cis-1-((1-(1-(4-Isopropylcyclohexyl)piperidin-4-yl)-1H-indol-3-yl)methyl)azetidin-3-ol

ID: ALA4556227

PubChem CID: 134563496

Max Phase: Preclinical

Molecular Formula: C26H39N3O

Molecular Weight: 409.62

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC(C)[C@H]1CC[C@@H](N2CCC(n3cc(CN4CC(O)C4)c4ccccc43)CC2)CC1

Standard InChI:  InChI=1S/C26H39N3O/c1-19(2)20-7-9-22(10-8-20)28-13-11-23(12-14-28)29-16-21(15-27-17-24(30)18-27)25-5-3-4-6-26(25)29/h3-6,16,19-20,22-24,30H,7-15,17-18H2,1-2H3/t20-,22+

Standard InChI Key:  LCHNDEARQJNFQA-GRGXKFILSA-N

Molfile:  

 
     RDKit          2D

 30 34  0  0  0  0  0  0  0  0999 V2000
   21.4342   -3.4662    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.9305   -2.8188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1590   -3.0991    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.9780   -4.1482    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1906   -3.9190    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.6020   -4.4883    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.7995   -5.2829    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.5910   -5.5050    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.1763   -4.9341    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.2510   -3.4377    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.6878   -4.1321    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.5051   -4.1048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.8918   -3.3845    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   23.4592   -2.6860    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.6357   -2.7119    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.7107   -3.3526    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.1448   -4.0528    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.9622   -4.0286    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.3517   -3.3057    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.9217   -2.6096    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.0981   -2.6324    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.1727   -3.2825    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.6053   -3.9824    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.5652   -2.5593    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4808   -2.6433    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7469   -3.0026    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   17.9721   -2.7360    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.7073   -3.5091    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.4804   -3.7740    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.9734   -3.8685    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  4  1  1  0
  1  2  1  0
  2  3  2  0
  3  5  1  0
  4  5  2  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  8  9  2  0
  9  4  1  0
 10 11  1  0
 10 15  1  0
 11 12  1  0
 12 13  1  0
 13 14  1  0
 14 15  1  0
  1 10  1  0
 16 17  1  0
 16 21  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 16 13  1  6
 19 22  1  6
 22 23  1  0
 22 24  1  0
  3 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  1  0
 29 26  1  0
 28 30  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4556227

   ---

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: 409.62

Molecular Weight (Monoisotopic): 409.3093

AlogP: 4.67

#Rotatable Bonds: 5

Polar Surface Area: 31.64

Molecular Species: BASE

HBA: 4

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 10.35

CX LogP: 4.28

CX LogD: 1.36

Aromatic Rings: 2

Heavy Atoms: 30

QED Weighted: 0.78

Np Likeness Score: -0.51

References

1. Kamakolanu UG, Meyer ME, Yasuda D, Polgar WE, Marti M, Mercatelli D, Pisanò CA, Brugnoli A, Morari M, Zaveri NT..  (2020)  Discovery and Structure-Activity Relationships of Nociceptin Receptor Partial Agonists That Afford Symptom Ablation in Parkinson's Disease Models.,  63  (5): [PMID:31951130] [10.1021/acs.jmedchem.9b02134]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

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

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

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

16. 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