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

ID: ALA4228624

PubChem CID: 129900325

Max Phase: Preclinical

Molecular Formula: C28H37N5O5S

Molecular Weight: 555.70

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CC(=O)NC1(C(=O)N[C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)NCc2ccc(-c3scnc3C)cc2)C(C)(C)C)CC1

Standard InChI:  InChI=1S/C28H37N5O5S/c1-16-22(39-15-30-16)19-8-6-18(7-9-19)13-29-24(36)21-12-20(35)14-33(21)25(37)23(27(3,4)5)31-26(38)28(10-11-28)32-17(2)34/h6-9,15,20-21,23,35H,10-14H2,1-5H3,(H,29,36)(H,31,38)(H,32,34)/t20-,21+,23-/m1/s1

Standard InChI Key:  SFLOLDSFURSREE-FUPPJEDESA-N

Molfile:  

     RDKit          2D

 39 42  0  0  0  0  0  0  0  0999 V2000
   20.2418  -24.2377    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.8334  -23.5251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4205  -24.2350    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.9835  -22.2960    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7001  -21.8876    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.9882  -21.4712    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7001  -23.5335    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.4146  -23.1210    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   21.9856  -23.1210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.7001  -24.3585    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   24.1681  -23.4514    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.7201  -22.8383    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.3076  -22.1238    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.5007  -22.2955    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.3419  -24.2580    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7304  -24.8117    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   25.1273  -24.5107    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   25.3010  -25.3172    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.0864  -25.5700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.2583  -26.3748    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0427  -26.6276    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6552  -26.0737    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.4780  -25.2635    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.6937  -25.0144    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.4410  -26.3253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.6981  -27.1054    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.5231  -27.1020    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   29.7749  -26.3162    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.1054  -25.8342    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   28.2160  -27.7749    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2712  -23.5335    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.6431  -21.3701    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   20.5567  -23.1210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.5567  -22.2960    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   21.2712  -21.8835    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.1261  -23.1080    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.4076  -23.5134    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6972  -23.0939    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3996  -24.3383    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
  5  4  1  0
  4  6  1  0
  7  8  1  0
  7  9  1  0
  7 10  2  0
  8 11  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14  8  1  0
 11 15  1  1
 15 16  2  0
 15 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 22 23  1  0
 23 24  2  0
 24 19  1  0
 22 25  1  0
 25 26  2  0
 26 27  1  0
 27 28  2  0
 28 29  1  0
 29 25  1  0
 26 30  1  0
  9  4  1  1
  9 31  1  0
 13 32  1  6
 31 33  1  0
 33 34  2  0
  4 35  1  0
 33  2  1  0
  2 36  1  0
 36 37  1  0
 37 38  1  0
 37 39  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA4228624

   ---

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: 555.70

Molecular Weight (Monoisotopic): 555.2515

AlogP: 1.90

#Rotatable Bonds: 8

Polar Surface Area: 140.73

Molecular Species: NEUTRAL

HBA: 7

HBD: 4

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 12.02

CX Basic pKa: 2.65

CX LogP: 0.26

CX LogD: 0.26

Aromatic Rings: 2

Heavy Atoms: 39

QED Weighted: 0.39

Np Likeness Score: -0.61

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