(2S,4R)-1-((S)-2-(cyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

ID: ALA4227893

PubChem CID: 129900322

Max Phase: Preclinical

Molecular Formula: C26H34N4O4S

Molecular Weight: 498.65

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2CC2)C(C)(C)C)cc1

Standard InChI:  InChI=1S/C26H34N4O4S/c1-15-21(35-14-28-15)17-7-5-16(6-8-17)12-27-24(33)20-11-19(31)13-30(20)25(34)22(26(2,3)4)29-23(32)18-9-10-18/h5-8,14,18-20,22,31H,9-13H2,1-4H3,(H,27,33)(H,29,32)/t19-,20+,22-/m1/s1

Standard InChI Key:  TXHVAXXHWXOMKR-RZUBCFFCSA-N

Molfile:  

     RDKit          2D

 35 38  0  0  0  0  0  0  0  0999 V2000
   31.0255  -13.3836    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.7422  -12.9752    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.0302  -12.5587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.7422  -14.6210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.4567  -14.2085    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.0277  -14.2085    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.7422  -15.4461    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   33.2102  -14.5391    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.7622  -13.9259    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.3497  -13.2114    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.5428  -13.3831    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.3840  -15.3456    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.7725  -15.8993    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.1693  -15.5983    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   34.3431  -16.4049    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.1285  -16.6576    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.3003  -17.4624    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.0849  -17.7153    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.6974  -17.1612    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.5201  -16.3511    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.7359  -16.1021    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.4830  -17.4129    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.7403  -18.1930    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.5653  -18.1897    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   38.8170  -17.4039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.1475  -16.9219    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   37.2582  -18.8626    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.3132  -14.6210    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   33.6852  -12.4577    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   29.5988  -14.2085    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.5988  -13.3836    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   30.3132  -12.9711    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.8843  -14.6210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.0598  -14.6257    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.4723  -15.3402    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  1  3  1  0
  4  5  1  0
  4  6  1  0
  4  7  2  0
  5  8  1  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11  5  1  0
  8 12  1  1
 12 13  2  0
 12 14  1  0
 14 15  1  0
 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
 19 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 22  1  0
 23 27  1  0
  6  1  1  1
  6 28  1  0
 10 29  1  6
 28 30  1  0
 30 31  2  0
  1 32  1  0
 30 33  1  0
 34 33  1  0
 35 34  1  0
 33 35  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4227893

   ---

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: 498.65

Molecular Weight (Monoisotopic): 498.2301

AlogP: 2.64

#Rotatable Bonds: 7

Polar Surface Area: 111.63

Molecular Species: NEUTRAL

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.51

CX Basic pKa: 2.65

CX LogP: 1.45

CX LogD: 1.45

Aromatic Rings: 2

Heavy Atoms: 35

QED Weighted: 0.54

Np Likeness Score: -0.68

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