公开(公告)号：US4500712A

公开(公告)日：1985-02-19

申请号：US438259

申请日：1982-11-01

申请人： Luigi Bernardi ,  Aldemio Temperilli ,  Daniela Ruggieri ,  Giuliana Arcari ,  Patricia Salvati

发明人： Luigi Bernardi ,  Aldemio Temperilli ,  Daniela Ruggieri ,  Giuliana Arcari ,  Patricia Salvati

IPC分类号： A61K31/48 ,  A61P1/04 ,  A61P9/12 ,  C07D457/02 ,  C07D457/12 ,  C07D457/04

CPC分类号： C07D457/02 ,  C07D457/12

摘要： There are provided ergoline derivatives of formula ##STR1## wherein R.sub.1 .dbd.H, CH.sub.3 ; R.sub.2 .dbd.H or halogen atom, or CH.sub.3,CN, alkyl- or phenyl-thio; R.sub.3 .dbd.H, OCH.sub.3 ; R.sub.4 .dbd.C.sub.1 -C.sub.4 hydrocarbon group; X.dbd.O, S, NH; A.dbd.CO, SO.sub.2 ; B.dbd.C.sub.1 -C.sub.4 hydrocarbon group, aryl, aralkyl, heterocyclic ring group, alkoxy, aryloxy; n.dbd.0, 1, 2; and pharmaceutically acceptable salts thereof.A process for preparing said compounds is also provided. The compounds show anti-hypertensive activity and are active on the gastroenteric system.

摘要翻译： 提供式（Ⅰ）的麦角灵衍生物，其中R1 = H，CH3; R2 = H或卤素原子，或CH3，CN，烷基或苯基 - 硫基; R3 = H，OCH3; R4 = C1-C4烃基; X = O，S，NH; A = CO，SO2; B = C1-C4烃基，芳基，芳烷基，杂环基，烷氧基，芳氧基; n = 0,1,2; 及其药学上可接受的盐。 还提供了制备所述化合物的方法。 这些化合物显示出抗高血压活性，并且对胃肠系统有活性。

公开(公告)号：US3957785A

公开(公告)日：1976-05-18

申请号：US493335

申请日：1974-07-31

申请人： Giuliana Arcari ,  Luigi Bernardi ,  Germano Bosisio ,  Maurizio Foglio ,  Alfredo Glasser ,  Aldemio Temperilli

发明人： Giuliana Arcari ,  Luigi Bernardi ,  Germano Bosisio ,  Maurizio Foglio ,  Alfredo Glasser ,  Aldemio Temperilli

IPC分类号： C07D457/02

CPC分类号： C07D457/02

摘要： Novel 8.beta.-pyrimidino-aminomethyl-10.alpha.-ergoline and 10.alpha.-methoxyergoline derivatives which possess a high and prolonged adrenolytic activity and a low toxicity, and some of which also possess hypotensive and analgesic activity are prepared by reacting a pyrimidine anion with an ergoline derivative in an aprotic solvent.

公开(公告)号：US3996228A

公开(公告)日：1976-12-07

申请号：US530617

申请日：1974-12-09

申请人： Giuliana Arcari ,  Luigi Bernardi ,  Germano Bosisio ,  Alfredo Glasser ,  Aldemio Temperilli

发明人： Giuliana Arcari ,  Luigi Bernardi ,  Germano Bosisio ,  Alfredo Glasser ,  Aldemio Temperilli

IPC分类号： C07D457/02

CPC分类号： C07D457/02

摘要： Pyrimidinoaminoethyl ergoline derivatives of the formula: ##STR1## wherein R is hydrogen or methyl; R.sub.1 and R.sub.2 are independently selected from the group consisting of hydrogen, alkyl having 1 to 3 carbon atoms, methoxy and phenyl;R.sub.3 is hydrogen, halogen, alkyl and alkoxy each having 1 to 3 carbon atoms, phenyl, nitro, amino, cyano, acylamino, carboxamido and carbalkoxy each having 1 to 3 carbon atoms, trifluoromethyl or --SO.sub.2 --Y wherein Y is hydroxyl, amino or methyl and R.sub.4 is hydrogen or methoxy are prepared by reacting an ergoline derivative of formula III and a 2-aminopyrimidine anion of formula II ##STR2##

摘要翻译： 具有下式的嘧啶基氨基乙基麦角灵衍生物：其中R是氢或甲基; R 1和R 2独立地选自氢，具有1至3个碳原子的烷基，甲氧基和苯基; R3是氢，卤素，烷基和烷氧基，各自具有1至3个碳原子，苯基，硝基，氨基，氰基，酰氨基，甲酰胺基和碳烷氧基，各自具有1至3个碳原子，三氟甲基或-SO2-Y，其中Y是羟基， 或甲基和R 4是氢或甲氧基通过使式III的麦角灵衍生物与式II的2-氨基嘧啶阴离子反应来制备。

公开(公告)号：US4317912A

公开(公告)日：1982-03-02

申请号：US129333

申请日：1980-03-11

申请人： Aldemio Temperilli ,  Sergio Mantegani ,  Giuliana Arcari ,  Anna M. Caravaggi

发明人： Aldemio Temperilli ,  Sergio Mantegani ,  Giuliana Arcari ,  Anna M. Caravaggi

IPC分类号： C07D457/02 ,  A61K31/40 ,  A61K31/48 ,  A61P9/12 ,  C07D487/06 ,  A61K31/445 ,  A61K31/535 ,  C07D487/00

CPC分类号： C07D487/06

摘要： A compound is disclosed of the formula (I): ##STR1## wherein R.sub.1 represents a hydrogen atom, or a carboxy, alkoxycarbonyl, piperidinocarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, carbamoyl or benzylcarbamoyl group, or an alkylcarbamoyl or dialkylcarbamoyl group in which the, or each, alkyl group has from 1 to 4 carbon atoms;R.sub.2 represents a hydrogen or fluorine atom, or a cyano, acetyl or carbamoyl group; andR.sub.3 represents a hydrogen atom or a methyl group; and represents a single or a double bond, with the proviso that R.sub.1 and R.sub.2 do not simultaneously represent hydrogen atoms;or a pharmaceutically acceptable salt thereof.

摘要翻译： 公开了式（I）的化合物：其中R 1表示氢原子，或羧基，烷氧基羰基，哌啶子基羰基，1-吡咯烷基羰基，吗啉代羰基，氨基甲酰基或苄基氨基甲酰基，或烷基氨基甲酰基或二烷基氨基甲酰基 其中或每个烷基具有1至4个碳原子; R2表示氢或氟原子，或氰基，乙酰基或氨基甲酰基; 并且R 3表示氢原子或甲基; 并且表示单键或双键，条件是R1和R2不同时表示氢原子; 或其药学上可接受的盐。

公开(公告)号：US4141899A

公开(公告)日：1979-02-27

申请号：US838844

申请日：1977-10-03

申请人： Giuliana Arcari ,  Luigi Bernardi ,  Giovanni Falconi ,  Fulvio Luini ,  Giorgio Palamidessi ,  Ugo Scarponi

发明人： Giuliana Arcari ,  Luigi Bernardi ,  Giovanni Falconi ,  Fulvio Luini ,  Giorgio Palamidessi ,  Ugo Scarponi

IPC分类号： C07D471/04

CPC分类号： Y10S514/926 ,  Y10S514/927

摘要： New 4,5,6,7-tetrahydroimidazo-[4,5-c]-pyridine derivatives are disclosed, and more particularly derivatives of Formula I ##STR1## where R.sub.1 is hydrogen or an alkyl having from 1 to 4 carbon atoms;R.sub.2 is hydrogen, an alkyl having from 1 to 4 carbon atoms, a cycloalkyl having from 3 to 6 carbon atoms, phenyl or a heterocycle;R.sub.3 is hydrogen, a saturated or unsaturated straight or branched alkyl having from 1 to 6 carbon atoms, a cycloalkyl having from 3 to 6 carbon atoms, benzoyl or phenyl; andX is O, S or NR.sub.4 where R.sub.4 is hydrogen, an alkyl having from 1 to 4 carbon atoms, cyano, amino, nitro or acylamino;Or pharmaceutically acceptable acid addition salts thereof. Also disclosed is a process of preparing these compounds which comprises condensing an appropriate 4,5,6,7-tetrahydroimidazo-[4,5-c]-pyridine with an appropriate alkyl isocyanate, alkyl isothiocyanate or substituted S-methyl thiourea, preferably in a solvent such as ethanol, acetonitrile or dioxane, usually under reflux for from 4 to 12 hours. The products can be isolated by crystallization as free bases or as salts of pharmaceutically acceptable acids. The new compounds have proved to be well tolerated and to inhibit both the number of experimental ulcers and the gastric secretion in experimental animals. Thus, they should prove useful in the therapy of gastric and duodenal ulcers in man.

摘要翻译： 公开了新的4,5,6,7-四氢咪唑并[4,5-c] - 吡啶衍生物，更具体地，其中R 1是氢或具有1至4个碳原子的烷基的式I的衍生物; R 2是氢，具有1至4个碳原子的烷基，具有3至6个碳原子的环烷基，苯基或杂环; R3是氢，具有1至6个碳原子的饱和或不饱和直链或支链烷基，具有3至6个碳原子的环烷基，苯甲酰基或苯基; 且X为O，S或NR 4，其中R 4为氢，具有1至4个碳原子的烷基，氰基，氨基，硝基或酰氨基; 或其药学上可接受的酸添加剂。 还公开了制备这些化合物的方法，其包括将合适的4,5,6,7-四氢咪唑并[4,5-c] - 吡啶与适当的烷基异氰酸酯，异硫氰酸烷基酯或取代的S-甲基硫脲缩合，优选在 溶剂如乙醇，乙腈或二恶烷，通常在回流下4至12小时。 可以通过结晶作为游离碱或药学上可接受的酸的盐分离产物。 这些新化合物已被证明是良好的耐受性，并且在实验动物中抑制实验性溃疡的数量和胃分泌。 因此，它们应该证明在治疗人和十二指肠溃疡方面是有用的。

公开(公告)号：US4223146A

公开(公告)日：1980-09-16

申请号：US959506

申请日：1978-11-13

申请人： Giuliana Arcari ,  Luigi Bernardi ,  Giovanni Falconi ,  Ugo Scarponi

发明人： Giuliana Arcari ,  Luigi Bernardi ,  Giovanni Falconi ,  Ugo Scarponi

IPC分类号： A61K31/4188 ,  A61K31/435 ,  A61K31/437 ,  A61P1/04 ,  A61P25/02 ,  C07D471/04

CPC分类号： C07D471/04 ,  Y10S514/925

摘要： Compounds are disclosed of the general formula (I): ##STR1## wherein R.sub.1 is a lower alkyl having from 1 to 4 carbon atoms; R.sub.2 is hydrogen or a lower alkyl having from 1 to 4 carbon atoms; and R.sub.3 is a saturated or unsaturated straight or branched alkyl having from 1 to 4 carbon atoms. A process for making such compounds is also disclosed. These compounds are useful as antiulcer agents and as inhibitors of gastric secretion.

摘要翻译： 公开了通式（I）的化合物：其中R 1是具有1至4个碳原子的低级烷基; R2是氢或具有1至4个碳原子的低级烷基; 并且R 3是具有1至4个碳原子的饱和或不饱和的直链或支链烷基。 还公开了制备这些化合物的方法。 这些化合物可用作抗溃疡剂和胃分泌抑制剂。

公开(公告)号：US3972883A

公开(公告)日：1976-08-03

申请号：US436927

申请日：1974-01-28

申请人： Giuliana Arcari ,  Luigi Bernardi ,  Germano Bosisio ,  Alfredo Glasser ,  Innocenzio Sinatra

发明人： Giuliana Arcari ,  Luigi Bernardi ,  Germano Bosisio ,  Alfredo Glasser ,  Innocenzio Sinatra

IPC分类号： A61K31/48 ,  C07D457/02

CPC分类号： C07D457/02

摘要： Ergoline derivatives are disclosed having the general formula ##SPC1##Wherein R is selected from the group consisting of a lower alkyl radical having from 1 to 4 carbon atoms; an --NH-lower alkyl radical having from 1 to 4 carbon atoms; a free or substituted phenyl- or 2-furanoyl radical; the --O--CH.sub.2 --C.sub.6 H.sub.5 radical; a (3)- or (4)-pyridine radical free or substituted by a methyl radical or a chlorine or bromine atom; a pyrrole radical of formula ##SPC2##WhereinY is hydrogen, a lower alkyl radical having from 1 to 4 carbon atoms or phenyl;R.sub.1 is hydrogen or methyl;R.sub.2 is hydrogen, methyl or halogen; andR.sub.3 and R.sub.4 are the same or different and are hydrogen, halogen, a lower alkyl radical having from 1 to 4 carbon atoms, carbethoxy, or a lower alkyloxy radical having from 1 to 4 carbon atoms.Novel processes for the preparation of these compounds are also disclosed.

摘要翻译： 公开了具有通式为WHEREIN R选自具有1至4个碳原子的低级烷基的衍生物， 具有1至4个碳原子的-NH-低级烷基; 游离或取代的苯基或2-呋喃酰基; -O-CH 2 -C 6 H 5基团; （3） - 或（4） - 吡啶基自由或被甲基或氯或溴原子取代; 式WHEREIN Y的吡咯基是氢，具有1至4个碳原子的低级烷基或苯基; R1是氢或甲基; R2是氢，甲基或卤素; 并且R 3和R 4相同或不同，为氢，卤素，具有1至4个碳原子的低级烷基，乙氧羰基或具有1至4个碳原子的低级烷氧基。

公开(公告)号：US4490376A

公开(公告)日：1984-12-25

申请号：US474887

申请日：1983-03-14

申请人： Gianfederico Doria ,  Carlo Passarotti ,  Giuliana Arcari

发明人： Gianfederico Doria ,  Carlo Passarotti ,  Giuliana Arcari

IPC分类号： A61K31/505 ,  A61K31/519 ,  A61P1/04 ,  C07D487/04

CPC分类号： C07D487/04 ,  Y10S514/925

摘要： Compounds of the formula (I) ##STR1## wherein R.sub.1 is:(a) hydrogen, or C.sub.1 -C.sub.6 alkyl;(b) an unsubstituted 2-pyridyl or 3-pyridyl group;(c) a benzyl group, wherein the phenyl ring is unsubstituted or substituted by halogen, C.sub.1 -C.sub.6 alkoxy or C.sub.1 -C.sub.6 alkyl;(d) a phenyl ring, unsubstituted or substituted by one or two groups chosen from halogen, trihalomethyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkanoylamino, nitro and amino;each of R.sub.2 and R.sub.3 independently represents hydrogen, halogen or C.sub.1 -C.sub.6 alkyl;R.sub.4 represents a 2-pyridyl, 3-pyridyl or 4-pyridyl group, unsubstituted or substituted by C.sub.1 -C.sub.6 alkyl;and the pharmaceutically acceptable salts thereof are disclosed. The compounds have activity in the gastroenteric system, particularly anti-ulcerogenic and gastric anti-secretory activity. Additionally, the compounds have activity in reducing the undesired gastrointestinal side-effects resulting from systemic administration of anti-inflammatory prostaglandin synthetase inhibitors.

摘要翻译： 式（I）化合物其中R 1是：（a）氢或C 1 -C 6烷基; （b）未取代的2-吡啶基或3-吡啶基; （c）苄基，其中所述苯环未被取代或被卤素，C 1 -C 6烷氧基或C 1 -C 6烷基取代; （d）未被取代或被一个或两个选自卤素，三卤甲基，C 1 -C 6烷氧基，C 1 -C 6烷基，C 2 -C 6烷酰氨基，硝基和氨基的基团取代的苯环; R 2和R 3各自独立地表示氢，卤素或C 1 -C 6烷基; R4表示未取代或被C1-C6烷基取代的2-吡啶基，3-吡啶基或4-吡啶基; 及其药学上可接受的盐。 该化合物在胃肠系统中具有活性，特别是抗溃疡和胃的抗分泌活性。 此外，该化合物具有降低由全身施用抗炎前列腺素合成酶抑制剂引起的不希望的胃肠道副作用的活性。

公开(公告)号：US4252941A

公开(公告)日：1981-02-24

申请号：US72289

申请日：1979-09-04

申请人： Sergio Mantegani ,  Giuliana Arcari ,  Anna M. Caravaggi ,  Germano Bosisio

发明人： Sergio Mantegani ,  Giuliana Arcari ,  Anna M. Caravaggi ,  Germano Bosisio

IPC分类号： C07D457/04 ,  A61K31/48 ,  A61P9/12 ,  C07D457/02

CPC分类号： C07D457/02

摘要： Compounds and process for making same are disclosed, the compounds having the formula (I): ##STR1## wherein R.sub.1 represents a methyl, phenyl, piperidino, 1-pyrrolidinyl, morpholino or 4-methyl-1-piperazinyl group, an alkyl or alkoxy group having from 1 to 4 carbon atoms, an amino group, a substituted amino group of the formula NHR' (wherein R' represents an alkyl group having from 1 to 4 carbon atoms, a cycloalkyl group, a benzyl group, or a phenyl group) or a substituted amino group of the formula NR" R"' (wherein R" and R"' both represent alkyl groups having from 1 to 4 carbon atoms);R.sub.2 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, or a phenyl group;R.sub.3 represents a fluorine atom, a cyano, difluoromethyl, difluorobromomethyl, trifluoromethyl, methylthio, methylsulphonyl, or sulphonamido group, an alkoxy group having from 1 to 4 carbon atoms, an acyl group having from 2 to 4 carbon atoms, or a benzoyl group;R.sub.4 represents a hydrocarbon group having from 1 to 4 carbon atoms;R.sub.5 represents a hydrogen atom or a methoxy group;R.sub.6 represents a hydrogen or halogen atom or a methyl group; andR.sub.7 represents a hydrogen atom or a methyl group.The 2-cyano derivatives are especially preferred.

摘要翻译： 公开了化合物及其制备方法，具有式（I）的化合物：其中R 1表示甲基，苯基，哌啶子基，1-吡咯烷基，吗啉代或4-甲基-1-哌嗪基， 具有1至4个碳原子的烷基或烷氧基，氨基，式NHR'的取代氨基（其中R'表示具有1至4个碳原子的烷基，环烷基，苄基或 苯基）或式NR“R”'的取代氨基（其中R“和R”“均表示具有1至4个碳原子的烷基）; R2表示氢原子，具有1至4个碳原子的烷基或苯基; R 3表示氟原子，氰基，二氟甲基，二氟溴甲基，三氟甲基，甲硫基，甲磺酰基或磺酰胺基，具有1至4个碳原子的烷氧基，具有2至4个碳原子的酰基或苯甲酰基; R4表示具有1至4个碳原子的烃基; R5表示氢原子或甲氧基; R6表示氢或卤素原子或甲基; 并且R 7表示氢原子或甲基。 2-氰基衍生物是特别优选的。

公开(公告)号：US4444773A

公开(公告)日：1984-04-24

申请号：US398302

申请日：1982-07-14

申请人： Gianfederico Doria ,  Carlo Passarotti ,  Giuliana Arcari ,  Ada Buttinoni

发明人： Gianfederico Doria ,  Carlo Passarotti ,  Giuliana Arcari ,  Ada Buttinoni

IPC分类号： A61K31/519 ,  A61P1/04 ,  A61P29/00 ,  C07D513/04 ,  C07F9/6561

CPC分类号： C07D513/04 ,  C07F9/6561 ,  Y10S514/927

摘要： Pharmacologically active thiazolo[3,2-a]pyrimidines of the formula ##STR1## wherein A is a bond between the .alpha. and .beta.-carbon atoms or (--CH.sub.2 --) group; R.sub.1 and R.sub.2 represent hydrogen or halogen, C.sub.1 -C.sub.4 alkyl, cyano, CF.sub.3, thienyl, pyridyl, biphenyl, naphtyl, phenyl optionally substituted, ##STR2## wherein R' and R" are hydrogen or alkyl; R.sub.3 represents hydrogen, halogen, alkyl, OH, formyloxy, alkanoyloxy, alkenyloxy; R.sub.4 represents pyridyl optionally substituted by alkyl. The compounds have antiinflammatory, antiulcerogenic and anti-gastric secretory activity.

摘要翻译： 药物活性的噻唑并[3,2-a]嘧啶，其结构式为：其中A是α和β-碳原子或（-CH 2 - ）基团之间的键; R 1和R 2表示氢或卤素，C 1 -C 4烷基，氰基，CF 3，噻吩基，吡啶基，联苯基，萘基，任选取代的苯基，其中R'和R“是氢或烷基; R 3表示氢，卤素，烷基，OH，甲酰氧基，烷酰氧基，烯氧基; R 4表示任选被烷基取代的吡啶基。 该化合物具有抗炎，抗溃疡和抗胃分泌活性。