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1. 发明公开

EP0160436A2 N-[(Amino)Alkyl]-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) with sulphur linked substitution in the 2, 3 or 4-position 失效
标题翻译： N - （氨基）烷基-1-吡咯烷，1-哌啶和1-高哌啶甲酰胺（和硫代羧酰胺），在2,3代4-Stellung中的Schwefelbindung
公开(公告)号：EP0160436A2
公开(公告)日：1985-11-06
申请号：EP85302526.0
申请日：1985-04-10
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr.
IPC分类号： C07D207/36 , C07D211/54 , C07D223/06
CPC分类号： C07D223/06 , C07D207/12 , C07D207/34 , C07D211/54
摘要： Pyrrolidine, piperidine and homopiperidine- carboxamide and thiocarboxamide compounds of the formula:
wherein X is -S-, -S(0)- or -S(0) 2 -; A is a loweralkalene chain and A 1 and A 2 are alkalene chains when p and d are one; R, R 1 and R 2 are hydrogen, loweralkyl, phenyl cycloalkyl or phenylalkyl and R 1 and R 2 may form a heterocyclic residue with the adjacent nitrogen atom; Q is a selected aromatic radical, and the pharmaceutically acceptable acid addition salts are useful as cardiac antiarrhythmia agents.
Chemical intermediates, unsubstituted on pyrrolidine, piperidine and homopiperidine nitrogen but with the -(A 2 ) p -X-(A 2 ) d -Q side chain are also disclosed.
摘要翻译：吡咯烷，哌啶和高哌啶甲酰胺和下式的硫代甲酰胺化合物：其中X是-S - ， - S（O） - 或-S（O）2 - ; A是下亚烯烃链，当p和d为1时，A 1和A 2为碱金属链; R 1，R 2和R 2是氢，低级烷基，苯基环烷基或苯基烷基，R 1和R 2可以与相邻的氮原子形成杂环残基; Q是选定的芳族基团，并且药学上可接受的酸加成盐可用作心脏抗心律失常药。还公开了在吡咯烷，哌啶和高哌啶氮上未取代但具有 - （A 2）p-X-（A 2）d-Q侧链的化学中间体。

2. 发明公开

EP0066415A3 N-(arylthioalkyl)-N'-(aminoalkyl)ureas 失效
标题翻译： N-（芳硫基烷基）-N' - （氨基烷基）脲
公开(公告)号：EP0066415A3
公开(公告)日：1983-09-14
申请号：EP82302557
申请日：1982-05-19
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr. , Johnson, Christopher Peter, III
IPC分类号： C07C149/437 , C07C147/00 , C07C157/00 , C07D295/12 , C07D307/38 , A61K31/17
CPC分类号： C07D209/48 , C07C255/00 , C07C317/28 , C07C323/00 , C07C323/44 , C07C335/08 , C07C2601/14 , C07D307/38
摘要： N-(Arylthioalkyl)-N'-(aminoalkyl)ureas and thioureas and oxidation derivatives having the formula
wherein B represents a thio, sulphinyl or sulphonyl group; R 1 and R 2 each represent a hydrogen atom or a loweralkyl, cycloalkyl, 2-furanyl, phenyl, substituted phenyl or phenyl-loweralkyl group and R 3 and R 4 each represent a hydrogen atom or a loweralkyl, phenyl or phenyl-loweralkyl group wherein phenyl is optionally substituted, or R 3 and R 4 taken with the adjacent nitrogen form a heterocyclic residue.
摘要翻译： N-（芳硫基烷基）-Nmin - （氨基烷基）脲和硫脲和具有式CHEM的氧化衍生物，其中B代表硫代，亚磺酰基或磺酰基; R 1和R 2各自表示氢原子或低级烷基，环烷基，2-呋喃基，苯基，取代的苯基或苯基 - 低级烷基，R 3和R 4各自表示氢原子或苯基或苯基 - 低级烷基，其中苯基任选被取代。或R 3和R 4与相邻的氮取代形成杂环残基。

3. 发明公开

EP0066987A2 N-(aryloxyalkyl)-N'-(amino-alkyl) ureas 失效
标题翻译： N-（芳氧基烷基）-N'（氨基烷基）-Harnstoffe。
公开(公告)号：EP0066987A2
公开(公告)日：1982-12-15
申请号：EP82302556.4
申请日：1982-05-19
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr. , Johnson, Christopher Peter, III
IPC分类号： C07C127/00 , C07C157/00 , A61K31/17 , C07C147/00 , C07D295/12
CPC分类号： C07D209/48 , C07C43/225 , C07C275/14 , C07C335/08 , C07D295/13
摘要： N-(Aryloxyalkyl)-N'-(aminoalkyl)ureas and thioureas having the formula:
wherein R 1 and R 2 each represent a hydrogen atom or a loweralkyl, cycloalkyl, phenyl or phenyllower alkyl group, and R 3 and R 4 each represent a hydrogen atom or a loweralkyl, phenyl or phenylalkyl group or R 3 and R 4 taken together with the adjacent nitrogen form a heterocyclic residue are disclosed for use in treating cardiac arrhythmias.
摘要翻译： N-（芳氧基烷基）-N min - （氨基烷基）脲和具有下式的硫脲：其中R 1和R 2各自表示氢原子或低级烷基，环烷基，苯基或苯基低级烷基， R 3和R 4各自表示氢原子或低级烷基，苯基或苯基烷基或R 3和R 4与相邻的氮一起形成杂环残基用于治疗心律失常。

4. 发明公开

EP0160436A3 N-[(Amino)Alkyl]-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) with sulphur linked substitution in the 2, 3 or 4-position 失效
标题翻译： N-Û（氨基）烷基-1-吡咯烷，1-PIPERIDINE和1-HOMOPIPERIDINARARAMAMESES（和硫代烟酰胺）在2,3或4位置具有连锁取代基
公开(公告)号：EP0160436A3
公开(公告)日：1988-06-08
申请号：EP85302526
申请日：1985-04-10
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr.
IPC分类号： C07D207/36 , C07D211/54 , C07D223/06
CPC分类号： C07D223/06 , C07D207/12 , C07D207/34 , C07D211/54
摘要： Pyrrolidine, piperidine and homopiperidine- carboxamide and thiocarboxamide compounds of the formula:
wherein X is -S-, -S(0)- or -S(0) 2 -; A is a loweralkalene chain and A 1 and A 2 are alkalene chains when p and d are one; R, R 1 and R 2 are hydrogen, loweralkyl, phenyl cycloalkyl or phenylalkyl and R 1 and R 2 may form a heterocyclic residue with the adjacent nitrogen atom; Q is a selected aromatic radical, and the pharmaceutically acceptable acid addition salts are useful as cardiac antiarrhythmia agents. Chemical intermediates, unsubstituted on pyrrolidine, piperidine and homopiperidine nitrogen but with the -(A 2 ) p -X-(A 2 ) d -Q side chain are also disclosed.

5. 发明授权

EP0066415B1 N-(arylthioalkyl)-N'-(aminoalkyl)ureas 失效
标题翻译： N-（芳硫基烷基）-N' - （氨基烷基）脲
公开(公告)号：EP0066415B1
公开(公告)日：1985-10-02
申请号：EP82302557.2
申请日：1982-05-19
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr. , Johnson, Christopher Peter, III
IPC分类号： C07C149/437 , C07C147/00 , C07C157/00 , C07D295/12 , C07D307/38 , A61K31/17
CPC分类号： C07D209/48 , C07C255/00 , C07C317/28 , C07C323/00 , C07C323/44 , C07C335/08 , C07C2601/14 , C07D307/38

6. 发明公开

EP0066415A2 N-(arylthioalkyl)-N'-(aminoalkyl)ureas 失效
标题翻译： N-（芳硫基烷基）-N'（氨基烷基）-Harnstoffe。
公开(公告)号：EP0066415A2
公开(公告)日：1982-12-08
申请号：EP82302557.2
申请日：1982-05-19
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr. , Johnson, Christopher Peter, III
IPC分类号： C07C149/437 , C07C147/00 , C07C157/00 , C07D295/12 , C07D307/38 , A61K31/17
CPC分类号： C07D209/48 , C07C255/00 , C07C317/28 , C07C323/00 , C07C323/44 , C07C335/08 , C07C2601/14 , C07D307/38
摘要： N-(Arylthioalkyl)-N'-(aminoalkyl)ureas and thioureas and oxidation derivatives having the formula
wherein B represents a thio, sulphinyl or sulphonyl group; R 1 and R 2 each represent a hydrogen atom or a loweralkyl, cycloalkyl, 2-furanyl, phenyl, substituted phenyl or phenyl-loweralkyl group and R 3 and R 4 each represent a hydrogen atom or a loweralkyl, phenyl or phenyl-loweralkyl group wherein phenyl is optionally substituted, or R 3 and R 4 taken with the adjacent nitrogen form a heterocyclic residue.
摘要翻译： N-（芳硫基烷基）-Nmin - （氨基烷基）脲和硫脲和具有式CHEM的氧化衍生物，其中B代表硫代，亚磺酰基或磺酰基; R 1和R 2各自表示氢原子或低级烷基，环烷基，2-呋喃基，苯基，取代的苯基或苯基 - 低级烷基，R 3和R 4各自表示氢原子或苯基或苯基 - 低级烷基，其中苯基任选被取代。或R 3和R 4与相邻的氮取代形成杂环残基。

7. 发明公开

EP0295010A1 Derivatives of alkylaminoalkyl ureas and cyanoguanidines 失效
标题翻译：衍生缬氨酸烷基氨基烷基硫代非氰基鸟嘌呤。
公开(公告)号：EP0295010A1
公开(公告)日：1988-12-14
申请号：EP88305059.3
申请日：1988-06-03
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr.
IPC分类号： C07C149/437 , C07C147/14 , C07C147/06 , C07C129/12 , C07C127/15 , C07C157/05 , C07C161/04 , C07C119/042 , C07C125/03 , C07C149/24 , C07D307/52
CPC分类号： C07D213/40 , C07C317/28 , C07C317/42 , C07C323/44 , C07C335/08 , C07D295/13 , C07D307/38
摘要： Compounds of general formula I
wherein,

Ar represents a 1-naphthyl group, a 2-naphthyl group, a 2,3-dihydro-1 H-inden-4(or 5)-yl group, a 2-furanylmethyl group, a 2-pyridinyl group, a phenyl group or a phenyl substituted by one to three substituents wherein the or each substituent independently represents a loweralkyl group, a loweralkoxy group, a diloweralkylamino group, a cyano group, a loweralkylthio group, a loweralkylsulfinyl group, a loweralkylsulfonyl group, an acyl group, an acylamino group, an aminocarbonyl group, a diloweral- kylaminoloweralkoxy group, a trifluoromethyl group, a nitro group or a halogen atom;
X represents a thio group, a sulfinyl group, a sulfonyl group or an oxygen atom;
d represents zero or one;
B represents a carbonyl group, a thioxomethyl group or a cyanoiminomethyl group;
each of n, m and p independently represents an integer from 2 to 6 inclusive;
each of Z and W independently represent an R group or a
group with the proviso that when Z represents R, W represents a -(CH 2 ) m- NR 1 R 2 group and when Z represents (CH 2 ) m- NR 1 R 2 , W represents R;
each of R, R 1 , R 2 , R 3 and R 4 independently represents a hydrogen atom, a loweralkyl group, a cycloalkyl group, a phenyl group or a phenylloweralkyl group wherein phenyl may be substituted by one to three radicals wherein each radical independently represents a loweralkyl group, a loweralkoxy group, a cyano group, a trifluoromethyl group, a nitro group or a halogen atom or
each of R 1 and R 2 , and R 3 and R 4 may, together with the adjacent nitrogen atom form the heterocyclic ring structure 1-homopiperidinyl, 1-piperidinyl, 4-morpholinyl, 1-pyrrolidinyl, 1-piperazinyl, or 4-substituted-1-piperazinyl;
with the further proviso that some meanings given for the symbols must not be realized simultaneously, as indicated specifically in claim 1, or the pharmaceutically acceptable salts thereof are useful in the treatment of cardiac arrhythmia.
摘要翻译：通式I 的化合物，其中Ar表示1-萘基，2-萘基，2,3-二氢-1H-茚-4（或5） - 基，2-呋喃基甲基， 2-吡啶基，苯基或被一至三个取代基取代的苯基，其中每个取代基独立地表示低级烷基，低级烷氧基，二低级烷基氨基，氰基，低级烷硫基，低级烷基亚磺酰基，酰基，酰氨基，氨基羰基，二低级烷基氨基低级烷氧基，三氟甲基，硝基或卤素原子; X表示硫基，亚磺酰基，磺酰基或氧原子; d表示0或1; B表示羰基，硫代甲基或氰基亚氨基甲基; n，m和p各自独立地表示2〜6的整数， Z和W各自独立地表示R基团或基团，条件是当Z表示R时，W表示 - （CH 2）m -NR A R 2基团，当Z表示（CH 2） m-NR 1 R 2，W表示R; R 1，R 2，R 2，R 3和R 4各自独立地表示氢原子，低级烷基，环烷基，苯基或苯基低级烷基，其中苯基可以被一至三个基团，其中每个基团独立地表示低级烷基，低级烷氧基，氰基，三氟甲基，硝基或卤素原子，或R 1和R 2各自独立地表示，且R 3，和R 4可以与相邻的氮原子一起形成杂环结构1-高哌啶基，1-哌啶基，4-吗啉基，1-吡咯烷基，1-哌嗪基或4-取代-1-哌嗪基; 进一步的条件是，符号给出的某些含义不能同时实现，如权利要求1中具体指出的，或其药学上可接受的盐可用于治疗心律失常。

8. 发明授权

EP0066987B1 N-(aryloxyalkyl)-N'-(amino-alkyl) ureas 失效
标题翻译： N-（氨基甲酰基）-N' - （氨基 - 烷基）脲
公开(公告)号：EP0066987B1
公开(公告)日：1986-08-27
申请号：EP82302556.4
申请日：1982-05-19
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr. , Johnson, Christopher Peter, III
IPC分类号： C07C127/00 , C07C157/00 , A61K31/17 , C07C147/00 , C07D295/12
CPC分类号： C07D209/48 , C07C43/225 , C07C275/14 , C07C335/08 , C07D295/13

9. 发明公开

EP0066987A3 N-(aryloxyalkyl)-N'-(amino-alkyl) ureas 失效
标题翻译： N-（氨基甲酰基）-N' - （氨基 - 烷基）脲
公开(公告)号：EP0066987A3
公开(公告)日：1983-09-14
申请号：EP82302556
申请日：1982-05-19
申请人： A.H. ROBINS COMPANY, INCORPORATED
发明人： Shanklin, James Robert, Jr. , Johnson, Christopher Peter, III
IPC分类号： C07C127/00 , C07C157/00 , A61K31/17 , C07C147/00 , C07D295/12 , C07C93/06
CPC分类号： C07D209/48 , C07C43/225 , C07C275/14 , C07C335/08 , C07D295/13
摘要： N-(Aryloxyalkyl)-N'-(aminoalkyl)ureas and thioureas having the formula:
wherein R 1 and R 2 each represent a hydrogen atom or a loweralkyl, cycloalkyl, phenyl or phenyllower alkyl group, and R 3 and R 4 each represent a hydrogen atom or a loweralkyl, phenyl or phenylalkyl group or R 3 and R 4 taken together with the adjacent nitrogen form a heterocyclic residue are disclosed for use in treating cardiac arrhythmias.

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