公开(公告)号：EP3808737A1

公开(公告)日：2021-04-21

申请号：EP20171586.9

申请日：2014-09-12

申请人： BIAL - Portela & Ca., S.A.

发明人： RUSSO, Domenico ,  WAHON, Jorge ,  MATON, William ,  WEBER, Beat T. ,  JERÓNIMO, Paula ,  SOUSA, Luisa ,  BARROCAS, Pedro ,  PIRES, Rita ,  LIMA, Ricardo ,  VASCONCELOS, Téofilo Cardoso de

IPC分类号： C07D311/12 ,  C07D311/20

摘要： The present invention provides a process for preparing the (R)-enantiomer (R-N) or the (R)-enantiomer (S-N) of a compound of formula N, the process comprising subjecting a compound of formula M to reduction using a reductase enzyme

The present invention also provides a process for preparing a nitro chromane compound of formula N, the process comprising reacting a nitro chromene compound of formula M with a suitable reducing agent.

The present invention also provides a process for preparing the (R)-or (S)-enantiomer of a compound of formula E or a salt thereof

公开(公告)号：EP3097082B1

公开(公告)日：2019-10-02

申请号：EP15706552.5

申请日：2015-01-23

申请人： BIAL - Portela & CA., S.A.

发明人： RUSSO, Domenico ,  WAHNON, Jorge Bruno Reis ,  MATON, William ,  ESZENYI, Tibor

IPC分类号： C07D233/61 ,  C07D401/04

公开(公告)号：EP2726454A2

公开(公告)日：2014-05-07

申请号：EP12738246.3

申请日：2012-06-29

申请人： Bial-Portela & CA, S.A.

发明人： BELIAEV, Alexander ,  WAHNON, Jorge Bruno Reis ,  LEARMONTH, David Alexander ,  MADEC, Jonathan ,  SCHNEIDER, Jean-Marie ,  MATON, William

IPC分类号： C07C311/19 ,  C07D403/04

CPC分类号： C07D405/04 ,  C07C235/80 ,  C07C311/16 ,  C07C311/17

摘要： 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.

公开(公告)号：EP2726454B1

公开(公告)日：2018-01-24

申请号：EP12738246.3

申请日：2012-06-29

申请人： Bial-Portela & CA, S.A.

发明人： BELIAEV, Alexander ,  WAHNON, Jorge Bruno Reis ,  LEARMONTH, David Alexander ,  MADEC, Jonathan ,  SCHNEIDER, Jean-Marie ,  MATON, William

IPC分类号： C07C311/19 ,  C07D403/04

CPC分类号： C07D405/04 ,  C07C235/80 ,  C07C311/16 ,  C07C311/17

摘要： 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.

公开(公告)号：EP3044215A1

公开(公告)日：2016-07-20

申请号：EP14772233.4

申请日：2014-09-12

申请人： Bial-Portela & CA, S.A.

发明人： RUSSO, Domenico ,  WAHNON, Jorge ,  MATON, William ,  WEBER, Beat T. ,  JERÓNIMO, Paula ,  SOUSA, Luísa ,  BARROCAS, Pedro ,  PIRES, Rita ,  LIMA, Ricardo ,  VASCONCELOS, Teófilo

IPC分类号： C07D311/12 ,  C07D311/20

CPC分类号： C07D311/58 ,  C07C51/41 ,  C07D311/12 ,  C07D311/20 ,  C07D405/04

摘要： The present invention provides a compound of formula N wherein: X is CH
2 , oxygen or sulphur; R
1 , R
2 and R
3 are the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group, wherein N is in the form of the individual R- and S-enantiomer or a mixture of the (R)- and (S)-enantiomer. The present invention also provides a compound of formula MA. The present invention also provides processes for preparing the above compounds, and processes involving their use. The compounds are particularly useful as intermediates in the synthesis of peripherally-selective inhibitors of dopamine-ß-hydroxylase.

公开(公告)号：EP2890684B1

公开(公告)日：2018-02-14

申请号：EP13750166.4

申请日：2013-07-24

申请人： Bial-Portela & CA, S.A.

发明人： ROSA, Carla Patrícia da Costa Pereira ,  GUSMÃO DE NORONHA, Rita ,  KISS, Laszlo Erno ,  SOARES DA SILVA, Patrício Manuel Vieira Araújo ,  RUSSO, Domenico ,  WAHNON, Jorge Bruno Reis ,  MATON, William

IPC分类号： C07D233/61 ,  C07C209/48 ,  C07D233/88 ,  A61K31/4178 ,  A61P31/00

CPC分类号： C07D233/64 ,  A61K31/4164 ,  A61K45/06 ,  C07C209/00 ,  C07C209/26 ,  C07D207/335 ,  C07D233/61 ,  C07D233/88 ,  C07C211/35

摘要： or a pharmaceutically acceptable salt or derivative thereof. The compound may be used in the treatment or prevention of a disorder selected from appetite regulation, obesity, metabolic disorders, cachexia, anorexia, pain, inflammation, neurotoxicity, neurotrauma, stroke, multiple sclerosis, spinal cord injury, Parkinson's disease, levodopa-induced dyskinesia, Huntington's disease, Gilles de la Tourette's syndrome, tardive dyskinesia, dystonia, amyotrophic lateral sclerosis, Alzheimer's disease, epilepsy, schizophrenia, anxiety, depression, insomnia, nausea, emesis, alcohol disorders, drug addictions such as opiates, nicotine, cocaine, alcohol and psychostimulants, hypertension, circulatory shock, myocardial reperfusion injury, atherosclerosis, asthma, glaucoma, retinopathy, cancer, inflammatory bowel disease, acute and chronic liver disease such as hepatitis and liver cirrhosis, arthritis and osteoporosis.

公开(公告)号：EP3097082A2

公开(公告)日：2016-11-30

申请号：EP15706552.5

申请日：2015-01-23

申请人： BIAL - Portela & CA., S.A.

发明人： RUSSO, Domenico ,  WAHNON, Jorge Bruno Reis ,  MATON, William ,  ESZENYI, Tibor

IPC分类号： C07D233/61 ,  C07D401/04

CPC分类号： C07D233/64 ,  C07C209/68 ,  C07C2601/08 ,  C07D233/61 ,  C07D401/04

摘要： The present invention concerns a process for preparing a compound having the Formula A; or a pharmaceutically acceptable salt or derivative thereof, or for preparing a substituted urea compound of Formula IIa, or a pharmaceutically acceptable salt or ester thereof, (Formula IIa) the process comprising the reaction of an imidazolyl intermediate of Formula IIa', with a carbamoyl halide of the formula: R1R2NC(=O)Hal, wherein Hal represents Cl, F, I or Br, wherein the intermediate of Formula IIa' is prepared by oxidation of the derivative of R5 and R6, R6-C(=O)CH2R5 to form a glyoxal intermediate R6-C(=O)(C=O)R5, which is subjected to treatment with ammonium hydroxide and an aldehyde R8CHO to provide the intermediate of Formula IIa', and wherein the compound substituents are as defined herein.

摘要翻译： 本发明涉及制备具有式A化合物的方法; 或其药学上可接受的盐或衍生物，或用于制备式IIa的取代的脲化合物或其药学上可接受的盐或酯，（式IIa）包括式IIa'的咪唑基中间体与氨基甲酰基 卤化物，其分子式如下：R1R2NC（= O）Hal，其中Hal表示Cl，F，I或Br，其中式IIa'的中间体是通过氧化R5和R6的衍生物，R6-C（= O）CH2R5 形成乙二醛中间体R6-C（= O）（C = O）R5，其用氢氧化铵和醛R 8 CHO进行处理以提供式IIa'的中间体，其中化合物取代基如本文所定义。

公开(公告)号：EP2890684A2

公开(公告)日：2015-07-08

申请号：EP13750166.4

申请日：2013-07-24

申请人： Bial-Portela & CA, S.A.

发明人： ROSA, Carla Patrícia da Costa Pereira ,  GUSMÃO DE NORONHA, Rita ,  KISS, Laszlo Erno ,  SOARES DA SILVA, Patrício Manuel Vieira Araújo ,  RUSSO, Domenico ,  WAHNON, Jorge Bruno Reis ,  MATON, William

IPC分类号： C07D233/61 ,  C07C209/48 ,  C07D233/88 ,  A61K31/4178 ,  A61P31/00

CPC分类号： C07D233/64 ,  A61K31/4164 ,  A61K45/06 ,  C07C209/00 ,  C07C209/26 ,  C07D207/335 ,  C07D233/61 ,  C07D233/88 ,  C07C211/35

摘要： or a pharmaceutically acceptable salt or derivative thereof. The compound may be used in the treatment or prevention of a disorder selected from appetite regulation, obesity, metabolic disorders, cachexia, anorexia, pain, inflammation, neurotoxicity, neurotrauma, stroke, multiple sclerosis, spinal cord injury, Parkinson's disease, levodopa-induced dyskinesia, Huntington's disease, Gilles de la Tourette's syndrome, tardive dyskinesia, dystonia, amyotrophic lateral sclerosis, Alzheimer's disease, epilepsy, schizophrenia, anxiety, depression, insomnia, nausea, emesis, alcohol disorders, drug addictions such as opiates, nicotine, cocaine, alcohol and psychostimulants, hypertension, circulatory shock, myocardial reperfusion injury, atherosclerosis, asthma, glaucoma, retinopathy, cancer, inflammatory bowel disease, acute and chronic liver disease such as hepatitis and liver cirrhosis, arthritis and osteoporosis.

摘要翻译： 或其药学上可接受的盐或衍生物。 该化合物可用于治疗或预防选自食欲调节，肥胖症，代谢紊乱，恶病质，厌食，疼痛，炎症，神经毒性，神经损伤，中风，多发性硬化，脊髓损伤，帕金森病，左旋多巴诱导 运动障碍，亨廷顿疾病，吉列斯杜拉特雷综合征，迟发性运动障碍，肌张力障碍，肌萎缩性侧索硬化，阿尔茨海默病，癫痫，精神分裂症，焦虑，抑郁，失眠，恶心，呕吐，酒精失调，药物成瘾如阿片剂，尼古丁，可卡因， 酒精和精神兴奋剂，高血压，循环休克，心肌再灌注损伤，动脉粥样硬化，哮喘，青光眼，视网膜病，癌症，炎症性肠病，急性和慢性肝病如肝炎和肝硬化，关节炎和骨质疏松症。