2-(4,5-Dichloro-6-oxopyridazin-1(6H)-yl)-N-(4-methyl-3-(N-(2-(pyridin-2-yl)ethyl)sulfamoyl)phenyl)acetamide

ID: ALA4862851

PubChem CID: 162727470

Max Phase: Preclinical

Molecular Formula: C20H19Cl2N5O4S

Molecular Weight: 496.38

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1ccc(NC(=O)Cn2ncc(Cl)c(Cl)c2=O)cc1S(=O)(=O)NCCc1ccccn1

Standard InChI:  InChI=1S/C20H19Cl2N5O4S/c1-13-5-6-15(26-18(28)12-27-20(29)19(22)16(21)11-24-27)10-17(13)32(30,31)25-9-7-14-4-2-3-8-23-14/h2-6,8,10-11,25H,7,9,12H2,1H3,(H,26,28)

Standard InChI Key:  GBGTXIJEYNBKMD-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
   11.7117  -11.6450    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.1284  -10.9326    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   11.3030  -10.9280    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.8435  -11.3450    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8424  -12.1723    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5571  -12.5852    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2736  -12.1719    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2707  -11.3414    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5553  -10.9322    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1288  -10.1078    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.1277  -12.5843    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9835  -10.9262    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.6996  -11.3360    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4124  -10.9208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7026  -12.1610    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   17.1284  -11.3306    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.1284  -12.1544    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.8435  -12.5642    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.5573  -12.1489    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.5516  -11.3197    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8358  -10.9138    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8291  -10.0888    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.2629  -10.9021    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   19.2738  -12.5577    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   12.8435   -9.6957    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8439   -8.8708    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5586   -8.4587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2709   -8.8751    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9851   -8.4637    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9860   -7.6379    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2668   -7.2251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5556   -7.6389    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  2  2  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
  4  2  1  0
  2 10  1  0
  5 11  1  0
  8 12  1  0
 12 13  1  0
 13 14  1  0
 13 15  2  0
 14 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 16  1  0
 21 22  2  0
 20 23  1  0
 19 24  1  0
 10 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  2  0
 28 29  1  0
 29 30  2  0
 30 31  1  0
 31 32  2  0
 32 27  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4862851

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 496.38

Molecular Weight (Monoisotopic): 495.0535

AlogP: 2.41

#Rotatable Bonds: 8

Polar Surface Area: 123.05

Molecular Species: NEUTRAL

HBA: 7

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 10.20

CX Basic pKa: 4.54

CX LogP: 2.07

CX LogD: 2.07

Aromatic Rings: 3

Heavy Atoms: 32

QED Weighted: 0.49

Np Likeness Score: -2.65

References

1. McKinney DC, McMillan BJ, Ranaghan MJ, Moroco JA, Brousseau M, Mullin-Bernstein Z, O'Keefe M, McCarren P, Mesleh MF, Mulvaney KM, Robinson F, Singh R, Bajrami B, Wagner FF, Hilgraf R, Drysdale MJ, Campbell AJ, Skepner A, Timm DE, Porter D, Kaushik VK, Sellers WR, Ianari A..  (2021)  Discovery of a First-in-Class Inhibitor of the PRMT5-Substrate Adaptor Interaction.,  64  (15.0): [PMID:34342224] [10.1021/acs.jmedchem.1c00507]

2. Smil, David D and 9 more authors.  2015-04-09  Discovery of a Dual PRMT5-PRMT7 Inhibitor.  [PMID:25893041]

3. Wang, Yuanxiang Y, Hu, Wenhao W and Yuan, Yanqiu Y.  2018-11-08  Protein Arginine Methyltransferase 5 (PRMT5) as an Anticancer Target and Its Inhibitor Discovery.  [PMID:29870258]

4. Bonday, Zahid Q ZQ and 17 more authors.  2018-07-12  LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity.  [PMID:30034588]

5. Zhu, Kongkai K and 5 more authors.  2018-12-15  Discovery of new potent protein arginine methyltransferase 5 (PRMT5) inhibitors by assembly of key pharmacophores from known inhibitors.  [PMID:30366617]

6. Lin, Hong and 7 more authors.  2019-07-11  Discovery of Potent and Selective Covalent Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors.  [PMID:31312404]

Source

Source(1):

• Scientific Literature