Stereochemical Studies on Medicinal Agents. 19. The X-Ray Crystal Structures of Two (±)-Allylprodine Diastereomers. The Role of the Allyl Group in Conferring High Stereoselectivity and Potency at Analgetic Receptors

Philip S Portoghese, Eli Shefter

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16 Citations (Scopus)

Abstract

X-Ray crystallographic studies have been performed on the two diasteromeric racemates of 3-allyl-1-methyl-4-propionoxypiperidine hydrochloride (allylprodine hydrochloride) in an effort to determine the role of conformation in their interaction with analgetic receptor sites. The chiral orientation of the phenyl group in the highly potent isomer, (+)-1, is qualitatively in conformity with the stereostructure-activity relationship found among other analgetic 4-phenylpiperidines. The fact that (+)-2, a relatively weak analgetic with no stereoselectivity, also possesses this feature indicates that this conformational arrangement per se does not ensure high potency. The data suggest that the very high potency and stereoselectivity which the allylic double bond confers to (+)-1 are due primarily to the interaction of this bond with an accessory site on the receptor.

Original languageEnglish (US)
Pages (from-to)55-57
Number of pages3
JournalJournal of Medicinal Chemistry
Volume19
Issue number1
DOIs
StatePublished - Jan 1 1976

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title = "Stereochemical Studies on Medicinal Agents. 19. The X-Ray Crystal Structures of Two (±)-Allylprodine Diastereomers. The Role of the Allyl Group in Conferring High Stereoselectivity and Potency at Analgetic Receptors",
abstract = "X-Ray crystallographic studies have been performed on the two diasteromeric racemates of 3-allyl-1-methyl-4-propionoxypiperidine hydrochloride (allylprodine hydrochloride) in an effort to determine the role of conformation in their interaction with analgetic receptor sites. The chiral orientation of the phenyl group in the highly potent isomer, (+)-1, is qualitatively in conformity with the stereostructure-activity relationship found among other analgetic 4-phenylpiperidines. The fact that (+)-2, a relatively weak analgetic with no stereoselectivity, also possesses this feature indicates that this conformational arrangement per se does not ensure high potency. The data suggest that the very high potency and stereoselectivity which the allylic double bond confers to (+)-1 are due primarily to the interaction of this bond with an accessory site on the receptor.",
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AU - Shefter, Eli

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N2 - X-Ray crystallographic studies have been performed on the two diasteromeric racemates of 3-allyl-1-methyl-4-propionoxypiperidine hydrochloride (allylprodine hydrochloride) in an effort to determine the role of conformation in their interaction with analgetic receptor sites. The chiral orientation of the phenyl group in the highly potent isomer, (+)-1, is qualitatively in conformity with the stereostructure-activity relationship found among other analgetic 4-phenylpiperidines. The fact that (+)-2, a relatively weak analgetic with no stereoselectivity, also possesses this feature indicates that this conformational arrangement per se does not ensure high potency. The data suggest that the very high potency and stereoselectivity which the allylic double bond confers to (+)-1 are due primarily to the interaction of this bond with an accessory site on the receptor.

AB - X-Ray crystallographic studies have been performed on the two diasteromeric racemates of 3-allyl-1-methyl-4-propionoxypiperidine hydrochloride (allylprodine hydrochloride) in an effort to determine the role of conformation in their interaction with analgetic receptor sites. The chiral orientation of the phenyl group in the highly potent isomer, (+)-1, is qualitatively in conformity with the stereostructure-activity relationship found among other analgetic 4-phenylpiperidines. The fact that (+)-2, a relatively weak analgetic with no stereoselectivity, also possesses this feature indicates that this conformational arrangement per se does not ensure high potency. The data suggest that the very high potency and stereoselectivity which the allylic double bond confers to (+)-1 are due primarily to the interaction of this bond with an accessory site on the receptor.

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