公开(公告)号：US4158005A

公开(公告)日：1979-06-12

申请号：US794923

申请日：1977-05-09

申请人： Nicolae S. Bodor ,  Sun-Shine Yuan

发明人： Nicolae S. Bodor ,  Sun-Shine Yuan

IPC分类号： C07D263/06 ,  C07D498/10

CPC分类号： C07D263/06

摘要： Optically and therapeutically active compounds of the formula: ##STR1## wherein R represents a member selected from the group consisting of a straight or branched alkyl group of from one to twenty carbon atoms (C.sub.1 -C.sub.5 being preferred), an ethoxycarbonyl group, a benzyloxycarbonyl group, a phenyl group, an ##STR2## WHEREIN R is as defined above and R.sub.3 is a member selected from the group consisting of a hydrogen atom, a methyl group and a phenyl group, and a 2-, 3-, or 4-pyridyl group, or the HX salts thereof, wherein X represents a pharmaceutically acceptable acid addition salt anion, are prepared optically active m-hydroxy-.alpha.-[methylamino)methyl]benzyl alcohol (phenylephrine).The compounds prepared by the process of this invention find therapeutic application to warm-blooded animals (e.g., humans) in the management of asthma, nasal congestion and as decongestants, vasoconstrictors, mydriatic agents, and anti-glaucomatous agents in the practice of ophthalmology.Upon administration, these compounds will enzymatically "cleave," thus releasing optically active phenylephrine (m-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohol, the therapeutically active moiety thereof.

摘要翻译： 光学和治疗活性的下式的化合物：其中R表示选自1-20个碳原子的直链或支链烷基（优选C1-C5），乙氧基羰基 ，苄氧基羰基，苯基，取代基如上所定义，R 3为选自氢原子，甲基和苯基的成员，以及2-，3-， 或4-吡啶基或其HX盐，其中X表示药学上可接受的酸加成盐阴离子，制备光学活性的间羟基-α-[甲基氨基]甲基]苄醇（去氧肾上腺素）。

公开(公告)号：US4035405A

公开(公告)日：1977-07-12

申请号：US703943

申请日：1976-07-09

申请人： Nicolae S. Bodor ,  Sun-Shine Yuan

发明人： Nicolae S. Bodor ,  Sun-Shine Yuan

IPC分类号： C07B61/00 ,  A61K31/135 ,  A61K31/24 ,  B01J23/00 ,  B01J23/42 ,  C07C67/14 ,  C07C219/28 ,  C07C219/30 ,  C07C225/16 ,  C07C233/54 ,  C07D213/55 ,  C07D213/79 ,  C07D213/81 ,  C07D213/82

CPC分类号： C07C323/20

摘要： Compounds of the formula: ##STR1## wherein R represents a straight or branched C.sub.1 -C.sub.5 alkyl group; and R.sub.1 in each occurrence represents an acyl member which is alkanoyl having 1-22 carbon atoms, alkenoyl having one or two double bonds and having 4-22 carbon atoms, ##STR2## having a total of 4-10 carbon atoms of which 3-7 are ring carbon atoms in cycloalkyl and wherein n is zero, one, or two, phenoxyacetyl, naphthalenecarbonyl, pyridinecarbonyl, ##STR3## wherein n is zero, one or two and phenyl is unsubstituted or is substituted by 1-3 alkyl having 1-4 carbon atoms, alkoxy having 1-4 carbon atoms, halo, trifluoromethyl, dialkylamino having 2-8 carbon atoms, or alkanoylamino having 1-6 carbon atoms groups; are prepared in substantial purity and yield, using as the chloride ion donor, cesium chloride (CsCl).The compounds prepared by the process claimed herein exhibit sympathomimetic activity and are thus useful in eliciting sympathomimetic responses in warm-blooded animals, e.g., reduction in intraocular pressure, miosis, mydriasis, bronchodilation, etc.

摘要翻译： 下式的化合物：其中R表示直链或支链的C 1 -C 5烷基; 并且R 1在每次出现时表示具有1-22个碳原子的烷酰基的酰基，具有一个或两个双键并且具有4-22个碳原子的烯酰基，其总共具有4-10个碳原子的“IMAGE” 7是环烷基中的环碳原子，其中n是0,1或2，苯氧基乙酰基，萘羰基，吡啶羰基，其中n是0,1或2，苯基是未取代的或被1-3个具有1- 4个碳原子，具有1-4个碳原子的烷氧基，卤素，三氟甲基，2-8个碳原子的二烷基氨基或具有1-6个碳原子的烷酰氨基; 以氯离子供体氯化铯（CsCl）的形式用大量纯度和收率制备。

公开(公告)号：US4028368A

公开(公告)日：1977-06-07

申请号：US671067

申请日：1976-03-29

申请人： Nicolae S. Bodor ,  Sun-Shine Yuan

发明人： Nicolae S. Bodor ,  Sun-Shine Yuan

IPC分类号： C07D263/06

CPC分类号： C07D263/06

摘要： Optically and therapeutically active compounds of the formula: ##STR1## wherein R represents a member selected from the group consisting of a straight or branched alkyl group of from one to twenty carbon atoms (C.sub.1 -C.sub.5 being preferred), an ethoxycarbonyl group, a benzyloxycarbonyl group, a phenyl group, an ##STR2## group, wherein R is as defined above and R.sub.3 is a member selected from the group consisting of a hydrogen atom, a methyl group and a phenyl group, and a 2-, 3-, or 4-pyridyl group, or the HX salts thereof, wherein X represents a pharmaceutically acceptable acid addition salt anion, are prepared using optically active m-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohol (phenylephrine).

摘要翻译： 光学和治疗活性的下式的化合物：其中R表示选自1-20个碳原子的直链或支链烷基（优选C1-C5），乙氧基羰基 ，苄氧基羰基，苯基，基团，其中R如上定义，R 3是选自氢原子，甲基和苯基的成员，以及2-，3 - （甲基氨基）甲基]苄醇（去氧肾上腺素）制备其中X表示药学上可接受的酸加成盐阴离子的HX盐或其HX盐。

公开(公告)号：US4088783A

公开(公告)日：1978-05-09

申请号：US732978

申请日：1976-10-18

申请人： Nicolae S. Bodor ,  Sun-Shine Yuan

发明人： Nicolae S. Bodor ,  Sun-Shine Yuan

IPC分类号： A61K31/225 ,  C07C91/34

摘要： Compounds of the formula: ##STR1## wherein R represents a member selected from the group consisting of a straight or branched alkyl group of from one to twenty carbon atoms (C.sub.1 -C.sub.5 being preferred), an ethoxycarbonyl group, a benzyloxycarbonyl group, a phenyl group, an ##STR2## WHEREIN R is as defined above and R.sub.3 is a member selected from the group consisting of a hydrogen atom, a methyl group and a phenyl group, and a 2-, 3-, or 4-pyridyl group, or the HX salts thereof, wherein X represents a pharmaceutically acceptable acid addition salt anion, are extremely valuable in the treatment of conditions responsive to sympathomimetic agents.The compounds of this invention find therapeutic application to warm-blooded animals (e.g., humans) in the management of asthma, nasal congestion and as decongestants, vasoconstrictors, mydriatic agents, and anti-glaucomatous agents in the practice of opthalmology.Upon administration, these compounds will enzymatically "cleave," thus releasing optically active phenylephrine (m-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohol, the therapeutically active moiety thereof.

摘要翻译： 下式的化合物：其中R表示选自具有1-20个碳原子的直链或支链烷基（优选C1-C5），乙氧基羰基，苄氧基羰基 苯基，其中R如上定义，R 3为选自氢原子，甲基和苯基的成员，以及2-，3-或4-吡啶基 基团或其HX盐，其中X表示药学上可接受的酸加成盐阴离子，在治疗对拟交感神经药物的病症方面非常有价值。

公开(公告)号：US4174450A

公开(公告)日：1979-11-13

申请号：US740063

申请日：1976-11-08

申请人： Nicolae S. Bodor ,  Sun-Shine Yuan

发明人： Nicolae S. Bodor ,  Sun-Shine Yuan

IPC分类号： C07D263/06 ,  C07D498/10

CPC分类号： C07D263/06

摘要： This invention deals with chemical intermediates having the formula ##STR1## wherein R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a single hetero atom member selected from the group consisting of a five-to seven-membered heterocycle containing one hetero-N-atom and a N-substituted five-to seven-membered heterocycle containing an hetero-N-atom whose substituent is C.sub.1 -C.sub.2 alkyl. These compounds are useful in the synthesis of compounds having a variety of uses as pharmaceuticals.

摘要翻译： 本发明涉及具有式“IMAGE”的化学中间体，其中R 1和R 2与它们所连接的碳原子一起形成选自含有一个杂原子的5至7元杂环的单个杂原子， N原子和含有取代基为C 1 -C 2烷基的杂N原子的N-取代的五至七元杂环。 这些化合物可用于合成具有各种用途的化合物作为药物。

公开(公告)号：US3966749A

公开(公告)日：1976-06-29

申请号：US548606

申请日：1975-02-10

申请人： Nicolae S. Bodor ,  Sun-Shine Yuan

发明人： Nicolae S. Bodor ,  Sun-Shine Yuan

IPC分类号： C07D263/06 ,  C07D213/02

CPC分类号： C07D263/06

摘要： Optically and therapeutically active compounds of the formula: ##SPC1##Wherein R represents a member selected from the group consisting of a straight or branched alkyl group of from one to twenty carbon atoms (C.sub.1 -C.sub.5 being preferred), an ethoxycarbonyl group, a benzyloxycarbonyl group, a phenyl group, an ##EQU1## group, wherein R is as defined above and R.sub.3 is a member selected from the group consisting of a hydrogen atom, a methyl group and a phenyl group, and a 2-, 3-, or 4-pyridyl group, or the HX salts thereof, wherein X represents a pharmaceutically acceptable acid addition salt anion, are prepared using optically active m-hydroxy-.alpha.-[(methylamino)-methyl]benzyl alcohol (phenylephrine).The compounds prepared by the process of this invention find therapeutic applicaton to warm-blooded animals (e.g., humans) in the management of asthma, nasal congestion and as decongestants, vasoconstrictors, mydriatic agents, and anti-glaucomatous agents in the practice of opthalmology.Upon administration, these compounds will enzymatically "cleave," thus releasing optically active phenylephrine (m-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohol, the therapeutically active moiety thereof.

摘要翻译： 光学和治疗活性的下式的化合物：

公开(公告)号：US4727151A

公开(公告)日：1988-02-23

申请号：US962948

申请日：1978-11-22

申请人： Nicolae S. Bodor

发明人： Nicolae S. Bodor

IPC分类号： C07D213/80 ,  C07D213/82 ,  C07D487/08 ,  C07D521/00 ,  C07D215/12 ,  C07C67/02 ,  C07D211/70 ,  C07D333/22

CPC分类号： C07D249/08 ,  C07D213/80 ,  C07D213/82 ,  C07D231/12 ,  C07D233/56 ,  C07D487/08

摘要： Labile quaternary ammonium salts of the following formula (I) and (II) are provided: ##STR1## wherein N represents a tertiary aliphatic amine; wherein N represents an unsaturated amine; wherein R represents a member selected from the group consisting of a hydrogen atom, a C.sub.1 -C.sub.8 open chain or cyclo alkyl group, a C.sub.1 -C.sub.8 alkoxyalkyl group, a C.sub.1 -C.sub.8 acyloxyalkyl group, a C.sub.1 -C.sub.8 haloalkyl group, a C.sub.1 -C.sub.8 carboxyalkyl group, a C.sub.2 -C.sub.8 alkenylphenyl group, an aryl group, and a substituted aryl group, whose substituents are selected from the group consisting of a halogen atom, an O-lower alkyl (C.sub.1 -C.sub.4) group, an O-acyl group, a nitro group, a carboxyl group, and a carboethoxy group; wherein R.sub.1 which may be the same or different, represents any member defined by R above with the proviso that R.sub.1 cannot be a hydrogen atom; wherein X is --O-- or --S--; and wherein Y represents a member selected from the group consisting of a halogen atom or any other organic or inorganic monovalent equivalent anion; with the further proviso that N and N, respectively cannot represent trimethylamine and pyridine or quinoline when R represents a hydrogen atom and R.sub.1 represents a methyl group or a phenyl group. The compounds described above are characterized by their extreme solubility and resistance to oxidation, dealkylation, and protonation prior to chemical and/or enzymatic hydrolysis. Upon chemical and/or enzymatic hydrolysis, these compounds will "cleave," thus releasing their active constituent or constituents, according to the following general scheme(s): ##STR2## In other words, the title compounds hydrolyze (chemically or enzymatically) releasing a tertiary amine or unsaturated amine derivative, an aldehyde, a carboxylic acid and a hydrogen halide (HX) per the above reaction scheme.

摘要翻译： 提供下式（I）和（II）的不定性季铵盐：其中N表示叔脂族胺;（I）其中N表示叔脂族胺; 其中N表示不饱和胺; 其中R表示选自氢原子，C1-C8开链或环烷基，C1-C8烷氧基烷基，C1-C8酰氧基烷基，C1-C8卤代烷基，C1- C8羧基烷基，C2-C8烯基苯基，芳基和取代的芳基，其取代基选自卤素原子，O-低级烷基（C1-C4）基，O-酰基 基，硝基，羧基和乙酰乙氧基; 其中R1可以相同或不同，表示由上述R定义的任何成员，条件是R 1不能为氢原子; 其中X是-O-或-S-; 并且其中Y表示选自卤素原子或任何其它有机或无机一价当量阴离子的成员; 进一步的条件是当R表示氢原子且R1表示甲基或苯基时，N和N分别不表示三甲胺和吡啶或喹啉。 上述化合物的特征在于其在化学和/或酶水解之前的极端溶解性和耐氧化性，脱烷基化和质子化。 在化学和/或酶水解时，这些化合物将“切割”，从而根据以下一般方案释放其活性组分或组分： + TR + TR In 换句话说，根据上述反应方案，标题化合物水解（化学或酶促）释放叔胺或不饱和胺衍生物，醛，羧酸和卤化氢（HX）。

公开(公告)号：US4061722A

公开(公告)日：1977-12-06

申请号：US680437

申请日：1976-04-26

申请人： Nicolae S. Bodor

发明人： Nicolae S. Bodor

IPC分类号： C07D405/06 ,  A61K31/415 ,  C07D233/64

CPC分类号： C07D405/06 ,  Y10S514/912

摘要： Compounds of the formula: ##STR1## wherein R represents a member selected from the group consisting of a hydrogen atom, a C.sub.1 -C.sub.20 open chain or cyclo alkyl group, a C.sub.1 -C.sub.20 alkoxyalkyl group, a C.sub.1 -C.sub.20 alkanoyloxyalkyl group, a C.sub.1 -C.sub.20 haloalkyl group, a C.sub.1 -C.sub.20 carboxyalkyl group, a phenyl group, a naphthyl group and a substituted phenyl or naphthyl group, whose substituents are selected from the group consisting of a halogen atom, an O-C.sub.1 -C.sub.4 alkyl group, an O-C.sub.1 -C.sub.8 alkanoyl group, a nitro group, a carboxyl group, and a carboethoxy group; wherein R.sub.1 represents a C.sub.9 -C.sub.22 straight or branched alkyl group, a ##STR2## group, wherein R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are each selected from the group consisting of a hydrogen atom, a methyl group, or an ethyl group, and wherein R.sub.1 further represents a member selected from the group consisting of a C.sub.0 -C.sub.22 straight or branched alkyl ##STR3## group, wherein n in each occurrence and m represent an integer of from 0 to 22, and an ##STR4## group, wherein A represents a -(CH.sub.2 CH.sub.2 O).sub.p group, wherein the p represents an integer of from 0 to 22 and a cholic acid residue; and wherein X represents a member selected from the group consisting of a halogen atom, a methanesulfonate group, a fluorosulfonate group and a tosylate group, useful in reducing intraocular pressure in warm-blooded animals are disclosed.

摘要翻译： 下式的化合物：其中R表示选自氢原子，C1-C20开链或环烷基，C1-C20烷氧基烷基，C1-C20烷酰氧基烷基，C1 -C 20卤代烷基，C 1 -C 20羧基烷基，苯基，萘基和取代的苯基或萘基，其取代基选自卤素原子，O-C 1 -C 4烷基， O-C 1 -C 8烷酰基，硝基，羧基和乙酰乙氧基; 其中R 1表示C 9 -C 22直链或支链烷基，其中R 3，R 4，R 5和R 6各自选自氢原子，甲基或乙基，其中 R1还表示选自C0-C22直链或支链烷基基团的成员，其中每次出现n，m表示0至22的整数，和A表示 a - （CH 2 CH 2 O）p基团，其中p表示0-22的整数和胆酸残基; 并且其中X表示选自用于降低温血动物中的眼内压的卤素原子，甲磺酸酯基，氟磺酸酯基和甲苯磺酸酯基的成员。

公开(公告)号：US4160099A

公开(公告)日：1979-07-03

申请号：US724914

申请日：1976-09-20

申请人： Nicolae S. Bodor

发明人： Nicolae S. Bodor

IPC分类号： C07D213/80 ,  C07D213/82 ,  C07D233/60 ,  C07D487/08 ,  C07D521/00 ,  C07C93/18

CPC分类号： C07D249/08 ,  C07D213/80 ,  C07D213/82 ,  C07D231/12 ,  C07D233/56 ,  C07D487/08

摘要： Labile quaternary ammonium salts of the following formula (I) and (II) are provided: ##STR1## wherein ##STR2## represents a tertiary aliphatic amine; wherein ##STR3## represents an unsaturated amine; wherein R represents a member selected from the group consisting of a hydrogen atom, a C.sub.1 -C.sub.8 open chain or cyclo alkyl group, a C.sub.1 -C.sub.8 alkoxyalkyl group, a C.sub.1 -C.sub.8 acyloxyalkyl group, a C.sub.1 -C.sub.8 haloalkyl group, a C.sub.1 -C.sub.8 carboxyalkyl group, a C.sub.2 -C.sub.8 alkenylphenyl group, an aryl group, and a substituted aryl group, whose substituents are selected from the group consisting of a halogen atom, an O-lower alkyl (C.sub.1 -C.sub.4) group, an O-acyl group, a nitro group, a carboxyl group, and a carboethoxy group; wherein R.sub.1 which may be the same or different, represents any member defined by R above with the proviso that R.sub.1 cannot be a hydrogen atom; wherein X is --O-- or --S--; and wherein Y represents a member selected from the group consisting of a halogen atom or any other organic or inorganic monovalent equivalent anion;With the further proviso that ##STR4## respectively cannot represent trimethylamine and pyridine or quinoline when R represents a hydrogen atom and R.sub.1 represents a methyl group or a phenyl group.The compounds described above are characterized by their extreme solubility and resistance to oxidation, dealkylation, and protonation prior to chemical and/or enzymatic hydrolysis. Upon chemical and/or enzymatic hydrolysis, these compounds will "cleave," thus releasing their active constituent or constituents, according to the following general scheme(s): ##STR5## In other words, the title compounds hydrolyze (chemically or enzymatically) releasing a tertiary amine or unsaturated amine derivative, an aldehyde, a carboxylic acid and a hydrogen halide (HX) per the above reaction scheme.

公开(公告)号：US4117232A

公开(公告)日：1978-09-26

申请号：US777074

申请日：1977-03-14

申请人： Nicolae S. Bodor ,  Kenneth B. Sloan

发明人： Nicolae S. Bodor ,  Kenneth B. Sloan

IPC分类号： C07D231/34

CPC分类号： C07D231/34

摘要： Novel, transient pro-drug forms of the anti-inflammatories phenylbutazone and oxyphenbutazone are disclosed, the same having the structural formulae: ##STR1## wherein R is a member selected from the group consisting of C.sub.1 -C.sub.2 alkylsulfonyl, phenylsulfonyl, p-tolylsulfonyl and naphthylsulfonyl, and ##STR2## wherein X and Y each represent a member selected from the group consisting of a hydrogen atom and ##STR3## with the proviso that either X or Y is a hydrogen atom, R.sub.1 is selected from the group consisting of C.sub.1 -C.sub.2 alkylsulfonyl, phenylsulfonyl, p-tolylsulfonyl and naphthylsulfonyl, and R.sub.2 is selected from the group consisting of straight or branched chain C.sub.1 -C.sub.5 alkyl and phenyl.

摘要翻译： 公开了化合物1,2-二苯基-3,5-二氟乙酰氧基-4-丁基-5-羟基-3-吡唑啉作为制备所选择的保泰松酮衍生物的中间体。