1-(2-Chloro-6-ethoxypyridin-4-yl)-3-(5-methyl-6-(1-methyl-3-trifluoromethyl-1H-pyrazol-4-y1)-pyridazin-3-yl)methyl)urea

ID: ALA4871481

PubChem CID: 137377865

Max Phase: Preclinical

Molecular Formula: C19H19ClF3N7O2

Molecular Weight: 469.86

Molecule Type: Unknown

Names and Identifiers

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

Standard InChI:  InChI=1S/C19H19ClF3N7O2/c1-4-32-15-7-11(6-14(20)26-15)25-18(31)24-8-12-5-10(2)16(28-27-12)13-9-30(3)29-17(13)19(21,22)23/h5-7,9H,4,8H2,1-3H3,(H2,24,25,26,31)

Standard InChI Key:  WBANUGXLMVIJLV-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 32 34  0  0  0  0  0  0  0  0999 V2000
   14.2389  -16.6286    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.4506  -16.4181    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6625  -17.2060    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.4825  -14.3058    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.0740  -15.0136    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.6211  -15.6207    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.6747  -16.6732    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   13.1499  -13.5593    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2819  -14.4755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0753  -15.6958    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.0742  -16.5153    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   15.7822  -16.9243    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.4919  -16.5149    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.4891  -15.6922    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7805  -15.2870    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.7780  -14.4698    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.3675  -15.2874    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.2003  -16.9224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.9073  -16.5127    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   18.6157  -16.9201    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.6170  -17.7373    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   19.3227  -16.5104    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.0311  -16.9179    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.0280  -17.7358    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.7355  -18.1432    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.4435  -17.7334    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   21.4396  -16.9120    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.7315  -16.5083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.7364  -18.9604    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   22.1452  -16.4998    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   22.8550  -16.9048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.5606  -16.4926    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
 25 29  1  0
 27 30  1  0
 30 31  1  0
 31 32  1  0
  6 17  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4871481

   ---

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: 469.86

Molecular Weight (Monoisotopic): 469.1241

AlogP: 3.97

#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: 12.45

CX Basic pKa: 1.55

CX LogP: 3.35

CX LogD: 3.35

Aromatic Rings: 3

Heavy Atoms: 32

QED Weighted: 0.53

Np Likeness Score: -1.93

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