公开(公告)号：US08399516B2

公开(公告)日：2013-03-19

申请号：US12446615

申请日：2007-11-01

Applicant: Morten Bryhn ,  Anne Kristin Holmeide ,  Jenny Rosman

Inventor： Morten Bryhn ,  Anne Kristin Holmeide ,  Jenny Rosman

IPC: A01N37/00

CPC classification number: C07C323/54 ,  A23D9/00 ,  A61K49/0004 ,  C07C57/03 ,  C07C57/12 ,  C07C69/587 ,  C07C211/20 ,  C07C229/30 ,  C07F9/091 ,  C07F9/106 ,  C07H15/04

Abstract: Omega-3 lipid compounds of the general formula (I): wherein R1 and R2 are the same or different and may be selected from a group of substituents consisting of hydrogen, a hydroxy group, an alkyl group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkenyl group, an alkynyl group, an aryl group, an alkylthio group, an alkoxycarbonyl group, a carboxy group, an alkylsulfinyl group, an alkylsulfonyl group, an amino group, and an alkylamino group; X represents a carboxylic acid or a derivative thereof, a carboxylate, a carboxylic anhydride or a carboxamide; and Y is a C6 to C22 alkene with two or more double bonds, having E and/or Z configuration, are disclosed. Also disclosed are pharmaceutical compositions and lipid compositions comprising such compounds, and to such compounds for use as medicaments in particular for the treatment of cardiovascular and metabolic diseases.

Abstract translation: 通式（I）的ω-3脂质化合物：其中R 1和R 2相同或不同，并且可以选自氢，羟基，烷基，卤素原子，烷氧基 酰氧基，烯基，炔基，芳基，烷硫基，烷氧基羰基，羧基，烷基亚磺酰基，烷基磺酰基，氨基和烷基氨基; X表示羧酸或其衍生物，羧酸酯，羧酸酐或羧酰胺; 并且Y是具有两个或更多个双键的具有E和/或Z构型的C6至C22烯烃。 还公开了包含这些化合物的药物组合物和脂质组合物，以及用作特别用于治疗心血管和代谢疾病的药物的这种化合物。

公开(公告)号：US08034842B2

公开(公告)日：2011-10-11

申请号：US12111589

申请日：2008-04-29

Applicant: Morten Bryhn ,  Jan Kopecky ,  Anne Kristin Holmeide

Inventor： Morten Bryhn ,  Jan Kopecky ,  Anne Kristin Holmeide

IPC: A61K31/20

CPC classification number: C07C57/03 ,  C07C69/587 ,  C07C69/618 ,  C07C69/65 ,  C07C69/732 ,  C07C69/734 ,  C07C229/30 ,  C07C233/09 ,  C07C235/28 ,  C07C237/16 ,  C07C317/44 ,  C07C323/54 ,  C07D209/48 ,  C07D263/22 ,  C07D263/24 ,  C11C3/00

Abstract: Compounds of formula (I); wherein R1 and R2 are the same or different and may be selected from the group consisting of a hydrogen atom, a hydroxy group, an alkyl group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkenyl group, an alkynyl group, an aryl group, an alkylthio group, an alkoxycarbonyl group, an alkylsulfinyl group, an alkylsulfonyl group, an amino group, and an alkylamino group; and X represents a carboxylic acid group, a carboxylate group, or a carboxamide group; or any pharmaceutically acceptable salt, solvate, complex or pro-drug thereof, with the provisos that the compound of formula (I) is not (all-Z)-4,7,10,13,16,19-docosahexaenoic acid (DHA), alpha-methyl-DHA, alpha-methyl DHA methyl ester, alpha-methyl-DHA ethyl ester or alpha-hydroxy DHA ethyl ester, are disclosed. A fatty acid composition and a pharmaceutical composition comprising such compounds are also disclosed. The use of such compounds as medicaments, in particular for the treatment of diabetes type 2, is also disclosed.

Abstract translation: 式（I）化合物; 其中R1和R2相同或不同，可以选自氢原子，羟基，烷基，卤素原子，烷氧基，酰氧基，酰基，烯基， 炔基，芳基，烷硫基，烷氧基羰基，烷基亚磺酰基，烷基磺酰基，氨基和烷基氨基; X表示羧酸基，羧酸酯基或羧酰胺基; 或其任何药学上可接受的盐，溶剂化物，复合物或前药，条件是式（I）化合物不是（全Z）-4,7,10,13,16,19-二十二碳六烯酸（DHA ），α-甲基-DHA，α-甲基DHA甲酯，α-甲基-DHA乙酯或α-羟基DHA乙酯。 还公开了脂肪酸组合物和包含这些化合物的药物组合物。 还公开了使用这些化合物作为药物，特别是用于治疗2型糖尿病的化合物。

公开(公告)号：US20110166228A1

公开(公告)日：2011-07-07

申请号：US12446249

申请日：2007-11-01

Applicant: Anne Kristin Holmeide ,  Jenny Rosman

Inventor： Anne Kristin Holmeide ,  Jenny Rosman

IPC: A61K31/202 ,  A61P3/10 ,  A61P9/10

CPC classification number: C07F9/113 ,  A61K31/045 ,  A61K31/047 ,  A61K31/075 ,  A61K31/10 ,  A61K31/22 ,  A61K31/225 ,  A61K31/232 ,  A61K31/255 ,  A61K31/265 ,  A61K31/661 ,  A61K45/06 ,  C07C69/007 ,  C07C69/24 ,  C07C69/40 ,  C07C69/587 ,  C07C69/96 ,  C07C305/14 ,  C07C323/14 ,  A61K2300/00

Abstract: The present invention relates to compositions comprising at least omega-3 lipid compounds substituted at the 2-positions having therapeutic activity. More specifically, the present invention relates to a composition comprising at least omega-3 lipid compounds substituted at the 2-position, counted from the functional group (X) of the omega-3 lipid compound, wherein the omega-3 lipid compounds comprise: a compound of general formula (I): and a compound of formula (II): wherein R1 and R2 are the same or different and are chosen from a hydrogen atom, a hydroxy group, an alkyl group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkenyl group, an alkynyl group, an aryl group, an alkylthio group, an alkoxycarbonyl group, a carboxy group, an alkylsulfinyl group, an alkylsulfonyl group, an amino group, and an alkylamino group; and X represents a carboxylic acid or a derivative thereof, a carboxylate, a carboxylic anhydride, a hydroxymethyl (—CH2OH) or a pro-drug thereof, or a carboxamide, or any pharmaceutically acceptable complex, salt, solvate, or pro-drug, with the provisos that: R1 and R2 are not simultaneously hydrogen.

Abstract translation: 本发明涉及包含至少在具有治疗活性的2位置取代的ω-3脂质化合物的组合物。 更具体地说，本发明涉及从ω-3脂质化合物的官能团（X）计数的至少包含在2位被取代的ω-3脂质化合物的组合物，其中ω-3脂质化合物包含： 通式（I）的化合物和式（II）的化合物：其中R 1和R 2相同或不同，并且选自氢原子，羟基，烷基，卤素原子，烷氧基 酰氧基，烯基，炔基，芳基，烷硫基，烷氧基羰基，羧基，烷基亚磺酰基，烷基磺酰基，氨基和烷基氨基; 羧酸酐，羧酸酐，羟甲基（-CH 2 OH）或其前药或羧酰胺，或任何药学上可接受的复合物，盐，溶剂合物或前药， 条件是：R1和R2不同时为氢。

公开(公告)号：US20080300306A1

公开(公告)日：2008-12-04

申请号：US12111589

申请日：2008-04-29

Applicant: Morten Bryhn ,  Jan Kopecky ,  Anne Kristin Holmeide

Inventor： Morten Bryhn ,  Jan Kopecky ,  Anne Kristin Holmeide

IPC: A61K31/202 ,  A61P3/00 ,  A61P29/00 ,  C07C51/00 ,  C07C57/02 ,  C07C57/03

CPC classification number: C07C57/03 ,  C07C69/587 ,  C07C69/618 ,  C07C69/65 ,  C07C69/732 ,  C07C69/734 ,  C07C229/30 ,  C07C233/09 ,  C07C235/28 ,  C07C237/16 ,  C07C317/44 ,  C07C323/54 ,  C07D209/48 ,  C07D263/22 ,  C07D263/24 ,  C11C3/00

Abstract: Compounds of formula (I); wherein R1 and R2 are the same or different and may be selected from the group consisting of a hydrogen atom, a hydroxy group, an alkyl group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkenyl group, an alkynyl group, an aryl group, an alkylthio group, an alkoxycarbonyl group, an alkylsulfinyl group, an alkylsulfonyl group, an amino group, and an alkylamino group; and X represents a carboxylic acid group, a carboxylate group, or a carboxamide group; or any pharmaceutically acceptable salt, solvate, complex or pro-drug thereof, with the provisos that the compound of formula (I) is not (all-Z)-4,7,10,13,16,19-docosahexaenoic acid (DHA), alpha-methyl-DHA, alpha-methyl DHA methyl ester, alpha-methyl-DHA ethyl ester or alpha-hydroxy DHA ethyl ester, are disclosed. A fatty acid composition and a pharmaceutical composition comprising such compounds are also disclosed. The use of such compounds as medicaments, in particular for the treatment of diabetes type 2, is also disclosed.

Abstract translation: 式（I）化合物; 其中R1和R2相同或不同，可以选自氢原子，羟基，烷基，卤素原子，烷氧基，酰氧基，酰基，烯基， 炔基，芳基，烷硫基，烷氧基羰基，烷基亚磺酰基，烷基磺酰基，氨基和烷基氨基; X表示羧酸基，羧酸酯基或羧酰胺基; 或其任何药学上可接受的盐，溶剂化物，复合物或前药，条件是式（I）化合物不是（全Z）-4,7,10,13,16,19-二十二碳六烯酸（DHA ），α-甲基-DHA，α-甲基DHA甲酯，α-甲基-DHA乙酯或α-羟基DHA乙酯。 还公开了脂肪酸组合物和包含这些化合物的药物组合物。 还公开了使用这些化合物作为药物，特别是用于治疗2型糖尿病的化合物。

公开(公告)号：US08741966B2

公开(公告)日：2014-06-03

申请号：US12741890

申请日：2008-11-06

Applicant: Anne Kristin Holmeide

Inventor： Anne Kristin Holmeide

IPC: A61K31/095 ,  A61K31/10 ,  A61K31/21 ,  C07C317/08 ,  C07C69/52 ,  C07C321/18 ,  C07C303/00

CPC classification number: A61K31/00 ,  A23L33/115 ,  A61K8/46 ,  A61K2800/92 ,  A61Q19/06 ,  C07C323/12

Abstract: The present disclosure relates to lipid compounds of formula (I): wherein: R1 is chosen from a C10-C21 alkyl, a C10-C21 alkenyl having 1-6 double bonds, and a C10-C21 alkynyl having 1-6 triple bonds; R2 and R3 are the same or different and are chosen from hydrogen and a C1-C6 alkyl; X is chosen from O, S, SO, SO2, Si, and Se; n=1 or 3; and P1 is chosen from hydrogen; a C10-C21 alkyl, a C10-C21 alkenyl having 1-6 double bonds, a C10-C21 alkynyl having 1-6 triple bonds, optionally substituted; a group of formula (II) or formula (III), wherein P2, P3, and P4 are chosen from hydrogen, an alkyl, an alkenyl, and an alkynyl, optionally substituted; and a group of formula (IV) or formula (V), wherein P5 is chosen from hydrogen and a C1-C6 alkyl; or a pharmaceutically acceptable salt, complex, or solvate thereof. Also disclosed are pharmaceutical compositions and lipid compositions comprising such compounds, and methods of use thereof, for example in the treatment of diseases related to cardiovascular, metabolic, and inflammatory conditions.

Abstract translation: 本公开涉及式（I）的脂质化合物：其中：R 1选自C 10 -C 21烷基，具有1-6个双键的C 10 -C 21烯基和具有1-6个三键的C 10 -C 21炔基; R2和R3相同或不同，并且选自氢和C1-C6烷基; X选自O，S，SO，SO2，Si和Se; n = 1或3; P1选自氢; C10-C21烷基，具有1-6个双键的C10-C21烯基，具有1-6个三键的C10-C21炔基，任选取代的; 式（II）或式（III）的基团，其中P2，P3和P4选自氢，烷基，烯基和炔基，任选取代; 和式（IV）或式（V）的基团，其中P 5选自氢和C 1 -C 6烷基; 或其药学上可接受的盐，络合物或溶剂化物。 还公开了包含这些化合物的药物组合物和脂质组合物及其使用方法，例如用于治疗与心血管，代谢和炎性病症有关的疾病。

公开(公告)号：US20120122940A1

公开(公告)日：2012-05-17

申请号：US13319101

申请日：2010-05-07

Applicant: Ragnar Hovland ,  Anne Kristin Holmeide ,  Tore Skjæret ,  Morten Brændvang

Inventor： Ragnar Hovland ,  Anne Kristin Holmeide ,  Tore Skjæret ,  Morten Brændvang

IPC: A61K31/19 ,  C07C69/734 ,  A61K31/22 ,  C07D263/26 ,  A61K31/421 ,  A61P29/00 ,  A61P1/00 ,  A61P9/10 ,  A61P3/10 ,  A61P7/00 ,  A61P3/06 ,  A61P3/04 ,  C07C51/42 ,  C07C67/48 ,  C07C57/03

CPC classification number: C07D263/26 ,  A61K31/19 ,  A61K31/22 ,  A61K31/421 ,  A61K45/06 ,  C07B2200/07 ,  C07C51/367 ,  C07C59/60 ,  C07C67/31 ,  C07C69/675 ,  C07C69/68 ,  C07C69/708

Abstract: The present disclosure relates to lipid compounds of the general formula (I): R1-O—C(R2)(R3)-X  (I) wherein R1 is a C10-C22 alkyl group, a C10-C22 alkenyl group having 1-6 double bonds, or a C10-C22 alkynyl group having 1-6 triple bonds; R2 and R3 are the same or different and may be chosen from different substituents; and X is a carboxylic acid or a derivative thereof, such as a carboxylic ester, a carboxylic anhydride, a phospholipid, triglyceride, or a carboxamide; or a pharmaceutically acceptable salt, solvate, solvate of such salt or a prodrug thereof. The present disclosure also relates to pharmaceutical compositions and lipid compositions comprising at least one compound according to the present disclosure, and to such compounds for use as medicaments or for use in therapy, in particular for the treatment of diseases related to the cardiovascular, metabolic, and inflammatory disease area.

Abstract translation: 本发明涉及通式（I）的脂类化合物：R1-O-C（R2）（R3）-X（Ⅰ）其中R1是C10-C22烷基，C10-C22烯基具有1- 6个双键或具有1-6个三键的C10-C22炔基; R2和R3相同或不同，可以选自不同的取代基; X是羧酸或其衍生物，例如羧酸酯，羧酸酐，磷脂，甘油三酸酯或羧酰胺; 或其药学上可接受的盐，溶剂合物，这种盐的溶剂合物或其前药。 本公开还涉及包含至少一种根据本公开的化合物的药物组合物和脂质组合物，以及用作药物或用于治疗的这类化合物，特别是用于治疗与心血管，代谢， 和炎症性疾病区域。

公开(公告)号：US20100280109A1

公开(公告)日：2010-11-04

申请号：US12741890

申请日：2008-11-06

Applicant: Anne Kristin Holmeide

Inventor： Anne Kristin Holmeide

IPC: A61K31/22 ,  A61K31/10 ,  C07C69/14 ,  C07C323/12 ,  A61P3/06

CPC classification number: A61K31/00 ,  A23L33/115 ,  A61K8/46 ,  A61K2800/92 ,  A61Q19/06 ,  C07C323/12

Abstract: The present disclosure relates to lipid compounds of formula (I): wherein: R1 is chosen from a C10-C21 alkyl, a C10-C21 alkenyl having 1-6 double bonds, and a C10-C21 alkynyl having 1-6 triple bonds; R2 and R3 are the same or different and are chosen from hydrogen and a C1-C6 alkyl; X is chosen from O, S, SO, SO2, Si, and Se; n=1 or 3; and P1 is chosen from hydrogen; a C10-C21 alkyl, a C10-C21 alkenyl having 1-6 double bonds, a C10-C21 alkynyl having 1-6 triple bonds, optionally substituted; a group of formula (II) or formula (III), wherein P2, P3, and P4 are chosen from hydrogen, an alkyl, an alkenyl, and an alkynyl, optionally substituted; and a group of formula (IV) or formula (V), wherein P5 is chosen from hydrogen and a C1-C6 alkyl; or a pharmaceutically acceptable salt, complex, or solvate thereof. Also disclosed are pharmaceutical compositions and lipid compositions comprising such compounds, and methods of use thereof, for example in the treatment of diseases related to cardiovascular, metabolic, and inflammatory conditions.

Abstract translation: 本公开涉及式（I）的脂质化合物：其中：R 1选自C 10 -C 21烷基，具有1-6个双键的C 10 -C 21烯基和具有1-6个三键的C 10 -C 21炔基; R2和R3相同或不同，并且选自氢和C1-C6烷基; X选自O，S，SO，SO2，Si和Se; n = 1或3; P1选自氢; C10-C21烷基，具有1-6个双键的C10-C21烯基，具有1-6个三键的C10-C21炔基，任选取代的; 式（II）或式（III）的基团，其中P2，P3和P4选自氢，烷基，烯基和炔基，任选取代; 和式（IV）或式（V）的基团，其中P 5选自氢和C 1 -C 6烷基; 或其药学上可接受的盐，络合物或溶剂化物。 还公开了包含这些化合物的药物组合物和脂质组合物及其使用方法，例如用于治疗与心血管，代谢和炎性病症有关的疾病。

公开(公告)号：US08759558B2

公开(公告)日：2014-06-24

申请号：US13054212

申请日：2009-07-13

Applicant: Anne Kristin Holmeide ,  Ragnar Hovland ,  Morten Brændvang

Inventor： Anne Kristin Holmeide ,  Ragnar Hovland ,  Morten Brændvang

IPC: C11D1/28 ,  A61K31/10

CPC classification number: C07C323/54 ,  A23L33/12 ,  C07C317/44 ,  C07C323/52 ,  C07C323/55 ,  C07C323/56 ,  C07C323/61 ,  C07C2601/04

Abstract: The present invention relates to lipid compounds of the general formula (I): wherein R1 is selected from a C10-C22 alkyl, a C10-C22 alkenyl having 1-6 double bonds, and a C10-C22alkynyl having 1-6 triple bonds; R2 and R3 are the same or different and may be selected from a group of different substituents; Y is selected from sulphur, sulfoxide, and sulfone; and X represents a carboxylic acid or a derivative thereof, a carboxylic ester, a carboxylic anhydride or a carboxamide; or a pharmaceutically acceptable salt, complex or solvate thereof.The invention also relates to pharmaceutical compositions and lipid compositions comprising such compounds, and to such compounds for use as medicaments or for use in therapy, in particular for the treatment of diseases related to the cardiovascular, metabolic and inflammatory disease area.

Abstract translation: 本发明涉及通式（I）的脂质化合物：其中R1选自C10-C22烷基，具有1-6个双键的C10-C22烯基和具有1-6个三键的C10-C22炔基; R2和R3相同或不同，并且可以选自不同取代基的一组; Y选自硫，亚砜和砜; X表示羧酸或其衍生物，羧酸酯，羧酸酐或羧酰胺; 或其药学上可接受的盐，复合物或溶剂合物。 本发明还涉及包含这种化合物的药物组合物和脂质组合物，以及用作药物或用于治疗，特别是用于治疗与心血管，代谢和炎性疾病区域有关的疾病的化合物。

公开(公告)号：US08178708B2

公开(公告)日：2012-05-15

申请号：US12293966

申请日：2007-03-23

Applicant: Anne Kristin Holmeide

Inventor： Anne Kristin Holmeide

IPC: A23D9/00 ,  A61K31/00 ,  A61K31/45

CPC classification number: C07C69/587 ,  C07C33/02 ,  C07C43/178 ,  C07C57/03 ,  C07C59/58 ,  C07C69/734

Abstract: The present invention relates to lipid compounds of the general formula (I): wherein -n=0-2, —R1 and R2 are the same or different and may be selected from a group of substituents consisting of a hydrogen atom, an alkyl group, a halogen atom, and an alkoxy group; -, X is COR3 or CH2OR4, wherein —R3 is selected from the group consisting of hydrogen, hydroxy, alkoxy, and amino, —wherein X further comprises carboxylic acid derivatives when R3 is hydroxy and —R4 is selected from the group consisting of hydrogen, alkyl or acyl, —Y is a C9 to C21 alkene with one or more double bonds with E or Z configuration; or any pharmaceutically acceptable complex, solvate or pro-drug thereof. The present invention also relates to pharmaceutical compositions comprising such lipid compounds, and to such lipid compounds for use as medicaments or for diagnostic purposes.

Abstract translation: 本发明涉及通式（I）的脂质化合物：其中-n = 0-2，-R1和R2相同或不同，并且可以选自由氢原子，烷基 卤素原子和烷氧基; - ，X是COR 3或CH 2 OR 4，其中-R 3选自氢，羟基，烷氧基和氨基，其中当R 3是羟基时，X还包含羧酸衍生物，-R 4选自氢 烷基或酰基，-Y是具有一个或多个具有E或Z构型的双键的C9至C21烯烃; 或其药学上可接受的复合物，溶剂合物或前体药物。 本发明还涉及包含这种脂质化合物的药物组合物以及用作药物或用于诊断目的的这种脂质化合物。

公开(公告)号：US20120065260A1

公开(公告)日：2012-03-15

申请号：US13225855

申请日：2011-09-06

Applicant: Morten Bryhn ,  Jan Kopecky ,  Anne Kristin Holmeide

Inventor： Morten Bryhn ,  Jan Kopecky ,  Anne Kristin Holmeide

IPC: A61K31/232 ,  A61P3/04 ,  C07C51/347 ,  A61K31/202 ,  A61P3/06 ,  A61P3/10 ,  A61P29/00

CPC classification number: C07C57/03 ,  C07C69/587 ,  C07C69/618 ,  C07C69/65 ,  C07C69/732 ,  C07C69/734 ,  C07C229/30 ,  C07C233/09 ,  C07C235/28 ,  C07C237/16 ,  C07C317/44 ,  C07C323/54 ,  C07D209/48 ,  C07D263/22 ,  C07D263/24 ,  C11C3/00

Abstract: Compounds of formula (I); wherein R1 and R2 are the same or different and may be selected from the group consisting of a hydrogen atom, a hydroxy group, an alkyl group, a halogen atom, an alkoxy group, an acyloxy group, an acyl group, an alkenyl group, an alkynyl group, an aryl group, an alkylthio group, an alkoxycarbonyl group, an alkylsulfinyl group, an alkylsulfonyl group, an amino group, and an alkylamino group; and X represents a carboxylic acid group, a carboxylate group, or a carboxamide group; or any pharmaceutically acceptable salt, solvate, complex or pro-drug thereof, with the provisos that the compound of formula (I) is not (all-Z)-4,7,10,13,16,19-docosahexaenoic acid (DHA), alpha-methyl DHA, alpha-methyl DHA methyl ester, alpha-methyl DHA ethyl ester or alpha-hydroxy DHA ethyl ester, are disclosed. A fatty acid composition and a pharmaceutical composition comprising such compounds are also disclosed. The use of such compounds as medicaments, in particular for the treatment of diabetes type 2, is also disclosed.

Abstract translation: 式（I）化合物; 其中R1和R2相同或不同，可以选自氢原子，羟基，烷基，卤素原子，烷氧基，酰氧基，酰基，烯基， 炔基，芳基，烷硫基，烷氧基羰基，烷基亚磺酰基，烷基磺酰基，氨基和烷基氨基; X表示羧酸基，羧酸酯基或羧酰胺基; 或其任何药学上可接受的盐，溶剂化物，复合物或前药，条件是式（I）化合物不是（全Z）-4,7,10,13,16,19-二十二碳六烯酸（DHA ），α-甲基DHA，α-甲基DHA甲酯，α-甲基DHA乙酯或α-羟基DHA乙酯。 还公开了脂肪酸组合物和包含这些化合物的药物组合物。 还公开了使用这些化合物作为药物，特别是用于治疗2型糖尿病的化合物。