公开(公告)号：US20240042039A1

公开(公告)日：2024-02-08

申请号：US18194540

申请日：2023-03-31

申请人： ARBUTUS BIOPHARMA CORPORATION

发明人： Muthiah Manoharan ,  Muthusamy Jayaraman ,  Kallanthottathil G. Rajeev ,  Laxman Eltepu ,  Steven Ansell ,  Jianxin Chen

IPC分类号： A61K47/44 ,  A61K31/7088 ,  A61K31/713 ,  A61K39/00 ,  A61K39/39 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  C07C229/08 ,  C07C229/30 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25 ,  C07D203/10 ,  C07D317/28 ,  C07D317/44 ,  C07D317/46 ,  C07D317/72 ,  C07D319/06 ,  C07D405/12 ,  C07D491/056 ,  C07D491/113 ,  C12N15/11 ,  C12N15/113 ,  A61K9/127

CPC分类号： A61K47/44 ,  C12N2320/32 ,  A61K31/713 ,  A61K39/00 ,  A61K39/39 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  C07C229/08 ,  C07C229/30 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25 ,  C07D203/10 ,  C07D317/28 ,  C07D317/44 ,  C07D317/46 ,  C07D317/72 ,  C07D319/06 ,  C07D405/12 ,  C07D491/056 ,  C07D491/113 ,  C12N15/111 ,  C12N15/113 ,  A61K9/1272 ,  Y02A50/30 ,  A61K2039/55555 ,  A61K2039/55561 ,  C12N2310/14 ,  C12N2310/3515 ,  A61K31/7088

摘要： The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure




wherein:



R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

公开(公告)号：US11712476B2

公开(公告)日：2023-08-01

申请号：US17357122

申请日：2021-06-24

申请人： ARBUTUS BIOPHARMA CORPORATION

发明人： Muthiah Mancharan ,  Muthusamy Jayaraman ,  Kallanthottathil G. Rajeev ,  Laxman Eltepu ,  Steven Ansell ,  Jianxin Chen

IPC分类号： A61K47/44 ,  A61K39/39 ,  C07C229/08 ,  A61K31/713 ,  C07D319/06 ,  C07D317/28 ,  C07D203/10 ,  C07C229/30 ,  C12N15/113 ,  A61K39/00 ,  C12N15/11 ,  A61K9/127 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25 ,  A61K31/7088 ,  C07D317/44 ,  C07D317/46 ,  C07D317/72 ,  C07D405/12 ,  C07D491/056 ,  C07D491/113

CPC分类号： A61K47/44 ,  A61K9/1272 ,  A61K31/7088 ,  A61K31/713 ,  A61K39/00 ,  A61K39/39 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  C07C229/08 ,  C07C229/30 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25 ,  C07D203/10 ,  C07D317/28 ,  C07D317/44 ,  C07D317/46 ,  C07D317/72 ,  C07D319/06 ,  C07D405/12 ,  C07D491/056 ,  C07D491/113 ,  C12N15/111 ,  C12N15/113 ,  A61K2039/55555 ,  A61K2039/55561 ,  C12N2310/14 ,  C12N2310/3515 ,  C12N2320/32 ,  Y02A50/30

摘要： The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

公开(公告)号：US20220023427A1

公开(公告)日：2022-01-27

申请号：US17357122

申请日：2021-06-24

申请人： ARBUTUS BIOPHARMA CORPORATION

发明人： Muthiah Manoharan ,  Muthusamy Jayaraman ,  Kallanthottathil G. Rajeev ,  Laxman Eltepu ,  Steven Ansell ,  Jianxin Chen

IPC分类号： A61K47/44 ,  A61K39/39 ,  C07C229/08 ,  A61K31/713 ,  C07D319/06 ,  C07D317/28 ,  C07D203/10 ,  C07C229/30 ,  C12N15/113 ,  A61K39/00 ,  C12N15/11 ,  A61K9/127 ,  A61K47/10 ,  A61K47/18 ,  A61K47/20 ,  A61K47/28 ,  C07C237/16 ,  C07C251/38 ,  C07C251/78 ,  C07C271/12 ,  C07C271/20 ,  C07C323/25 ,  A61K31/7088 ,  C07D317/44 ,  C07D317/46 ,  C07D317/72 ,  C07D405/12 ,  C07D491/056 ,  C07D491/113

摘要： The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

公开(公告)号：US10533008B2

公开(公告)日：2020-01-14

申请号：US16083128

申请日：2017-03-01

申请人： UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, IONC.

发明人： Chung K. Chu ,  Varughese Alexander Mulamootttil ,  Ram C. Mishra ,  Uma Sharan Singh

IPC分类号： C07D473/34 ,  C07D317/44 ,  C07C41/26 ,  C07C41/30 ,  C07D473/18 ,  C07D473/26 ,  C07D473/40 ,  C07F9/6561 ,  C07C41/28 ,  A61P31/20 ,  C07C43/196

摘要： The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R,4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

公开(公告)号：US20190100523A1

公开(公告)日：2019-04-04

申请号：US16083128

申请日：2017-03-01

申请人： UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, IONC.

发明人： Chung K. Chu ,  Varughese Alexander Mulamootttil ,  Ram C. Mishra ,  Uma Sharan Singh

IPC分类号： C07D473/34 ,  C07D317/44 ,  C07C41/28 ,  C07F9/6561

摘要： The invention provides a new convergent approach for the synthesis of 2′-fluoro-6′- methylene-carbocyclic adenosine (FMCA) and 2′-fluoro-6′-methylene-carbocyclic guanosine (FMCG) from a readily available starting material in eight steps. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, (1S,3R,4R)-3-tert-butoxy-4-(tert-butoxymethyl)-2-fluoro-5-methylenecyclopentanol (compound 8 of scheme 1A or a) in only six (6) steps is also provided. Prodrugs of these compounds are also prepared.

公开(公告)号：US09850223B2

公开(公告)日：2017-12-26

申请号：US15207906

申请日：2016-07-12

申请人： KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

发明人： Hyunwoo Kim ,  Yuseop Lee

IPC分类号： C07D317/44 ,  C07D317/46 ,  C07D317/70 ,  C07D493/04 ,  B01J31/22

CPC分类号： C07D317/44 ,  B01J31/2295 ,  B01J2231/49 ,  B01J2531/31 ,  B01J2531/842 ,  C07D317/46 ,  C07D317/70 ,  C07D493/04

摘要： Provided are a novel metal catalyst for preparing cyclic carbonate, and a method for preparing cyclic carbonate using the same, and more particularly, a method for selectively preparing cyclic carbonate in a high yield and at a higher conversion rate as compared to the existing catalysts, using the metal complex including a ligand represented by Chemical Formula 1 below and a trivalent metal in Group 8 or Group 13 as a catalyst and using various structures of epoxide compounds and carbon dioxide as raw materials. In addition, provided are the prepared cyclic carbonate, and an electrolyte including the same: in Chemical Formula 1, R1 is hydrogen, (C1-C20)alkyl or halogen; R2 is hydrogen, (C1-C20)alkyl, (C1-C20)alkoxy, halogen or nitro.

公开(公告)号：US09604991B2

公开(公告)日：2017-03-28

申请号：US14975785

申请日：2015-12-20

申请人： SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.

发明人： Xuenong Xu

IPC分类号： C07D471/00 ,  C07D487/00 ,  C07D491/00 ,  C07D487/04 ,  C07D317/44 ,  C07D405/04

CPC分类号： C07D487/04 ,  C07D317/44 ,  C07D405/04

摘要： Disclosed in the present invention is a method for preparing Ticagrelor (I), comprising the following steps: a cyclization reaction of 5-amino-1,4-di-substituted-1,2,3-triazole (II) and dialkyl carbonate (HI), to obtain 9-substituted-2,6-dihydroxy-8-azapurine (IV); chlorination of intermediate (IV), to obtain 9-substituted-2,6-dichloro-8-azapurine (V); an amination reaction of intermediate (V) and trans-(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine (VI) generates 9-substituted-6-amino-substituted-2-chloro-8-azapurine (VII); and a propanethiolation reaction of intermediate (VII) and propanethiol (VIII), to obtain Ticagrelor (I). The preparation method is simple in process, has a high chemical and chiral purity and provides a new preparation method for industrializing Ticagrelor. In addition, also provided in the present invention are intermediates of Ticagrelor and a preparation method thereof, wherein raw materials of the preparation method are easily available, the conditions thereof are mild, and the yield thereof is high.

公开(公告)号：US09533958B2

公开(公告)日：2017-01-03

申请号：US14845968

申请日：2015-09-04

申请人： Rexahn Pharmaceuticals, Inc.

发明人： Haifeng Yin ,  Deog Joong Kim ,  Eliezer Falb ,  Leigh Andre Pearcey ,  Jonathan Cummins ,  Petra Dieterich ,  Jean-Francois Carniaux ,  Yi Wang ,  Vikram Chandrakant Purohit

IPC分类号： C07D239/47 ,  C07F7/18 ,  C07D317/44 ,  C07D405/04

CPC分类号： C07D239/47 ,  C07D317/22 ,  C07D317/44 ,  C07D405/04 ,  C07F7/1892

摘要： Processes for the preparation of 4-amino-1-((1S,4R,5S)-2-fluoro-4,5-dihydroxy-3-hydroxymethyl-cyclopent-2-enyl)-1H-pyrimidin-2-one (13, RX-3117) and its intermediates are described.

摘要翻译： 制备4-氨基-1 - （（1S，4R，5S）-2-氟-4,5-二羟基-3-羟甲基 - 环戊-2-烯基）-1H-嘧啶-2-酮（13 ，RX-3117）及其中间体。

公开(公告)号：US09150520B2

公开(公告)日：2015-10-06

申请号：US14216242

申请日：2014-03-17

申请人： Rexahn Pharmaceuticals, Inc.

发明人： Haifeng Yin ,  Deog J. Kim ,  Eliezer Falb ,  Leigh A. Pearcey ,  Jonathan Cummins ,  Petra Dieterich ,  Jean-Francois Carniaux ,  Yi Wang ,  Vikram Chandrakant Purohit

IPC分类号： C07D239/47 ,  C07F7/18 ,  C07D317/44

CPC分类号： C07D239/47 ,  C07D317/22 ,  C07D317/44 ,  C07D405/04 ,  C07F7/1892

摘要： Processes for the preparation of 4-amino-1-((1S,4R,5S)-2-fluoro-4,5-dihydroxy-3-hydroxymethyl-cyclopent-2-enyl)-1H-pyrimidin-2-one (13, RX-3117) and its intermediates are described.

摘要翻译： 制备4-氨基-1 - （（1S，4R，5S）-2-氟-4,5-二羟基-3-羟甲基 - 环戊-2-烯基）-1H-嘧啶-2-酮（13 ，RX-3117）及其中间体。

公开(公告)号：US08987262B2

公开(公告)日：2015-03-24

申请号：US13678802

申请日：2012-11-16

申请人： Universite de Bordeaux ,  Centre Hospitalier Universitaire de Bordeaux

发明人： Christine Leaute-Labreze ,  Eric Dumas De La Roque ,  Alain Taieb ,  Jean-Benoit Thambo

IPC分类号： A61K31/535 ,  A01N43/42 ,  A61K31/47 ,  A01N43/38 ,  A61K31/40 ,  A61K31/405 ,  A01N43/16 ,  A61K31/35 ,  A01N43/40 ,  A61K31/36 ,  A01N37/12 ,  A61K31/24 ,  A01N37/02 ,  A61K31/22 ,  A01N47/28 ,  A61K31/17 ,  A01N41/06 ,  A61K31/18 ,  A01N37/18 ,  A61K31/165 ,  A61K31/16 ,  A01N33/02 ,  A61K31/135 ,  A01N35/00 ,  A61K31/12 ,  A01N31/00 ,  A61K31/045 ,  C07D417/00 ,  C07D215/00 ,  C07D209/10 ,  C07D311/00 ,  C07D317/44 ,  C07C69/00 ,  C07C335/00 ,  C07C303/00 ,  C07C307/00 ,  C07C309/00 ,  C07C311/00 ,  C07C273/00 ,  C07C275/00 ,  C07C233/00 ,  C07C235/00 ,  C07C239/00 ,  C09B11/02 ,  C07C211/00 ,  C07C213/00 ,  C07C221/00 ,  C07C225/00 ,  A61K31/138 ,  A61K31/167

CPC分类号： A61K31/138 ,  A61K31/167

摘要： The present technology relates the use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas, for example of infantile hemangiomas. The beta blocker may be a non-selective beta-blocker, for example propranolol. The present technology provides an alternative to the known compounds, e.g. corticosteroïds, interferon or vincristine, generally used for the treatment of hemangiomas.

摘要翻译： 本技术涉及β-阻滞剂在制备用于治疗血管瘤（例如婴儿血管瘤）的药物中的用途。 β受体阻滞剂可以是非选择性β-受体阻滞剂，例如普萘洛尔。 本技术提供了已知化合物的替代物，例如 皮质激素，干扰素或长春新碱，通常用于治疗血管瘤。