1-(3-Benzyl-pyrrolidin-1-yl)-2-(1H-indol-3-yl)-ethanone

ID: ALA32940

PubChem CID: 10336036

Max Phase: Preclinical

Molecular Formula: C21H22N2O

Molecular Weight: 318.42

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(Cc1c[nH]c2ccccc12)N1CCC(Cc2ccccc2)C1

Standard InChI:  InChI=1S/C21H22N2O/c24-21(13-18-14-22-20-9-5-4-8-19(18)20)23-11-10-17(15-23)12-16-6-2-1-3-7-16/h1-9,14,17,22H,10-13,15H2

Standard InChI Key:  TYSLMXDXDTVHKA-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 24 27  0  0  0  0  0  0  0  0999 V2000
    5.2625   -3.9417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.0125   -5.9917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2792   -4.7667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6250   -7.2750    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.3542   -6.4917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0000   -5.1667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6917   -6.4667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4500   -7.2542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9167   -3.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5875   -3.4750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5667   -5.1917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.6542   -2.6667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1292   -2.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8292   -2.6792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.9500   -2.0667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4917   -6.2875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0042   -7.8542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2917   -2.8167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4167   -1.3917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0542   -6.8792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.8125   -7.6750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2417   -1.4667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1167   -2.8917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5917   -2.2167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  6  1  0
  3  1  1  0
  4  5  1  0
  5  2  2  0
  6  3  1  0
  7  2  1  0
  8  7  2  0
  9  1  1  0
 10  1  1  0
 11  3  2  0
 12  9  1  0
 13 12  1  0
 14 10  1  0
 15 13  1  0
 16  7  1  0
 17  8  1  0
 18 15  2  0
 19 15  1  0
 20 16  2  0
 21 20  1  0
 22 19  2  0
 23 18  1  0
 24 22  1  0
 14 12  1  0
  8  4  1  0
 24 23  2  0
 21 17  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA32940

   1-(3-Benzyl-pyrrolidin-1-yl)-2-(1H-indol-3-yl)-ethanone

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: 318.42

Molecular Weight (Monoisotopic): 318.1732

AlogP: 3.80

#Rotatable Bonds: 4

Polar Surface Area: 36.10

Molecular Species: NEUTRAL

HBA: 1

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 3

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 3.70

CX LogD: 3.70

Aromatic Rings: 3

Heavy Atoms: 24

QED Weighted: 0.78

Np Likeness Score: -0.73

References

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2. Horwell DC, Naylor D, Willems HM.  (1997)  2,3-Substituted 2-azanorbornanes as polar -turn mimetics,  7  (1): [10.1016/S0960-894X(96)00570-7]

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4. Hale, J J JJ and 17 more authors.  1998-11-05  Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist.  [PMID:9804700]

5. Rumsey, W L WL and 16 more authors.  2001-07  Pharmacological characterization of ZD6021: a novel, orally active antagonist of the tachykinin receptors.  [PMID:11408556]

6. Watanabe, Yumi Y and 7 more authors.  2008-01  Pharmacological characterization of T-2328, 2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride, as a brain-penetrating antagonist of tachykinin NK1 receptor.  [PMID:18187929]

7. Yamamoto, Takashi and 11 more authors.  2008-10-23  The importance of micelle-bound states for the bioactivities of bifunctional peptide derivatives for delta/mu opioid receptor agonists and neurokinin 1 receptor antagonists.  [PMID:18821747]

8. Yamamoto, Takashi and 8 more authors.  2009-10-15  The biological activity and metabolic stability of peptidic bifunctional compounds that are opioid receptor agonists and neurokinin-1 receptor antagonists with a cystine moiety.  [PMID:19762245]

9. Huang, Shih-Chung SC and Korlipara, Vijaya L VL.  2010-08  Neurokinin-1 receptor antagonists: a comprehensive patent survey.  [PMID:20533894]

10. Yamamoto, Takashi and 12 more authors.  2009-08-27  Improving metabolic stability by glycosylation: bifunctional peptide derivatives that are opioid receptor agonists and neurokinin 1 receptor antagonists.  [PMID:20560643]

11. Yamamoto, Takashi and 11 more authors.  2010-08-12  Biological and conformational evaluation of bifunctional compounds for opioid receptor agonists and neurokinin 1 receptor antagonists possessing two penicillamines.  [PMID:20617791]

12. Keith, Dove J; Eshleman, Amy J and Janowsky, Aaron.  2011-01-15  Melittin stimulates fatty acid release through non-phospholipase-mediated mechanisms and interacts with the dopamine transporter and other membrane-spanning proteins.  [PMID:20969853]

13. Yamamoto, Takashi and 10 more authors.  2011-04-14  Discovery of a potent and efficacious peptide derivative for δ/μ opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies.  [PMID:21366266]

14. Ballet, Steven and 13 more authors.  2011-04-14  Design of novel neurokinin 1 receptor antagonists based on conformationally constrained aromatic amino acids and discovery of a potent chimeric opioid agonist-neurokinin 1 receptor antagonist.  [PMID:21413804]

15. Germain, Andrew R AR and 14 more authors.  2013-03-15  Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.  [PMID:23403082]

16. Di Fabio, Romano R and 15 more authors.  2013-11-01  Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.  [PMID:24075145]

17. Hanessian, Stephen S and 5 more authors.  2014-01-15  Design and synthesis of potential dual NK(1)/NK(3) receptor antagonists.  [PMID:24374277]

18. Guillemyn, Karel and 21 more authors.  2015-03-06  Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist - neurokinin-1 antagonist peptidomimetics.  [PMID:25544687]

19. Nair, Padma and 11 more authors.  2015-09-01  Discovery of tripeptide-derived multifunctional ligands possessing delta/mu opioid receptor agonist and neurokinin 1 receptor antagonist activities.  [PMID:26212775]

20. Giri, Aswini Kumar and 11 more authors.  2015-11-12  Discovery of Novel Multifunctional Ligands with μ/δ Opioid Agonist/Neurokinin-1 (NK1) Antagonist Activities for the Treatment of Pain.  [PMID:26465170]

Source

Source(1):

• Scientific Literature