Pfizer Corporation

Other

David Alker

Peter E Cross

Simon F Campbell

Robert M Wallis

Robert J Bass

Sandra Marina Monaghan

Christopher John Burns

Donald Stuart Middleton

Alexander Roderick MacKenzie

Graham Nigel Maw

John Edward Kemp

Kelvin Cooper

Thomas Victor Magee

Quaternary ammonium compounds

Azetidinylpropylpiperidine derivatives, intermediates and use as tachykinin antagonists

The present invention provides a compound of formula (I) wherein R is phenyl, C,-C,cycloalkyl or heteroaryl, each of which being optionally benzo- or C,-C,cycloalkyl-fused and optionally substituted, including in the benzo- or C,-C,cycloalkyl-fused portion, by from 1 to 3 substituents each independently selected from C,-C,alkyl, fluoro(C,-C,)alkyl, C,-C,alkoxy, fluoro(C,-C,)alkoxy, phenoxy, C,-C,alkanoyl, halo, C,-C,alkoxycarbonyl, C,-C,cycloalkyl, &mdash;S(O),(C,-C,alkyl), cyano, &mdash;NR,R,, &mdash;S(O),NR,R,, &mdash;NR,(C,-C,alkanoyl) and &mdash;CONR,R,, or R is 2,3-dihydrobenzo&lsqb;b&rsqb;furanyl or chromanyl; R,is H or C,-C,alkyl; W is a direct link, methylene or ethylene; X is unbranched C,-C,alkylene; Y is phenyl, naphthyl, benzyl, pyridyl, thienyl or C,-C,cycloalkyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C,-C,alkyl, fluoro(C,-C,)alkyl, C,-C,alkoxy, fluoro(C,-C,)alkoxy, halo and cyano; Ar is phenyl, naphthyl, benzyl, thienyl, benzo&lsqb;b&rsqb;thienyl or indolyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C,-C,alkyl, fluoro(C,-C,)alkyl, C,-C,alkoxy, fluoro(C,-C,)alkoxy, halo and cyano, or Ar is 1,3-benzodioxolan-4 or 5-yl or 1,4-benzodioxan-5 or 6-yl; Z,is a pharmaceutically acceptable anion; with the proviso that when W is a direct link and R is optionally fused and optionally substituted heteroaryl, said heteroaryl is linked by a ring carbon atom to the carbonyl group. The compounds are tachykinin antagonists.

Quaternary ammonium compounds as tachykinin antagonists

The invetion is a method of treating irritable bowel syndrome with a compound selected from the formula ##STR1## wherein R, R.sup.1, m, n p are as defined in the specification, or a pharmaceutically acceptable salt thereof.

Muscarinic receptor antagonists

Synthetic intermediates of 1-arylethyl-3-substituted piperidines. The Intermediates include the 3R,S- and 3R-forms of the compounds having the following formulae: ##STR1##

1-arylethyl-3-substituted piperidines

Selective muscarinic receptor antagonists of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are both optionally substituted phenyl, the broken line is an optional bond, X is &gt;COH--, &gt;SiOH-- or CH-- when the double bond is absent or is &gt;C.dbd. when the double bond is present, X being attached to a carbon atom of A, A is selected from certain piperidine and pyrrolidine groups, n is 1 to 3 and R.sup.3 is optionally substituted phenyl or thienyl, pyridyl or pyrazinyl.

Anticholinergic agents

A compound of the formula ##STR1## wherein X, R.sup.1, R.sup.2, R.sup.3, R.sup..sup.4, Y, m and n are defined herein are useful as muscarinic receptor antagonists.

Synthetic intermediates of 1-arylethyl-3-substituted piperidines. The Intermediates includes the 3R,S- and 3R-forms of the compounds having the following formulae: ##STR1##

Certain 1-azabicyclo[2.2.1]heptanes useful as muscarinic receptor

Imidazopyridine PAF/H.sub.1 antagonists

Piperidine and pyrrolidine derivatives

A series of novel 1-(phenethyl) and 1-(2-heteroarylethyl)-3-substituted piperidine derivatives have been prepared, including their pharmaceutically acceptable salts and various novel key intermediates therefor. The 3-substituent present in these compounds is an unsubstituted or substituted diphenylmethoxy group or a diphenylmethoxy-derived group, while the 1-substituent is unsubstituted or substituted phenethyl or 1-(2-heteroarylethyl) wherein the heteroaryl moiety is thienyl, pyridyl or pyrazinyl. These compounds in the form of both their racemates and 3R-isomers, are useful in therapy as smooth muscle muscarinic receptor antagonists and therefore, are of value in the treatment diseases associated with altered motility and/or smooth muscle tone.

Certain amines which are muscarinic receptor antagonists

A series of novel 1-(phenethyl) and 1-(1-heteroarylethyl)-3-substituted piperidine derivatives have been prepared, including their pharmaceutically acceptable salts and various novel key intermediates therefor. The 3-substituent present in these compounds is an unsubstituted or substituted diphenylmethoxy group or a diphenylmethoxy-derived group, while the 1-substituent is unsubstituted or substituted phenethyl or 1-(2-heteroarylethyl) wherein the heteroaryl moiety is thienyl, pyridyl or pyrazinyl. These compounds in the form of both their racemates and 3R-isomers, are useful in therapy as smooth muscle muscarinic receptor antagonists and therefore, are of value in the treatment diseases associated with altered motility and/or smooth muscle tone. The most preferred compound is (3R)-diphenylmethoxy-1-(3,4-methylenedioxyphenethyl)piperidine. Methods for preparing these compounds from known starting materials are provided.

The invention provides compounds of the formula: ##STR1## wherein k is 1, 2 or 3;

Growing community of inventors

Birchington, United Kingdom

David Alker