公开(公告)号：US09567296B2

公开(公告)日：2017-02-14

申请号：US14707796

申请日：2015-05-08

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

IPC: C07C323/25 ,  C07C271/22 ,  C07C333/04 ,  C07C235/12 ,  C07C237/12 ,  C12N15/11 ,  A61K47/18 ,  A61K47/20 ,  C11C3/04 ,  C07C323/60 ,  C07J41/00

CPC classification number: C07C323/52 ,  A61K47/18 ,  A61K47/20 ,  C07C235/12 ,  C07C237/12 ,  C07C271/22 ,  C07C323/25 ,  C07C323/60 ,  C07C333/04 ,  C07J41/0055 ,  C11C3/04 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/32

Abstract: What are described are compounds of formula II. The compound of formula II consists of a compound in which R1 and R2 are both a linear alkyl consisting of 1 to 12 carbons, an alkenyl or alkynyl consisting of 2 to 12 carbons; L1 and L2 both consist of a linear alkylene or alkenylene consisting of 5 to 18 carbons; X is S; L3 consists of a bond; R3 consists of a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each consisting of hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract translation: 描述的是式（1）的化合物，其中R 1和R 2相同或不同，各自为具有1-9个碳的直链或支链烷基或具有2至11个碳原子的烯基或炔基; L1和L2相同或不同，各自为具有5至18个碳原子的直链烷基，或与N形成杂环; X1为键，或为-CO-O-，由此形成L2-CO-O-R2; X2是S或O; L3是键或低级烷基，或与N形成杂环; R3是低级烷基; 和R 4和R 5相同或不同，各自为低级烷基; 或其药学上可接受的盐。

公开(公告)号：US09365610B2

公开(公告)日：2016-06-14

申请号：US14707876

申请日：2015-05-08

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula ,  David Webb

IPC: C07J41/00 ,  C07C333/04 ,  C07C271/22 ,  C07C235/12 ,  C07C237/12 ,  C12N15/11 ,  A23D9/013 ,  A61K9/127 ,  A61K9/107

CPC classification number: C07C333/04 ,  A23D9/013 ,  A61K9/1075 ,  A61K9/1272 ,  A61K31/713 ,  C07C235/12 ,  C07C237/12 ,  C07C271/22 ,  C07J41/0055 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/32

Abstract: What is described is a compound of formula I wherein R1 consists of a linear or branched alkyl consisting of 1-18 carbons, an alkenyl or alkynyl consisting of 2 to 12 carbons, or a cholesteryl; R2 consists of a linear or branched alkyl or an alkenyl consisting of 1 to 18 carbons; L1 consists of a linear alkyl consisting of 5 to 9 carbons or, when R1 consists of a cholesteryl then L1 consists of a linear alkylene or alkenyl consisting of 3 to 4 carbons; X1 consists of —O—(CO)— or —(CO)—O—; X2 consists of S or O; L2 consists of a bond or a linear alkylene of 1 to 6 carbons; R3 consists of a linear or branched alkylene with 1 to 6 carbons; and R4 and R5 are the same or different, each consisting of a linear or branched alkyl of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract translation: 描述的是式I的化合物，其中R 1由1-18个碳组成的直链或支链烷基，由2至12个碳组成的烯基或炔基或胆固醇基; R2由直链或支链烷基或由1至18个碳组成的烯基组成; L1由5至9个碳原子的直链烷基组成，或当R1由胆甾醇基组成时，则L1由直链亚烷基或由3至4个碳组成的烯基组成; X1由-O-（CO） - 或 - （CO）-O-组成; X2由S或O组成; L2由1至6个碳原子的键或直链亚烷基组成; R3由具有1至6个碳的直链或支链亚烷基组成; 并且R 4和R 5相同或不同，各自由1至6个碳的直链或支链烷基组成; 或其药学上可接受的盐。

公开(公告)号：US20150307881A1

公开(公告)日：2015-10-29

申请号：US14667680

申请日：2015-03-25

Applicant: Arcturus Therapeutics, Inc.

Inventor： Kiyoshi Tachikawa ,  Joseph E. Payne ,  Padmanabh Chivukula

IPC: C12N15/113 ,  A61K47/14 ,  A61K31/713

CPC classification number: C12N15/113 ,  A61K31/713 ,  A61K47/14 ,  C12N2310/14 ,  C12N2310/323

Abstract: This invention provides UNA oligomers for gene silencing with reduced off-target effects. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and various nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis with reduced off-target effects by administering a UNA oligomer to a subject.

Abstract translation: 本发明提供用于基因沉默的UNA寡聚体，具有降低的脱靶效应。 UNA低聚物可以具有第一链和第二链，每条链长度为19-29个单体，单体为UNA单体和各种核酸单体。 实施方案包括通过向受试者施用UNA寡聚体来治疗或预防TTR相关淀粉样变性的药物组合物和方法，其具有减少的脱靶效应。

公开(公告)号：US20150239926A1

公开(公告)日：2015-08-27

申请号：US14707876

申请日：2015-05-08

Applicant: Arcturus Therapeutics, Inc.

Inventor： Joseph E. Payne ,  Padmanabh Chivukula

IPC: C07J41/00 ,  A61K47/28 ,  A61K47/20 ,  C07C333/04

CPC classification number: C07C333/04 ,  A23D9/013 ,  A61K9/1075 ,  A61K9/1272 ,  A61K31/713 ,  C07C235/12 ,  C07C237/12 ,  C07C271/22 ,  C07J41/0055 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/32

Abstract: What is described is a compound of formula I wherein R1 consists of a linear or branched alkyl consisting of 1-18 carbons, an alkenyl or alkynyl consisting of 2 to 12 carbons, or a cholesteryl; R2 consists of a linear or branched alkyl or an alkenyl consisting of 1 to 18 carbons; L1 consists of a linear alkyl consisting of 5 to 9 carbons or, when R1 consists of a cholesteryl then L1 consists of a linear alkylene or alkenyl consisting of 3 to 4 carbons; X1 consists of —O—(CO)— or —(CO)—O—; X2 consists of S or O; L2 consists of a bond or a linear alkylene of 1 to 6 carbons; R3 consists of a linear or branched alkylene with 1 to 6 carbons; and R4 and R5 are the same or different, each consisting of a linear or branched alkyl of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.

Abstract translation: 描述的是式I的化合物，其中R 1由1-18个碳组成的直链或支链烷基，由2至12个碳组成的烯基或炔基或胆固醇基; R2由直链或支链烷基或由1至18个碳组成的烯基组成; L1由5至9个碳原子的直链烷基组成，或当R1由胆甾醇基组成时，则L1由直链亚烷基或由3至4个碳组成的烯基组成; X1由-O-（CO） - 或 - （CO）-O-组成; X2由S或O组成; L2由1至6个碳原子的键或直链亚烷基组成; R3由具有1至6个碳的直链或支链亚烷基组成; 并且R 4和R 5相同或不同，各自由1至6个碳的直链或支链烷基组成; 或其药学上可接受的盐。