2-Phenyl-N-(5-{[(3R)-1-[5-(2-phenylacetamido)-1,3,4-thiadiazol-2-yl]pyrrolidin-3-yl]amino}-1,3,4-thiadiazol-2-yl)acetamide

ID: ALA3770355

PubChem CID: 118988615

Max Phase: Preclinical

Molecular Formula: C24H24N8O2S2

Molecular Weight: 520.64

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(Cc1ccccc1)Nc1nnc(N[C@@H]2CCN(c3nnc(NC(=O)Cc4ccccc4)s3)C2)s1

Standard InChI:  InChI=1S/C24H24N8O2S2/c33-19(13-16-7-3-1-4-8-16)26-22-29-28-21(35-22)25-18-11-12-32(15-18)24-31-30-23(36-24)27-20(34)14-17-9-5-2-6-10-17/h1-10,18H,11-15H2,(H,25,28)(H,26,29,33)(H,27,30,34)/t18-/m1/s1

Standard InChI Key:  XKAUHJUBYCZSGD-GOSISDBHSA-N

Molfile:  

     RDKit          2D

 36 40  0  0  0  0  0  0  0  0999 V2000
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   -5.7991   -4.7128    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2110   -7.0199    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9229   -6.5127    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0944   -8.4623    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5047   -7.9514    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4264   -9.1348    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5857  -10.3771    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1617   -9.9480    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    2.2469   -8.7527    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.7673   -8.8452    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4117  -10.3025    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6878  -11.0910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8320  -10.1210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6747   -6.1134    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
    3.1332   -7.5416    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6332   -7.5468    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.1017   -6.1218    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8912   -5.2578    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5951   -3.0039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5973   -1.5031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5548   -3.6021    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.8933   -3.7570    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.2564   -4.3540    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.6772   -2.9142    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.1344   -2.5586    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  -10.1710   -3.6428    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.7503   -5.0826    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.2931   -5.4382    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1  3  2  0
  1  4  1  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  5  9  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 11 15  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 16 20  1  0
 21 22  1  0
 21 23  2  0
 21 24  1  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28 29  2  0
 29 30  1  0
 25 30  2  0
 22 25  1  0
 20 24  1  0
 11 17  1  0
 13 10  1  1
  9 10  1  0
  4  6  1  0
 31 32  1  0
 32 33  2  0
 33 34  1  0
 34 35  2  0
 35 36  1  0
 31 36  2  0
  2 31  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3770355

   ---

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: 520.64

Molecular Weight (Monoisotopic): 520.1464

AlogP: 3.44

#Rotatable Bonds: 9

Polar Surface Area: 125.03

Molecular Species: NEUTRAL

HBA: 10

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 6.78

CX Basic pKa: 0.02

CX LogP: 3.74

CX LogD: 2.84

Aromatic Rings: 4

Heavy Atoms: 36

QED Weighted: 0.31

Np Likeness Score: -1.52

References

1. McDermott LA, Iyer P, Vernetti L, Rimer S, Sun J, Boby M, Yang T, Fioravanti M, O'Neill J, Wang L, Drakes D, Katt W, Huang Q, Cerione R..  (2016)  Design and evaluation of novel glutaminase inhibitors.,  24  (8): [PMID:26988803] [10.1016/j.bmc.2016.03.009]

2. Finlay MRV, Anderton M, Bailey A, Boyd S, Brookfield J, Cairnduff C, Charles M, Cheasty A, Critchlow SE, Culshaw J, Ekwuru T, Hollingsworth I, Jones N, Leroux F, Littleson M, McCarron H, McKelvie J, Mooney L, Nissink JWM, Perkins D, Powell S, Quesada MJ, Raubo P, Sabin V, Smith J, Smith PD, Stark A, Ting A, Wang P, Wilson Z, Winter-Holt JJ, Wood JM, Wrigley GL, Yu G, Zhang P..  (2019)  Discovery of a Thiadiazole-Pyridazine-Based Allosteric Glutaminase 1 Inhibitor Series That Demonstrates Oral Bioavailability and Activity in Tumor Xenograft Models.,  62  (14): [PMID:31199640] [10.1021/acs.jmedchem.9b00260]

Source

Source(1):

• Scientific Literature