1-(3,4-dichlorophenyl)-N-(3-(trifluoromethyl)benzyl)-1H-indazole-4-carboxamide

ID: ALA4557554

PubChem CID: 58138911

Max Phase: Preclinical

Molecular Formula: C22H14Cl2F3N3O

Molecular Weight: 464.27

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  O=C(NCc1cccc(C(F)(F)F)c1)c1cccc2c1cnn2-c1ccc(Cl)c(Cl)c1

Standard InChI:  InChI=1S/C22H14Cl2F3N3O/c23-18-8-7-15(10-19(18)24)30-20-6-2-5-16(17(20)12-29-30)21(31)28-11-13-3-1-4-14(9-13)22(25,26)27/h1-10,12H,11H2,(H,28,31)

Standard InChI Key:  IIJWGWHORFYKGB-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 31 34  0  0  0  0  0  0  0  0999 V2000
    3.0362   -3.4049    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0351   -4.2245    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7431   -4.6334    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7413   -2.9961    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4500   -3.4013    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4547   -4.2199    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2348   -4.4684    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.7121   -3.8033    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2270   -3.1439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7389   -2.1789    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4454   -1.7682    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.0300   -1.7724    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.4429   -0.9510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1494   -0.5403    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8553   -0.9466    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5613   -0.5366    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5593    0.2881    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8454    0.6908    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1424    0.2777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2735   -0.9429    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9184   -1.3130    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    7.4119   -1.7856    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    8.0710   -0.6374    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    5.4905   -5.2395    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9455   -5.8499    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2020   -6.6250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0031   -6.7909    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5472   -6.1755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2878   -5.4028    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2611   -7.5663    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    7.3481   -6.3379    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  6  2  0
  5  4  2  0
  4  1  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  2  0
  9  5  1  0
  4 10  1  0
 10 11  1  0
 10 12  2  0
 11 13  1  0
 13 14  1  0
 14 15  2  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 14  1  0
 20 21  1  0
 20 22  1  0
 20 23  1  0
 16 20  1  0
 24 25  2  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28 29  2  0
 29 24  1  0
  7 24  1  0
 27 30  1  0
 28 31  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4557554

   1-(3,4-dichlorophenyl)-N-[[3-(trifluoromethyl)phenyl]methyl]indazole-4-carboxamide

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: 464.27

Molecular Weight (Monoisotopic): 463.0466

AlogP: 6.28

#Rotatable Bonds: 4

Polar Surface Area: 46.92

Molecular Species: NEUTRAL

HBA: 3

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 0.11

CX LogP: 5.96

CX LogD: 5.96

Aromatic Rings: 4

Heavy Atoms: 31

QED Weighted: 0.39

Np Likeness Score: -2.03

References

1. Harcken C, Kuzmich D, Cook B, Mao C, Disalvo D, Razavi H, Swinamer A, Liu P, Zhang Q, Kukulka A, Skow D, Patel M, Patel M, Fletcher K, Sherry T, Joseph D, Smith D, Canfield M, Souza D, Bogdanffy M, Berg K, Brown M..  (2019)  Identification of novel azaindazole CCR1 antagonist clinical candidates.,  29  (3): [PMID:30595446] [10.1016/j.bmcl.2018.12.024]

2. Ng, H P HP and 10 more authors.  1999-11-04  Discovery of novel non-peptide CCR1 receptor antagonists.  [PMID:10579830]

3. Sabroe, I I and 7 more authors.  2000-08-25  A small molecule antagonist of chemokine receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry.  [PMID:10854442]

4. Naya, A A and 7 more authors.  2001-04-26  Design, synthesis, and discovery of a novel CCR1 antagonist.  [PMID:11311066]

5. Gladue, Ronald P RP and 19 more authors.  2003-10-17  CP-481,715, a potent and selective CCR1 antagonist with potential therapeutic implications for inflammatory diseases.  [PMID:12909630]

6. Revesz, Laszlo L and 12 more authors.  2005-12-01  Novel CCR1 antagonists with oral activity in the mouse collagen induced arthritis.  [PMID:16198561]

7. Xie, Yun Feng YF and 15 more authors.  2007-06-15  Structure-activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists.  [PMID:17446072]

8. Liu, Huaqing H and 18 more authors.  2008-11-27  cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.  [PMID:18983139]

9. Merritt, J Robert JR and 19 more authors.  2009-03-12  Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists.  [PMID:19183043]

10. Furber, Mark M and 15 more authors.  2012-12-15  Discovery and evolution of phenoxypiperidine hydroxyamide dual CCR3/H₁ antagonists. Part I.  [PMID:23142617]

11. Gardner, Daniel S DS and 23 more authors.  2013-07-01  The discovery of BMS-457, a potent and selective CCR1 antagonist.  [PMID:23707259]

12. Santella, Joseph B JB and 26 more authors.  2014-09-25  Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis.  [PMID:25101488]

13. Gege, Christian and 15 more authors.  2018-05-15  Identification and biological evaluation of thiazole-based inverse agonists of RORγt.  [PMID:29631962]

14. Ortiz Zacarías, Natalia V and 12 more authors.  2018-10-25  Pyrrolone Derivatives as Intracellular Allosteric Modulators for Chemokine Receptors: Selective and Dual-Targeting Inhibitors of CC Chemokine Receptors 1 and 2.  [PMID:30256641]

15. Harcken, Christian C and 21 more authors.  2019-02-01  Discovery and optimization of pyrazole amides as antagonists of CCR1.  [PMID:30455146]

16. Harcken, Christian C and 21 more authors.  2019-02-01  Identification of novel azaindazole CCR1 antagonist clinical candidates.  [PMID:30595446]

Source

Source(1):

• Scientific Literature