Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinan

S K Srivastava; [No Value] Shefali; C N Miller; M D Aceto; J R Traynor; J W Lewis; S M Husbands

doi:10.1021/jm040817t

Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinan

S K Srivastava
, [No Value] Shefali
, C N Miller
, M D Aceto
, J R Traynor
, J W Lewis
, S M Husbands

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

24 Citations (SciVal)

Abstract

The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4‘-phenyl-6,7:2‘,3‘-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent δ opioid receptor (DOR) antagonists while the TNTI derivatives (7) were potent DOR antagonists or low-efficacy DOR partial agonists without substantial selectivity. The TOMI derivatives (8) were DOR agonists with significant selectivity. In vivo the DOR antagonist activity of 7d was confirmed, but the predominant agonist effect of 8d was shown to be μ opioid receptor mediated.

Original language	English
Pages (from-to)	6645-6648
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	47
DOIs	https://doi.org/10.1021/jm040817t
Publication status	Published - 2004

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@article{4c31541e10e0426cad7f99fa5faf6dda,

title = "Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinan",

abstract = "The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4{\textquoteleft}-phenyl-6,7:2{\textquoteleft},3{\textquoteleft}-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent δ opioid receptor (DOR) antagonists while the TNTI derivatives (7) were potent DOR antagonists or low-efficacy DOR partial agonists without substantial selectivity. The TOMI derivatives (8) were DOR agonists with significant selectivity. In vivo the DOR antagonist activity of 7d was confirmed, but the predominant agonist effect of 8d was shown to be μ opioid receptor mediated. ",

author = "Srivastava, \{S K\} and Shefali, \{[No Value]\} and Miller, \{C N\} and Aceto, \{M D\} and Traynor, \{J R\} and Lewis, \{J W\} and Husbands, \{S M\}",

year = "2004",

doi = "10.1021/jm040817t",

language = "English",

volume = "47",

pages = "6645--6648",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

}

TY - JOUR

T1 - Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinan

AU - Srivastava, S K

AU - Shefali, [No Value]

AU - Miller, C N

AU - Aceto, M D

AU - Traynor, J R

AU - Lewis, J W

AU - Husbands, S M

PY - 2004

Y1 - 2004

N2 - The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4‘-phenyl-6,7:2‘,3‘-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent δ opioid receptor (DOR) antagonists while the TNTI derivatives (7) were potent DOR antagonists or low-efficacy DOR partial agonists without substantial selectivity. The TOMI derivatives (8) were DOR agonists with significant selectivity. In vivo the DOR antagonist activity of 7d was confirmed, but the predominant agonist effect of 8d was shown to be μ opioid receptor mediated.

AB - The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4‘-phenyl-6,7:2‘,3‘-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent δ opioid receptor (DOR) antagonists while the TNTI derivatives (7) were potent DOR antagonists or low-efficacy DOR partial agonists without substantial selectivity. The TOMI derivatives (8) were DOR agonists with significant selectivity. In vivo the DOR antagonist activity of 7d was confirmed, but the predominant agonist effect of 8d was shown to be μ opioid receptor mediated.

U2 - 10.1021/jm040817t

DO - 10.1021/jm040817t

M3 - Article

SN - 0022-2623

VL - 47

SP - 6645

EP - 6648

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

ER -

Effects of substitution on the pyrrole N atom in derivatives of tetrahydronaltrindole, tetrahydrooxymorphindole, and a related 4,5-epoxyphenylpyrrolomorphinan

Abstract

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