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

ID: ALA4225537

Cas Number: 2097381-85-4

PubChem CID: 122199236

Product Number: V287785, Order Now?

Max Phase: Preclinical

Molecular Formula: C27H33N5O4S

Molecular Weight: 523.66

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)C2(C#N)CC2)C(C)(C)C)cc1

Standard InChI:  InChI=1S/C27H33N5O4S/c1-16-21(37-15-30-16)18-7-5-17(6-8-18)12-29-23(34)20-11-19(33)13-32(20)24(35)22(26(2,3)4)31-25(36)27(14-28)9-10-27/h5-8,15,19-20,22,33H,9-13H2,1-4H3,(H,29,34)(H,31,36)/t19-,20+,22-/m1/s1

Standard InChI Key:  NDVQUNZCNAMROD-RZUBCFFCSA-N

Molfile:  

     RDKit          2D

 37 40  0  0  0  0  0  0  0  0999 V2000
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   14.5318  -14.3341    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2600  -10.2553    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5779  -13.2754    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8301  -10.2553    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   14.3631  -13.5293    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9941  -10.7963    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6672  -12.1825    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.3810  -13.7950    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   12.5836  -10.0822    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5441   -9.8406    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2622  -11.0803    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5441  -11.4908    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.4912  -15.7332    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4919  -12.2185    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9717  -15.0644    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   15.7535  -13.2214    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   18.0497  -14.2754    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7967  -15.0610    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.6902  -11.0803    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.8301  -11.0803    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.3161  -14.5883    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4018  -11.0801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9762   -9.8449    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6180  -12.2190    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9695  -12.9752    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9166   -9.3289    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.1114  -11.4842    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9762  -12.3159    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   15.9317  -14.0315    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.4032  -12.4690    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.2648   -9.4303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4433  -11.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7172  -14.2845    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 21  9  1  0
 27  3  1  0
 10 30  1  6
 33 19  1  0
 20 23  1  0
  7 10  1  0
 33 37  1  0
  2 25  1  0
 24 31  1  0
 12  3  1  1
 24  5  2  0
 12 13  1  0
 16 14  1  0
 16 22  1  0
 18 23  1  0
 29  6  1  0
  8 31  1  0
 31 15  1  0
 13 24  1  0
 28 17  2  0
  4  6  1  0
 26  1  3  0
 28 34  1  0
 34  4  1  0
 19 29  2  0
  3 35  1  0
 15  8  1  0
 23 36  1  0
 20 32  2  0
  9 37  1  0
 37 16  2  0
 22 21  2  0
 20 12  1  0
 31 26  1  0
  3 11  1  0
  6  2  2  0
 25 33  2  0
 36 28  1  1
 10 18  1  0
 36  7  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4225537

   VH 298

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: 523.66

Molecular Weight (Monoisotopic): 523.2253

AlogP: 2.53

#Rotatable Bonds: 7

Polar Surface Area: 135.42

Molecular Species: NEUTRAL

HBA: 7

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 11.53

CX Basic pKa: 2.65

CX LogP: 1.25

CX LogD: 1.25

Aromatic Rings: 2

Heavy Atoms: 37

QED Weighted: 0.51

Np Likeness Score: -0.59

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]

2. Li Z, You Q, Zhang X..  (2019)  Small-Molecule Modulators of the Hypoxia-Inducible Factor Pathway: Development and Therapeutic Applications.,  62  (12): [PMID:30682255] [10.1021/acs.jmedchem.8b01596]

3. Blaquiere N, Villemure E, Staben ST..  (2020)  Medicinal Chemistry of Inhibiting RING-Type E3 Ubiquitin Ligases.,  63  (15): [PMID:32142281] [10.1021/acs.jmedchem.9b01451]

4. Klein VG,Townsend CE,Testa A,Zengerle M,Maniaci C,Hughes SJ,Chan KH,Ciulli A,Lokey RS.  (2020)  Understanding and Improving the Membrane Permeability of VH032-Based PROTACs.,  11  (9): [PMID:32939229] [10.1021/acsmedchemlett.0c00265]

5. Kato JY, Korenaga S, Iwakura M..  (2023)  Discovery of a potent and subtype-selective TYK2 degrader based on an allosteric TYK2 inhibitor.,  79  [PMID:36414177] [10.1016/j.bmcl.2022.129083]

Source

Source(1):

• Scientific Literature