(S)-2-Amino-6-diazo-5-oxo-hexanoic acid

ID: ALA97485

Max Phase: Preclinical

Molecular Formula: C6H9N3O3

Molecular Weight: 171.16

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  [N-]=[N+]=CC(=O)CC[C@H](N)C(=O)O

Standard InChI:  InChI=1S/C6H9N3O3/c7-5(6(11)12)2-1-4(10)3-9-8/h3,5H,1-2,7H2,(H,11,12)/t5-/m0/s1

Standard InChI Key:  YCWQAMGASJSUIP-YFKPBYRVSA-N

Molfile:  

     RDKit          2D

 12 11  0  0  0  0  0  0  0  0999 V2000
   -1.9054   -6.2583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9054   -7.6871    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4927   -6.9727    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6674   -6.9727    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2547   -7.6871    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5706   -7.6871    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9832   -6.9727    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7307   -6.2583    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4927   -5.5440    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.9832   -8.4015    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.8085   -6.9727    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6338   -6.9727    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  3  2  1  6
  1  3  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  1  8  2  0
  1  9  1  0
  6 10  2  0
 11 12  2  0
  7 11  2  0
M  CHG  2  11   1  12  -1
M  END

Alternative Forms

1. Parent:

   

   ALA97485

   6-DIAZO-5-OXO-L-NORLEUCINE

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: 171.16

Molecular Weight (Monoisotopic): 171.0644

AlogP: -0.95

#Rotatable Bonds: 5

Polar Surface Area: 116.79

Molecular Species: ZWITTERION

HBA: 3

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 1.87

CX Basic pKa: 9.36

CX LogP: -4.22

CX LogD: -4.29

Aromatic Rings: ┄

Heavy Atoms: 12

QED Weighted: 0.31

Np Likeness Score: 1.31

References

1. Walker B, Brown MF, Lynas JF, Martin SL, McDowell A, Badet B, Hill AJ..  (2000)  Inhibition of Escherichia coli glucosamine synthetase by novel electrophilic analogues of glutamine--comparison with 6-diazo-5-oxo-norleucine.,  10  (24): [PMID:11133094] [10.1016/s0960-894x(00)00565-5]

2. Santana L, González-Díaz H, Quezada E, Uriarte E, Yáñez M, Viña D, Orallo F..  (2008)  Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.,  51  (21): [PMID:18834112] [10.1021/jm800656v]

3. Samanta S, Alam SM, Panda P, Jha T..  (2009)  Possible anticancer agents: QSAR analogs of glutamamide: synthesis and pharmacological activity of 1,5-N,N'-disubstituted-2-(substituted benzenesulphonyl) glutamamides.,  44  (1): [PMID:18456372] [10.1016/j.ejmech.2008.03.008]

4. Halder AK, Adhikary N, Maity MK, Jha T..  (2010)  Synthesis, pharmacological activity and comparative QSAR modeling of 1,5-N,N'-substituted-2-(substituted naphthalenesulphonyl) glutamamides as possible anticancer agents.,  45  (5): [PMID:20133022] [10.1016/j.ejmech.2010.01.008]

5. Wakiec R, Gabriel I, Prasad R, Becker JM, Payne JW, Milewski S..  (2008)  Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.,  52  (11): [PMID:18794383] [10.1128/aac.01648-07]

6. PubChem BioAssay data set, 

7. Rais R, Jančařík A, Tenora L, Nedelcovych M, Alt J, Englert J, Rojas C, Le A, Elgogary A, Tan J, Monincová L, Pate K, Adams R, Ferraris D, Powell J, Majer P, Slusher BS..  (2016)  Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.,  59  (18): [PMID:27560860] [10.1021/acs.jmedchem.6b01069]

8.  (2014)  D-serine transporter inhibitors as pharmaceutical compositions for the treatment of central nervous system disorders, 

9. Nedelcovych MT, Tenora L, Kim BH, Kelschenbach J, Chao W, Hadas E, Jančařík A, Prchalová E, Zimmermann SC, Dash RP, Gadiano AJ, Garrett C, Furtmüller G, Oh B, Brandacher G, Alt J, Majer P, Volsky DJ, Rais R, Slusher BS..  (2017)  N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo-l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive Disorders.,  60  (16): [PMID:28759224] [10.1021/acs.jmedchem.7b00966]

10. Tenora L, Alt J, Dash RP, Gadiano AJ, Novotná K, Veeravalli V, Lam J, Kirkpatrick QR, Lemberg KM, Majer P, Rais R, Slusher BS..  (2019)  Tumor-Targeted Delivery of 6-Diazo-5-oxo-l-norleucine (DON) Using Substituted Acetylated Lysine Prodrugs.,  62  (7): [PMID:30892035] [10.1021/acs.jmedchem.8b02009]

11. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

12. Jo M, Koizumi K, Suzuki M, Kanayama D, Watanabe Y, Gouda H, Mori H, Mizuguchi M, Obita T, Nabeshima Y, Toyooka N, Okada T..  (2023)  Design, synthesis, structure-activity relationship studies, and evaluation of novel GLS1 inhibitors.,  87  [PMID:37011768] [10.1016/j.bmcl.2023.129266]

Source

Source(4):

• Scientific Literature
• PubChem BioAssays
• Patent Bioactivity Data
• IMI-CARE SARS-CoV-2 Data