2-{[(4-Amino-but-2-enyl)-methyl-amino]-methyl}-5-(6-amino-purin-9-yl)-tetrahydro-furan-3,4-diol

ID: ALA381751

Cas Number: 123642-27-3

PubChem CID: 6436013

Max Phase: Preclinical

Molecular Formula: C15H23N7O3

Molecular Weight: 349.40

Molecule Type: Small molecule

Names and Identifiers

Synonyms: MDL-73811 | Abeado|123642-27-3|MDL-73811|mdl73811|7GI49JB39O|CHEMBL381751|5'-(((Z)-4-Amino-2-butenyl)methylamino)-5'-deoxyadenosine|MDL 73811|(2R,3S,4R,5R)-2-[[[(Z)-4-aminobut-2-enyl]-methylamino]methyl]-5-(6-aminopurin-9-yl)oxolane-3,4-diol|Adenosine,5'-[[(2Z)-4-amino-2-buten-1-yl]methylamino]-5'-deoxy-|UNII-7GI49JB39O|5'-{[(Z)-4-amino-2-butenyl]methylamino}-5'-deoxyadenosine|SCHEMBL952291|Adenosine, 5'-((4-amino-2-butenyl)methylamino)-5'-deoxy-, (Z)-|BDBM50335525|5-{[(Z)-4-aminobut-2-enyl](metShow More⌵

Canonical SMILES:  CN(C/C=C\CN)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O

Standard InChI:  InChI=1S/C15H23N7O3/c1-21(5-3-2-4-16)6-9-11(23)12(24)15(25-9)22-8-20-10-13(17)18-7-19-14(10)22/h2-3,7-9,11-12,15,23-24H,4-6,16H2,1H3,(H2,17,18,19)/b3-2-/t9-,11-,12-,15-/m1/s1

Standard InChI Key:  YWJCZGDVJQLZET-GGHFOJMISA-N

Molfile:  

     RDKit          2D

 25 27  0  0  0  0  0  0  0  0999 V2000
   -4.7590    2.2412    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7604    1.4137    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0473    1.0008    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0493    2.6541    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3312    2.2453    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3307    1.4137    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5396    1.1572    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0512    1.8303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5404    2.5027    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2863    0.3722    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7708   -0.2955    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2855   -0.9626    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5009   -0.7072    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5016    0.1178    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0533    3.4791    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8345    0.6031    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8332   -1.1916    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5400   -1.7473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3469   -1.9194    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6013   -2.7041    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8993   -1.3067    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6447   -0.5218    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1972    0.0909    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.0040   -0.0812    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2585   -0.8659    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  3  6  2  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14 10  1  0
 10  7  1  1
  1  2  2  0
  4 15  1  0
  5  4  2  0
 14 16  1  6
  6  7  1  0
 13 17  1  6
  7  8  1  0
 12 18  1  1
  8  9  2  0
 18 19  1  0
  9  5  1  0
 19 20  1  0
 10 11  1  0
 19 21  1  0
  4  1  1  0
 21 22  1  0
  5  6  1  0
 22 23  2  0
 23 24  1  0
  2  3  1  0
 24 25  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA381751

   Abeado

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: 349.40

Molecular Weight (Monoisotopic): 349.1862

AlogP: -1.53

#Rotatable Bonds: 6

Polar Surface Area: 148.57

Molecular Species: BASE

HBA: 10

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 12.47

CX Basic pKa: 9.65

CX LogP: -1.65

CX LogD: -4.27

Aromatic Rings: 2

Heavy Atoms: 25

QED Weighted: 0.46

Np Likeness Score: 0.62

References

1. Marasco CJ, Kramer DL, Miller J, Porter CW, Bacchi CJ, Rattendi D, Kucera L, Iyer N, Bernacki R, Pera P, Sufrin JR..  (2002)  Synthesis and evaluation of analogues of 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine as inhibitors of tumor cell growth, trypanosomal growth, and HIV-1 infectivity.,  45  (23): [PMID:12408722] [10.1021/jm0201621]

2. Rapp M, Haubrich TA, Perrault J, Mackey ZB, McKerrow JH, Chiang PK, Wnuk SF..  (2006)  Antitrypanosomal activity of 5'-deoxy-5'-(iodomethylene)adenosine and related 6-N-cyclopropyladenosine analogues.,  49  (6): [PMID:16539398] [10.1021/jm0511379]

3. Roberts SC, Jiang Y, Gasteier J, Frydman B, Marton LJ, Heby O, Ullman B..  (2007)  Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.,  51  (2): [PMID:17116678] [10.1128/aac.01193-06]

4. Hirth B, Barker RH, Celatka CA, Klinger JD, Liu H, Nare B, Nijjar A, Phillips MA, Sybertz E, Willert EK, Xiang Y..  (2009)  Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT).,  19  (11): [PMID:19419862] [10.1016/j.bmcl.2009.04.096]

5. Barker RH, Liu H, Hirth B, Celatka CA, Fitzpatrick R, Xiang Y, Willert EK, Phillips MA, Kaiser M, Bacchi CJ, Rodriguez A, Yarlett N, Klinger JD, Sybertz E..  (2009)  Novel S-adenosylmethionine decarboxylase inhibitors for the treatment of human African trypanosomiasis.,  53  (5): [PMID:19289530] [10.1128/aac.01674-08]

6. Bacchi CJ, Barker RH, Rodriguez A, Hirth B, Rattendi D, Yarlett N, Hendrick CL, Sybertz E..  (2009)  Trypanocidal activity of 8-methyl-5'-{[(Z)-4-aminobut-2-enyl]-(methylamino)}adenosine (Genz-644131), an adenosylmethionine decarboxylase inhibitor.,  53  (8): [PMID:19451291] [10.1128/aac.00076-09]

7. Brockway AJ, Volkov OA, Cosner CC, MacMillan KS, Wring SA, Richardson TE, Peel M, Phillips MA, De Brabander JK..  (2017)  Synthesis and evaluation of analogs of 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (MDL 73811, or AbeAdo) - An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity.,  25  (20): [PMID:28807574] [10.1016/j.bmc.2017.07.063]

Source

Source(1):

• Scientific Literature