公开(公告)号：US3932398A

公开(公告)日：1976-01-13

申请号：US352850

申请日：1973-04-19

申请人： Abraham Nudelman ,  Ronald J. McCaully

发明人： Abraham Nudelman ,  Ronald J. McCaully

IPC分类号： C07D213/20 ,  C07D215/10 ,  C07D501/10 ,  C07D501/14 ,  C07D501/18

CPC分类号： C07D215/10 ,  C07D213/20

摘要： Penicillin sulfoxides are converted to 3-halo-3-methyl-cepham-4-carboxylic acid esters and amides or the corresponding cephem derivatives by heating the penicillin sulfoxide precursor in a polyhaloalkane solvent to a temperature between 50.degree. to about 150.degree.C. in the presence of an equimolar amount of a neutral or basic catalyst, respectively. The catalysts employed are bases such as pyridine, picoline, lutidine, quinoline, isoquinoline, dimethylaniline or a quaternary ammonium salt. The 3-halo-cepham intermediates produced with a quaternary ammonium catalyst are dehydrohalogenated to afford known cephem derivatives or converted to the free 4-carboxylic acid and the alkali metal, alkaline earth metal or ammonium salts thereof to afford novel antibacterial agents.

摘要翻译： 将青霉素亚砜转化为3-卤代-3-甲基 - 头孢烯-4-羧酸酯和酰胺或相应的头孢烯衍生物，通过将多卤烷溶剂中的青霉素亚砜前体加热至50℃至约150℃的温度 分别存在等摩尔量的中性或碱性催化剂。 所使用的催化剂是诸如吡啶，甲基吡啶，二甲基吡啶，喹啉，异喹啉，二甲基苯胺或季铵盐的碱。 用季铵催化剂制备的3-卤代 - 头孢烯中间体被脱卤化氢以提供已知的头孢烯衍生物或转化为游离的4-羧酸及其碱金属，碱土金属或铵盐，得到新的抗菌剂。

公开(公告)号：US4010156A

公开(公告)日：1977-03-01

申请号：US602623

申请日：1975-08-07

申请人： Abraham Nudelman ,  Ronald J. McCaully

发明人： Abraham Nudelman ,  Ronald J. McCaully

IPC分类号： C07D213/20 ,  C07D215/10 ,  C07D501/10

CPC分类号： C07D215/10 ,  C07D213/20

摘要： Penicillin sulfoxides are converted to 3-halo-3-methyl-cepham-4-carboxylic acid esters and amides or the corresponding cephem derivatives by heating the penicillin sulfoxide precursor in a polyhaloalkane solvent to a temperature between 50.degree. to about 150.degree. C. in the presence of an equimolar amount of a neutral or basic catalyst, respectively. The catalysts employed are bases such as pyridine, picoline, lutidine, quinoline, isoquinoline, dimethylaniline or a quaternary ammonium salt. The 3-halo-cepham intermediates produced with a quaternary ammonium catalyst are dehydrohalogenated to afford known cephem derivatives or converted to the free 4-carboxylic acid and the alkali metal, alkaline earth metal or ammonium salts thereof to afford novel antibacterial agents.

摘要翻译： 将青霉素亚砜转化为3-卤代-3-甲基 - 头孢烯-4-羧酸酯和酰胺或相应的头孢烯衍生物，通过将多卤烷溶剂中的青霉素亚砜前体加热至50℃至约150℃的温度 分别存在等摩尔量的中性或碱性催化剂。 所使用的催化剂是诸如吡啶，甲基吡啶，二甲基吡啶，喹啉，异喹啉，二甲基苯胺或季铵盐的碱。 用季铵催化剂制备的3-卤代 - 头孢烯中间体被脱卤化氢以提供已知的头孢烯衍生物或转化为游离的4-羧酸及其碱金属，碱土金属或铵盐，得到新的抗菌剂。

公开(公告)号：US4065451A

公开(公告)日：1977-12-27

申请号：US223712

申请日：1972-02-04

申请人： Ronald J. McCaully ,  Abraham Nudelman ,  Stanley C. Bell

发明人： Ronald J. McCaully ,  Abraham Nudelman ,  Stanley C. Bell

IPC分类号： A61K31/55 ,  C07D243/24 ,  C07D243/26 ,  C07D243/30 ,  C07D403/06 ,  C07D403/12

CPC分类号： C07D243/24 ,  A61K31/55 ,  C07D403/06

摘要： This invention is directed to novel central nervous system depressants of Formula I ##STR1## wherein R.sup.1 is selected from the group consisting of (lower)alkyl and ar(lower)alkyl; R.sup.2 is selected from the group consisting of di(lower)alkylamino(lower)alkyl and diaryl(lower)alkylamino(lower)alkyl; R.sup.1 and R.sup.2 may be concatenated to form a radical selected from the group consisting of ##STR2## wherein R.sup.4 is selected from the group consisting of (lower)alkyl, aryl, hydroxy(lower)alkyl, ar(lower)alkyl and (lower)alkoxy(lower)alkyl; R.sup.5 is selected from the group consisting of (lower)-alkylamino and piperidino; n is an integer from 3 to 5; m is an integer from 1-2; r is an integer from 2 to 3; s is an integer from 0 to 6; t is an integer from 0-6; with the proviso that the sum of s and t is 3 to 6; R.sup.3 is selected from the group consisting of hydrogen, (lower)alkyl, ar(lower)alkyl and (lower)alkoxy(lower)alkyl; X is selected from the group consisting of halogen, cyano, trifluoromethyl, nitro and (lower)alkylthio; Y is selected from the group consisting of hydrogen, halogen, trifluoromethyl, nitro and (lower)alkylthio; and the pharmaceutically acceptable salts thereof, in addition to the method of their preparation and administration and administrable compositions containing the active compounds.

摘要翻译： 本发明涉及式I的新型中枢神经系抑制剂，其中R 1选自（低级）烷基和芳（低级）烷基; R2选自二（低级）烷基氨基（低级）烷基和二芳基（低级）烷基氨基（低级）烷基; R 1和R 2可以连接形成选自下列的基团：其中R 4选自（低级）烷基，芳基，羟基（低级）烷基，芳基（低级）烷基和（低级）烷基， 烷氧基（低级）烷基; R5选自（低级） - 烷基氨基和哌啶子基; n为3〜5的整数; m是1-2的整数; r为2〜3的整数; s为0〜6的整数; t是0-6的整数; 条件是s和t之和为3至6; R3选自氢，（低级）烷基，芳（低级）烷基和（低级）烷氧基（低级）烷基; X选自卤素，氰基，三氟甲基，硝基和（低级）烷硫基; Y选自氢，卤素，三氟甲基，硝基和（低级）烷硫基; 及其药学上可接受的盐，以及其制备和给药方法以及含有活性化合物的可施用组合物。

公开(公告)号：US3935202A

公开(公告)日：1976-01-27

申请号：US452017

申请日：1974-03-18

申请人： Peter H. L. Wei ,  Ronald J. McCaully

发明人： Peter H. L. Wei ,  Ronald J. McCaully

IPC分类号： C07D499/00 ,  C07D499/46 ,  C07D501/20 ,  C07D499/44

CPC分类号： C07D499/00

摘要： The antibacterial agents of this invention present the following structural formula: ##SPC1##In whichA is a member selected from the group consisting of ##EQU1## M is a member selected from the group consisting of --H, an alkali metal and --NH.sub.4 ; andY is a member selected from the group consisting of ##EQU2## wherein R is --H, alkanoyloxy of 2 to 6 carbon atoms, ##SPC2##Or,When taken with the 3-carboxy group, ##SPC3##.

摘要翻译： 本发明的抗菌剂具有以下结构式：

公开(公告)号：US4454291A

公开(公告)日：1984-06-12

申请号：US391080

申请日：1982-06-22

申请人： Dong H. Kim ,  Ronald J. McCaully

发明人： Dong H. Kim ,  Ronald J. McCaully

IPC分类号： C07D209/42 ,  C07D513/04

CPC分类号： C07D513/04 ,  C07D209/42 ,  Y02P20/55

摘要： Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substituted on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl;R.sub.2 is hydrogen or lower alkyl;R.sub.3 is hydrogen, lower alkyl or aroyl;R.sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;Y is hydrogen, lower alkyl, or aryl;R.sub.4 is ##STR2## wherein: L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl);M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl);A is O, NR.sub.13 or S;R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkylor aryl;R.sub.13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3;R.sub.20 is hydrogen or aryl; andR.sub.21 is hydroxy or lower alkoxy; or pharmaceutically acceptable salts thereof.Claimed compounds are intermediates of the formula: ##STR3## wherein R.sub.13 is hydrogen or lower alkyl; R.sub.14 is R.sub.5 or OZ, where R.sub.5 is hydroxy, amino, or lower alkoxy, and Z is a carboxylic acid protecting group.

摘要翻译： 本文公开了在氮上与3-巯基-2-烷基-1-氧代烷基，3-磷酰基-2-烷基-1-氧代丙基或2-氨基取代的2,3-二氢-1H-吲哚-2-羧酸 -2-烷基-1-氧代烷基衍生物，其作为血管紧张素转化酶的抑制剂和抗高血压药。 本发明的化合物（不包括所公开的中间体）具有以下通式：其中n为1或0; R1是氢，低级烷基，芳基或芳烷基; R2是氢或低级烷基; R3是氢，低级烷基或芳酰基; R5是羟基，氨基或低级烷氧基; X是氢，羟基，低级烷基，低级烷氧基或卤素; Y是氢，低级烷基或芳基; Y是氢，低级烷基或芳基; R 4是O，NR 7或S（其中R 7是氢或低级烷基）; M是R 8，OR 8，SR 8或NR 9 R 10（其中R 8是氢，低级烷基，芳基或芳烷基;且R 9和R 10独立地是氢，低级烷基或芳基）。 A为O，NR 13或S; R 11和R 12独立地为氢，烷基，芳烷基或芳基; R 13是氢或低级烷基; m为0,1,2或3; R 20是氢或芳基; 和R 21是羟基或低级烷氧基; 或其药学上可接受的盐。 所要求的化合物是下式的中间体：其中R 13是氢或低级烷基; R14是R5或OZ，其中R5是羟基，氨基或低级烷氧基，Z是羧酸保护基。

公开(公告)号：US4350633A

公开(公告)日：1982-09-21

申请号：US284433

申请日：1981-07-20

申请人： Dong H. Kim ,  Ronald J. McCaully

发明人： Dong H. Kim ,  Ronald J. McCaully

IPC分类号： C07D209/42 ,  C07D513/04 ,  C07D209/04

CPC分类号： C07D513/04 ,  C07D209/42

摘要： Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substituted on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl;R.sub.2 is hydrogen or lower alkyl;R.sub.3 is hydrogen, lower alkyl or aroyl;R.sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;Y is hydrogen, lower alkyl, or aryl;R.sub.4 is ##STR2## wherein: L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl);M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl);A is O, NR.sub.13 or S;R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkyl or aryl;R.sub.13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3;R.sub.20 is hydrogen or aryl; andR.sub.21 is hydroxy or lower alkoxy;or pharmaceutically acceptable salts thereof.

摘要翻译： 本文公开了在氮上与3-巯基-2-烷基-1-氧代烷基，3-磷酰基-2-烷基-1-氧代丙基或2-氨基取代的2,3-二氢-1H-吲哚-2-羧酸 -2-烷基-1-氧代烷基衍生物，其作为血管紧张素转化酶的抑制剂和抗高血压药。 本发明的化合物（不包括所公开的中间体）具有以下通式：其中n为1或0; R1是氢，低级烷基，芳基或芳烷基; R2是氢或低级烷基; R3是氢，低级烷基或芳酰基; R5是羟基，氨基或低级烷氧基; X是氢，羟基，低级烷基，低级烷氧基或卤素; Y是氢，低级烷基或芳基; Y是氢，低级烷基或芳基; R 4是O，NR 7或S（其中R 7是氢或低级烷基）; M是R 8，OR 8，SR 8或NR 9 R 10（其中R 8是氢，低级烷基，芳基或芳烷基;且R 9和R 10独立地是氢，低级烷基或芳基）。 A为O，NR 13或S; R 11和R 12独立地为氢，烷基，芳烷基或芳基; R 13是氢或低级烷基; m为0,1,2或3; R 20是氢或芳基; 和R 21是羟基或低级烷氧基; 或其药学上可接受的盐。

公开(公告)号：US4349674A

公开(公告)日：1982-09-14

申请号：US970295

申请日：1978-12-18

申请人： Elisabeth H. Freed, deceased ,  Peter H. L. Wei ,  Ronald J. McCaully

发明人： Elisabeth H. Freed, deceased ,  Peter H. L. Wei ,  Ronald J. McCaully

IPC分类号： C07D241/44 ,  C07D241/42 ,  A61K31/495 ,  C07D401/12

CPC分类号： C07D241/44

摘要： The compounds of this invention are designated as quinoxalinyl esters of carbamimidothioic acids and exhibit the pharmacological properties of preventing gastric ulcers, reducing gastric secretions and lowering blood pressure. The compounds have the following structural formula: ##STR1## in which Q is hydrogen or nitro;A is hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, carbomethoxy, carbethoxy, carbopropoxy, carbisopropoxy, carbobutoxy, carbisobutoxy, or carbo-t-butoxy; andR.sup.1, R.sup.2, and R.sup.3 are, independently, hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, allyl, or R.sup.1 and R.sup.3 may be concatenated with a carbon chain having 4 carbon atoms with R.sup.2 then being hydrogen; except that, when A and Q are hydrogen, R.sup.1, R.sup.2, and R.sup.3 may not all be hydrogen; and with the further exception that, where A is methyl and R.sup.1, R.sup.2, and Q are all hydrogen, R.sup.3 may not be ethyl;or a pharmaceutically acceptable salt thereof.

摘要翻译： 本发明的化合物被指定为氨基亚氨基硫酸的喹喔啉基，并且具有预防胃溃疡，减少胃分泌和降低血压的药理学特性。 该化合物具有以下结构式：其中Q是氢或硝基的 A是氢，甲基，乙基，丙基，异丙基，正丁基，甲酯基，乙酯基，碳丙氧基，碳异丙氧基，羰基丁氧基，碳代异丁氧基或碳 - 并且R 1，R 2和R 3独立地是氢，甲基，乙基，丙基，异丙基，正丁基，异丁基，叔丁基，烯丙基，或者R 1和R 3可以与具有4个碳原子的碳链连接在一起 然后是氢; 除了当A和Q为氢时，R 1，R 2和R 3可以不全部为氢; 并且另外例外的是，当A是甲基且R 1，R 2和Q都是氢时，R 3可以不是乙基; 或其药学上可接受的盐。

公开(公告)号：US4585879A

公开(公告)日：1986-04-29

申请号：US700371

申请日：1985-02-11

申请人： Michael W. Winkley ,  Ronald J. McCaully

发明人： Michael W. Winkley ,  Ronald J. McCaully

IPC分类号： C07D209/42

CPC分类号： C07D209/42

摘要： Disclosed herein is a process for obtaining indoline-2-carboxylic acid (or derivatives thereof) comprising the following steps: (a) reducing .alpha.-oxo-2-nitrobenzenepropanoic acid to .alpha.-hydroxy-2-nitrobenzenepropanoic acid, (b) replacing the hydroxyl group of the latter with a chlorine atom utilizing a selected Vilsmeier chlorinating reagent at temperatures of at least 20.degree. C., (c) reducing the nitro group of the resulting .alpha.-chloro-2-nitrobenzenepropanoic acid to obtain .alpha.-chloro-2-aminobenzenepropanoic acid, and (d) cyclizing the latter in aqueous base to form the desired indoline-2-carboxylic acid. Alternately, steps (c) and (d) may be combined in a one pot step by using, for example, a Raney nickel-hydrazine reducing medium.

公开(公告)号：US4396773A

公开(公告)日：1983-08-02

申请号：US306012

申请日：1981-09-28

申请人： Dong H. Kim ,  Ronald J. McCaully

发明人： Dong H. Kim ,  Ronald J. McCaully

IPC分类号： C07D209/42 ,  C07D513/04

CPC分类号： C07D513/04 ,  C07D209/42

摘要： Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl;R.sub.2 is hydrogen or lower alkyl;R.sub.3 is hydrogen, lower alkyl or aroyl;R.sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;R.sub.4 is -SH, ##STR2## wherein L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl);M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl);A is O, NR.sub.13 or S;R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkyl or aryl;R.sub.13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3;R.sub.20 is hydrogen or aryl; andR.sub.21 is hydroxy or lower alkoxy;or pharmaceutically acceptable salts thereof.

摘要翻译： 本文公开了作为血管紧张素转化酶抑制剂和作为抗高血压剂的N-（3-巯基-2-烷基-1-氧代丙基）-2,3-二氢-1H-吲哚-2-羧酸及其衍生物 。 衍生物包括其中3-巯基被磷酸酯衍生物取代或被不同取代的氨基取代的衍生物。 本发明的化合物（不包括所公开的中间体）具有以下通式：其中n为1或0; R1是氢，低级烷基，芳基或芳烷基; R2是氢或低级烷基; R3是氢，低级烷基或芳酰基; R5是羟基，氨基或低级烷氧基; X是氢，羟基，低级烷基，低级烷氧基或卤素; Y是氢，低级烷基或芳基; R4是-SH，其中L是O，NR7或S（其中R7是氢或低级烷基）; M是R 8，OR 8，SR 8或NR 9 R 10（其中R 8是氢，低级烷基，芳基或芳烷基;且R 9和R 10独立地是氢，低级烷基或芳基）。 A为O，NR 13或S; R 11和R 12独立地为氢，烷基，芳烷基或芳基; R 13是氢或低级烷基; m为0,1,2或3; R 20是氢或芳基; 和R 21是羟基或低级烷氧基; 或其药学上可接受的盐。

公开(公告)号：US3962228A

公开(公告)日：1976-06-08

申请号：US452087

申请日：1974-03-18

申请人： Peter H. L. Wei ,  Ronald J. McCaully

发明人： Peter H. L. Wei ,  Ronald J. McCaully

IPC分类号： C07D499/00 ,  C07D501/20 ,  C07D499/44

CPC分类号： C07D499/00

摘要： The antibacterial agents of this invention present the following structural formula: ##SPC1##In whichR.sup.1 is --OH, alkoxycarbonyloxy of 2 to 6 carbon atoms, arylsulfonyl of 6 to 10 carbon atoms or thiocyanato;R.sup.2 is --H, halo or phenyl;R.sup.3 is --H, an alkali metal or --NH.sub.4 ; andY is ##EQU1## wherein R.sup.4 is --H, alkanoyloxy of 2 to 6 carbon atoms, ##EQU2## or WHEN TAKEN WITH THE 3-CARBOXY GROUP, ##SPC2##