1-(2,6-Dichloro-4-pyridyl)-3-((4-methyl-6-(1-methylpyrazol-4-yl)-2-pyridyl)amino)urea

ID: ALA4877928

PubChem CID: 164628297

Max Phase: Preclinical

Molecular Formula: C16H15Cl2N7O

Molecular Weight: 392.25

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1cc(NNC(=O)Nc2cc(Cl)nc(Cl)c2)nc(-c2cnn(C)c2)c1

Standard InChI:  InChI=1S/C16H15Cl2N7O/c1-9-3-12(10-7-19-25(2)8-10)21-15(4-9)23-24-16(26)20-11-5-13(17)22-14(18)6-11/h3-8H,1-2H3,(H,21,23)(H2,20,22,24,26)

Standard InChI Key:  FODKFQLREONTAR-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 26 28  0  0  0  0  0  0  0  0999 V2000
    3.4572  -28.2343    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4561  -29.0539    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1641  -29.4628    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.8738  -29.0534    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8709  -28.2307    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1623  -27.8255    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5821  -29.4609    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.2892  -29.0512    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.9975  -29.4587    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7046  -29.0490    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.9988  -30.2759    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.1599  -27.0083    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4129  -29.4564    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.4098  -30.2743    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1173  -30.6817    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8254  -30.2719    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.8215  -29.4505    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.1134  -29.0468    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.5271  -29.0383    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    9.1182  -31.4989    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    2.7480  -29.4619    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0003  -29.1304    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4530  -29.7373    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.8611  -30.4453    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6605  -30.2759    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5282  -31.1916    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
  4  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
  9 11  2  0
  6 12  1  0
 10 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17 18  2  0
 18 13  1  0
 17 19  1  0
 15 20  1  0
  2 21  1  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  1  0
 25 21  2  0
 24 26  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4877928

   ---

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: 392.25

Molecular Weight (Monoisotopic): 391.0715

AlogP: 3.64

#Rotatable Bonds: 4

Polar Surface Area: 96.76

Molecular Species: NEUTRAL

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.88

CX Basic pKa: 4.96

CX LogP: 3.76

CX LogD: 3.76

Aromatic Rings: 3

Heavy Atoms: 26

QED Weighted: 0.47

Np Likeness Score: -2.14

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