Chemical design of peripherally acting compounds

W. Roy Jackson; Fred C. Copp; John D. Cullen; Frances J. Guyett; Ian D. Rae; Andrea J. Robinson; Helen Pothoulackis; Algirdas K. Serelis; Margaret Wong

doi:10.1111/j.1440-1681.1992.tb00392.x

Chemical design of peripherally acting compounds

W. Roy Jackson, Fred C. Copp, John D. Cullen, Frances J. Guyett, Ian D. Rae, Andrea J. Robinson, Helen Pothoulackis, Algirdas K. Serelis, Margaret Wong

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

13 Citations (Scopus)

Abstract

1. Some guanidines, related in structure to mianserin and to 2‐methyl‐1,2,9,13b‐tetrahydro‐3H‐dibenz[c,f]irnadazo[l,5a]azepin‐3‐imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5‐HT₂ antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity. 2. Computer‐aided molecular modelling has been used to establish a 5‐HT₂ pharmacophore. 3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.

Original language	English
Pages (from-to)	17-23
Number of pages	7
Journal	Clinical and Experimental Pharmacology and Physiology
Volume	19
Issue number	1
DOIs	https://doi.org/10.1111/j.1440-1681.1992.tb00392.x
Publication status	Published - 1 Jan 1992

Keywords

analgesics
peripherally acting drugs
S‐HT antagonists

Access to Document

10.1111/j.1440-1681.1992.tb00392.x

Link to publication in Scopus

Cite this

Jackson, W. R., Copp, F. C., Cullen, J. D., Guyett, F. J., Rae, I. D., Robinson, A. J., Pothoulackis, H., Serelis, A. K., & Wong, M. (1992). Chemical design of peripherally acting compounds. Clinical and Experimental Pharmacology and Physiology, 19(1), 17-23. https://doi.org/10.1111/j.1440-1681.1992.tb00392.x

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abstract = "1. Some guanidines, related in structure to mianserin and to 2‐methyl‐1,2,9,13b‐tetrahydro‐3H‐dibenz[c,f]irnadazo[l,5a]azepin‐3‐imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5‐HT2 antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity. 2. Computer‐aided molecular modelling has been used to establish a 5‐HT2 pharmacophore. 3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.",

keywords = "analgesics, peripherally acting drugs, S‐HT antagonists",

author = "Jackson, {W. Roy} and Copp, {Fred C.} and Cullen, {John D.} and Guyett, {Frances J.} and Rae, {Ian D.} and Robinson, {Andrea J.} and Helen Pothoulackis and Serelis, {Algirdas K.} and Margaret Wong",

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doi = "10.1111/j.1440-1681.1992.tb00392.x",

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Chemical design of peripherally acting compounds. / Jackson, W. Roy; Copp, Fred C.; Cullen, John D.; Guyett, Frances J.; Rae, Ian D.; Robinson, Andrea J.; Pothoulackis, Helen; Serelis, Algirdas K.; Wong, Margaret.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 19, No. 1, 01.01.1992, p. 17-23.

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

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AU - Copp, Fred C.

AU - Cullen, John D.

AU - Guyett, Frances J.

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AU - Robinson, Andrea J.

AU - Pothoulackis, Helen

AU - Serelis, Algirdas K.

AU - Wong, Margaret

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AB - 1. Some guanidines, related in structure to mianserin and to 2‐methyl‐1,2,9,13b‐tetrahydro‐3H‐dibenz[c,f]irnadazo[l,5a]azepin‐3‐imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5‐HT2 antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity. 2. Computer‐aided molecular modelling has been used to establish a 5‐HT2 pharmacophore. 3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.

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