N-((S)-3-hydroxy-1-((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-ylamino)-1-oxopropan-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxamide

ID: ALA4100295

Cas Number: 1629052-78-3

PubChem CID: 117611788

Max Phase: Preclinical

Molecular Formula: C21H23N3O6

Molecular Weight: 413.43

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C[C@]1(C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CO)NC(=O)c2cccc(=O)[nH]2)CO1

Standard InChI:  InChI=1S/C21H23N3O6/c1-21(12-30-21)18(27)15(10-13-6-3-2-4-7-13)23-20(29)16(11-25)24-19(28)14-8-5-9-17(26)22-14/h2-9,15-16,25H,10-12H2,1H3,(H,22,26)(H,23,29)(H,24,28)/t15-,16-,21+/m0/s1

Standard InChI Key:  QYDASSGXBXGRBS-CKJXQJPGSA-N

Molfile:  

     RDKit          2D

 30 32  0  0  0  0  0  0  0  0999 V2000
   18.8210  -10.9584    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   17.9959  -10.9584    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.4085  -11.6729    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2829  -10.9625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9974  -10.5500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7119  -10.9625    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.9974   -9.7251    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   14.4263  -10.5500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1409  -10.9625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.4263   -9.7251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.1409  -11.7875    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   15.8554  -10.5500    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.5698  -10.9625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2843  -10.5500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.5698  -11.7875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2843  -12.2001    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2807  -13.0262    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9943  -13.4386    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7098  -13.0260    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7071  -12.1967    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9929  -11.7880    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2843   -9.7250    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   18.4043  -10.2417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5746  -10.5466    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.8623  -10.9557    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8580  -11.7810    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5723  -12.1957    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2909  -11.7850    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1494  -10.5404    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   15.1409   -9.3126    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  2  1  0
  1  3  1  0
  4  5  1  0
  5  6  1  0
  5  7  2  0
  6  8  1  0
  8  9  1  0
  8 10  1  1
  9 11  2  0
  9 12  1  0
 12 13  1  0
 13 14  1  0
 13 15  1  6
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21 16  1  0
 14  2  1  0
 14 22  2  0
  2 23  1  1
  4 24  1  0
  4 28  2  0
 24 25  1  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 25 29  2  0
 10 30  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4100295

   N-((S)-3-Hydroxy-1-(((S)-1-((R)-2-methyloxiran-2-YL)-1-oxo-3-phenylpropan-2-YL)amino)-1-oxopropan-2-YL)-6-oxo-1,6-dihydropyridine-2-carboxamide

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: Yes

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: 413.43

Molecular Weight (Monoisotopic): 413.1587

AlogP: -0.45

#Rotatable Bonds: 9

Polar Surface Area: 140.89

Molecular Species: NEUTRAL

HBA: 6

HBD: 4

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 4

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 9.57

CX Basic pKa: ┄

CX LogP: -0.19

CX LogD: -0.19

Aromatic Rings: 2

Heavy Atoms: 30

QED Weighted: 0.41

Np Likeness Score: 0.38

References

1. Johnson HWB, Anderl JL, Bradley EK, Bui J, Jones J, Arastu-Kapur S, Kelly LM, Lowe E, Moebius DC, Muchamuel T, Kirk C, Wang Z, McMinn D..  (2017)  Discovery of Highly Selective Inhibitors of the Immunoproteasome Low Molecular Mass Polypeptide 2 (LMP2) Subunit.,  8  (4): [PMID:28435528] [10.1021/acsmedchemlett.6b00496]

2. Johnson HWB, Lowe E, Anderl JL, Fan A, Muchamuel T, Bowers S, Moebius DC, Kirk C, McMinn DL..  (2018)  Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide).,  61  (24): [PMID:30380863] [10.1021/acs.jmedchem.8b01201]

3. Bhattarai D, Lee MJ, Baek A, Yeo IJ, Miller Z, Baek YM, Lee S, Kim DE, Hong JT, Kim KB..  (2020)  LMP2 Inhibitors as a Potential Treatment for Alzheimer's Disease.,  63  (7): [PMID:32189500] [10.1021/acs.jmedchem.0c00416]

Source

Source(1):

• Scientific Literature