公开(公告)号：US5130309A

公开(公告)日：1992-07-14

申请号：US684313

申请日：1991-04-12

Applicant: James R. Shanklin, Jr. ,  Mark R. Hellberg

Inventor： James R. Shanklin, Jr. ,  Mark R. Hellberg

IPC: A61K31/395 ,  C07D205/04

CPC classification number: A61K31/395 ,  C07D205/04

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US4812451A

公开(公告)日：1989-03-14

申请号：US845148

申请日：1986-03-27

Applicant: James R. Shanklin, Jr. ,  James M. Wilkinson, II

Inventor： James R. Shanklin, Jr. ,  James M. Wilkinson, II

IPC: C07D207/08 ,  C07D211/34 ,  C07D211/42 ,  C07D223/04 ,  A61K31/445

CPC classification number: C07D207/08 ,  C07D211/34 ,  C07D211/42 ,  C07D223/04

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US4724235A

公开(公告)日：1988-02-09

申请号：US846534

申请日：1986-03-31

Applicant: James R. Shanklin, Jr. ,  Christopher P. Johnson, III

Inventor： James R. Shanklin, Jr. ,  Christopher P. Johnson, III

IPC: A61K31/495 ,  C07C317/28 ,  C07C323/44 ,  C07C335/08 ,  C07D209/48 ,  C07D307/38 ,  A61K31/55 ,  A61K31/445 ,  A61K31/535

CPC classification number: C07D209/48 ,  C07C255/00 ,  C07C317/28 ,  C07C323/00 ,  C07C323/44 ,  C07C335/08 ,  C07D307/38 ,  C07C2101/14 ,  Y10S514/821

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US4593102A

公开(公告)日：1986-06-03

申请号：US750156

申请日：1985-07-01

Applicant: James R. Shanklin, Jr.

Inventor： James R. Shanklin, Jr.

IPC: C07D207/34 ,  C07D207/36 ,  C07D211/54 ,  C07D223/06 ,  C07D211/46

CPC classification number: C07D223/06 ,  C07D207/34 ,  C07D207/36 ,  C07D211/54

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US4500529A

公开(公告)日：1985-02-19

申请号：US492534

申请日：1983-05-09

Applicant: James R. Shanklin, Jr. ,  Christopher P. Johnson, III

Inventor： James R. Shanklin, Jr. ,  Christopher P. Johnson, III

IPC: C07C43/225 ,  C07C275/14 ,  C07C335/08 ,  C07D209/48 ,  C07D295/13 ,  A61K31/535 ,  A61K31/17

CPC classification number: C07D209/48 ,  C07C275/14 ,  C07C335/08 ,  C07C43/225 ,  C07D295/13 ,  Y10S514/821

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5198449A

公开(公告)日：1993-03-30

申请号：US515620

申请日：1990-04-27

Applicant: James R. Shanklin, Jr.

Inventor： James R. Shanklin, Jr.

IPC: C07D211/28 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D513/04

CPC classification number: C07D401/04 ,  C07D211/28 ,  C07D401/06 ,  C07D401/12 ,  C07D513/04

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5070087A

公开(公告)日：1991-12-03

申请号：US349247

申请日：1989-05-08

Applicant: Lina C. Teng ,  David A. Walsh ,  James R. Shanklin, Jr.

Inventor： Lina C. Teng ,  David A. Walsh ,  James R. Shanklin, Jr.

IPC: A61K31/40 ,  A61K31/44 ,  A61K31/445 ,  A61K31/55

CPC classification number: A61K31/40 ,  A61K31/44 ,  A61K31/445 ,  A61K31/55

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US4895840A

公开(公告)日：1990-01-23

申请号：US60266

申请日：1987-06-10

Applicant: James R. Shanklin, Jr.

Inventor： James R. Shanklin, Jr.

IPC: 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 classification number: C07D213/40 ,  C07C317/28 ,  C07C317/42 ,  C07C323/44 ,  C07C335/08 ,  C07D295/13 ,  C07D307/38

Abstract: 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.

公开(公告)号：US4812452A

公开(公告)日：1989-03-14

申请号：US845170

申请日：1986-03-27

Applicant: James R. Shanklin, Jr. ,  James M. Wilkinson, II

Inventor： James R. Shanklin, Jr. ,  James M. Wilkinson, II

IPC: C07D207/08 ,  C07D211/34 ,  C07D211/42 ,  C07D223/04 ,  A61K31/445

CPC classification number: C07D207/08 ,  C07D211/34 ,  C07D211/42 ,  C07D223/04

Abstract: 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## 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.

Abstract translation: 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乙腈：其中; n为零，一或二; X是氧或硫; Z是或 - （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。

公开(公告)号：US4810703A

公开(公告)日：1989-03-07

申请号：US882743

申请日：1986-07-07

Applicant: James R. Shanklin, Jr. ,  James M. Wilkinson, II

Inventor： James R. Shanklin, Jr. ,  James M. Wilkinson, II

IPC: C07D207/08 ,  C07D211/34 ,  C07D211/42 ,  C07D223/04 ,  A61K31/445

CPC classification number: C07D207/08 ,  C07D211/34 ,  C07D211/42 ,  C07D223/04

Abstract: 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## 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.

Abstract translation: 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是或 - （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。