Janssen Pharmaceutica Nv

Other

Frans Josef Cornelius Compernolle

Georges Joseph Cornelius Hoornaert

Tomasz Kozlecki

Hua Mao

Andrés Avelino Trabanco-Suárez

José Maria Cid-Núñez

Francisco Javier Fernández-Gadea

Mohamed Koukni

Sushil Chandra Jha

Jan Heeres

Paul Adriaan Jan Janssen

Lucien Maria Henricus Koymans

Paulus Joannes Lewi

Koen Jeanne Alfons Van Aken

Marc René De Jonge

Amuri Kilonda

Antonius Adrianus Hendrikus Petrus Megens

Yolande Lydia Lang

Michel Joseph Maurice André Guillaume

Bart Petrus Anna Maria Jozef Medaer

Antonius Andrianus Hendrikus Petrus Megens

Mao Hua

Thierry Brossette

This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HTand 5-HTreceptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim

Substituted tetracyclic tetahydrofuran, pyrrolidine and tetrahydrothiophene derivatives

The present invention concerns a process for preparing each of the 4 individual diastereomers of formula (I) in stereochemically pure form from a single enantiomerically pure precursor. The tetracyclic ringsystem having cis-fused five and seven membered rings is formed in a base-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates and methanamine end-products, and the methanamine end-products for use as a medicine, in particular as CNS active medicines 

Preparation of cis-fused 3,3a,8,12b-tetrahydro-2H-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan derivatives

This invention concerns a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein Ris hydrogen, hydroxy, cyano, amino, mono-or di(Calkyl)amino, formyl, carboxyl, Calkyl, hydroxyCalkyl, polyhaloCalkyl, Calkenyl, Calkynyl, Ccycloalkyl, Calkyloxy, Calkylcarbonyl, aminocarbonyl, &#x2014;S(&#x2550;O)&#x2014;NH, mono-or di(Calkyl)aminocarbonyl, Calkyloxycarbonyl, Calkylcarbonyloxy, aryl, arylCalkyl or aryloxy; Ris hydrogen; halo; mercapto; formyl; cyano; carboxy; azido; hydroxy; oxiranyl; amino; mono- or di(Calkyl)amino; formylamino; RRN&#x2014;C(&#x2550;O)&#x2014;; R&#x2014;N&#x2550;C(R)&#x2014;; Calkyl-S(&#x2550;O)m; aryl-S(&#x2550;O); optionally substituted Calkenyl; optionally substituted Calkynyl; Calkyloxy; hydroxyCalkyloxy; aminoCalkyloxy; mono- or di(Calkyl)amino-Calkyloxy; Calkylcarbonyl; arylcarbonyl; Hetcarbonyl; Calkyloxycarbonyl; Calkylcarbonyloxy; aryl; aryloxy; arylCalkyloxy; arylthio; arylCalkylthio; mono- or di(aryl)amino; Het; Hetoxy; Hetthio; HetCalkyloxy; HetCalkylthio; mono- or di(Het)amino; Ccycloalkyl; Ccycloalkyloxy; Ccycloalkylthio; Calkylthio; hydroxyCalkylthio; aminoCalkylthio; mono- or di(Calkyl)aminoCalkylthio; optionally substituted Calkyl; Ror Reach independently represent optionally be substituted phenyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl; &#x2014;X&#x2014; is a bivalent radical selected from &#x2014;NR&#x2014;, &#x2014;NH&#x2014;NH&#x2014;, &#x2014;N&#x2550;N&#x2014;, &#x2014;O&#x2014;, &#x2014;Calkanediyl-, &#x2014;C(&#x2550;O)&#x2014;, &#x2014;CHOH&#x2014;, &#x2014;S&#x2014;, &#x2014;S(&#x2550;O)&#x2014;; aryl is optionally substituted phenyl; Het, Hetor Hetrepresent an optionally substituted monocyclic or bicyclic heterocycle; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

HIV inhibiting pyrazinone derivatives

The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I)in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

Preparation of trans-fused 3,3a,8,12b-tetrahydro-2h-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan derivatives

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Herent, Belgium

Frans Josef Cornelius Compernolle