1-((5-(1,3-Dimethylpyrazol-4-yl)amino)-4-methyl-2-pyridyl)-methyl)-3-(2-ethoxy-6-(trifluoromethyl)-4-pyridyl)urea

ID: ALA4869752

PubChem CID: 164621933

Max Phase: Preclinical

Molecular Formula: C21H24F3N7O2

Molecular Weight: 463.46

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CCOc1cc(NC(=O)NCc2cc(C)c(Nc3cn(C)nc3C)cn2)cc(C(F)(F)F)n1

Standard InChI:  InChI=1S/C21H24F3N7O2/c1-5-33-19-8-14(7-18(29-19)21(22,23)24)27-20(32)26-9-15-6-12(2)16(10-25-15)28-17-11-31(4)30-13(17)3/h6-8,10-11,28H,5,9H2,1-4H3,(H2,26,27,29,32)

Standard InChI Key:  JZXDEGLEWCFEOC-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 33 35  0  0  0  0  0  0  0  0999 V2000
   21.4657  -12.3941    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   20.6485  -12.3941    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.0571  -13.1018    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   14.9887   -9.1335    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9875   -9.9531    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6956  -10.3620    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.4052   -9.9526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4024   -9.1299    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6938   -8.7247    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6913   -7.9075    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.1136  -10.3601    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.8207   -9.9504    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.5290  -10.3578    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.5303  -11.1750    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.2361   -9.9481    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.9444  -10.3556    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.9413  -11.1735    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.6488  -11.5809    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.3569  -11.1711    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   21.3529  -10.3497    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.6449   -9.9460    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.0586   -9.9375    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.7683  -10.3425    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.4740   -9.9303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2809   -8.7251    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.5733   -9.1339    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8295   -8.8033    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.2828   -9.4107    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.6916  -10.1184    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.4909   -9.9482    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6592   -8.0040    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3595  -10.8650    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.9424  -12.8074    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  2  1  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
  9 10  1  0
  7 11  1  0
 11 12  1  0
 12 13  1  0
 13 14  2  0
 13 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21 16  1  0
 20 22  1  0
 22 23  1  0
 23 24  1  0
  4 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  2  0
 28 29  1  0
 29 30  1  0
 30 26  2  0
 27 31  1  0
 29 32  1  0
 18  2  1  0
  2 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4869752

   ---

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: 463.46

Molecular Weight (Monoisotopic): 463.1944

AlogP: 4.31

#Rotatable Bonds: 7

Polar Surface Area: 105.99

Molecular Species: NEUTRAL

HBA: 7

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.48

CX Basic pKa: 5.20

CX LogP: 3.04

CX LogD: 3.04

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.48

Np Likeness Score: -1.96

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