公开(公告)号：US4005090A

公开(公告)日：1977-01-25

申请号：US560106

申请日：1975-03-19

申请人： Miroslav Semonsky ,  Antonin Cerny ,  Oldrich Nemecek ,  Karel Rezabek ,  Miroslav Seda ,  Vaclav Trcka ,  Jaroslava Grimova

发明人： Miroslav Semonsky ,  Antonin Cerny ,  Oldrich Nemecek ,  Karel Rezabek ,  Miroslav Seda ,  Vaclav Trcka ,  Jaroslava Grimova

IPC分类号： A61K31/48 ,  C07D457/02

CPC分类号： C07D457/02

摘要： 8-(.beta.-AMINOETHYL)ERGOLINES-I of the general formula ##STR1## wherein R.sup.1 is a hydrogen atom or an acyl group of the general formula R.sup.3 --CO, R.sup.3 being a hydrogen atom, an alkyl group having from 1-5 carbon atoms, a phenyl group, a phenylalkyl group or a pyridyl group or substituents thereof, and R.sup.2 is a hydrogen atom or a methyl group. Acid addition salts of the described ergolines evidence pharmacological activity in the anti-inflammation and hypotensive fields.

摘要翻译： 其中R1是氢原子或通式R3-CO的酰基，R3是氢原子的烷基，具有1-5个碳原子的烷基 原子，苯基，苯基烷基或吡啶基或​​其取代基，R2是氢原子或甲基。 所述ergolines的酸加成盐表明抗炎和降血压领域的药理活性。

公开(公告)号：US4775673A

公开(公告)日：1988-10-04

申请号：US851339

申请日：1986-04-14

申请人： Jan Koenig ,  Miroslav Rajsner ,  Vaclav Trcka ,  Sverluse Macova

发明人： Jan Koenig ,  Miroslav Rajsner ,  Vaclav Trcka ,  Sverluse Macova

IPC分类号： C07D295/18 ,  A61K31/505 ,  A61K31/517 ,  A61P9/12 ,  C07D239/95 ,  C07D403/04

CPC分类号： C07D239/95

摘要： Substituted acylpiperazinoquinazolines of formula I ##STR1## wherein n is 0 or 1, R represents an alkyl group with 1 to 4 carbon atoms or a benzyl group, and R.sub.1 is a hydrogen atom, a methyl group or a phenyl group. Addition salts of these compounds with inorganic and organic acids are also disclosed. The compounds possess a significant antihypertensive activity. They can be prepared by the reaction of 2-halogeno quinazoline derivatives with the corresponding acylpiperazines, followed (if required) by neutralization of the respective base with a suitable acid to form its pharmaceutically convenient addition salt.The acid addition salts, especially hydrochlorides, are readily soluble in water and give stable, almost neutral aqueous solutions which can be used in parenteral (injectable) and peroral medicinal dosage forms.

摘要翻译： 取代的式I的酰基哌嗪喹唑啉其中n为0或1，R表示具有1至4个碳原子的烷基或苄基，R 1为氢原子，甲基或苯基。 还公开了这些化合物与无机和有机酸的加成盐。 该化合物具有显着的抗高血压活性。 它们可以通过2-卤代喹唑啉衍生物与相应的酰基哌嗪的反应制备，随后（如果需要）通过用合适的酸中和相应的碱以形成其药学上方便的加成盐。 酸加成盐，特别是盐酸盐，易溶于水，得到稳定的，几乎中性的水溶液，可用于肠胃外（可注射）和口服药物剂型。

公开(公告)号：US5424456A

公开(公告)日：1995-06-13

申请号：US150047

申请日：1993-11-18

申请人： Gabriel Butora ,  Miroslav Rajsner ,  Ivan Helfert ,  Vaclav Trcka

发明人： Gabriel Butora ,  Miroslav Rajsner ,  Ivan Helfert ,  Vaclav Trcka

IPC分类号： A61K31/35 ,  A61K31/357 ,  A61P7/02 ,  A61P9/12 ,  A61P25/02 ,  C07D319/20

CPC分类号： C07D319/20

摘要： New N-Arylalkylderivatives of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and its (+)- and (-)- enantiomers represented by general formula (I), where R.sub.1, R.sub.2 and R.sub.3 represent H, or R.sub.1 and R.sub.2 represent H and R.sub.3 represent H or R.sub.1 and R.sub.2 represent methoxy and R.sub.3 represents H and their pharmaceutically acceptable organic or inorganic acid addition salts exhibit in pharmacological tests pronounced hypotensive activity as a result of their calcium channel blocking and alpha.sub.1 -adrenergic blocking activity and pronounced antithrombotic action. In a form of pharmaceutical preparations, they are suitable for the treatment and prevention of cardiovascular diseases and other disorders. New compounds of general formula (I) by N-alkylation of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and its (+)- and (-)-enantiomers by derivatives of 2 phenyl-2-isopropyl-5-oxovaleronitrile under the conditions of reductive alkylation or with derivatives of 5-bromo-2-phenyl-2-isopropylvaleronitrile, which can be prepared by allylation of alpha-isopropylbenzyl cyanide and subsequent addition of hydrogen bromide under free radical conditions to the obtained alpha-allyl-alpha-isopropylbenzyl cyanide and its derivatives.

摘要翻译： PCT No.PCT / CS92 / 00015 Sec。 371日期：1993年11月18日 102（e）日期1993年11月18日PCT提交1992年5月27日PCT公布。 WO92 / 21671 PCT出版物 日期：1992年12月10日。2-氨基甲基-2,3-二氢-1,4-苯并二恶英的新N-芳基烷基衍生物及其由通式（I）表示的（+） - 和（ - ） - 对映异构体，其中R1， R2和R3表示H，或R1和R2表示H，R3表示H或R1，R2表示甲氧基，R3表示H，其药学上可接受的有机或无机酸加成盐在药理学试验中表现为由于钙通道而导致的降血压活性 阻断和α1-肾上腺素能阻断活性和明显的抗血栓形成作用。 以药物制剂的形式，它们适用于治疗和预防心血管疾病和其它疾病。 通过2-苯基-2-异丙基 - 苯并二恶烷衍生物的2-氨基甲基-2,3-二氢-1,4-苯并二氧杂环己烷及其（+） - 和（ - ） - 对映异构体的N-烷基化，得到通式（I）的新化合物， 在还原性烷基化的条件下或与5-溴-2-苯基-2-异丙基戊腈的衍生物反应，其可以通过α-异丙基苄基氰化物的烯丙基化和随后在自由基条件下将溴化氢在所得的α 烯丙基-α-异丙基苄基氰化物及其衍生物。

公开(公告)号：US4847403A

公开(公告)日：1989-07-11

申请号：US74801

申请日：1987-07-17

申请人： Luedvik Blaha ,  Miroslav Rajsner ,  Ivan Helfert ,  Vaclav Trcka

发明人： Luedvik Blaha ,  Miroslav Rajsner ,  Ivan Helfert ,  Vaclav Trcka

IPC分类号： C07C255/42 ,  A61K31/275 ,  A61P9/06 ,  A61P9/12 ,  C07C67/00 ,  C07C253/00 ,  C07C255/24 ,  C07C255/32 ,  C07C255/43 ,  C07D317/60

CPC分类号： C07C255/00

摘要： 2-Isopropyl-2-(2-methylphenyl)-5-(N-methylhomoveratrylamino)-valeronitrile ("mepamil") of the Formula I: ##STR1## preferably administered in the form of water-soluble acid addition salts such as e.g. hydrochloride. The claimed compound is advantageously prepared by alkylation of 2-(2-methylphenyl)-3-methylbutyronitrile with 3,3-diethoxypropylchloride. Subsequently, the obtained 5,5-diethoxy-2-isopropyl-2-(2-Methylphenyl)-valeronitrile is mildly, acidically hydrolisized to yield the appropriate aldehye, i.e. 2-isopropyl-2-(2-methylphenyl)-5-oxovaleronitrile. This aldehyde is then reacted with N-methylhomoveratrylamine under conditions of reductive alkylation, suitably by catalytic hydrogenation over a platinum or palladium catalyst or by chemical reduction with the use of formic acid as a reducing agent. The resulting base is optionally converted by neutralization with a pharmaceutically acceptable organic or inorganic acid, i.e. hydrochloric or fumaric acid, into the corresponding acid addition salt.