Eli Lilly and Company

Independent Pharmaceutica Ab

Anette Margareta Johansson

Peter Thaddeus Gallagher

Sandra Ann Filla

Serge Louis Boulet

John Joseph Masters

Brian Michael Mathes

Maria Ann Whatton

Richard Edmund Rathmell

Kevin John Hudziak

Victor Giulio Matassa

Rushad Eruch Karanjawala

Chad Nolan Wolfe

Barry P Clark

John Fairhurst

Magnus Wilhelm Walter

Nicolas Jacques Francois Dreyfus

Eric George Tromiczak

Virginia Ann Wood

Torgny Svensson

Jikesh Arvind Shah

Thierry J Masquelin

Maria Ann (nee Fagan) Whatton

Barry Peter Clark

A serotonin and norepinephrine reuptake inhibitor of the formula: its uses, and methods for its preparation are described.

Serotonin and norepinephrine reuptake inhibitor

The present invention provides compounds of formula (I) where n, R1, R2, R3, R4, R5 and Heteroaryl are defined herein. The compounds are inhibitors of the uptake of one or more monoamines selected from serotonin, norepinephrine and dopamine and, as such, may be useful in the treatment of disorders of the central and/or peripheral nervous system. 

4-Amino-piperidine derivatives as monoamine uptake inhibitors

There is provided a compound of formula (I) wherein A is selected from &#x2014;O&#x2014; and &#x2014;S&#x2014;; X is selected from C-Calkyl, C-Calkenyl, C-Ccycloalkyl and C-Ccycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C-Calkyl, C-Calkoxy, C-Calkyl-S(O)&#x2014; where n is 0, 1 or 2, &#x2014;CF, &#x2014;CN and &#x2014;CONH; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, 5 substituents each independently selected from halo, C-Calkyl, C-Calkoxy, C-Calkyl-S(O)&#x2014; where n is 0, 1 or 2, nitro, acetyl, &#x2014;CF, &#x2014;SCFand cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C-Calkyl; Z is selected from H, ORor F, wherein Ris selected from H, C-Calkyl and phenyl C-Calkyl; Rand Rare each independently H or C-Calkyl; with the proviso that, when Z is H, then Y may not be optionally substituted phenyl or optionally substituted naphthyl. 

3-aryloxy/thio-3-substituted propanamines and their use in inhibiting serotonin and norepinephrine reuptake

There is provided a compound of formula (I) wherein A is selected from &#x2014;O&#x2014; and &#x2014;S&#x2014;; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C-Calkyl and C-Calkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C-Calkyl, and C-Calkyl, C-Calkenyl, C-Ccycloalkyl and C-Ccycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C-Calkyl, C-Calkoxy, C-Calkyl-S(O)&#x2014; where n is 0, 1 or 2, &#x2014;CF, &#x2014;CN and &#x2014;CONH; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C-Calkyl, C-Calkoxy, C-Calkyl-S(O)&#x2014; where n is 0, 1 or 2, nitro, acetyl, &#x2014;CF, &#x2014;SCFand cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C-Calkyl; Z is selected from ORor F, wherein Ris selected from H, C-Calkyl and phenyl C-Calkyl; Rand Rare each independently H or C-Calkyl; and pharmaceutically acceptable salts thereof with the proviso that when Y is optionally substituted phenyl or optionally substituted 1,3-benzodioxolyl and Z is ORand X is optionally substituted phenyl then A is &#x2014;S&#x2014;. 

3-aryloxy/thio-2,3-substituted propanamines and their use in inhibiting serotonin and norepinephrine reuptake

There is provided a heretoaryloxy/thio 3-substituted propanamine compound of formula (I) wherein A is selected from &#x2014;O&#x2014; and &#x2014;S&#x2014;; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C-Calkyl and C-Calkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C-Calkyl, and C-Calkyl, C-Calkenyl, C-Ccycloalkyl and C-Ccycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C-Calkyl, C-Calkoxy, C-Calkyl &#x2014;S(O)&#x2014; where n is 0, 1 or 2, &#x2014;CF, &#x2014;CN and &#x2014;CONH; Y is selected from dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, and thienopyridyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C-Calkyl, C-Calkoxy, C-Calkyl-S(O)&#x2014; where n is 0, 1 or 2, nitro acetyl, &#x2014;CF, &#x2014;SCFand cyano; Z is selected from H, ORor F, wherein Ris selected from H, C-Calkyl and phenyl CCalkyl; Rand Rare each independently H or C-Calkyl; and pharmaceutically acceptable salts thereof. 

Propanamine derivatives as serotonin and norepinephrine reuptake inhibitors

A method of producing a 6-substituted (S)-nicotine derivative with the general formula (III), wherein R is an optionally substituted alkyl, alkenyl, alkynyl, amido or amino group, optionally coupled to a carrier protein, is disclosed. An intermediate compound useful in the method is also comprised by the invention. The formula of the compound is (A) in which A represents the cationic radical of an organic nitrogen base, Y represents an anion formed by an electrophilic compound.

Method of producing 6-substituted (s)-nicotine derivatives and intermediate compounds

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Indianapolis, IN, United States of America

Anette Margareta Johansson