Weight (Monoisotopic): 377.0891

AlogP: 0.83

#Rotatable Bonds: 4

Polar Surface Area: 125.55

Molecular Species: NEUTRAL

HBA: 9

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.44

CX Basic pKa: 2.34

CX LogP: 0.78

CX LogD: 0.78

Aromatic Rings: 3

Heavy Atoms: 26

QED Weighted: 0.53

Np Likeness Score: 0.08

References

1. Kusachi S, Thompson RD, Yamada N, Daly DT, Olsson RA..  (1986)  Dog coronary artery adenosine receptor: structure of the N6-aryl subregion.,  29  (6): [PMID:3012086] [10.1021/jm00156a016]

2. Hayallah, Alaa M AM and 7 more authors.  2002-03-28  1,8-disubstituted xanthine derivatives: synthesis of potent A2B-selective adenosine receptor antagonists.  [PMID:11906291]

3. Saki, Mayumi M, Tsumuki, Hiroshi H, Nonaka, Hiromi H, Shimada, Junichi J and Ichimura, Michio M.  2002-05-31  KF26777 (2-(4-bromophenyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one dihydrochloride), a new potent and selective adenosine A3 receptor antagonist.  [PMID:12063073]

4. Yan, Luo L, Burbiel, Joachim C JC, Maass, Astrid A and Müller, Christa E CE.  2003-11  Adenosine receptor agonists: from basic medicinal chemistry to clinical development.  [PMID:14662005]

5. Kase, Hiroshi H and 27 more authors.  2003-12-09  Progress in pursuit of therapeutic A2A antagonists: the adenosine A2A receptor selective antagonist KW6002: research and development toward a novel nondopaminergic therapy for Parkinson's disease.  [PMID:14663020]

6. Vu, Chi B CB and 14 more authors.  2004-08-12  Piperazine derivatives of [1,2,4]triazolo[1,5-a][1,3,5]triazine as potent and selective adenosine A2a receptor antagonists.  [PMID:15294001]

7. Jacobson, Kenneth A KA and Gao, Zhan-Guo ZG.  2006-03  Adenosine receptors as therapeutic targets.  [PMID:16518376]

8. Vu, Chi B CB and 10 more authors.  2006-11-30  Tricyclic imidazoline derivatives as potent and selective adenosine A1 receptor antagonists.  [PMID:17125265]

9. Kalk, P P and 9 more authors.  2007-08  The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure.  [PMID:17558436]

10. Kuno, Atsushi A and 9 more authors.  2007-09  Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A2b-dependent signaling during early reperfusion.  [PMID:17632123]

11. Elzein, Elfatih E and Zablocki, Jeff J.  2008-12  A1 adenosine receptor agonists and their potential therapeutic applications.  [PMID:19012505]

12. Gillespie, Roger J RJ and 6 more authors.  2009-05-15  Antagonists of the human A(2A) receptor. Part 5: Highly bio-available pyrimidine-4-carboxamides.  [PMID:19362836]

13. Bedford, Simon T ST and 20 more authors.  2009-10-15  Discovery and optimization of potent and selective functional antagonists of the human adenosine A2B receptor.  [PMID:19733067]

14. Fredholm, Bertil B BB, IJzerman, Adriaan P AP, Jacobson, Kenneth A KA, Linden, Joel J and Müller, Christa E CE.  2011-03  International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors--an update.  [PMID:21303899]

15. Baraldi, Pier Giovanni PG and 8 more authors.  2012-01-15  Pyrrolo- and pyrazolo-[3,4-e][1,2,4]triazolo[1,5-c]pyrimidines as adenosine receptor antagonists.  [PMID:22204739]

16. Congreve, Miles and 11 more authors.  2012-03-08  Discovery of 1,2,4-triazine derivatives as adenosine A(2A) antagonists using structure based drug design.  [PMID:22220592]

17. Inamdar, Gajanan S GS and 8 more authors.  2013-05  New insight into adenosine receptors selectivity derived from a novel series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamides and furamides.  [PMID:23685887]

18. Gràcia, Jordi J and 20 more authors.  2016-12-08  Biphenyl Pyridazinone Derivatives as Inhaled PDE4 Inhibitors: Structural Biology and Structure-Activity Relationships.  [PMID:27933955]

19. Basu, Sujay and 25 more authors.  2017-01-26  Design, Synthesis of Novel, Potent, Selective, Orally Bioavailable Adenosine A2A Receptor Antagonists and Their Biological Evaluation.  [PMID:28055204]

20. Basu, Sujay S and 26 more authors.  2017-07-07  Design and synthesis of novel xanthine derivatives as potent and selective A2B adenosine receptor antagonists for the treatment of chronic inflammatory airway diseases.  [PMID:28415011]

21. Paz, Odailson Santos OS, de Jesus Pinheiro, Milena M, do Espirito Santo, Renan Fernandes RF, Villarreal, Cristiane Flora CF and Castilho, Marcelo Santos MS.  2017-08-18  Nanomolar anti-sickling compounds identified by ligand-based pharmacophore approach.  [PMID:28528302]

22. Aurelio, Luigi and 10 more authors.  2018-03-08  A Structure-Activity Relationship Study of Bitopic N6-Substituted Adenosine Derivatives as Biased Adenosine A1 Receptor Agonists.  [PMID:29446948]

23. Härter, Michael M and 8 more authors.  2019-02-01  Novel non-xanthine antagonist of the A2B adenosine receptor: From HTS hit to lead structure.  [PMID:30576906]

24. Abdelrahman, Aliaa and 6 more authors.  2020-01-15  Substituted 4-phenylthiazoles: Development of potent and selective A1, A3 and dual A1/A3 adenosine receptor antagonists.  [PMID:31780082]

Source

Source(1):

• Scientific Literature