8-(1R,3aR)-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one

ID: ALA412098

PubChem CID: 10763594

Max Phase: Preclinical

Molecular Formula: C26H31N3O

Molecular Weight: 401.55

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Ro-64-6198 | CHEMBL412098|BDBM21844|8-[(1R,3aR)-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one

Canonical SMILES:  O=C1NCN(c2ccccc2)C12CCN([C@@H]1CC[C@H]3CCCc4cccc1c43)CC2

Standard InChI:  InChI=1S/C26H31N3O/c30-25-26(29(18-27-25)21-9-2-1-3-10-21)14-16-28(17-15-26)23-13-12-20-7-4-6-19-8-5-11-22(23)24(19)20/h1-3,5,8-11,20,23H,4,6-7,12-18H2,(H,27,30)/t20-,23-/m1/s1

Standard InChI Key:  JLFMYEAXZNPWBK-NFBKMPQASA-N

Molfile:  

     RDKit          2D

 31 36  0  0  1  0  0  0  0  0999 V2000
   -2.7784    1.4726    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0662    1.8891    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2422    2.6952    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0633    2.7769    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3946    2.0213    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9163   -1.4245    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9175   -2.2515    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2047   -1.0118    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4897   -1.4208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0472   -2.2477    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0506   -1.4149    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7741   -0.9991    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4862   -2.2536    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2002   -2.6630    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2027   -3.4816    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4928   -3.8969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7787   -3.4875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7746   -2.6627    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0660   -3.0739    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7786   -0.1745    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0624    0.2373    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0650    1.0584    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4934    1.0556    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4925    0.2283    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3109    1.5578    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1947    1.8449    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7497    2.4564    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.5548    2.2810    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.8059    1.4945    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2458    0.8834    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4429    1.0619    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  1  0
  9  8  2  0
  8  6  1  0
 13 18  1  0
 14 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
  9 13  1  0
 18 19  1  6
  3  4  1  0
 12 20  1  6
 20 21  1  0
  4  5  1  0
  5  1  1  0
  1  2  1  0
  9 12  1  0
 20 24  1  0
 21 22  1  0
 22  1  1  0
  1 23  1  0
 23 24  1  0
 18 10  1  0
  2 25  2  0
 10 11  1  0
 11 12  1  0
 26 27  2  0
 13 14  2  0
 27 28  1  0
 28 29  2  0
  6  7  2  0
 29 30  1  0
  7 14  1  0
 30 31  2  0
 31 26  1  0
  5 26  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA412098

   8-[(1R,3aR)-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 401.55

Molecular Weight (Monoisotopic): 401.2467

AlogP: 4.37

#Rotatable Bonds: 2

Polar Surface Area: 35.58

Molecular Species: BASE

HBA: 3

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.83

CX Basic pKa: 9.34

CX LogP: 4.66

CX LogD: 2.73

Aromatic Rings: 2

Heavy Atoms: 30

QED Weighted: 0.81

Np Likeness Score: 0.09

References

1. Mustazza C, Borioni A, Sestili I, Sbraccia M, Rodomonte A, Del Giudice MR..  (2008)  Synthesis and pharmacological evaluation of 1,2-dihydrospiro[isoquinoline-4(3H),4'-piperidin]-3-ones as nociceptin receptor agonists.,  51  (4): [PMID:18232652] [10.1021/jm7009606]

2. Del Giudice MR, Borioni A, Bastanzio G, Sbraccia M, Mustazza C, Sestili I..  (2011)  Synthesis and pharmacological evaluation of bivalent antagonists of the nociceptin opioid receptor.,  46  (4): [PMID:21330016] [10.1016/j.ejmech.2011.01.040]

3. Zaveri NT..  (2016)  Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility.,  59  (15): [PMID:26878436] [10.1021/acs.jmedchem.5b01499]

4. Ghirmai, Senait; Azar, Marc R and Cashman, John R.  2009-09-15  Synthesis and pharmacological evaluation of 6-naltrexamine analogs for alcohol cessation.  [PMID:19683449]

5. Toll, Lawrence L and 5 more authors.  2009-12  Comparison of the antinociceptive and antirewarding profiles of novel bifunctional nociceptin receptor/mu-opioid receptor ligands: implications for therapeutic applications.  [PMID:19773529]

6. McLeod, Robbie L and 20 more authors.  2010-03-25  Pharmacological profile of the NOP agonist and cough suppressing agent SCH 486757 (8-[Bis(2-Chlorophenyl)Methyl]-3-(2-Pyrimidinyl)-8-Azabicyclo[3.2.1]Octan-3-Ol) in preclinical models.  [PMID:20006596]

7. Pike, Victor W and 14 more authors.  2011-04-28  Synthesis and evaluation of radioligands for imaging brain nociceptin/orphanin FQ peptide (NOP) receptors with positron emission tomography.  [PMID:21438532]

8. Cami-Kobeci, Gerta; Polgar, Willma E; Khroyan, Taline V; Toll, Lawrence and Husbands, Stephen M.  2011-10-13  Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine.  [PMID:21866885]

9. Zaveri, Nurulain T; Jiang, Faming; Olsen, Cris; Polgar, Willma E and Toll, Lawrence.  2013-06-01  Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP receptor-selective scaffolds. Part I.  [PMID:23623415]

10. Journigan, V Blair VB, Polgar, Willma E WE, Khroyan, Taline V TV and Zaveri, Nurulain T NT.  2014-04-15  Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP-receptor selective scaffolds. Part II.  [PMID:24657054]

11. Linz, Klaus K and 13 more authors.  2014-06  Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist.  [PMID:24713140]

12. Kumar, Vinod and 10 more authors.  2014-05-22  Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity.  [PMID:24761755]

13. Cueva, Juan Pablo and 8 more authors.  2015-05-28  C7β-methyl analogues of the orvinols: the discovery of kappa opioid antagonists with nociceptin/orphanin FQ peptide (NOP) receptor partial agonism and low, or zero, efficacy at mu opioid receptors.  [PMID:25898137]

14. and Zaveri, Nurulain T NT.  2016-08-11  Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility.  [PMID:26878436]

15. Guillemyn, Karel and 18 more authors.  2016-04-28  Bifunctional Peptide-Based Opioid Agonist-Nociceptin Antagonist Ligands for Dual Treatment of Acute and Neuropathic Pain.  [PMID:27035422]

16. Arcuri, Ludovico L and 12 more authors.  2018-03  Anti-Parkinsonian and anti-dyskinetic profiles of two novel potent and selective nociceptin/orphanin FQ receptor agonists.  [PMID:29232769]

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

18. Kamakolanu, Uma Gayathri and 9 more authors.  2020-03-12  Discovery and Structure-Activity Relationships of Nociceptin Receptor Partial Agonists That Afford Symptom Ablation in Parkinson's Disease Models.  [PMID:31951130]

Source

Source(1):

• Scientific Literature