(2S,4R)-1-((R)-2-(1-fluorocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-3-(methylamino)-1-(4-(4-methylthiazol-5-yl)phenyl)-3-oxopropyl)pyrrolidine-2-carboxamide

ID: ALA5274336

Max Phase: Preclinical

Molecular Formula: C29H38FN5O5S

Molecular Weight: 587.72

Names and Identifiers

Canonical SMILES:  CNC(=O)C[C@H](NC(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@H](NC(=O)C1(F)CC1)C(C)(C)C)c1ccc(-c2scnc2C)cc1

Standard InChI:  InChI=1S/C29H38FN5O5S/c1-16-23(41-15-32-16)18-8-6-17(7-9-18)20(13-22(37)31-5)33-25(38)21-12-19(36)14-35(21)26(39)24(28(2,3)4)34-27(40)29(30)10-11-29/h6-9,15,19-21,24,36H,10-14H2,1-5H3,(H,31,37)(H,33,38)(H,34,40)/t19-,20+,21+,24+/m1/s1

Standard InChI Key:  PTPPMFQIIPBSRV-XBJMDHIQSA-N

Molfile:  

 
     RDKit          2D

 41 44  0  0  0  0  0  0  0  0999 V2000
   44.0787   -6.5791    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.2829   -6.7957    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.8684   -7.3766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5815   -5.1999    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5803   -6.0273    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.2951   -6.4401    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0115   -6.0268    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0087   -5.1962    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.2933   -4.7872    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.2909   -3.9622    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0040   -3.5475    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   39.7198   -3.9579    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.4330   -3.5433    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.7222   -4.7829    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   41.1882   -3.8748    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   41.7384   -3.2601    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.3238   -2.5469    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.5173   -2.7209    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.6570   -1.7921    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   41.3630   -4.6811    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.7522   -5.2356    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   42.1487   -4.9328    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.3235   -5.7391    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   42.7595   -4.3783    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.5452   -4.6301    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.5847   -3.5721    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.3000   -7.2651    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.6325   -7.7499    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.8872   -8.5346    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   38.7123   -8.5348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.9672   -7.7502    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   36.8479   -7.4948    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5751   -3.5518    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.5727   -2.7268    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.8570   -2.3164    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   38.2860   -2.3122    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   36.8545   -1.4915    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.3411   -3.7875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.1091   -5.9908    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   43.7199   -5.4363    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   42.6731   -7.3516    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  2  1  0
  1  3  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9  4  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 13 12  1  6
 12 14  2  0
 13 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 13  1  0
 17 19  1  1
 15 20  1  0
 20 21  2  0
 20 22  1  0
 22 23  1  1
 22 24  1  0
 24 25  1  0
 24 26  1  0
 27 28  2  0
 28 29  1  0
 29 30  2  0
 30 31  1  0
 31 27  1  0
  6 27  1  0
 28 32  1  0
 10 33  1  6
 33 34  1  0
 34 35  1  0
 34 36  2  0
 35 37  1  0
 24 38  1  0
 23 39  1  0
 39  2  1  0
 39 40  2  0
  2 41  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5274336

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 587.72

Molecular Weight (Monoisotopic): 587.2578

AlogP: 2.41

#Rotatable Bonds: 9

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: 11.15

CX Basic pKa: 2.65

CX LogP: 0.63

CX LogD: 0.63

Aromatic Rings: 2

Heavy Atoms: 41

QED Weighted: 0.36

Np Likeness Score: -0.44

References

1. Han X, Wang C, Qin C, Xiang W, Fernandez-Salas E, Yang CY, Wang M, Zhao L, Xu T, Chinnaswamy K, Delproposto J, Stuckey J, Wang S..  (2019)  Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer.,  62  (2): [PMID:30629437] [10.1021/acs.jmedchem.8b01631]

Source

Source(1):

• Scientific Literature