(2S,4R)-1-((S)-3,3-dimethyl-2-(N-methylacetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

ID: ALA4226127

PubChem CID: 122528924

Max Phase: Preclinical

Molecular Formula: C25H34N4O4S

Molecular Weight: 486.64

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(=O)N(C)[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)C

Standard InChI:  InChI=1S/C25H34N4O4S/c1-15-21(34-14-27-15)18-9-7-17(8-10-18)12-26-23(32)20-11-19(31)13-29(20)24(33)22(25(3,4)5)28(6)16(2)30/h7-10,14,19-20,22,31H,11-13H2,1-6H3,(H,26,32)/t19-,20+,22-/m1/s1

Standard InChI Key:  IIPLOHQVELTIPV-RZUBCFFCSA-N

Molfile:  

     RDKit          2D

 34 36  0  0  0  0  0  0  0  0999 V2000
    3.7584  -13.5626    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9001  -12.3250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6167  -11.9168    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9047  -11.5002    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6167  -13.5626    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    8.0847  -13.4806    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    8.2242  -12.1529    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4173  -12.3245    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2585  -14.2870    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6469  -14.8408    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.0438  -14.5398    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.2176  -15.3463    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   11.3945  -15.2926    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6103  -15.0435    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3575  -16.3544    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6147  -17.1345    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4397  -17.1312    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.6915  -16.3454    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.0219  -15.8633    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   12.1326  -17.8040    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1877  -13.5626    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.5597  -11.3993    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.4733  -13.1500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4733  -12.3250    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.1877  -11.9125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1877  -14.3876    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  3  2  1  0
  2  4  1  0
  5  6  1  0
  5  7  1  0
  5  8  2  0
  6  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12  6  1  0
  9 13  1  1
 13 14  2  0
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 15 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 22 17  1  0
 20 23  1  0
 23 24  2  0
 24 25  1  0
 25 26  2  0
 26 27  1  0
 27 23  1  0
 24 28  1  0
  7  2  1  1
  7 29  1  0
 11 30  1  6
 29 31  1  0
 31 32  2  0
  2 33  1  0
 31  1  1  0
 29 34  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4226127

   ---

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: 486.64

Molecular Weight (Monoisotopic): 486.2301

AlogP: 2.59

#Rotatable Bonds: 6

Polar Surface Area: 102.84

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 2.65

CX LogP: 0.89

CX LogD: 0.89

Aromatic Rings: 2

Heavy Atoms: 34

QED Weighted: 0.65

Np Likeness Score: -0.57

References

1. Soares P, Gadd MS, Frost J, Galdeano C, Ellis L, Epemolu O, Rocha S, Read KD, Ciulli A..  (2018)  Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298).,  61  (2): [PMID:28853884] [10.1021/acs.jmedchem.7b00675]

Source

Source(1):

• Scientific Literature