(5-Chloro-2-(2-((methyl-d3)amino)thiazol-4-yl)-pyridin-4-yl)(4-(4-chlorobenzyl)piperazin-1-yl)methanone

ID: ALA4098876

PubChem CID: 137660903

Max Phase: Preclinical

Molecular Formula: C21H21Cl2N5OS

Molecular Weight: 462.41

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  [2H]C([2H])([2H])Nc1nc(-c2cc(C(=O)N3CCN(Cc4ccc(Cl)cc4)CC3)c(Cl)cn2)cs1

Standard InChI:  InChI=1S/C21H21Cl2N5OS/c1-24-21-26-19(13-30-21)18-10-16(17(23)11-25-18)20(29)28-8-6-27(7-9-28)12-14-2-4-15(22)5-3-14/h2-5,10-11,13H,6-9,12H2,1H3,(H,24,26)/i1D3

Standard InChI Key:  MVXAYIXYYOVALX-FIBGUPNXSA-N

Molfile:  

     RDKit          2D

 33 36  0  0  0  0  0  0  0  0999 V2000
   34.7705  -23.2734    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.7693  -24.0971    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.4815  -24.5060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.4797  -22.8604    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.1925  -23.2698    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.1932  -24.0929    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.0606  -22.8610    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.4834  -25.3315    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.7725  -25.7417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.1962  -25.7384    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.0604  -25.3321    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.3516  -25.7389    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.3493  -26.5605    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   34.0619  -26.9738    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.7769  -26.5612    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.6369  -26.9722    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.9256  -26.5584    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.9311  -25.7399    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.2207  -25.3304    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.5114  -25.7380    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   30.5128  -26.5635    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.2197  -26.9735    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   29.7996  -25.3293    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   33.9761  -22.0490    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.1746  -21.8788    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   32.7622  -22.5888    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.3114  -23.1991    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.9453  -22.6736    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   31.4655  -22.0079    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.9021  -24.4995    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   31.7984  -21.2616    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   30.6485  -22.0969    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   31.0450  -21.2965    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  6  2  0
  5  4  2  0
  4  1  1  0
  5  6  1  0
  1  7  1  0
  3  8  1  0
  8  9  1  0
  8 10  2  0
  9 11  1  0
  9 15  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
 13 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 21 22  2  0
 22 17  1  0
 20 23  1  0
  7 24  2  0
 24 25  1  0
 25 26  1  0
 26 27  2  0
 27  7  1  0
 26 28  1  0
 28 29  1  0
  6 30  1  0
 29 31  1  0
 29 32  1  0
 29 33  1  0
M  ISO  3  31   2  32   2  33   2
M  END

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: 462.41

Molecular Weight (Monoisotopic): 461.0844

AlogP: 4.51

#Rotatable Bonds: 5

Polar Surface Area: 61.36

Molecular Species: NEUTRAL

HBA: 6

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 5.74

CX LogP: 4.07

CX LogD: 4.06

Aromatic Rings: 3

Heavy Atoms: 30

QED Weighted: 0.60

Np Likeness Score: -2.05

References

1. Yamada K, Levell J, Yoon T, Kohls D, Yowe D, Rigel DF, Imase H, Yuan J, Yasoshima K, DiPetrillo K, Monovich L, Xu L, Zhu M, Kato M, Jain M, Idamakanti N, Taslimi P, Kawanami T, Argikar UA, Kunjathoor V, Xie X, Yagi YI, Iwaki Y, Robinson Z, Park HM..  (2017)  Optimization of Allosteric With-No-Lysine (WNK) Kinase Inhibitors and Efficacy in Rodent Hypertension Models.,  60  (16): [PMID:28771350] [10.1021/acs.jmedchem.7b00708]

Source

Source(1):

• Scientific Literature