Bial-portela Ca & S.a.

Portela, C.a., S.a.

Bial-portela & Cª, S.a.

Alexander Beliaev

David Alexander Learmonth

Laszlo Erno Kiss

Pedro Nuno Leal Palma

Patricio Manuel Soares Da Silva

Patrício Manuel Vieira Araújo Soares Da Silva

Tino Rossi

Jean-Marie Schneider

Jorge Bruno Reis Wahnon

William Maton

Jonathan Madec

Patricio Manuel Viera Araújo Soares Da Silva

Patrício Soares Da Silva

Patricia Andres

Antonio Zanotti-Gerosa

Ekaterina Albert

Patricio Manuel Vieira Araujo Soares Da Silva

Gabriela Alexandra Grasa

Wenge Li

Rita Gusmao De Noronha

Brian Broadbelt

Carla Patrícia Da Costa Pereira Rosa

Rita Gusmãmo De Noronha

Patrício Manuel Vieira Araujo Soares Da Silva

Rui Pinto

Francisco Cardona

Carla Patricia Rosa

Pedro Nuno Palma

This invention relates to: (a) compounds of formula Ia (with R1, R4 to R6, n and A as defined herein) and pharmaceutically acceptable salts or solvates thereof that are useful as dopamine-&#x3b2;-hydroxylase inhibitors; (b) pharmaceutical compositions (comprising such compounds, salts or solvates; (c) the use of such compounds, salts or solvates in therapy; (d) therapeutic methods of treatment using such compounds, salts or solvates; and (e) processes and intermediates useful for the synthesis of such compounds. 

Dopamine-b-hydroxylase inhibitors

This invention relates to: (a) compounds of Formula Ia (with R1, R4, R5, R6, n and A as defined herein) and pharmaceutically acceptable salts or solvates thereof that are useful as dopamine-&#x3b2;-hydroxylase inhibitors; (b) pharmaceutical compositions comprising such compounds, salts or solvates; (c) the use of such compounds, salts or solvates in therapy; (d) therapeutic methods of treatment using such compounds, salts or solvates; and (e) processes and intermediates useful for the synthesis of such compounds. 

Dopamine-&#x3b2;-hydroxylase inhibitors

This invention relates to: (a) compounds of formula (I) (with Rto R, n and A as defined herein) and pharmaceutically acceptable salts or solvates thereof that are useful as dopamine-&#x3b2;-hydroxylase inhibitors; (b) pharmaceutical compositions comprising such compounds, salts or solvates; (c) the use of such compounds, salts or solvates in therapy; (d) therapeutic methods of treatment using such compounds, salts or solvates; and (e) processes and intermediates useful for the synthesis of such compounds. 

Blood-brain barrier-penetrant dopamine-&#x3b2;-hydroxylase inhibitors

The present invention relates to a process for preparing (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione, and pharmaceutically acceptable salts thereof, especially the hydrochloride salt. The invention also relates to a process for making intermediates useful in the formation of said compound, and to the intermediates, per se.

Process for preparing 1,3-dihydroimidazole-2-thione derivatives

Compounds of formula I and a method for their preparation are described: where R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, nitro, amino, alkylcarbonylamino, alkylamino or dialkylamino group; Rsignifies -alkyl-aryl or -alkyl-heteroaryl; X signifies CH, oxygen atom or sulphur atom; n is 2 or 3; including the individual (R)- and (S)-enantiomers or mixtures of enantiomers thereof; and including pharmaceutically acceptable salts and esters thereof. The compounds have potentially valuable pharmaceutical properties for the treatment of cardiovascular disorders such as hypertension and chronic heart failure.

1,3-dihydroimidazole-2-thione derivatives as inhibitors of dopamine-beta-hydroxylase

The invention relates to compounds and compositions for inhibiting the enzyme fatty acid amide hydrolase (FAAH), the use of the compounds in therapy and, in particular, for treating or preventing conditions whose development or symptoms are linked to substrates of the FAAH enzyme, and methods of treatment or prevention using the compounds and compositions.

Pharmaceutical compounds

Process for preparing 1, 3-Dihydroimidazole-2-Thione Derivatives

A process for preparing the S or R enantiomer of a compound of formula A, the process comprising subjecting a compound of formula B to asymmetric hydrogenation in the presence of a chiral transition metal catalyst and a source of hydrogen, wherein X is CH, oxygen, or sulphur; R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino, or dialkylamino group; and Ris alkyl or aryl, wherein the transition metal catalyst comprises a chiral ligand having the formula wherein p is from 1 to 6, and Ar means aryl group; wherein the term alkyl means hydrocarbon chains, straight or branched, containing from one to six carbon atoms, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups; the term aryl means an aromatic or heteroaromatic group, optionally substituted by alkyloxy, halogen, or nitro group; and the term halogen means fluorine, chlorine, bromine, or iodine.

Process for preparing intermediates of peripherally-selective inhibitors of dopamine-&#x3b2;-hydroxylase involving catalytic asymmetric hydrogenation

The present invention relates to crystalline Form A of 1-[(3R)-6,8-difluoro-3,4-dihydro-2H-1-benzopyran-3-yl]-1,3-dihydro-5-[2-[(phenylmethyl)amino]ethyl]-2H-imidazole-2-thione and crystalline Form B of 1-[(3R)-6,8-difluoro-3,4-dihydro-2H-1-benzopyran-3-yl]-1,3-dihydro-5-[2-[(phenylmethyl)amino]ethyl]-2H-imidazole-2-thione, processes for preparing the forms and their uses in medicine. The present invention also relates to the amorphous form of 1-[(3R)-6,8-difluoro-3,4-dihydro-2H-1-benzopyran-3-yl]-1,3-dihydro-5-[2-[(phenylmethyl)amino]ethyl]-2H-imidazole-2-thione processes for preparing it and its uses in medicine.

Crystalline forms and processes for their preparation

A process for preparing the S or R enantiomer of a compound of formula A, the process comprising subjecting a compound of formula B to asymmetric hydrogenation in the presence of a chiral catalyst and a source of hydrogen, wherein X is CH, oxygen or sulphur; R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group; and Ris alkyl or aryl, wherein the term alkyl means hydrocarbon chains, straight or branched, containing from one to six carbon atoms, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups; the term aryl means a phenyl or naphthyl group, optionally substituted by alkyloxy, halogen or nitro group; and the term halogen means fluorine, chlorine, bromine or iodine.

Process for preparing synthetic intermediates of peripherally-selective inhibitors of dopamine-&#x3b2;-hydroxylase involving catalytic asymmetric hydrogenation

A process for preparing the S or R enantiomer of a compound of formula A, the process comprising subjecting a compound of formula B to asymmetric hydrogenation in the presence of a chiral catalyst and a source of hydrogen, wherein: X is CH, oxygen or sulphur; R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group; and Ris alkyl or aryl, wherein: the term alkyl means hydrocarbon chains, straight or branched, containing from one to six carbon atoms, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups; the term aryl means a phenyl or naphthyl group, optionally substituted by alkyloxy, halogen or nitro group; and the term halogen means fluorine, chlorine, bromine or iodine.

Catalytic hydrogenation of ene-carbamates

Compounds of formula I and a method for their preparation are described:  where R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, nitro, amino, alkylcarbonylamino, alkylamino or dialkylamino group; Rsignifies -alkyl-aryl or -alkyl-heteroaryl; X signifies CH, oxygen atom or sulphur atom; n is 2 or 3; including the individual (R)- and (S)-enantiomers or mixtures of enantiomers thereof; and including pharmaceutically acceptable salts and esters thereof. The compounds have potentially valuable pharmaceutical properties for the treatment of cardiovascular disorders such as hypertension and chronic heart failure.

A process for making (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione and pharmaceutically acceptable salts thereof, and for making intermediates useful in the formation of said compound.

Process for the preparation of (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-YL)-1,3-dihydroimidazole-2-thione

Compounds of formula I: where R, Rand Rare the same or different and signify hydrogens, halogens, alkyl, alkylaryl, alkyloxy, hydroxy, nitro, amino, alkylcarbonylamino, alkylamino or dialkylamino group; Rsignifies hydrogen, alkyl or alkylaryl group; X is CH, O or S, and n is 1, 2 or 3, with the proviso that if X is CH, n is not 1, and a method for their preparation. The compounds have potentially valuable pharmaceutical properties for the treatment of cardiovascular disorders such as hypertension and chronic heart failure.

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S. Mamede do Coronado, Portugal

Alexander Beliaev