公开(公告)号：WO1993011107A1

公开(公告)日：1993-06-10

申请号：PCT/HU1992000050

申请日：1992-12-01

申请人： RICHTER GEDEON VEGYÉSZETI GYAR RT. ,  HARSANYI, Kálmán ,  GIZUR, Tibor ,  AGAI-CSONGOR, Éva ,  KALLAY-SOHONYAI, Anna ,  KAPOLNAS-PAP, Márta ,  CSIZÉR, Éva ,  HEGEDÜS, Béla ,  SZPORNY, László ,  KISS, Béla ,  KARPATI, Egon ,  PALOSI, Éva ,  SZOMBATHELYI, Zsolt ,  SARKADI, Adám ,  GERE, Anikó ,  BODO, Mihály ,  CSOMOR, Katalin ,  LASZY, Judit ,  SZENTIRMAI, Zsolt ,  LAPIS, Erzsébet ,  SZABO, Sándor ,  BOD, Péter ,  CSEHI, Attila

发明人： RICHTER GEDEON VEGYÉSZETI GYAR RT.

IPC分类号： C07D211/06

CPC分类号： C07D211/52 ,  C07D211/14 ,  C07D211/70

摘要： The invention relates to novel N-hydroxy-substituted 1,2,3,6-tetrahydropyridine and piperidine derivatives of formula (I) wherein A stands for hydrogen or halogen; alkoxy; cyano; phenyl; phenyl monosubstituted by halogen; benzyl; benzyl monosubstituted by halogen; 2-phenylethyl monosubstituted by halogen on the phenyl moiety; or 2-picolyl group; B represents hydrogen; alkoxy or nitro group; D represents hydrogen or halogen; or alkoxy group; or B and D together stand for a -CH=CH-CH=CH- group; R represents hydrogen; alkyl or phenyl group; G is hydrogen; I stands for hydrogen or hydroxy group; or G and I together represent a single chemical bond; E stands for hydrogen or halogen; alkoxy or trifluoromethyl group; and m is 0, 1 or 2, with the proviso that: m is 0 or 2, or both G and I mean hydrogen, when A stands for benzyl or halogen-monosubstituted benzyl group; and m is 1, when A stands for 2-picolyl group, as well as their acid addition salts. The invention further relates to pharmaceutical compositions containing these compounds as active ingredients as well as to a process for the preparation of compounds of formula (I) and their intermediates. The compounds of formula (I) are useful for enhancing the tolerance of mammals (including man) against hypoxic and/or ischaemic states as well as for treating the degenerative and functional disturbances arising from hypoxic and/or ischaemic insults.

摘要翻译： 本发明涉及式（I）的新型N-羟基取代的1,2,3,6-四氢吡啶和哌啶衍生物，其中A代表氢或卤素; 烷氧基; 氰基; 苯基; 被卤素单取代的苯基; 苄基; 被卤素单取代的苄基; 在苯基部分被卤素单取代的2-苯基乙基; 或2-吡啶甲基; B表示氢; 烷氧基或硝基; D表示氢或卤素; 或烷氧基; 或B和D一起代表-CH = CH-CH = CH-基团; R代表氢; 烷基或苯基; G是氢; 我代表氢或羟基; 或G和I一起代表单一化学键; E代表氢或卤素; 烷氧基或三氟甲基; m为0,1或2，条件是：m为0或2，或者G和I均为氢，A表示苄基或卤素 - 单取代苄基; 并且当A代表2-吡啶甲基时，m为1，以及它们的酸加成盐。 本发明还涉及含有这些化合物作为活性成分的药物组合物以及制备式（I）化合物及其中间体的方法。 式（I）化合物可用于增强哺乳动物（包括人）对缺氧和/或缺血状态的耐受性，以及用于治疗由缺氧和/或缺血损伤引起的退行性和功能障碍。

公开(公告)号：WO1992010495A1

公开(公告)日：1992-06-25

申请号：PCT/HU1991000051

申请日：1991-12-06

申请人： RICHTER GEDEON VEGYÉSZETI GYAR RT. ,  SZPORNY, László ,  KISS, Béla ,  KARPATI, Egon ,  PALOSI, Éva ,  SZOMBATHELYI, Zsolt ,  SARKADI, Adám ,  GERE, Anikó ,  BODO, Mihály ,  CSOMOR, Katalin ,  LASZY, Judit ,  SZENTIRMAY, Zsolt ,  LAPIS, Erzsébet ,  SZABO, Sándor ,  KREIDL, János ,  VISKY, György ,  CZIBULA, László ,  NEMES, András

发明人： RICHTER GEDEON VEGYÉSZETI GYAR RT.

IPC分类号： C07D461/00

CPC分类号： C07D461/00

摘要： The invention relates to novel, optically active cis and trans 14-(N-substituted aminomethyl)eburnane derivatives of formula (I), wherein R1 stands for hydrogen, a C1-6alkyl or C2-6alkenyl group; R2 means a C1-6alkyl, C2-6alkenyl or a hydroxy-C1-6alkyl group; or R1 and R2 represent together with the adjacent nitrogen atom to which they are attached, a 5 to 7-membered saturated ring, optionally containing one oxygen atom and/or one optionally substituted nitrogen atom as heteroatom; and n is 2 or 3, as well as pharmaceutically acceptable salts of these compounds. The compounds of the invention possess an antioxidative (lipid peroxidation-inhibiting) effect and therefore, they are useful for treating diseases connected with lipid peroxidation, such as ischaemic intestinal diseases, myocardial ischaemia, ischaemic cerebrovascular disturbances as well as some diseases of connective tissues, e.g. rheumatoid arthritis. The compounds of the invention are also suitable for treating or preventing cognitive disorders.

摘要翻译： 本发明涉及式（I）的新型光学活性顺式和反式14-（N-取代氨基甲基）艾本烷衍生物，其中R1代表氢，C1-6烷基或C2-6烯基; R 2表示C 1-6烷基，C 2-6烯基或羟基-C 1-6烷基; 或R 1和R 2与它们所连接的相邻氮原子一起表示5至7元饱和环，任选地含有一个氧原子和/或一个任选取代的氮原子作为杂原子; 和n为2或3，以及这些化合物的药学上可接受的盐。 本发明的化合物具有抗氧化（脂质过氧化抑制）效果，因此可用于治疗与脂质过氧化相关的疾病，例如缺血性肠病，心肌缺血，缺血性脑血管障碍以及结缔组织的一些疾病， 例如 类风湿关节炎。 本发明的化合物也适用于治疗或预防认知障碍。

公开(公告)号：WO1993012118A1

公开(公告)日：1993-06-24

申请号：PCT/HU1992000053

申请日：1992-12-11

申请人： RICHTER GEDEON VEGYÉSZETI GYAR RT. ,  KOBOR, Jeno ,  LAZAR, László ,  HUBER, Imre ,  ARVA, Judit ,  SZPORNY, László ,  KISS, Béla ,  KARPATI, Egon ,  PALOSI, Éva ,  SZOMBATHELYI, Zsolt ,  SARKADI, Adám ,  GERE, Anikó ,  BODO, Mihály ,  CSOMOR, Katalin ,  LASZY, Judit ,  SZENTIRMAI, Zsolt ,  LAPIS, Erzsébet ,  SZABO, Sándor ,  BERNATH, Gábor ,  FÜLÖP, Ferenc

发明人： RICHTER GEDEON VEGYÉSZETI GYAR RT.

IPC分类号： C07D498/04

CPC分类号： C07D498/04

摘要： This invention relates to novel, therapeutically active oxazinoisoquinoline derivatives of formula (I), wherein R means hydrogen, a C1-4 alkyl, phenyl or phenyl-C1-4 alkyl group; one of R and R stands for a C1-4 alkoxy group and the other one represents a phenyl-C1-4 alkoxy group optionally substituted by a C1-4 alkyl group in the aromatic nucleus; and R stands for a phenyl group optionally substituted by a C1-4 alkyl group in the aromatic nucleus and their solvates, their individual optically active and geometric isomers and mixtures of isomers as well as acid additon salts thereof. The invention further relates to pharmaceutical compositions containing the above compounds and a process for their preparation. The compounds of formula (I) are capable of inhibiting the calcium uptake to brain cells and have a protective effect in hypobaric hypoxia. Thus, they are useful in the protection from brain injuries of hypoxic origin.

摘要翻译： 本发明涉及式（I）的新型治疗活性的恶嗪基异喹啉衍生物，其中R 1表示氢，C 1-4烷基，苯基或苯基-C 1-4烷基; R 2和R 3中的一个代表C 1-4烷氧基，另一个表示任选被芳族核中的C 1-4烷基取代的苯基-C 1-4烷氧基; 并且R 4代表任选被芳族核中的C 1-4烷基取代的苯基及其溶剂合物，它们各自的光学活性和几何异构体以及异构体的混合物以及其酸加成盐。 本发明还涉及含有上述化合物的药物组合物及其制备方法。 式（I）的化合物能够抑制钙对脑细胞的吸收，并且在低压缺氧中具有保护作用。 因此，它们可用于保护缺氧来源的脑损伤。

公开(公告)号：WO1991008200A1

公开(公告)日：1991-06-13

申请号：PCT/HU1990000076

申请日：1990-11-22

申请人： RICHTER GEDEON VEGYÉSZETI GYAR RT. ,  NADOR, Károly ,  SCHEIBER, Pál ,  NEMES, Péter ,  KARPATT, Egon ,  KISS, Béla ,  SZPORNY, László ,  PALOSI, Éva ,  GROO, Dóra ,  LAPIS, Erzsébet ,  SZOMBATHELYI, Zsolt ,  SARKADI, Adám ,  BODO, Mihály ,  LASZLOVSZKY, István ,  GERE, Aniko ,  CSOMOR, Katalin ,  LASZY, Judit ,  SZENTIRMAI, Zsolt

发明人： RICHTER GEDEON VEGYÉSZETI GYAR RT.

IPC分类号： C07D211/70

CPC分类号： C07D211/70

摘要： The invention relates to novel tetrahydropyridine derivatives, a process for their preparation and pharmaceutical compositions containing such compounds as active agents. In formula (I), Ar means a phenyl group optionally mono- or polysubstituted, Ar means a phenyl group optionally substituted, R means a hydrogen atom or an alkyl group with 1-6 carbon atoms, n can be either 0 or 1 with the proviso that if n = 0 then R can only mean a hydrogen atom and Ar is in any case substituted.

摘要翻译： 本发明涉及新的四氢吡啶衍生物，其制备方法和含有这些化合物作为活性剂的药物组合物。 在式（I）中，Ar 1表示任选被一个或多个取代的苯基，Ar 2表示任选被取代的苯基，R 1表示氢原子或1-6个碳原子的烷基， n可以是0或1，条件是如果n = 0，则R 1只能表示氢原子，Ar 2在任何情况下都被取代。