4-(2,3-Dichlorophenyl)-N-(1H-indazol-5-yl)piperazine-1-carboxamide

ID: ALA5197704

PubChem CID: 168288198

Max Phase: Preclinical

Molecular Formula: C18H17Cl2N5O

Molecular Weight: 390.27

Names and Identifiers

Canonical SMILES:  O=C(Nc1ccc2[nH]ncc2c1)N1CCN(c2cccc(Cl)c2Cl)CC1

Standard InChI:  InChI=1S/C18H17Cl2N5O/c19-14-2-1-3-16(17(14)20)24-6-8-25(9-7-24)18(26)22-13-4-5-15-12(10-13)11-21-23-15/h1-5,10-11H,6-9H2,(H,21,23)(H,22,26)

Standard InChI Key:  FWKPVZBGIQUFFA-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 26 29  0  0  0  0  0  0  0  0999 V2000
    4.5756    0.4320    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    3.8581    0.8393    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1443    0.4173    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4268    0.8330    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4268    1.6623    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1370    2.0759    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8581    1.6686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7130    0.4195    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7130   -0.4054    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9988   -0.8210    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2779   -0.4115    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.2779    0.4174    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9990    0.8330    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4358   -0.8251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4358   -1.6501    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1510   -0.4136    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8648   -0.8271    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5809   -0.4163    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2970   -0.8260    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2970   -1.6568    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5809   -2.0759    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8648   -1.6568    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0872   -1.9134    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5756   -1.2414    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0872   -0.5692    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1443   -0.4076    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  3  2  1  0
  4  3  2  0
  4  5  1  0
  6  5  2  0
  2  7  2  0
  7  6  1  0
  4  8  1  0
  9  8  1  0
 10  9  1  0
 11 10  1  0
 11 12  1  0
  8 13  1  0
 13 12  1  0
 11 14  1  0
 14 15  2  0
 14 16  1  0
 17 16  1  0
 18 17  2  0
 19 18  1  0
 19 20  2  0
 20 21  1  0
 17 22  1  0
 22 21  2  0
 20 23  1  0
 23 24  1  0
 24 25  2  0
 19 25  1  0
 26  3  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5197704

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 390.27

Molecular Weight (Monoisotopic): 389.0810

AlogP: 4.22

#Rotatable Bonds: 2

Polar Surface Area: 64.26

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.11

CX Basic pKa: 1.70

CX LogP: 3.59

CX LogD: 3.59

Aromatic Rings: 3

Heavy Atoms: 26

QED Weighted: 0.69

Np Likeness Score: -2.26

References

1. Liang Q, Qiao Z, Zhou Q, Xue D, Wang K, Shao L..  (2022)  Discovery of Potent and Selective Transient Receptor Potential Vanilloid 1 (TRPV1) Agonists with Analgesic Effects In Vivo Based on the Functional Conversion Induced by Altering the Orientation of the Indazole Core.,  65  (17.0): [PMID:36008373] [10.1021/acs.jmedchem.2c00469]

2. Caterina, M J MJ and 5 more authors.  1997-10-23  The capsaicin receptor: a heat-activated ion channel in the pain pathway.  [PMID:9349813]

3. McIntyre, P P and 14 more authors.  2001-03  Pharmacological differences between the human and rat vanilloid receptor 1 (VR1).  [PMID:11226139]

4. Valenzano, Kenneth J KJ and 12 more authors.  2003-07  N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: I. in vitro characterization and pharmacokinetic properties.  [PMID:12721338]

5. Voets, Thomas T and 5 more authors.  2004-08-12  The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels.  [PMID:15306801]

6. Fletcher, Stephen Robert SR and 10 more authors.  2006-06-01  The search for novel TRPV1-antagonists: from carboxamides to benzimidazoles and indazolones.  [PMID:16563760]

7. Gunthorpe, Martin J MJ and 15 more authors.  2007-06  Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor.  [PMID:17392405]

8. Rogosch, Tobias and 10 more authors.  2012-01-01  Novel bioactive metabolites of dipyrone (metamizol).  [PMID:22172309]

9. Dorange, Ismet I and 8 more authors.  2012-11-15  Discovery of novel pyrrolopyridazine scaffolds as transient receptor potential vanilloid (TRPV1) antagonists.  [PMID:23058884]

10. Han, Sangdon S, Thatte, Jayant J, Buzard, Daniel J DJ and Jones, Robert M RM.  2013-11-14  Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.  [PMID:23865723]

11. Washburn, David G DG and 22 more authors.  2013-09-01  The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore.  [PMID:23886683]

12. Lim, Kwang Su and 11 more authors.  2013-10  The carbonate analogues of 5'-halogenated resiniferatoxin as TRPV1 ligands.  [PMID:23981530]

13. Voight, Eric A EA and 27 more authors.  2014-09-11  Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy.  [PMID:25100568]

14. Rose, Tyler M; Reilly, Christopher A; Deering-Rice, Cassandra E; Brewster, Clinton and Brewster, Chelsea.  2014-12-15  Inhibition of FAAH, TRPV1, and COX2 by NSAID-serotonin conjugates.  [PMID:25467164]

15. Pereira, Gustavo José Vasco GJV and 10 more authors.  2019-07-01  Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: Design, synthesis and molecular modeling.  [PMID:31104785]

16. Lee, Hobin and 13 more authors.  2019-11-15  Discovery of dual-acting opioid ligand and TRPV1 antagonists as novel therapeutic agents for pain.  [PMID:31472474]

Source

Source(1):

• Scientific Literature