(S)-2-Amino-N-((S)-1-(2-(hydroxyamino)-2-oxoethyl)-2,6-dioxopiperidin-3-yl)-3-(4-hydroxyphenyl)propanamidehydrochloride

ID: ALA1095254

PubChem CID: 46193025

Max Phase: Preclinical

Molecular Formula: C16H21ClN4O6

Molecular Weight: 364.36

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cl.N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H]1CCC(=O)N(CC(=O)NO)C1=O

Standard InChI:  InChI=1S/C16H20N4O6.ClH/c17-11(7-9-1-3-10(21)4-2-9)15(24)18-12-5-6-14(23)20(16(12)25)8-13(22)19-26;/h1-4,11-12,21,26H,5-8,17H2,(H,18,24)(H,19,22);1H/t11-,12-;/m0./s1

Standard InChI Key:  JVSBMSRMKGNOQQ-FXMYHANSSA-N

Molfile:  

     RDKit          2D

 27 27  0  0  0  0  0  0  0  0999 V2000
    5.7381  -23.4436    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -2.5674  -24.2218    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8497  -23.8098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2851  -23.8098    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1321  -24.2218    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8497  -22.9817    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4143  -23.8098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2983  -24.2233    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0096  -23.8148    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.0138  -22.9864    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3005  -22.5682    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4212  -22.9824    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2953  -25.0514    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.7331  -22.5731    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.7258  -24.2295    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4450  -23.8202    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1611  -24.2348    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.4481  -22.9922    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5674  -25.0457    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2809  -25.4576    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9929  -25.0408    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7059  -25.4520    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7063  -26.2768    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9879  -26.6887    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2777  -26.2750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4193  -26.6898    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.8751  -23.8238    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  7  8  1  0
  9 15  1  0
  2  4  1  6
 15 16  1  0
 16 17  1  0
  3  5  1  0
 16 18  2  0
  2  3  1  0
  2 19  1  0
  3  6  2  0
 19 20  1  0
  7 12  1  0
 20 21  2  0
  8  9  1  0
 21 22  1  0
  9 10  1  0
 22 23  2  0
 10 11  1  0
 23 24  1  0
 11 12  1  0
 24 25  2  0
 25 20  1  0
 23 26  1  0
  8 13  2  0
 17 27  1  0
  7  5  1  1
 10 14  2  0
M  END

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: 364.36

Molecular Weight (Monoisotopic): 364.1383

AlogP: -1.60

#Rotatable Bonds: 6

Polar Surface Area: 162.06

Molecular Species: NEUTRAL

HBA: 7

HBD: 5

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 8.68

CX Basic pKa: 7.69

CX LogP: -2.09

CX LogD: -2.34

Aromatic Rings: 1

Heavy Atoms: 26

QED Weighted: 0.23

Np Likeness Score: 0.01

References

1. Li Q, Fang H, Wang X, Xu W..  (2010)  Novel cyclic-imide peptidomimetics as aminopeptidase N inhibitors. Structure-based design, chemistry and activity evaluation. II.,  45  (4): [PMID:20129718] [10.1016/j.ejmech.2009.12.071]

2. Chen, H H, Noble, F F, Roques, B P BP and Fournié-Zaluski, M C MC.  2001-10-11  Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and APN) inhibitor prodrugs.  [PMID:11585456]

3. Vassiliou, Stamatia S and 7 more authors.  2014-10-09  Structure-guided, single-point modifications in the phosphinic dipeptide structure yield highly potent and selective inhibitors of neutral aminopeptidases.  [PMID:25192493]

4. Węglarz-Tomczak, Ewelina and 5 more authors.  2016-07-19  A structural insight into the P1S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases.  [PMID:27100031]

5. Singh, Rohit R, Williams, Jessica J and Vince, Robert R.  2017-10-20  Puromycin based inhibitors of aminopeptidases for the potential treatment of hematologic malignancies.  [PMID:28803047]

6. Pascual, Isel and 10 more authors.  2017-11  Discovery of novel non-competitive inhibitors of mammalian neutral M1 aminopeptidase (APN).  [PMID:28964831]

Source

Source(1):

• Scientific Literature