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首页> 外国专利> Hexaciclopenta c pyrrole derivatives as activators of Central Histamine Systems, a process for their preparation, Pharmaceutical compositions containing them and Drugs for the treatment of neuropathologies associated with Brain Aging

Hexaciclopenta c pyrrole derivatives as activators of Central Histamine Systems, a process for their preparation, Pharmaceutical compositions containing them and Drugs for the treatment of neuropathologies associated with Brain Aging

机译：作为中央组胺系统活化剂的六氯吡喃并[c]吡咯衍生物，其制备方法，含有它们的药物组合物以及用于治疗与脑衰老相关的神经病理学的药物

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Drug synthesis and drugs have stimulative effects on the central histamine system in the treatment of diseases related to brain aging. ILO Convention No. 1: formula compounds (1)Where m and N may be the same or different, each representing an integer between 0 and 2, including an integer between 2 and 3; P and Q may be the same or different, each representing an integer between 0 and 2; ALK representing a tar chain, Alquenileno or tar; and E and ',They may be the same or different, respectively representing a hydrogen atom, a halogenated atom or a group of asphalt, oxygen, asphalt, asphalt, asphalt, polycarbonate, mercato, hydroxi, perhalogeo, Niro, amino (uncured or replaced by one or two groups of asphalt),Acid, carbamate (optionally substituted in Nitrobenzene by one or two tar groups),Ammonium acid (optionally replaced in Nitrobenzene by a group of bitumen),Oxygen carbide, carboxi, sulfur or cyanogen; X represents oxygen atom, sulfur atom or n (R) group, R represents hydrogen atom or tar group; W represents selected group of cyanogen (X represents oxygen atom or NR group),-N (R1) - z1r2 and z2-nr1r2, where Z1 represents - C (or)-C (S) --C (NR4) --C (O) -N (R3) --C (S) -N (R3) --C (NR4) -N (R3) --C (O) -O*-C (s) - O-O-S (o) r - r = 1 or 2, y * is equivalent to n (R1);Z2 for - C (o)-C (S) --C (NR4) --S (o) r - or link; R1, R2, R3, and R4 may be the same or different, representing a hydrogen atom, an optional tar group, an optional substitute group, an optional alternative tar group, an alcoxi group, an optional alternative cyclopentane group, and an isocyclopentadine group, respectively Alternative, alternative arilo group, or alternative heteromorphic group; or R1 and R2 or R2 and R3, together with atoms carrying these substances, form an alternative or alternative heterocyclopropene group; its counterpart, symmetric isomer,como as tambi na sus sales de adicion con uno oms cidos o bases farmac uticamente aceptables donde el t rmino alquilo indica una cadena de hidrocarburo lineal o ramificada C1-6 el t rmino alquenilo indica un grupo lineal o ramificada C3-6 y entre 1 y el t rmino acilo indica un grupo RaC (O) - en el que Ra representa un tomo de hidrogeno o un grupo alquilo el t rmino perhaloalquilo indica una cadena de carbono lineal o ramificada C1-3 y entre 1 y 7 tomos de halogeno el t The term heterosexual refers to a single or double ring group, at least one of which is an aromatic ring, consisting of 5 to 11 rings, with 1 to 4 heteroatoms selected from nitro, oxygen and sulfur. The term cyclopentanediol refers to a single ring or single c3-11 hydrocarbon, which can optionally be unsaturated or unsaturated by one or two unsaturated chains, or unsaturated or unsaturated by one or two unsaturated chains, 1. It contains 4 to 11 rings and 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur;Alternative expressions for the terms cyclopentanediol, arilo, isoacrylonitrile and isopropylisopropyl isopropyl alcohol indicate that (I) these substances can be replaced by the same or different substitutes selected from asphalt, propoxy, asphalt, asphalt, asphalt, asphalt, halogen, hydroxyl, mercato, Perchloride tar, ammonium nitrate (not adsorbed or replaced by one or two groups of bitumen),Acid, carbamate (optionally substituted in Nitrobenzene by one or two tar groups),Ammonium acid (optionally replaced in Nitrobenzene by a group of bitumen),Oxycarbides, anthrax, sulfur or cyanogens; or (II) these groups may be replaced by arilo, heteromorphic, cyclopentadiene, isocyclopropyl or benzodiene groups, on the understanding that in a group of non aromatic and non aromatic components, arilo group or heteromorphic group may also be replaced by one or two oxo groups. Aromatic and isopropyl isopropyl compounds can also be replaced by one or two oxo groups; alternative expressions of the word tar, starch or tar indicate that these groups can be replaced by one or two same or different groups selected from asphalt or pitch,Tar, alcoxi, halogeno, hydroxi, mercato, Niro, amino, ACIO, amino, amino, acomini, alcoxibonio, carboxi, sulfo, Ciano, optional alternative arilo, optional alternative heteromorph, optional alternative cyclopentyl, optional alternative isocyclopentadienyl and optional alternative ariloxi. ILO Convention No. 31: a procedure for the preparation of formula compounds (1) in accordance with ILO Convention No. 1, characterized by the use of a formula compound (2) as a starting material,Where: ALK is (1) defined in the formula,Hal represents a halogenated atom, X represents an oxygen atom, a sulfur atom or an n (P) group,In (P), it represents the convection protection group of a hydrogen atom, a nitrogen atom or a tar group, and W, e and y 'are defined in the formula (1),This formula compound (2),After non selective protection, it is condensed in the basic intermediate with the bicycle formula (3),Where: n, m, P and Q are defined by the formula (1),a. A formula compound (1) is provided;When w represents a cyanogen group, it can optionally react with sodium hydroxide or potassium hydroxide to produce a formula compound (4),A special formula compound (1) in which ALK, N, m, P, Q, x, e y's is defined as formula (1),1. Formula compound (1): if desired, it can be purified according to conventional purification technology; it can be selectively separated into isomers according to conventional separation technology; if desired, it can be converted into addictive salt containing one or more acids or acceptable bases of drugs; Understanding: at any time deemed appropriate in the above procedures, rental groups or groups of carbide, hydrogen sulfide, ammonia, initial reagent (II) can be protected, and then, after condensation, they will not be protected if necessary for synthesis;Reagents (II) and (III) were produced according to known procedures described in the literature.
机译：药物合成和药物对中枢组胺系统具有促进作用，可治疗与脑衰老有关的疾病。国际劳工组织第1号公约：式（1）其中m和N可以相同或不同，分别表示0到2之间的整数，包括2到3之间的整数; P和Q可以相同或不同，每个代表0到2之间的整数;代表焦油链，Alquenileno或tar的ALK; E和'，它们可以相同或不同，分别代表氢原子，卤原子或一组沥青，氧，沥青，沥青，沥青，聚碳酸酯，巯基，羟基，过卤素，Niro，氨基（未固化或酸，氨基甲酸酯（在硝基苯中可选地被一个或两个焦油基团取代），铵酸（在硝基苯中可选地被一组沥青取代），碳化氧，羧酸，硫或氰; X代表氧原子，硫原子或n（R）基团，R代表氢原子或焦油基团; W代表选定的氰基基团（X代表氧原子或NR基团），-N（R1）-z1r2和z2-nr1r2，其中Z1代表-C（或）-C（S）--C（NR4）--C （O）-N（R3）-C（S）-N（R3）-C（NR4）-N（R3）-C（O）-O * -C（s）-OOS（o）r -r = 1或2，y *等效于n（R1）;-C（o）-C（S）--C（NR4）--S（o）r-或链为Z2; R 1，R 2，R 3和R 4可以相同或不同，分别代表氢原子，任选的焦油基团，任选的取代基，任选的替代焦油基，醇盐基，任选的替代环戊烷基和异环戊二烯基，分别为Alternate，Alternate arilo基团或Alternate异构基团; R 1和R 2或R 2和R 3与携带这些物质的原子一起形成一个或多个杂环丙烯基;或它的对应物，对称异构体，com，作为tambi na sus销售协定书，以农作物为基础的可接受的价格，d的t rmino alquilo印第安纳和caden de hidrocarburo的o ramificada C1-6的el t rmino alquenilo印第安克unupupo的o ramificada -6月1日，印第安纳州的拉古米诺拉科（Ra）（O）-印第安纳州立大学的水溶代用品（C）从左到右依次为C1-3路线图。 7卤代甲苯。术语“异性”是指单环或双环基团，其中至少一个是由5至11个环组成，并具有1-4个选自硝基，氧和硫的杂原子的芳族环。术语环戊二醇是指单环或单c3-11烃，其可以任选地被一个或两个不饱和链为不饱和或不饱和，或被一个或两个不饱和链为不饱和或不饱和的。其包含4至11个环和1最多3个选自氮，氧和硫的杂原子;环戊二醇，芳基，异丙烯腈和异丙基异丙基异丙醇的术语替代表示（I）这些物质可以被选自沥青，丙氧基，沥青，沥青的相同或不同替代物取代，沥青，沥青，卤素，羟基，巯基，高氯化物焦油，硝酸铵（不被一或两组沥青吸附或代替），酸，氨基甲酸酯（在硝基苯中可选地被一或两个焦油基团取代），铵酸（可选在硝基苯中被一组沥青，碳氧化物，炭疽，硫或氰取代;或（II）这些基团可以被芳基，杂晶基，环戊二烯，异环丙基或苯甲二烯基团取代，但要理解在一组非芳族和非芳族组分中，芳基或杂晶基团也可以被一个或两个氧代取代。组。芳族和异丙基异丙基化合物也可以被一个或两个氧代基团取代;单词tar，淀粉或tar的替代表达表示这些基团可以被一个或两个相同或不同的基团取代，这些基团选自沥青或沥青，塔尔，醇，卤素，羟基，巯基，Niro，氨基，ACIO，氨基，氨基，阿科尼尼，阿科西伯尼奥，羧甲基，磺基，Ciano，可选的替代芳基，可选的替代杂晶，可选的替代环戊基，可选的替代异环戊二烯基和可选的替代ariloxi。国际劳工组织第31号公约：根据国际劳工组织第1号公约，制备通式化合物（1）的方法，其特征在于使用通式化合物（2）作为起始原料，其中：ALK定义为（1）式中，Hal表示卤原子，X表示氧原子，硫原子或n（P）基，In（P）表示氢原子，氮原子或焦油基的对流保护基，和W，e和y'定义在式（1）中，该式化合物（2），经过非选择性保护后，与自行车式（3）缩合在基本中间体中，其中：n，m， P和Q由公式（1）定义，一种。提供了一种式（1）的化合物;当w表示氰基时，它可以任选地与氢氧化钠或氢氧化钾反应生成式（4），一种特殊的式（1），其中ALK，N，m， P，Q，x，ey's定义为公式（1），1。式（1）化合物：如果需要，可以按照常规的纯化技术进行纯化;可以根据常规分离技术将其选择性地分离为异构体。如果需要，可以将其转化成含有一种或多种酸或可接受的药物碱的成瘾性盐;理解：在上述程序中认为合适的任何时候，可以保护租赁基团或碳化物，硫化氢，氨，起始试剂（II）的基团，然后在缩合后如果需要合成则将不被保护;试剂（II）和（III）是根据文献中描述的已知方法制备的。

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