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1. 发明授权

US5140026A N-aminoalkyl-S-aryl-S-alkyl (or substituted alkyl) sulfoximines as antiarrhythmic agents 失效
标题翻译： N-氨基烷基-S-芳基-S-烷基（或取代的烷基）亚磺酰亚胺作为抗心律不齐药
公开(公告)号：US5140026A
公开(公告)日：1992-08-18
申请号：US697825
申请日：1991-05-09
申请人： Mark R. Hellberg , James R. Shanklin, Jr.
发明人： Mark R. Hellberg , James R. Shanklin, Jr.
IPC分类号： C07C381/10 , C07D295/13 , C07D333/34 , C07D521/00
CPC分类号： C07D295/13 , C07C381/10 , C07D231/12 , C07D233/56 , C07D249/08 , C07D333/34
摘要： Compounds of this invention are represented by the formula: ##STR1## wherein Z is a C.sub.1 -C.sub.6 alkylene group and R is an alkyl or substituted alkyl group. Class III antiarrhythmic activity is determined in vitro using an electrophysiological test where prolongation of the action potential duration is an indication of activity.
摘要翻译：本发明的化合物由下式表示：其中Z是C1-C6亚烷基，R是烷基或取代的烷基。使用电生理测试在体外测定III类抗心律失常活性，其中动作电位持续时间的延长是活动的指示。

2. 发明授权

US5130309A Aryloxy and aryloxyalklazetidines as antiarrhythmic and anticonvulsant agents 失效
标题翻译：芳氧基和芳氧基亚油酸作为抗心律失常药和抗惊厥药
公开(公告)号：US5130309A
公开(公告)日：1992-07-14
申请号：US684313
申请日：1991-04-12
申请人： James R. Shanklin, Jr. , Mark R. Hellberg
发明人： James R. Shanklin, Jr. , Mark R. Hellberg
IPC分类号： A61K31/395 , C07D205/04
CPC分类号： A61K31/395 , C07D205/04
摘要： Methods of treating cardiac arrhythmias and convulsions in warm-blooded animas and pharmaceutical compositions therefor are disclosed. The compounds useful in the methods of treatment and compositions are represented by the formula ##STR1## where n is 0 to 3 and R is H, C.sub.1 -C.sub.4 alkyl or arylalkyl and Ar is phenyl or substituted phenyl.
摘要翻译：公开了在温血动物及其药物组合物中治疗心律失常和抽搐的方法。用于处理方法和组合物的化合物由式（I）表示，其中n为0至3，R为H，C 1 -C 4烷基或芳基烷基，Ar为苯基或取代的苯基。

3. 发明授权

US4812451A 1-(aminoalkyl and aminoalkylamino)carbonyl and thiocarbonyl)-.alpha.,.alpha . 失效
标题翻译： 1-（氨基烷基和氨基烷基氨基）羰基和硫代羰基）-α，α二芳基吡咯烷，哌啶和高哌啶乙酰胺和乙腈
公开(公告)号：US4812451A
公开(公告)日：1989-03-14
申请号：US845148
申请日：1986-03-27
申请人： James R. Shanklin, Jr. , James M. Wilkinson, II
发明人： James R. Shanklin, Jr. , James M. Wilkinson, II
IPC分类号： C07D207/08 , C07D211/34 , C07D211/42 , C07D223/04 , A61K31/445
CPC分类号： C07D207/08 , C07D211/34 , C07D211/42 , C07D223/04
摘要： Novel 1-[(aminoalkyl and aminoalkylamino)carbonyl and thiocarbonyl-.alpha.,.alpha.-diaryl-pyrrolidine, piperidine and homopiperidineacetamides and acetonitriles having the formula: ##STR1## wherein; n is zero, one or two;X is oxygen or sulfur;Z is ##STR2## 10 or --(CH.sub.2); p is 0 to 5 inclusive with the proviso that when Z is ##STR3## p is at least one; Y is aminocarbonyl or cyano;Ar.sup.1 and Ar.sup.2 are 2, 3 or 4-pyrido, phenyl or substituted phenyl;R is hydrogen or loweralkyl;R.sup.1, R.sup.2 and R.sup.3 are hydrogen, cycloalkyl, loweralkyl, phenyl, substituted phenyl, phenylloweralkyl, and R.sup.2 and R.sup.3 taken with the adjacent nitrogen may form a heterocyclic residue, and diastereoisomers when possible and pharmaceutical salts; and the method and pharmaceutical compositions for treating cardiac arrhythmias therewith are disclosed.
摘要翻译：新颖的1- [（氨基烷基和氨基烷基氨基）羰基和硫代羰基-α，α-二芳基 - 吡咯烷，哌啶和高哌啶乙酰胺和具有下式的丙酮：其中; n为零，一或二; X是氧或硫; Z为10或 - （CH2）; p为0至5，其条件是当Z为至少1时; Y是氨基羰基或氰基; Ar1和Ar2是2,3或4-吡啶基，苯基或取代的苯基; R是氢或低级烷基; R 1，R 2和R 3是氢，环烷基，低级烷基，苯基，取代的苯基，苯基低级烷基，与相邻的氮取代的R 2和R 3可以形成杂环残基，当可能时可以形成非对映异构体和药用盐; 并公开了用于治疗心律失常的方法和药物组合物。

4. 发明授权

US4724235A N-(arylthioalkyl)-N'-(aminoalkyl)ureas useful in the treatment of arrhythmia 失效
标题翻译：可用于治疗心律失常的N-（芳基硫代烷基）-N' - （氨基烷基）脲
公开(公告)号：US4724235A
公开(公告)日：1988-02-09
申请号：US846534
申请日：1986-03-31
申请人： James R. Shanklin, Jr. , Christopher P. Johnson, III
发明人： James R. Shanklin, Jr. , Christopher P. Johnson, III
IPC分类号： A61K31/495 , C07C317/28 , C07C323/44 , C07C335/08 , C07D209/48 , C07D307/38 , A61K31/55 , A61K31/445 , A61K31/535
CPC分类号： C07D209/48 , C07C255/00 , C07C317/28 , C07C323/00 , C07C323/44 , C07C335/08 , C07D307/38 , C07C2101/14 , Y10S514/821
摘要： N-(Arylthioalkyl)-N'-(aminoalkyl)ureas and thioureas and oxidation derivatives having the formula ##STR1## wherein B is thio, sulfinyl or sulfonyl; R.sup.1 and R.sup.2 are hydrogen, loweralkyl, cycloalkyl, 2-furanyl, phenyl, substituted phenyl or phenyl-loweralkyl and R.sup.3 and R.sup.4 are hydrogen, loweralkyl, phenyl or phenyl-loweralkyl wherein phenyl is optionally substituted, or R.sup.3 and R.sup.4 taken with the adjacent nitrogen form a heterocyclic residue. The compounds are useful in the treatment of cardiac arrhythmia.
摘要翻译： N-（芳硫基烷基）-N' - （氨基烷基）脲和硫脲和具有式“IMAGE”的氧化衍生物，其中B是硫代，亚磺酰基或磺酰基; R 1和R 2是氢，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是氢，低级烷基，苯基或苯基 - 低级烷基，其中苯基是任选取代的，或者R 3和R 4与相邻氮形成杂环残基。该化合物可用于治疗心律失常。

5. 发明授权

US4593102A N-[(amino)alkyl]-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) with sulfur linked substitution in the 2, 3 or 4-position 失效
标题翻译：在2,3或4位具有硫连接取代基的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）
公开(公告)号：US4593102A
公开(公告)日：1986-06-03
申请号：US750156
申请日：1985-07-01
申请人： James R. Shanklin, Jr.
发明人： James R. Shanklin, Jr.
IPC分类号： C07D207/34 , C07D207/36 , C07D211/54 , C07D223/06 , C07D211/46
CPC分类号： C07D223/06 , C07D207/34 , C07D207/36 , C07D211/54
摘要： Novel pyrrolidine, piperidine and homopiperidinecarboxamide and thiocarboxamide compounds having the formula: ##STR1## wherein X is --S--, --S(O)-- or --S(O).sub.2 --; A is a loweralkalene chain and A.sup.1 and A.sup.2 are alkalene chains when p and d are one; R, R.sup.1 and R.sup.2 are hydrogen, loweralkyl, phenyl cycloalkyl or phenylalkyl and R.sup.1 and R.sup.2 may form a heterocyclic residue with the adjacent nitrogen atom; Q is a selected aromatic radical, and the pharmaceutically acceptable acid addition salts useful as cardiac antiarrhythmia agents are disclosed.Novel chemical intermediates, unsubstituted on pyrrolidine, piperidine and homopiperidine nitrogen but with --(A.sup.2).sub.p --X--(A.sup.2).sub.d --Q side chain are also disclosed.
摘要翻译：具有下式的新型吡咯烷，哌啶和高哌啶甲酰胺和硫代甲酰胺化合物：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，R 1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是选择的芳族基团，并且公开了可用作心脏抗心律失常药物的药学上可接受的酸加成盐。还公开了在吡咯烷，哌啶和高哌啶氮上未取代的新型化学中间体，但具有 - （A2）p -X-（A2）d-Q侧链。

6. 发明授权

US4500529A Method of treating cardiac disorders with N-(aryloxyalkyl)-N'-(aminoalkyl)ureas 失效
标题翻译：用N-（芳氧基烷基）-N' - （氨基烷基）脲处理心脏病的方法
公开(公告)号：US4500529A
公开(公告)日：1985-02-19
申请号：US492534
申请日：1983-05-09
申请人： James R. Shanklin, Jr. , Christopher P. Johnson, III
发明人： James R. Shanklin, Jr. , Christopher P. Johnson, III
IPC分类号： C07C43/225 , C07C275/14 , C07C335/08 , C07D209/48 , C07D295/13 , A61K31/535 , A61K31/17
CPC分类号： C07D209/48 , C07C275/14 , C07C335/08 , C07C43/225 , C07D295/13 , Y10S514/821
摘要： N-(Aryloxyalkyl)-N'-(aminoalkyl)ureas and thioureas having the formula: ##STR1## wherein R.sup.1 and R.sup.2 are hydrogen, loweralkyl, cycloalkyl, phenyl or phenyllower alkyl, and R.sup.3 and R.sup.4 are hydrogen, loweralkyl, phenyl and phenylalkyl or R.sup.3 and R.sup.4 taken together with the adjacent nitrogen form a heterocyclic residue are disclosed in a method of suppressing cardiac arrhythmias.
摘要翻译：具有下式的N-（芳氧基烷基）-N' - （氨基烷基）脲和硫脲其中R1和R2是氢，低级烷基，环烷基，苯基或苯基低级烷基，R3和R4是氢，低级烷基，苯基和苯基烷基或R 3和R 4与相邻的氮一起形成杂环残基，在抑制心律失常的方法中公开。

7. 发明授权

US06258761B1 Lubricating oil additives 失效
标题翻译：润滑油添加剂
公开(公告)号：US06258761B1
公开(公告)日：2001-07-10
申请号：US09329891
申请日：1999-06-10
申请人： Richard M. Lange , James R. Shanklin, Jr. , Jeffry G. Dietz , Richard Yodice , Naresh C. Mathur
发明人： Richard M. Lange , James R. Shanklin, Jr. , Jeffry G. Dietz , Richard Yodice , Naresh C. Mathur
IPC分类号： C10M15212
CPC分类号： C10L1/236 , C08F8/30 , C10L1/221 , C10L1/238 , C10M159/12
摘要： A composition prepared by reacting (A) an esterified carboxy-containing interpolymer, said interpolymer being derived from at least two monomers, (i) one of said monomers being at least one vinyl aromatic monomer and (ii) the other of said monomers being at least one alpha, beta-unsaturated acylating agent, and having, before esterification, {overscore (M)}n determined by gel permeation chromatography ranging from about 8,000 to about 350,000, wherein from about 80% to about 99% of the carboxylic groups of said interpolymer are esterified, wherein from about 80 to about 100% of the ester groups contain from 8 to about 23 carbon atoms and from 0 to about 20% of the ester groups contain from 2 to 7 carbon atoms, with (B) a hydrocarbyl substituted carboxylic acid or functional derivative thereof wherein the hydrocarbyl group comprises from about 10 to about 400 carbon atoms, and (C) an amine having an average of more than 1 condensable N—H group, in any order or simultaneously, or with the preformed reaction product of (B) and (C) wherein said preformed reaction product has at least one condensable N—H group. Depending upon the relative amounts of reactant (A) and (B) used, a composition which acts primarily as a viscosity improver with dispersant properties (DVM) or primarily as a dispersant with viscosity improving properties (VMD) may be prepared or compositions with properties intermediate between these.
摘要翻译：一种组合物，其通过（A）含酯化的含羧基的互聚物，所述互聚物衍生自至少两种单体，（i）所述单体之一是至少一种乙烯基芳族单体和（ii）所述单体中的另一种在至少一种α，β-不饱和酰化剂，并且在酯化之前，通过凝胶渗透色谱测定的超过（M）} n为约8,000至约350,000，其中约80％至约99％的羧基所述互聚物被酯化，其中约80至约100％的酯基含有8至约23个碳原子，0至约20％的酯基含有2至7个碳原子，（B）烃基取代的羧酸或其官能衍生物，其中烃基包含约10至约400个碳原子，和（C）平均大于1个可冷凝NH基团的胺，以任何顺序或同时或与（B）和（C）的预成型反应产物，其中所述预成型反应产物具有至少一个可冷凝的N-H基团。取决于所用的反应物（A）和（B）的相对量，可以制备主要作为粘度改进剂的分散剂性能（DVM）或主要作为具有粘度改进性能（VMD）的分散剂的组合物或具有性质的组合物这些之间的中间。

8. 发明授权

US5198449A N-substituted alpha-arylazacycloalkylmethanamines and their use as cardiovascular agents 失效
标题翻译： N-取代的α-芳基氮杂环烷基甲胺及其作为心血管剂的用途
公开(公告)号：US5198449A
公开(公告)日：1993-03-30
申请号：US515620
申请日：1990-04-27
申请人： James R. Shanklin, Jr.
发明人： James R. Shanklin, Jr.
IPC分类号： C07D211/28 , C07D401/04 , C07D401/06 , C07D401/12 , C07D513/04
CPC分类号： C07D401/04 , C07D211/28 , C07D401/06 , C07D401/12 , C07D513/04
摘要： Novel compounds of the formula below wherein W is azetidine, pyrrolidine or piperidine, Q is a straight chain hydrocarbon radical of 1-4 carbons and may contain a double bond, and ##STR1## Ar is phenyl, pyridinyl or pyrimidinyl, a process for their preparation, and novel intermediates are disclosed. The novel compounds and the pharmaceutical compositions of this invention are useful in the treatment of hypertension, arrhythmias and angina.
摘要翻译：下式的新化合物，其中W是氮杂环丁烷，吡咯烷或哌啶，Q是1-4个碳的直链烃基，并且可以含有双键，并且Ar是苯基，吡啶基或嘧啶基，它们是制备和新型中间体。本发明的新型化合物和药物组合物可用于治疗高血压，心律失常和心绞痛。

9. 发明授权

US5070087A Aryl(alkyland alkylene)-N-((phenoxy and phenylthio)alkyl) aminoheterocyclics as cardiovascular, anthihistaminic, antisecretory and antiallergy agents 失效
标题翻译：芳基（烷基和亚烷基）-N - （（苯氧基和苯硫基）烷基）氨基杂环作为心血管，组织结构，抗分泌和抗过敏剂
公开(公告)号：US5070087A
公开(公告)日：1991-12-03
申请号：US349247
申请日：1989-05-08
申请人： Lina C. Teng , David A. Walsh , James R. Shanklin, Jr.
发明人： Lina C. Teng , David A. Walsh , James R. Shanklin, Jr.
IPC分类号： A61K31/40 , A61K31/44 , A61K31/445 , A61K31/55
CPC分类号： A61K31/40 , A61K31/44 , A61K31/445 , A61K31/55
摘要： A method of treating cardiac dysfunction, the effects of histamine, and gastric secretion excesses with aryl(alkyl and alkylene)-N-[(phenoxy and phenythio)alkyl]aminoheterocyclics corresponding to the formula: ##STR1## wherein Ar is phenyl or substituted phenyl; R is phenyl, substituted phenyl, pyridinyl or cycloalkyl; A is hydrogen, hydroxy, cyano, amido and amino; Q is --CH.sub.2 --, --CH--, or --CHOH--; d and n are zero or one and the dotted lines form double bonds consistent with the valence of carbon; p is zero, one or two; m is one to six inclusive; B is oxygen, nitrogen, sulfur, sulfinyl or sulfonyl; z is zero or one; l is zero or one; W is hydrogen, loweralkyl, halo, nitro, loweralkoxy or hydroxy; X is hydrogen, loweralkyl, halogen, loweralkoxy or hydroxy; Y is --CH(OH)CH.sub.2 OH, --CH(OH)C(O)OH, --C(O)C(O)OH, --C(O)CH.sub.2 OH,--C(O)C(O)OCH.sub.3, --C(O)C(O)OC.sub.2 H.sub.5, --CH.sub.2 C(O)OC.sub.2 H.sub.5, --CH(OH)C(O)OCH.sub.3, --CH(OH)C(O)OC.sub.2 H.sub.5 or --C(O)CH.sub.2 OC(O)CH.sub.3 ; and the pharmaceutically acceptable salts thereof; in addition to the above methods of treatment, compounds wherein (B).sub.z is oxygen are useful in a method of treating Gell and Coombs type 1 allergic responses in mammals.
摘要翻译：一种治疗心脏功能障碍的方法，组胺和胃分泌过度与芳基（烷基和亚烷基）-N - [（苯氧基和苯基）烷基]氨基杂环对应于下式：其中Ar是苯基或取代的苯基 ; R是苯基，取代的苯基，吡啶基或环烷基; A是氢，羟基，氰基，酰氨基和氨基; Q是-CH 2 - ， - CH-或-CHOH-; d和n为零或一个，虚线形成与碳化合价一致的双键; p为零，一或二; m是一到六个包含; B是氧，氮，硫，亚磺酰基或磺酰基; z为零或一; l为零或一; W是氢，低级烷基，卤素，硝基，低级烷氧基或羟基; X是氢，低级烷基，卤素，低级烷氧基或羟基; Y是-CH（OH）CH 2 OH，-CH（OH）C（O）OH，-C（O）C（O）OH，-C（O）CH 2 OH，-C（O）C（O） C（O）C（O）OC 2 H 5，-CH 2 C（O）OC 2 H 5，-CH（OH）C（O）OCH 3，-CH（OH）C（O）OC 2 H 5或-C（O）CH 2 OC（O）及其药学上可接受的盐; 除了上述治疗方法之外，其中（B）z是氧的化合物可用于治疗哺乳动物中凝胶和1型过敏反应的方法。

10. 发明授权

US4895840A N-(aryl-,aryloxy-,arylthio-arylsulfinyl-and arylsulfonyl-)alkyl-N,N'-(or n'n')alkylaminoalkyl ureas and cyanoguanidines 失效
标题翻译： N-（芳基 - ，芳氧基 - ，芳硫基 - 芳基亚磺酰基 - 和芳基磺酰基）烷基-N，N' - （或n'n'）烷基氨基烷基脲和氰基胍
公开(公告)号：US4895840A
公开(公告)日：1990-01-23
申请号：US60266
申请日：1987-06-10
申请人： James R. Shanklin, Jr.
发明人： James R. Shanklin, Jr.
IPC分类号： A61K31/17 , A61K31/00 , A61K31/275 , A61K31/34 , A61K31/341 , A61P9/06 , C07C67/00 , C07C239/00 , C07C275/14 , C07C275/24 , C07C279/28 , C07C313/00 , C07C317/28 , C07C317/32 , C07C317/36 , C07C317/40 , C07C317/42 , C07C317/44 , C07C323/20 , C07C323/44 , C07C323/65 , C07C335/08 , C07D213/40 , C07D213/64 , C07D213/70 , C07D213/71 , C07D295/13 , C07D307/38 , C07D307/40
CPC分类号： C07D213/40 , C07C317/28 , C07C317/42 , C07C323/44 , C07C335/08 , C07D295/13 , C07D307/38
摘要： Novel N-(Aryl-,aryloxy-,arylthio-,arylsulfinyl-and arylsulfonyl-)alkyl-N,N'-(or N',N')alkylaminoalkyl ureas, thioureas and cyanoguanidines represented by the following formula: ##STR1## wherein Ar is aryl selected from the group consisting of 1- and 2-naphthyl, 2,3-dihydro-1H-inden-4(or 5)-yl,2-furanylmethyl,2-pyridinyl, phenyl and phenyl substituted by 1-3 radicals commonly used in the pharmaceutical art; (X).sub.d is oxygen, thio, sulfinyl, sulfonyl or d is zero; Z and W are each R or-(CH.sub.2).sub.m -NR.sup.1 R.sup.2 wtih the proviso that when Z is R, W is-(CH.sub.2).sub.m -NR.sup.1 R.sup.2 and when Z is-(CH.sub.2).sub.m -NR.sup.1 R.sup.2, W is R; B is carbonyl, thioxomethyl, or cyanoiminomethyl; R, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are selected from the group consisting of hydrogen, loweralkyl, cycloalkyl, phenyl or phenyl-loweralkyl wherein phenyl may be substituted by 1-3 radicals commonly used in the pharmaceutical art; R.sup.1 and R.sup.2, and R.sup.3 and R.sup.4 may together with the adjacent nitrogen form the heterocyclic ring structure 1-homopiperidinyl, 4-morpholinyl, 1-piperazinyl, 4-substituted-1-piperazinyl, 1-pyrrolidinyl or 1-piperidinyl and the pharmaceutically acceptable salts thereof are disclosed. A pharmaceutical method for administering the compounds for their cardiac antiarrhythmic effect and pharmaceutical compositions for the treatment of cardiac arrhythmia are also disclosed.

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