(S)-2-Amino-N-((S)-1-(2-(hydroxyamino)-2-oxoethyl)-2,6-dioxopiperidin-3-yl)-3-phenylpropanamide hydrochloride

ID: ALA1099248

PubChem CID: 24884567

Max Phase: Preclinical

Molecular Formula: C16H21ClN4O5

Molecular Weight: 348.36

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cl.N[C@@H](Cc1ccccc1)C(=O)N[C@H]1CCC(=O)N(CC(=O)NO)C1=O

Standard InChI:  InChI=1S/C16H20N4O5.ClH/c17-11(8-10-4-2-1-3-5-10)15(23)18-12-6-7-14(22)20(16(12)24)9-13(21)19-25;/h1-5,11-12,25H,6-9,17H2,(H,18,23)(H,19,21);1H/t11-,12-;/m0./s1

Standard InChI Key:  AZFNNISMELGQEG-FXMYHANSSA-N

Molfile:  

     RDKit          2D

 26 26  0  0  0  0  0  0  0  0999 V2000
   17.7565  -11.4562    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    9.6751  -12.1470    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3928  -11.7350    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9575  -11.7350    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.1106  -12.1470    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.3928  -10.9069    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.8283  -11.7350    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5410  -12.1486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2524  -11.7401    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.2567  -10.9117    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5433  -10.4933    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.8214  -10.9076    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5380  -12.9766    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.9759  -10.4982    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   13.9685  -12.1548    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.6878  -11.7455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4040  -12.1602    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.6909  -10.9173    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.6751  -12.9709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9615  -13.3829    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2496  -12.9661    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5365  -13.3774    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5361  -14.2022    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2547  -14.6140    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.9647  -14.2004    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1180  -11.7491    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 10 14  2  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
 17 26  1  0
  8 13  2  0
  7  5  1  1
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: 348.36

Molecular Weight (Monoisotopic): 348.1434

AlogP: -1.30

#Rotatable Bonds: 6

Polar Surface Area: 141.83

Molecular Species: NEUTRAL

HBA: 6

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 5

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 8.75

CX Basic pKa: 7.67

CX LogP: -1.76

CX LogD: -2.01

Aromatic Rings: 1

Heavy Atoms: 25

QED Weighted: 0.29

Np Likeness Score: -0.22

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