(3S,16aS)-N-((S)-4-Methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)-1,12-dioxotetradecahydro-6H-pyrrolo[2,1-f][1]oxa[4,7]-diazacyclotetradecine-3-carboxamide

ID: ALA4863075

PubChem CID: 164623131

Max Phase: Preclinical

Molecular Formula: C24H39N3O6

Molecular Weight: 465.59

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(C)C[C@H](NC(=O)[C@@H]1COCCCCCCC(=O)N2CCC[C@H]2C(=O)N1)C(=O)[C@@]1(C)CO1

Standard InChI:  InChI=1S/C24H39N3O6/c1-16(2)13-17(21(29)24(3)15-33-24)25-22(30)18-14-32-12-7-5-4-6-10-20(28)27-11-8-9-19(27)23(31)26-18/h16-19H,4-15H2,1-3H3,(H,25,30)(H,26,31)/t17-,18-,19-,24+/m0/s1

Standard InChI Key:  KBVGKKIIWKCHBO-GSRZOBFVSA-N

Molfile:  

 
     RDKit          2D

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   18.4062   -2.5753    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.8248   -3.2884    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.2371   -2.5716    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.7972   -3.6619    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4037   -4.2231    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.1224   -3.8177    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9635   -3.0045    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1437   -2.9111    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.8754   -4.1596    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9503   -4.9876    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   14.5512   -3.6863    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
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   15.9766   -3.5577    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7263   -3.9020    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.9059   -2.7337    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
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   18.1483   -3.7707    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.2232   -4.5947    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   17.3244   -2.6050    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9675   -1.9715    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9237   -1.3065    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7143   -2.1869    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.5755   -3.6428    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5293   -3.1052    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   12.3096   -5.0262    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5670   -5.3464    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.9581   -5.5093    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6722   -5.6646    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.8641   -6.3124    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5126   -6.7954    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2552   -6.4753    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9037   -6.9583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6462   -6.6381    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
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 18  2  1  0
  2 24  1  6
  6 25  1  6
  5 26  1  0
 26 27  2  0
 26 28  1  0
 16 29  1  0
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 32 33  1  0
 33 34  1  0
 34 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4863075

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 465.59

Molecular Weight (Monoisotopic): 465.2839

AlogP: 1.33

#Rotatable Bonds: 6

Polar Surface Area: 117.34

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.02

CX Basic pKa: ┄

CX LogP: 1.48

CX LogD: 1.48

Aromatic Rings: ┄

Heavy Atoms: 33

QED Weighted: 0.57

Np Likeness Score: 0.44

References

1. Lee MJ, Bhattarai D, Jang H, Baek A, Yeo IJ, Lee S, Miller Z, Lee S, Hong JT, Kim DE, Lee W, Kim KB..  (2021)  Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer's Disease.,  64  (15.0): [PMID:34309393] [10.1021/acs.jmedchem.1c00291]

2. de Bruin, Gerjan G and 11 more authors.  2014-07-24  Structure-based design of β1i or β5i specific inhibitors of human immunoproteasomes.  [PMID:25006746]

3. Johnson, Henry W B HWB and 12 more authors.  2017-04-13  Discovery of Highly Selective Inhibitors of the Immunoproteasome Low Molecular Mass Polypeptide 2 (LMP2) Subunit.  [PMID:28435528]

4. Xie, Stanley C and 20 more authors.  2018-11-21  Target Validation and Identification of Novel Boronate Inhibitors of the Plasmodium falciparum Proteasome.  [PMID:30373366]

5. Johnson, Henry W B HWB and 8 more authors.  2018-12-27  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).  [PMID:30380863]

6. Bhattarai, Deepak and 9 more authors.  2020-04-09  LMP2 Inhibitors as a Potential Treatment for Alzheimer's Disease.  [PMID:32189500]

Source

Source(1):

• Scientific Literature