公开(公告)号：US5166205A

公开(公告)日：1992-11-24

申请号：US735431

申请日：1991-07-25

申请人： Maria R. Cuberes-Altisent ,  Jordi Frigola-Constansa ,  Juan Pares-Corominas

发明人： Maria R. Cuberes-Altisent ,  Jordi Frigola-Constansa ,  Juan Pares-Corominas

IPC分类号： A61K31/495 ,  A61P37/08 ,  A61P43/00 ,  C07D207/32 ,  C07D207/325 ,  C07D231/14 ,  C07D231/16 ,  C07D233/56 ,  C07D249/08 ,  C07D521/00

CPC分类号： C07D207/325 ,  C07D231/12 ,  C07D231/14 ,  C07D231/16 ,  C07D233/56 ,  C07D249/08

摘要： The present invention relates to novel derivatives of 1-diphenylmethyl piperazinyl, characterized in that they correspond to the general formula I, and their therapeutically acceptable salts, ##STR1## in which: R.sub.1 and R.sub.2, equal or different, represent a hydrogen atom, a halogen, a lower alkyl radical, a hydroxy radical, an alkoxy radical, an alkyl carboxylate radical, an aryl or substituted aryl radical,n may have the values 2 to 4,X, Y, Z and W, equal or different, represent a nitrogen atom or a carbon atom linked to a hydrogen atom, a halogen or to another alkyl, aryl, carboxyalkyl, carbonyl, hydroxyl, sulfonyl and alkylsulfonyl radical.The present invention also relates to the process of preparing these compounds and their use for the manufacture of medicaments intended for prophylaxis and for the treatment of various allergic disorders caused by histamine.

摘要翻译： 本发明涉及1-二苯基甲基哌嗪基的新衍生物，其特征在于它们对应于通式Ⅰ及其治疗上可接受的盐，其中：R1和R2等同或不同，表示氢原子， 卤素，低级烷基，羟基，烷氧基，烷基羧酸酯基，芳基或取代的芳基，n可以具有2至4，X，Y，Z和W相等或不同，表示 连接到氢原子的氮原子或碳原子，卤素或另一个烷基，芳基，羧基烷基，羰基，羟基，磺酰基和烷基磺酰基。 本发明还涉及制备这些化合物的方法及其制备用于预防和治疗由组胺引起的各种过敏性疾病的药物的用途。

公开(公告)号：US5162323A

公开(公告)日：1992-11-10

申请号：US615257

申请日：1990-11-19

申请人： Jordi Frigola-Constansa ,  Juan Pares-Corominas

发明人： Jordi Frigola-Constansa ,  Juan Pares-Corominas

IPC分类号： C07D403/14 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61P3/02 ,  A61P25/20 ,  A61P25/30 ,  A61P25/32 ,  A61P43/00 ,  C07D403/12 ,  C07D521/00

CPC分类号： C07D231/12 ,  A61K31/505 ,  C07D233/56 ,  C07D249/08 ,  C07D403/12

摘要： The present invention relates to the use of the derivatives of general formula I ##STR1## in which: n can have the values 1 to 6, andR represents a hydrogen atom, a halogen, a C.sub.1 to C.sub.4 lower alkyl radical, a nitro radical, a hydroxyl radical, an oxo radical, a C.sub.1 to C.sub.4 lower alkoxy radical, a cyano radical, a C.sub.1 to C.sub.4 lower alkyl carboxylate radical, an aryl or substituted aryl radical, or an amino or substituted amino radical of formula ##STR2## in which R.sub.1 and R.sub.2, which may be identical or different, represent a hydrogen atom, an alkyl radical, an aryl radical, an alkylcarboxy radical, an arylcarboxy radical, an alkylsulphonyl radical or an arylsulphonyl radical, the alkyl fragments of these radicals containing from 1 to 4 carbon atomsfor the manufacture of medicinal products intended for the treatment of disorders associated with the withdrawal syndrome induced by the discontinuation of benzodiazepines such as diazepam, cocaine, alcohol and/or nicotine.

摘要翻译： 本发明涉及通式I（I）的衍生物的用途，其中：n可以具有1至6的数值，R代表氢原子，卤素，C1至C4低级烷基， 硝基，羟基，氧基，C 1至C 4低级烷氧基，氰基，C 1至C 4低级烷基羧酸酯基，芳基或取代的芳基或氨基或取代的氨基， IMAGE>其中可以相同或不同的R 1和R 2表示氢原子，烷基，芳基，烷基羧基，芳基羧基，烷基磺酰基或芳基磺酰基，这些基团的烷基 含有1至4个碳原子用于制造旨在治疗由停止苯二氮卓类例如地西泮，可卡因，醇和/或尼古丁引起的戒断综合征相关疾病的药用产品。

公开(公告)号：US07998996B2

公开(公告)日：2011-08-16

申请号：US10589743

申请日：2005-02-14

申请人： Rosa Cuberes Altisen ,  Bonifacio Gutierrez Silva ,  Jordi Frigola-Constansa

发明人： Rosa Cuberes Altisen ,  Bonifacio Gutierrez Silva ,  Jordi Frigola-Constansa

IPC分类号： A61K31/415 ,  C07D231/06

CPC分类号： C07D231/06 ,  C07D401/12

摘要： The present invention relates to substituted pyrazoline compounds, methods for their preparation, medicaments comprising these compounds as well as their use for the preparation of a medicament for the treatment of humans and animal.

摘要翻译： 本发明涉及取代的吡唑啉化合物，其制备方法，包含这些化合物的药物及其用于制备治疗人和动物的药物的用途。

公开(公告)号：US07176200B2

公开(公告)日：2007-02-13

申请号：US10933951

申请日：2004-09-03

申请人： Ramón Merce-Vidal ,  Blas Andaluz-Mataro ,  Jordi Frigola-Constansa

发明人： Ramón Merce-Vidal ,  Blas Andaluz-Mataro ,  Jordi Frigola-Constansa

IPC分类号： A61K31/5375 ,  A61K31/404 ,  C07D413/02 ,  C07D209/04

CPC分类号： C04B35/632 ,  C07D209/14 ,  C07D209/16 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04

摘要： The present invention relates to new derivatives of sulphonamides, with the general formula (I), as well as to their physiologically acceptable salts, the processes for their preparation, their application as medicaments in human and/or veterinary therapy and the pharmaceutical compositions that contain them

摘要翻译： 本发明涉及具有通式（I）的磺酰胺的新衍生物，以及它们的生理上可接受的盐，其制备方法，它们作为人和/或兽医治疗中的药物的用途，以及含有 他们

公开(公告)号：US20050096474A1

公开(公告)日：2005-05-05

申请号：US11006931

申请日：2004-12-08

申请人： Monserrat Alcon-Marrugat ,  Miguel Pericas-Brondo ,  Maria Cuberes-Altisen ,  Jordi Frigola-Constansa

发明人： Monserrat Alcon-Marrugat ,  Miguel Pericas-Brondo ,  Maria Cuberes-Altisen ,  Jordi Frigola-Constansa

IPC分类号： C07D231/06 ,  C07D231/12

CPC分类号： C07D231/06

摘要： Procedure for preparation of compounds with the general formula 1, which include the racemic mixtures (±)-1, and the enantiomerically pure compounds (−)-1 and (+)-1, wherein R1 and R3, like or different, represent an atom of hydrogen, chlorine, fluorine, a methyl, trifluoromethyl or methoxy group; R2 represents an atom of hydrogen, chlorine, fluorine, a methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylsulphonyl or aminosulphonyl group; R4 represents an atom of hydrogen, chlorine, fluorine, a methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylsulphonyl or aminosulphonyl group, with the condition that one of the substituents R2 or R4 is a methylsulphonyl or aminosulphonyl group; which involves obtaining the racemic mixture with the general formula (±)-1 by reacting an (E)-1,1,1-trifluoro-4-aryl-3-buten-2-one with a phenylhydrazine, followed by a treatment with chlorosulphonic acid, or by reacting with chlorosulphonic acid followed by a reaction with sodium hydroxide and, finally, with thionyl chloride. The product obtained by either of these methods is made to react with ammonium carbonate or ammonia, or with sodium sulphite and methyl iodide or methyl sulphate. In addition, to obtain the enantiomerically pure compounds with the general formula 1 by resolving the racemic mixture with the general formula (±)-1, a reaction is effected with optically active ephedrine, followed by formation of the sodium salt of each enantiomer, reaction with thionyl chloride and ammonium carbonate or ammonia, or instead with thionyl chloride followed by sodium sulphite and methyl iodide or methyl sulphate to thereby obtain separately the enantiomerically pure compounds with the general formulae (−)-1 and (+)-1.

公开(公告)号：US06846935B2

公开(公告)日：2005-01-25

申请号：US10312194

申请日：2002-06-06

申请人： Montserrat Alcon-Marruga ,  Miguel Angel Pericas-Brondo ,  Maria Rosa Cuberes-Altisen ,  Jordi Frigola-Constansa

发明人： Montserrat Alcon-Marruga ,  Miguel Angel Pericas-Brondo ,  Maria Rosa Cuberes-Altisen ,  Jordi Frigola-Constansa

IPC分类号： C07D231/06 ,  C07D231/12

CPC分类号： C07D231/06

摘要： Procedure for preparation of compounds with the general formula 1, which include the racemic mixtures (±)-1, and the enantiomeric ally pure compounds (−)-1 and (+)-1, wherein R1 and R3, like or different, represent an atom of hydrogen, chlorine, fluorine, a methyl, trifluoromethyl or methoxy group; R2 represents an atom of hydrogen, chlorine, fluorine, a methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylsulphonyl or aminosulphonyl group; R4 represents an atom of hydrogen, chlorine, fluorine, a methyl, trifluoromethyl, methoxy, trifluoromethoxy, methylsulphonyl or aminosulphonyl group, with the condition that one of the substituents R2 or R4 is a methylsulphonyl or aminosulphonyl group; which involves obtaining the racemic mixture with the general formula (±)-1 by reacting an (E)-1,1,1-trifluoro-4-aryl-3-buten-2-one with a phenylhydrazine, followed by a treatment with chlorosulphonic acid, or by reacting with chlorosulphonic acid followed by a reaction with sodium hydroxide and, finally, with thionyl chloride. The product obtained by either of these methods is made to react with ammonium carbonate or ammonia, or with sodium sulphite and methyl iodide or methyl sulphate. In addition, to obtain the enantiomerically pure compounds with the general formula 1 by resolving the racemic mixture with the general formula (±)-1, a reaction is effected with optically active ephedrine, followed by formation of the sodium salt of each enantiomer, reaction with thionyl chloride and ammonium carbonate or ammonia, or instead with thionyl chloride followed by sodium sulphite and methyl iodide or methyl sulphate to thereby obtain separately the enantiomerically pure compounds with the general formulae (−)-1 and (+)-1.

摘要翻译： 制备具有通式1的化合物的方法，其包括外消旋混合物（±）-1和对映异构体烯丙基化合物（ - ）-1和（+） - 1，其中R1和R3等同或不同表示 氢，氯，氟，甲基，三氟甲基或甲氧基的原子; R2代表氢，氯，氟，甲基，三氟甲基，甲氧基，三氟甲氧基，甲基磺酰基或氨基磺酰基的原子; R4表示氢，氯，氟，甲基，三氟甲基，甲氧基，三氟甲氧基，甲基磺酰基或氨基磺酰基的原子，条件是取代基R2或R4中的一个为甲基磺酰基或氨基磺酰基; 其包括通过（E）-1,1,1-三氟-4-芳基-3-丁烯-2-酮与苯肼反应获得具有通式（±）-1的外消旋混合物，然后用 或通过与氯磺酸反应，然后与氢氧化钠反应，最后与亚硫酰氯反应。 通过这些方法得到的产物与碳酸铵或氨，或与亚硫酸钠和甲基碘或甲基硫酸盐反应。 另外，为了通过拆分通式（±）-1的外消旋混合物来获得具有通式1的对映异构体纯的化合物，用光学活性麻黄碱进行反应，随后形成各对映异构体的钠盐，反应 与亚硫酰氯和碳酸铵或氨反应，或代之以亚硫酰氯，然后加入亚硫酸钠和甲基碘或甲基硫酸盐，从而分别得到具有通式（ - ） - 1和（+） - 1的对映体纯的化合物。

公开(公告)号：US06518295B1

公开(公告)日：2003-02-11

申请号：US09762079

申请日：2001-02-01

申请人： Ramón Merce-Vidal ,  Jordi Frigola-Constansa

发明人： Ramón Merce-Vidal ,  Jordi Frigola-Constansa

IPC分类号： A61K31415

CPC分类号： A61K31/415 ,  A61K31/00 ,  A61K31/4164 ,  A61K31/5517

摘要： The present invention relates to the use of derivatives of aryl (or heteroaryl) azolylcarbinols of general formula (1) of the specification, as well as their physiologically acceptable salts, in the manufacture of medicaments, useful in human and/or veterinary therapy, for the treatment of disorders that are mediated by an excess of substance P, and especially disorders of the central nervous system such as anxiety, depression, schizophrenia, manic depressive psychosis, sexual dysfunction, drug addiction, cognitive disorders, and locomotive disorders.

摘要翻译： 本发明涉及本说明书通式（1）的芳基（或杂芳基）唑基甲醇衍生物及其生理上可接受的盐在制备用于人和/或兽医疗法的药物中的用途，其用于 治疗由过量的物质P介导的疾病，特别是中枢神经系统的障碍如焦虑，抑郁，精神分裂症，躁狂抑郁精神病，性功能障碍，药物成瘾，认知障碍和机车病症。

公开(公告)号：US06372746B1

公开(公告)日：2002-04-16

申请号：US09462880

申请日：2000-02-24

申请人： Jordi Corbera-Arjona ,  David Vaño-Domenech ,  Jordi Frigola-Constansa

发明人： Jordi Corbera-Arjona ,  David Vaño-Domenech ,  Jordi Frigola-Constansa

IPC分类号： C07D40304

CPC分类号： C07D405/12 ,  C07D239/42 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D417/12

摘要： The derivatives of acyl-piperazinyl-pyrimidines of general formula (I), where X is O or S; R1 is alkoxy or trifluoromethyl; R2 is alkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl, show activity in the central nervous system. Compounds of general formula (I) in which X is O can be obtained by reacting a derivative of pyrimidine with a derivative of piperazine or by reacting a derivative of piperazinyl-pyrimidine with a carboxylic acid or a salt or derivative thereof. Compounds of general formula (I) in which X is S can be obtained by reacting (I) in which X is O with Lawesson's reagent or with phosphorous pentasulphide. The compounds (I) show sedative activity, anticonvulsant, sleep-inducing or general anaesthetic activity and can be applied in human or veterinary medicine

摘要翻译： 通式（I）的酰基哌嗪基 - 嘧啶衍生物，其中X为O或S; R1是烷氧基或三氟甲基; R2是烷基，环烷基，杂环烷基，芳基，芳基烷基，杂芳基或杂芳基烷基，在中枢神经系统中显示活性。 其中X为O的通式（I）化合物可以通过使嘧啶衍生物与哌嗪的衍生物反应或通过使哌嗪基 - 嘧啶的衍生物与羧酸或其盐或衍生物反应来获得。 其中X为S的通式（I）的化合物可以通过（I）其中X为O与Lawesson's试剂或五硫化磷反应而获得。 化合物（I）显示镇静活性，抗惊厥，睡眠诱导或全身麻醉活性，可应用于人或兽药

公开(公告)号：US5849931A

公开(公告)日：1998-12-15

申请号：US875806

申请日：1997-08-05

申请人： Jordi Frigola-Constansa ,  Juana Maria Berrocal Romero ,  Maria Rosa Cuberes Altisent ,  Vicente Gotor Santamaria

发明人： Jordi Frigola-Constansa ,  Juana Maria Berrocal Romero ,  Maria Rosa Cuberes Altisent ,  Vicente Gotor Santamaria

IPC分类号： C07D231/12

CPC分类号： C07D231/12

摘要： A method for predominantly preparing the enantiomer (R)-(+)-5-(phenyl)hydroxymethyl-1-methyl-1H-pyrazole, (R)-(+)-1, by separating the racemate (+)-5-(phenyl)hydroxymethyl-1-methyl-1H-pyrazole of formula (1), comprising the series of steps of using a lipase or material derived therefrom having enzymatic activity in a transesterification reaction, as well as hydrolysing the resulting ester, (S)-(-)-5-(phenyl)alkylcarbonyloxymethyl-1-methyl-1H-pyrazole, of formula (S)-(-)-4, wherein R.sub.1 is a methyl or ethyl radical.

摘要翻译： PCT No.PCT / EP96 / 05596 Sec。 371日期：1997年8月5日 102（e）日期1997年8月5日PCT 1997年12月4日PCT PCT。 出版物WO97 / 20817 日期：1997年6月12日主要通过将外消旋体（R） - （+） - （ - ） - （+） - +） - 5-（苯基）羟甲基-1-甲基-1H-吡唑，其包括使用脂肪酶或其衍生的物质在酯交换反应中具有酶活性的一系列步骤，以及水解所得 酯，（S） - （ - ） - （ - ） - （ - ） - 5-（苯基）烷基羰基氧基甲基-1-甲基-1H-吡唑，其中R1是甲基或乙基。

公开(公告)号：US5182281A

公开(公告)日：1993-01-26

申请号：US824995

申请日：1992-01-24

申请人： Jordi Frigola-Constansa ,  Juan Pares-Corominas

发明人： Jordi Frigola-Constansa ,  Juan Pares-Corominas

IPC分类号： A61K31/505 ,  A61K9/20 ,  A61K9/48 ,  A61K31/496 ,  A61K31/506 ,  A61P25/28 ,  C07D403/12 ,  C07D403/14 ,  C07D513/04 ,  C07D521/00

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D403/12 ,  C07D403/14

摘要： The present invention relates to the use of the derivatives of general formula I ##STR1## in which: n can have values 1 to 6, andR represents a hydrogen atom, a halogen, a C.sub.1 to C.sub.4 lower alkyl radical, a heteroaryl radical, a sulpho radical, an N-substituted or N,N-disubstituted sulphamoyl radical, a nitro radical, a hydroxyl radical, an oxo radical, a C.sub.1 to C.sub.4 lower alkoxy radical, a cyano radical, a C.sub.1 to C.sub.4 lower alkylcarboxylate radical, an aryl or substituted aryl radical, or an amino or substituted amino radical of formula ##STR2## in which R.sub.1 and R.sub.2, which may be identical or different, represent a hydrogen atom, an alkyl radical, an aryl radical, an alkylcarbonyl radical, an arylcarbonyl radical, an alkylsulphonyl radical or an arylsulphonyl radical, the alkyl fragments of these radicals containing from 1 to 4 carbon atoms,and their therapeutically acceptable salts, for the manufacture of medicinal products intended for the treatment of disorders of cognitive funciton, such as presenile dementia, senile dementia, memory dysfunctions, deterioration of awareness and Alzheimer's disease.

摘要翻译： 本发明涉及通式I（I）的衍生物的用途，其中：n可以具有1-6的数值，R代表氢原子，卤素，C1-C4低级烷基， 杂芳基，磺酰基，N-取代或N，N-二取代的氨磺酰基，硝基，羟基，氧代基，C 1至C 4低级烷氧基，氰基，C 1至C 4低级烷基羧酸酯 基团，芳基或取代的芳基，或式“IMAGE”的氨基或取代的氨基，其中可以相同或不同的R 1和R 2表示氢原子，烷基，芳基，烷基羰基 ，芳基羰基，烷基磺酰基或芳基磺酰基，这些含有1至4个碳原子的基团的烷基片段及其治疗上可接受的盐，用于制造旨在治疗认知功能障碍的药物，例如 作为老年痴呆症，老年痴呆，记忆功能障碍，意识恶化和阿尔茨海默病。