(+/-)-2-Amino-4-(3-nitro-phenyl)-4-oxo-butyric acid[(+/-)-m-nicotinylbenzoylalanine]

ID: ALA23983

Cas Number: 153212-71-6

PubChem CID: 127868

Max Phase: Preclinical

Molecular Formula: C10H10N2O5

Molecular Weight: 238.20

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  NC(CC(=O)c1cccc([N+](=O)[O-])c1)C(=O)O

Standard InChI:  InChI=1S/C10H10N2O5/c11-8(10(14)15)5-9(13)6-2-1-3-7(4-6)12(16)17/h1-4,8H,5,11H2,(H,14,15)

Standard InChI Key:  KBJZPNMDKSNLIZ-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 17 17  0  0  0  0  0  0  0  0999 V2000
    3.8167   -4.1792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.8542   -2.3667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3792   -2.6667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8167   -3.5792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4167   -2.6542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3417   -2.6667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3417   -3.2792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8917   -2.3667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3042   -4.4792    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.3417   -4.4792    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.9375   -2.3542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.8542   -1.7667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.8917   -1.7667    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.4167   -3.2542    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.3042   -3.2792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8167   -2.3667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3042   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  6  1  0
  3  2  1  0
  4  1  1  0
  5  8  1  0
  6  7  1  0
  7  4  2  0
  8  3  1  0
  9  1  1  0
 10  1  2  0
 11  5  2  0
 12  2  2  0
  8 13  1  0
 14  5  1  0
 15  4  1  0
 16 17  1  0
 17 15  2  0
  6 16  2  0
M  CHG  2   1   1   9  -1
M  END

Alternative Forms

1. Parent:

   

   ALA23983

   (m-Nitrobenzoyl)alanine

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: 238.20

Molecular Weight (Monoisotopic): 238.0590

AlogP: 0.58

#Rotatable Bonds: 5

Polar Surface Area: 123.53

Molecular Species: ZWITTERION

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 1.05

CX Basic pKa: 8.96

CX LogP: -1.79

CX LogD: -1.80

Aromatic Rings: 1

Heavy Atoms: 17

QED Weighted: 0.44

Np Likeness Score: -0.49

References

1. Drysdale MJ, Hind SL, Jansen M, Reinhard JF..  (2000)  Synthesis and SAR of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids and esters and 2-amino-4-aryl-4-oxobut-2-enoic acids and esters: potent inhibitors of kynurenine-3-hydroxylase as potential neuroprotective agents.,  43  (1): [PMID:10633043] [10.1021/jm990396t]

2. Natalini B, Mattoli L, Pellicciari R, Carpenedo R, Chiarugi A, Moroni F.  (1995)  Synthesis and activity of enantiopure (S) (m-nitrobenzoyl) alanine, potent kynurenine-3-hydroxylase inhibitor,  5  (14): [10.1016/0960-894X(95)00255-R]

3. Röver S, Cesura AM, Huguenin P, Kettler R, Szente A..  (1997)  Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase.,  40  (26): [PMID:9435907] [10.1021/jm970467t]

4. Pellicciari R, Natalini B, Costantino G, Mahmoud MR, Mattoli L, Sadeghpour BM, Moroni F, Chiarugi A, Carpenedo R..  (1994)  Modulation of the kynurenine pathway in search for new neuroprotective agents. Synthesis and preliminary evaluation of (m-nitrobenzoyl)alanine, a potent inhibitor of kynurenine-3-hydroxylase.,  37  (5): [PMID:8126705] [10.1021/jm00031a015]

5. Toledo-Sherman LM, Prime ME, Mrzljak L, Beconi MG, Beresford A, Brookfield FA, Brown CJ, Cardaun I, Courtney SM, Dijkman U, Hamelin-Flegg E, Johnson PD, Kempf V, Lyons K, Matthews K, Mitchell WL, O'Connell C, Pena P, Powell K, Rassoulpour A, Reed L, Reindl W, Selvaratnam S, Friley WW, Weddell DA, Went NE, Wheelan P, Winkler C, Winkler D, Wityak J, Yarnold CJ, Yates D, Munoz-Sanjuan I, Dominguez C..  (2015)  Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.,  58  (3): [PMID:25590515] [10.1021/jm501350y]

6. Dounay AB, Tuttle JB, Verhoest PR..  (2015)  Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.,  58  (22): [PMID:26207924] [10.1021/acs.jmedchem.5b00461]

7. Pellicciari R, Liscio P, Giacchè N, De Franco F, Carotti A, Robertson J, Cialabrini L, Katsyuba E, Raffaelli N, Auwerx J..  (2018)  α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis.,  61  (3): [PMID:29345930] [10.1021/acs.jmedchem.7b01254]

Source

Source(1):

• Scientific Literature