1-(2-Chloro-6-ethoxy-4-pyridyl)-3-((5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridyl)methyl)urea

ID: ALA4874736

PubChem CID: 164626769

Max Phase: Preclinical

Molecular Formula: C20H23ClN6O2

Molecular Weight: 414.90

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CCOc1cc(NC(=O)NCc2cc(C)c(-c3cn(C)nc3C)cn2)cc(Cl)n1

Standard InChI:  InChI=1S/C20H23ClN6O2/c1-5-29-19-8-14(7-18(21)25-19)24-20(28)23-9-15-6-12(2)16(10-22-15)17-11-27(4)26-13(17)3/h6-8,10-11H,5,9H2,1-4H3,(H2,23,24,25,28)

Standard InChI Key:  UNCLUWWJNQDLPU-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 29 31  0  0  0  0  0  0  0  0999 V2000
    3.1486   -2.7583    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1474   -3.5856    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8622   -3.9985    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.5786   -3.5852    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5758   -2.7547    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8604   -2.3455    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8579   -1.5205    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4340   -2.3460    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3475   -1.5263    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5405   -1.3549    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.1282   -2.0696    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.6804   -2.6824    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3077   -2.1561    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9604   -0.9740    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2938   -3.9965    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0075   -3.5829    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.7227   -3.9943    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7240   -4.8193    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.4366   -3.5807    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.1516   -3.9921    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1485   -4.8177    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8628   -5.2291    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5776   -4.8154    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.5736   -3.9861    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8587   -3.5786    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8637   -6.0540    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   10.2860   -3.5700    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.2818   -2.7450    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.9941   -2.3288    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  1  1  0
  6  7  1  0
  1  8  1  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  1  0
 12  8  2  0
 11 13  1  0
  9 14  1  0
  4 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  2  0
 17 19  1  0
 19 20  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  2  0
 25 20  1  0
 22 26  1  0
 24 27  1  0
 27 28  1  0
 28 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4874736

   ---

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: 414.90

Molecular Weight (Monoisotopic): 414.1571

AlogP: 3.87

#Rotatable Bonds: 6

Polar Surface Area: 93.96

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.45

CX Basic pKa: 4.41

CX LogP: 2.81

CX LogD: 2.81

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.60

Np Likeness Score: -1.91

References

1. Mammoliti O, Palisse A, Joannesse C, El Bkassiny S, Allart B, Jaunet A, Menet C, Coornaert B, Sonck K, Duys I, Clément-Lacroix P, Oste L, Borgonovi M, Wakselman E, Christophe T, Houvenaghel N, Jans M, Heckmann B, Sanière L, Brys R..  (2021)  Discovery of the S1P2 Antagonist GLPG2938 (1-[2-Ethoxy-6-(trifluoromethyl)-4-pyridyl]-3-[[5-methyl-6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]pyridazin-3-yl]methyl]urea), a Preclinical Candidate for the Treatment of Idiopathic Pulmonary Fibrosis.,  64  (9.0): [PMID:33939425] [10.1021/acs.jmedchem.1c00138]

2. Osada, Makoto M, Yatomi, Yutaka Y, Ohmori, Tsukasa T, Ikeda, Hitoshi H and Ozaki, Yukio Y.  2002-12-06  Enhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist.  [PMID:12445827]

3. Sanna, M Germana MG and 10 more authors.  2004-04-02  Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.  [PMID:14732717]

4. Deng, Hongfeng H and 6 more authors.  2013-10-10  Discovery of Clinical Candidate GSK1842799 As a Selective S1P1 Receptor Agonist (Prodrug) for Multiple Sclerosis.  [PMID:24900589]

5. Demont, Emmanuel H EH and 22 more authors.  2016-02-11  Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses.  [PMID:26751273]

6. Scott, F L FL and 12 more authors.  2016-06  Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.  [PMID:26990079]

Source

Source(1):

• Scientific Literature