公开(公告)号：US20140024678A1

公开(公告)日：2014-01-23

申请号：US14032425

申请日：2013-09-20

Applicant: Muhammad Safadi ,  Daniella Licht ,  Ioana Lovinger ,  Aharon M. Eyal ,  Tomas Fristedt ,  Karl Jansson

Inventor： Muhammad Safadi ,  Daniella Licht ,  Ioana Lovinger ,  Aharon M. Eyal ,  Tomas Fristedt ,  Karl Jansson

IPC: A61K31/4704 ,  C07D471/10 ,  B65B25/00 ,  C07D209/34

CPC classification number: B65B25/00 ,  A61K9/1623 ,  A61K9/2004 ,  A61K9/2018 ,  A61K31/438 ,  A61K31/4704 ,  C07D209/34 ,  C07D209/42 ,  C07D471/10 ,  Y10T436/145555

Abstract: The subject invention provides a pharmaceutical composition comprising N-ethyl-N-phenyl-1,2,-dihydro-4-hydroxy-5- chloro-1-methyl-2-oxoquinoline-3-carboxamide or the salt thereof; a pharmaceutically acceptable carrier; and not more than 0.5% w/w relative to N-ethyl-N-phenyl-1,2,-dihydro-4 -hydroxy-5-chloro-1-methyl-2-oxoquinoline-3-carboxamide of 2-Chloro-6-(1-ethyl-N-methyl-2-oxoindoline-3-carboxamido) benzoic acid, 1H,3H-spiro[5-chloro-1-methylquinoline-2,4 -dione-3,3′-[1]ethylindolin-[2]-one], or 5-Chloro-N-ethyl-3-hydroxy-1-methyl-2,4-dioxo-N-phenyl-1,2,3,4 -tetrahydro-quinoline-3-carboxamide.

Abstract translation: 本发明提供包含N-乙基-N-苯基-1,2-二氢-4-羟基-5-氯-1-甲基-2-氧代喹啉-3-甲酰胺或其盐的药物组合物; 药学上可接受的载体; 并且相对于2-氯 - 苯基-1,2-二氢-4-羟基-5-氯-1-甲基-2-氧代喹啉-3-甲酰胺，相对于N-乙基-N-苯基-1,2-二氢-4-羟基-5-氯-1-甲基-2-氧代喹啉-3-甲酰胺为0.5％w / 6-（1-乙基-N-甲基-2-氧代二氢吲哚-3-甲酰氨基）苯甲酸，1H，3H-螺[5-氯-1-甲基喹啉-2,4-二酮-3,3' - [1] 乙基吲哚并[2] - 酮]或5-氯-N-乙基-3-羟基-1-甲基-2,4-二氧代-N-苯基-1,2,3,4-四氢 - 甲酰胺。

公开(公告)号：US07589208B2

公开(公告)日：2009-09-15

申请号：US11050441

申请日：2005-02-04

Applicant: Karl Jansson ,  Tomas Fristedt ,  Hans Wännman ,  Anders Björk

Inventor： Karl Jansson ,  Tomas Fristedt ,  Hans Wännman ,  Anders Björk

IPC: C07D215/38

CPC classification number: A61K31/47 ,  A61K9/1617 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2054 ,  A61K9/2059 ,  A61K31/4706

Abstract: A stable solid pharmaceutical composition consisting essentially of an effective amount of a salt of formula (II) together with an alkaline-reacting component maintaining the pH preferably above 8, or a salt with a divalent metal cation; and at least one pharmaceutical excipient; said salt of formula (II) being essentially stable during storage at room temperature for a period of at least 3 years. A process for stabilizing the salt of formula (II). A crystalline salt of formula (II) and a process for preparing said salt.

Abstract translation: 一种稳定的固体药物组合物，其基本上由有效量的式（II）的盐与保持pH优选高于8的碱反应组分或与二价金属阳离子的盐组成; 和至少一种药物赋形剂; 所述式（II）的盐在室温下储存至少3年的时间基本上是稳定的。 稳定式（II）的盐的方法。 式（II）的结晶盐和制备所述盐的方法。

公开(公告)号：US06875869B2

公开(公告)日：2005-04-05

申请号：US10459718

申请日：2003-06-12

Applicant: Karl Jansson

Inventor： Karl Jansson

IPC: C07D215/56 ,  C07D491/00 ,  C07D215/16 ,  C07D215/20 ,  C07D498/00 ,  C07D515/00

CPC classification number: C07D215/56

Abstract: A process for the preparation of the compounds of general formula (I) wherein R is selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and allyl; R5 is selected from the methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, methylthio, ethylthio, n-propylthio, methylsulphinyl, ethylsulphinyl, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy; wherein x=0-2, y=1-3 with the proviso that x+y=3; R6 is hydrogen; or R5 and R6 taken together are methylenedioxy; R′ is selected from methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy, wherein x=0-2, y=1-3 with the proviso that x+y=3; R″ is selected form hydrogen, fluoro and chloro, with the proviso that R″ is selected from fluoro and chloro only when R′ is selected from fluoro and chloro; by reacting a quinoline-3-carboxylic acid ester derivative of formula A with an aniline derivative of formula B in a solvent selected from straight or branched alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200° C.

Abstract translation: 制备通式（I）的化合物的方法，其中R选自甲基，乙基，正丙基，异丙基，正丁基，异丁基，仲丁基和烯丙基; R5选自甲基，乙基，正丙基，异丙基，甲氧基，乙氧基，甲硫基，乙硫基，正丙硫基，甲基亚磺酰基，乙基亚磺酰基，氟，氯，溴，三氟甲基和OCH x Fy; 其中x = 0-2，y = 1-3，条件是x + y = 3; R6是氢; 或R5和R6一起是亚甲二氧基; R'选自甲基，甲氧基，氟，氯，溴，三氟甲基和OCH x Fy，其中x = 0-2，y = 1-3，条件是x + y = 3; R“选自氢，氟和氯，条件是当R'选自氟和氯时，R”选自氟和氯; 通过使式A的喹啉-3-羧酸酯衍生物与式Bin的苯胺衍生物使选自直链或支链烷烃和环烷烃的溶剂或其混合物的沸点为80-200℃。

公开(公告)号：US4871837A

公开(公告)日：1989-10-03

申请号：US007330

申请日：1987-01-27

Applicant: Hans G. Magnusson ,  Karl Jansson

Inventor： Hans G. Magnusson ,  Karl Jansson

IPC: C07F7/08 ,  C07H3/06 ,  C07H13/06 ,  C07H13/08 ,  C07H15/04 ,  C07H19/044 ,  C07H23/00

CPC classification number: C07H13/06 ,  C07F7/0812 ,  C07H13/08 ,  C07H15/04 ,  C07H19/044 ,  C07H23/00 ,  C07H3/06

Abstract: The present invention concerns a method for preparing unprotected hydroxy compounds or acylated derivatives thereof by conversion of silyl alkyl-protected hydroxy compounds. The invention also relates to novel intermediates useful in the method and for other purposes.

Abstract translation: 本发明涉及通过甲硅烷基保护的羟基化合物的转化制备未保护的羟基化合物或其酰化衍生物的方法。 本发明还涉及可用于该方法和其它目的的新型中间体。

公开(公告)号：US08545885B2

公开(公告)日：2013-10-01

申请号：US13471175

申请日：2012-05-14

Applicant: Muhammad Safadi ,  Daniella Licht ,  Ioana Lovinger ,  Aharon M. Eyal ,  Tomas Fristedt ,  Karl Jansson

Inventor： Muhammad Safadi ,  Daniella Licht ,  Ioana Lovinger ,  Aharon M. Eyal ,  Tomas Fristedt ,  Karl Jansson

IPC: A61K9/20

CPC classification number: B65B25/00 ,  A61K9/1623 ,  A61K9/2004 ,  A61K9/2018 ,  A61K31/438 ,  A61K31/4704 ,  C07D209/34 ,  C07D209/42 ,  C07D471/10 ,  Y10T436/145555

Abstract: The subject invention provides a pharmaceutical composition comprising N-ethyl-N-phenyl-1,2,-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxoquinoline-3-carboxamide or the salt thereof; a pharmaceutically acceptable carrier; and not more than 0.5% w/w relative to N-ethyl-N-phenyl-1,2,-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxoquinoline-3-carboxamide of 2-Chloro-6-(1-ethyl-N-methyl-2-oxoindoline-3-carboxamido)benzoic acid, 1H,3H-spiro[5-chloro-1-methylquinoline-2,4-dione-3,3′-[1]ethylindolin-[2]-one], or 5-Chloro-N-ethyl-3-hydroxy-1-methyl-2,4-dioxo-N-phenyl-1,2,3,4-tetrahydro-quinoline-3-carboxamide.

Abstract translation: 本发明提供了包含N-乙基-N-苯基-1,2-二氢-4-羟基-5-氯-1-甲基-2-氧代喹啉-3-甲酰胺或其盐的药物组合物; 药学上可接受的载体; 并且相对于2-氯 - 苯基-1,2-二氢-4-羟基-5-氯-1-甲基-2-氧代喹啉-3-甲酰胺，相对于N-乙基-N-苯基-1,2-二氢-4-羟基-5-氯-1-甲基-2-氧代喹啉-3-甲酰胺为0.5％w / 6-（1-乙基-N-甲基-2-氧代二氢吲哚-3-甲酰氨基）苯甲酸，1H，3H-螺[5-氯-1-甲基喹啉-2,4-二酮-3,3' - [1] 乙醛基 - [2] - 酮]或5-氯-N-乙基-3-羟基-1-甲基-2,4-二氧代-N-苯基-1,2,3,4-四氢 - 甲酰胺。

公开(公告)号：US20050215586A1

公开(公告)日：2005-09-29

申请号：US11084192

申请日：2005-03-21

Applicant: Karl Jansson

Inventor： Karl Jansson

IPC: C07D215/56 ,  A61K31/4706 ,  C07D215/20

CPC classification number: C07D215/56

Abstract: A process for the preparation of the compounds of general formula (I) wherein R is selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and allyl; R5 is selected from methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, methylthio, ethylthio, n-propylthio, methylsulphinyl, ethylsulphinyl, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy; wherein x=0−2, y=1−3 with the proviso that x+y=3; R6 is hydrogen; or R5 and R6 taken together are methylenedioxy; R′ is selected from hydrogen, methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy, wherein x=0−2, y=1−3 with the proviso that x+y=3; R″ is selected from hydrogen, fluoro and chloro, with the proviso that R″ is selected from fluoro and chloro only when R′ is selected from fluoro and chloro; by reacting a quinoline-3-carboxylic acid ester derivative of formula A, where Z is methyl, with an aniline derivative of formula B according to the following reaction diagram, to give the compound of general formula (I), designated “C”, and an alcohol, designated “D”. in a solvent selected from straight or branched alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200° C.

Abstract translation: 制备通式（I）的化合物的方法，其中R选自甲基，乙基，正丙基，异丙基，正丁基，异丁基，仲丁基和烯丙基; R 5选自甲基，乙基，正丙基，异丙基，甲氧基，乙氧基，甲硫基，乙硫基，正丙硫基，甲基亚磺酰基，乙基亚磺酰基，氟，氯，溴，三氟甲基和OCH ＆lt; x＆gt;＆lt;＆lt; 其中x = 0-2，y = 1-3，条件是x + y = 3; R 6是氢; 或R 5和R 6一起是亚甲二氧基; R'选自氢，甲基，甲氧基，氟，氯，溴，三氟甲基和OCHX x Y，其中x = 0-2，y = 1- 3，条件是x + y = 3; R“选自氢，氟和氯，条件是当R'选自氟和氯时，R”选自氟和氯; 通过根据下列反应图使Z为甲基的式A的喹啉-3-羧酸酯衍生物与式B的苯胺衍生物反应，得到标题为“C”的通式（I）的化合物， 和称为“D”的酒精。 在选自直链或支链烷烃和环烷烃或其混合物的溶剂中，沸点在80和200℃之间。

公开(公告)号：US20050192315A1

公开(公告)日：2005-09-01

申请号：US11050441

申请日：2005-02-04

Applicant: Karl Jansson ,  Tomas Fristedt ,  Hans Wannman ,  Anders Bjork

Inventor： Karl Jansson ,  Tomas Fristedt ,  Hans Wannman ,  Anders Bjork

IPC: A61K9/00 ,  A61K9/16 ,  A61K9/20 ,  A61K31/47 ,  A61K31/4706

CPC classification number: A61K31/47 ,  A61K9/1617 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2054 ,  A61K9/2059 ,  A61K31/4706

Abstract: A stable solid pharmaceutical composition consisting essentially of an effective amount of a salt of formula (II) together with an alkaline-reacting component maintaining the pH preferably above 8, or a salt with a divalent metal cation; and at least one pharmaceutical excipient; said salt of formula (II) being essentially stable during storage at room temperature for a period of at least 3 years. A process for stabilizing the salt of formula (II). A crystalline salt of formula (II) and a process for preparing said salt.

Abstract translation: 一种稳定的固体药物组合物，其基本上由有效量的式（II）的盐与保持pH优选高于8的碱反应组分或与二价金属阳离子的盐组成; 和至少一种药物赋形剂; 所述式（II）的盐在室温下储存至少3年的时间基本上是稳定的。 稳定式（II）的盐的方法。 式（II）的结晶盐和制备所述盐的方法。

公开(公告)号：US5730479A

公开(公告)日：1998-03-24

申请号：US674212

申请日：1996-07-01

Applicant: Karl Jansson

Inventor： Karl Jansson

IPC: F17C13/08 ,  B25D23/10

CPC classification number: F17C13/084 ,  F17C2201/0109 ,  F17C2201/0119 ,  F17C2201/032 ,  F17C2201/058 ,  F17C2205/0165 ,  F17C2221/031 ,  F17C2223/0123

Abstract: A device (10) for carrying an elongated, cylindrical gas canister (8) consists of a head (1) adapted to engage a portion of one end (14) of the canister (8), a handle (2) connected to the head (1), and a securing member (4) for essentially encircling a portion of the canister (8), wherein the securing member (4) is connected to the handle (2) at a position displaced lengthwise along the handle (2) from the head (1) to enable secure lifting and transportation of the canister (8). The head (1) is preferably formed of flexible material to accommodate a range of gas canisters (8). Alternatively, the head (1) is of a fixed shape to accommodate a specific type of gas canister (8). The securing member (4) is a strap arranged substantially as a loop and is made of a cross-stitched/woven nylon material. The handle (2) is made of metal, plastics, wood, or a combination thereof.

Abstract translation: 用于承载细长的圆柱形气体罐（8）的装置（10）包括适于接合罐（8）的一端（14）的一部分的头部（1），连接到头部的手柄（2） （1）和用于基本上环绕所述罐（8）的一部分的固定构件（4），其中所述固定构件（4）在沿着所述手柄（2）沿纵向移位的位置处连接到所述手柄（2） 所述头部（1）能够确保所述罐（8）的提升和运输。 头部（1）优选地由柔性材料形成以容纳一系列气体罐（8）。 或者，头部（1）具有固定形状以适应特定类型的气体罐（8）。 固定构件（4）是基本上作为环布置并且由交叉缝合/编织尼龙材料制成的带。 手柄（2）由金属，塑料，木材或其组合制成。

公开(公告)号：US20090232889A1

公开(公告)日：2009-09-17

申请号：US12405413

申请日：2009-03-17

Applicant: Karl Jansson ,  Tomas Fristedt ,  Hans Wannman ,  Anders Bjork

Inventor： Karl Jansson ,  Tomas Fristedt ,  Hans Wannman ,  Anders Bjork

IPC: A61K9/28 ,  C07D215/22 ,  A61K31/4704

CPC classification number: A61K31/4704 ,  A61K31/4706 ,  C07D215/56

Abstract: A stable solid pharmaceutical composition consisting essentially of an effective amount of a crystalline salt of formula (II) together with an alkaline-reacting component maintaining the pH preferably above 8, or a salt with a divalent metal cation; and at least one pharmaceutical excipient; said salt of formula (II) being essentially stable during storage at room temperature for a period of at least 3 years. A process for stabilizing the salt of formula (II). A crystalline salt of formula (II) and a process for preparing said salt.

Abstract translation: 一种稳定的固体药物组合物，其基本上由有效量的式（II）的结晶盐与保持pH优选高于8的碱反应组分或与二价金属阳离子形成的盐组成; 和至少一种药物赋形剂; 所述式（II）的盐在室温下储存至少3年的时间基本上是稳定的。 稳定式（II）的盐的方法。 式（II）的结晶盐和制备所述盐的方法。

公开(公告)号：US07560557B2

公开(公告)日：2009-07-14

申请号：US11084192

申请日：2005-03-21

Applicant: Karl Jansson

Inventor： Karl Jansson

IPC: C07D215/00

CPC classification number: C07D215/56

Abstract: A process for the preparation of the compounds of general formula (I) wherein R is selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and allyl; R5 is selected from methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, methylthio, ethylthio, n-propylthio, methylsulphinyl, ethylsulphinyl, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy; wherein x=0-2, y=1-3 with the proviso that x+y=3; R6 is hydrogen; or R5 and R6 taken together are methylenedioxy; R′ is selected from hydrogen, methyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and OCHxFy, wherein x=0-2, y=1−3 with the proviso that x+y=3; R″ is selected from hydrogen, fluoro and chloro, with the proviso that R″ is selected from fluoro and chloro only when R′ is selected from fluoro and chloro; by reacting a quinoline-3-carboxylic acid ester derivative of formula A, where Z is methyl, with an aniline derivative of formula B according to the following reaction diagram, to give the compound of general formula (I), designated “C”, and an alcohol, designated “D”. in a solvent selected from straight or branched alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200° C.

Abstract translation: 制备通式（I）的化合物的方法，其中R选自甲基，乙基，正丙基，异丙基，正丁基，异丁基，仲丁基和烯丙基; R5选自甲基，乙基，正丙基，异丙基，甲氧基，乙氧基，甲硫基，乙硫基，正丙硫基，甲基亚磺酰基，乙基亚磺酰基，氟，氯，溴，三氟甲基和OCH x Fy; 其中x = 0-2，y = 1-3，条件是x + y = 3; R6是氢; 或R5和R6一起是亚甲二氧基; R'选自氢，甲基，甲氧基，氟，氯，溴，三氟甲基和OCH x Fy，其中x = 0-2，y = 1-3，条件是x + y = 3; R“选自氢，氟和氯，条件是当R'选自氟和氯时，R”选自氟和氯; 通过根据下列反应图使Z为甲基的式A的喹啉-3-羧酸酯衍生物与式B的苯胺衍生物反应，得到标题为“C”的通式（I）的化合物， 和称为“D”的酒精。 在选自直链或支链烷烃和环烷烃或其混合物的溶剂中，沸点在80和200℃之间。