1-(6-Cyano-2-ethoxy-3-methy1-4-pyridy1)-3-((5-methyl-6-(1-methyl-3-(trifluoromethyl)pyrazol-4-yl)pyridazin-3-yl)methyl)urea

ID: ALA4877484

PubChem CID: 137377731

Max Phase: Preclinical

Molecular Formula: C21H21F3N8O2

Molecular Weight: 474.45

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CCOc1nc(C#N)cc(NC(=O)NCc2cc(C)c(-c3cn(C)nc3C(F)(F)F)nn2)c1C

Standard InChI:  InChI=1S/C21H21F3N8O2/c1-5-34-19-12(3)16(7-13(8-25)27-19)28-20(33)26-9-14-6-11(2)17(30-29-14)15-10-32(4)31-18(15)21(22,23)24/h6-7,10H,5,9H2,1-4H3,(H2,26,27,28,33)

Standard InChI Key:  CHANXQOERSRNGA-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 34 36  0  0  0  0  0  0  0  0999 V2000
   14.0780  -18.3703    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.2897  -18.1598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.5015  -18.9477    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.3215  -16.0475    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   12.9131  -16.7553    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.4601  -17.3624    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5138  -18.4149    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   12.9890  -15.3010    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1209  -16.2172    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9144  -17.4375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.9132  -18.2570    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.6213  -18.6660    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.3309  -18.2566    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.3281  -17.4339    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6195  -17.0286    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6171  -16.2115    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2066  -17.0291    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.0393  -18.6641    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7464  -18.2543    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.4547  -18.6618    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.4560  -19.4790    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.1618  -18.2521    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   19.8701  -18.6596    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.8670  -19.4775    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.5745  -19.8849    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.2826  -19.4751    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   21.2787  -18.6537    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.5706  -18.2500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.9843  -18.2415    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.6941  -18.6465    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.3997  -18.2343    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.5661  -17.4328    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.5754  -20.7021    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.5763  -21.5193    0.0000 N   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
 28 32  1  0
 25 33  1  0
 33 34  3  0
M  END

Alternative Forms

1. Parent:

   

   ALA4877484

   ---

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: 474.45

Molecular Weight (Monoisotopic): 474.1740

AlogP: 3.50

#Rotatable Bonds: 6

Polar Surface Area: 130.64

Molecular Species: NEUTRAL

HBA: 8

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 10

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.52

CX Basic pKa: 1.59

CX LogP: 3.28

CX LogD: 3.28

Aromatic Rings: 3

Heavy Atoms: 34

QED Weighted: 0.56

Np Likeness Score: -1.80

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