1-(2-Ethoxy-6-methy1-4-pyridyl)-3-((5-methyl-6-(1-methyl-3-(trifluoromethyl)pyrazol-4-yl)pyridazin-3-yl)methyl)urea

ID: ALA4878889

PubChem CID: 137377733

Max Phase: Preclinical

Molecular Formula: C20H22F3N7O2

Molecular Weight: 449.44

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CCOc1cc(NC(=O)NCc2cc(C)c(-c3cn(C)nc3C(F)(F)F)nn2)cc(C)n1

Standard InChI:  InChI=1S/C20H22F3N7O2/c1-5-32-16-8-13(7-12(3)25-16)26-19(31)24-9-14-6-11(2)17(28-27-14)15-10-30(4)29-18(15)20(21,22)23/h6-8,10H,5,9H2,1-4H3,(H2,24,25,26,31)

Standard InChI Key:  VGPGNWPIKCWAKB-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
   16.0879  -28.1064    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   15.2996  -27.8959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5115  -28.6839    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   15.3315  -25.7836    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.9230  -26.4914    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.4701  -27.0985    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.5237  -28.1510    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   14.9989  -25.0371    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1309  -25.9533    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9243  -27.1736    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9232  -27.9932    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.6312  -28.4021    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.3409  -27.9927    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3381  -27.1700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6295  -26.7648    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.6270  -25.9476    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2165  -26.7652    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.0493  -28.4002    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.7563  -27.9905    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.4647  -28.3980    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.4660  -29.2152    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   21.1717  -27.9883    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   21.8801  -28.3957    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.8770  -29.2136    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.5845  -29.6210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.2925  -29.2112    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   23.2886  -28.3898    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.5805  -27.9861    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.9942  -27.9776    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   24.7040  -28.3826    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.4096  -27.9704    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.5854  -30.4382    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  2  1  0
  4  5  1  0
  5  6  2  0
  6  2  1  0
  2  7  1  0
  4  8  1  0
  4  9  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 15 10  1  0
 15 16  1  0
 10 17  1  0
 17  9  2  0
 13 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  2  0
 20 22  1  0
 22 23  1  0
 23 24  2  0
 24 25  1  0
 25 26  2  0
 26 27  1  0
 27 28  2  0
 28 23  1  0
 27 29  1  0
 29 30  1  0
  6 17  1  0
 30 31  1  0
 25 32  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4878889

   ---

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: 449.44

Molecular Weight (Monoisotopic): 449.1787

AlogP: 3.63

#Rotatable Bonds: 6

Polar Surface Area: 106.85

Molecular Species: NEUTRAL

HBA: 7

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.65

CX Basic pKa: 4.15

CX LogP: 2.65

CX LogD: 2.65

Aromatic Rings: 3

Heavy Atoms: 32

QED Weighted: 0.60

Np Likeness Score: -1.89

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