公开(公告)号：US11724982B2

公开(公告)日：2023-08-15

申请号：US16868343

申请日：2020-05-06

Applicant: Ming-Yu Ngai ,  Katarzyna N. Hojczyk

Inventor： Ming-Yu Ngai ,  Katarzyna N. Hojczyk

IPC: C07C233/25 ,  C07C259/06 ,  C07C259/10 ,  C07C269/06 ,  C07C273/18 ,  C07C231/14 ,  C07C253/30 ,  C07D213/75 ,  C07D213/76 ,  C07D347/00 ,  C07D239/47 ,  C07D239/91 ,  C07D473/40 ,  C07D263/57 ,  C07D209/08 ,  C07D215/40 ,  C07D401/04 ,  C07D471/04 ,  C07J43/00 ,  C07D417/04 ,  C07D405/04 ,  C07C231/12 ,  C07C233/33 ,  C07C233/54 ,  C07C233/80 ,  C07C233/81 ,  C07C255/60 ,  C07C255/58 ,  C07C271/38 ,  C07C275/34

CPC classification number: C07C233/25 ,  C07C231/12 ,  C07C231/14 ,  C07C233/33 ,  C07C233/54 ,  C07C233/80 ,  C07C233/81 ,  C07C253/30 ,  C07C255/58 ,  C07C255/60 ,  C07C259/06 ,  C07C259/10 ,  C07C269/06 ,  C07C271/38 ,  C07C273/1809 ,  C07C273/1854 ,  C07C275/34 ,  C07D209/08 ,  C07D213/75 ,  C07D213/76 ,  C07D215/40 ,  C07D239/47 ,  C07D239/91 ,  C07D263/57 ,  C07D347/00 ,  C07D401/04 ,  C07D405/04 ,  C07D417/04 ,  C07D471/04 ,  C07D473/40 ,  C07J43/003 ,  C07C273/1854 ,  C07C275/64 ,  C07C269/06 ,  C07C271/38 ,  C07C231/14 ,  C07C233/25 ,  C07C253/30 ,  C07C255/60 ,  C07C253/30 ,  C07C255/58 ,  C07C273/1809 ,  C07C275/34

Abstract: The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure:




wherein

A is an aryl or heteroaryl, each with or without substitution; and

R1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl)2, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising:

(a) reacting a compound having the structure:





with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:





and

(b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

公开(公告)号：US10060892B2

公开(公告)日：2018-08-28

申请号：US15310601

申请日：2014-12-11

Applicant: University of Oregon

Inventor： Michelle Watt ,  Darren W. Johnson ,  Michael M. Haley

IPC: G01N31/00 ,  G01N31/22 ,  C07C275/30 ,  C07C275/34 ,  C07C335/18 ,  C07C275/42 ,  C07C335/16 ,  C07D251/24

CPC classification number: G01N31/227 ,  C07C275/30 ,  C07C275/34 ,  C07C275/42 ,  C07C335/16 ,  C07C335/18 ,  C07C335/20 ,  C07D251/24 ,  G01N31/22

Abstract: A compound, or a protonate or salt thereof, having a formula I of: wherein Y represents an optionally substituted aromatic group; n is 1 or 2; a is 0 to 4; R1 and R2 are each independently H; optionally substituted alkyl; optionally substituted aralkyl; acyl; phosphonyl; —SO2R12; —C(O)R13; —C(O)OR14; —C(O)NR15R16; —C(O)CH2R17; or —C(S)—NR18R19; —S(O)R20; or —SO2NR21R22, wherein R12-R22 are each independently H, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted aryl, or —C(O)R23, wherein R23 is H, optionally substituted alkyl, optionally substituted aralkyl, or optionally substituted aryl; and each R3 is independently optionally substituted alkyl, halogen, optionally substituted alkoxy, optionally substituted carboxyl, amide; amino; or nitro.

公开(公告)号：US20170298008A1

公开(公告)日：2017-10-19

申请号：US15516610

申请日：2015-10-09

Applicant: Ming-Yu Ngai ,  Katarzyna N. Hojczyk

Inventor： Ming-Yu Ngai ,  Katarzyna N. Hojczyk

IPC: C07C233/25 ,  C07C231/12 ,  C07D239/91 ,  C07D215/40 ,  C07D213/76 ,  C07D213/75 ,  C07D209/08 ,  C07C259/10 ,  C07C259/06 ,  C07C255/60 ,  C07C253/30 ,  C07C233/81 ,  C07C233/80 ,  C07C233/54 ,  C07C233/33 ,  C07D401/04 ,  C07D473/40

CPC classification number: C07C233/25 ,  C07C231/12 ,  C07C231/14 ,  C07C233/33 ,  C07C233/54 ,  C07C233/80 ,  C07C233/81 ,  C07C253/30 ,  C07C255/60 ,  C07C259/06 ,  C07C259/10 ,  C07C269/06 ,  C07C273/1809 ,  C07C273/1854 ,  C07D209/08 ,  C07D213/75 ,  C07D213/76 ,  C07D215/40 ,  C07D239/47 ,  C07D239/91 ,  C07D263/57 ,  C07D347/00 ,  C07D401/04 ,  C07D405/04 ,  C07D417/04 ,  C07D471/04 ,  C07D473/40 ,  C07J43/003 ,  C07C275/64 ,  C07C271/38 ,  C07C255/58 ,  C07C275/34

Abstract: The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: wherein A is an aryl or heteroaryl, each with or without subsutitution; and R1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl)7, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising: (a) reacting a compound having the structure: with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

公开(公告)号：US20170035710A1

公开(公告)日：2017-02-09

申请号：US15231187

申请日：2016-08-08

Applicant: H. Lee Moffitt Cancer Center and Research Institute, Inc. ,  Board of Trustees of The University of Illinois

Inventor： Eduardo M. Sotomayor ,  Joel Bergman ,  Alan Kozikowski ,  Karrune Veeraprasert Woan ,  Alejandro V. Villagra

IPC: A61K31/17 ,  A61K31/506 ,  A61K31/42 ,  A61K31/437 ,  A61K31/4045 ,  A61K31/44

CPC classification number: A61K31/17 ,  A61K31/167 ,  A61K31/4045 ,  A61K31/42 ,  A61K31/422 ,  A61K31/437 ,  A61K31/44 ,  A61K31/454 ,  A61K31/505 ,  A61K31/506 ,  A61K31/69 ,  A61K38/00 ,  A61K45/06 ,  C07C275/28 ,  C07C275/34 ,  C07D209/14 ,  C07D213/75 ,  C07D239/42 ,  A61K2300/00

Abstract: Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

Abstract translation: 公开了具有式（I）的选择性组蛋白去甲酰化酶抑制剂（HDACi）。 还公开了制备和使用这些抑制剂治疗癌症，特别是黑素瘤的方法。

公开(公告)号：US20160318856A1

公开(公告)日：2016-11-03

申请号：US14917718

申请日：2014-09-11

Applicant: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

Inventor： Bertal Aktas ,  Michael Chorev

IPC: C07C275/30 ,  C07D213/65 ,  C07C275/40 ,  C07C275/34 ,  C07C335/16

CPC classification number: C07C275/30 ,  C07C275/28 ,  C07C275/34 ,  C07C275/40 ,  C07C275/42 ,  C07C335/16 ,  C07C335/18 ,  C07C335/20 ,  C07C2601/08 ,  C07C2601/14 ,  C07D213/64 ,  C07D213/65 ,  C07D295/13

Abstract: This disclosure relates to substituted urea eIF2α kinase activators including methods of making and using the same. For example, such activators can include cycloalkyl aryl ureas, which activate at least one eIF2α kinase. These compounds may be useful for treatment of diseases such as, for example, cancer, hemolytic anemia not caused by infectious agents, Wolcott-Rallison syndrome, neurodegenerative disease, tuberous sclerosis complex, fragile-X syndrome, autism spectrum disorder, and ribosomal defect disease.

Abstract translation: 本公开涉及取代的脲eIF2α激酶激活剂，包括制备和使用其的方法。 例如，这种活化剂可以包括活化至少一种eIF2α激酶的环烷基芳基脲。 这些化合物可用于治疗疾病，例如癌症，不由感染因素引起的溶血性贫血，Wolcott-Rallison综合征，神经变性疾病，结节性硬化综合征，脆性X综合征，自闭症谱系障碍和核糖体缺陷病 。

公开(公告)号：US09421211B2

公开(公告)日：2016-08-23

申请号：US13322607

申请日：2010-05-28

Applicant: Bertal Huseyin Aktas ,  José A. Halperin ,  Michael Chorev

Inventor： Bertal Huseyin Aktas ,  José A. Halperin ,  Michael Chorev

IPC: A61K31/41 ,  A61K31/5377 ,  C07D213/75 ,  C07D249/14

CPC classification number: C07C275/30 ,  A61K31/5377 ,  C07C275/34 ,  C07C275/38 ,  C07C275/40 ,  C07C2601/02 ,  C07C2602/08 ,  C07D213/75 ,  C07D213/81 ,  C07D215/06 ,  C07D231/56 ,  C07D233/36 ,  C07D237/30 ,  C07D239/34 ,  C07D239/42 ,  C07D249/14 ,  C07D261/14 ,  C07D271/12 ,  C07D277/18 ,  C07D277/66 ,  C07D285/14 ,  C07D295/088 ,  C07D295/135 ,  C07D295/192 ,  C07D307/88 ,  C07D317/66 ,  C07D319/08 ,  C07D333/20 ,  C07D333/38 ,  C07D405/12 ,  C07D409/04

Abstract: Compositions and methods for inhibiting translation initiation are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, and/or (4) disorders associated with viral infections, using N,N′-diarylureas and/or N,N′-diarylthiourea compounds are described.

Abstract translation: 提供了抑制翻译起始的组合物和方法。 用于治疗（1）细胞增殖性疾病的组合物，方法和试剂盒，（2）非增殖性，退行性病症，（3）病毒感染和/或（4）与病毒感染相关的病症，使用N，N'-二芳基脲和 /或N，N'-二芳基硫脲化合物。

公开(公告)号：US09115164B2

公开(公告)日：2015-08-25

申请号：US14003907

申请日：2012-03-09

Applicant: Masamichi Yamanaka ,  Daisuke Higashi

Inventor： Masamichi Yamanaka ,  Daisuke Higashi

IPC: C07C275/34 ,  C07C275/28 ,  C07C275/04 ,  C07H15/08 ,  C07H15/18 ,  C07H15/203 ,  A23L1/05

CPC classification number: C07H15/203 ,  C07C275/34 ,  C07H15/18 ,  C09K3/00 ,  G01N27/44747

Abstract: According to the present invention, a substituted aromatic compound represented by the following general formula (I) is provided. In general formula (I), A1, A2, and A3 each independently represent an aryl group substituted by a hydrophilic group.

Abstract translation: 根据本发明，提供由以下通式（I）表示的取代的芳族化合物。 在通式（I）中，A1，A2和A3各自独立地表示被亲水基取代的芳基。

公开(公告)号：US08952031B2

公开(公告)日：2015-02-10

申请号：US13412252

申请日：2012-03-05

Applicant: Sean G. Trapp ,  Michael R. Leadbetter ,  Daniel D. Long ,  Lan Jiang ,  Sabine Axt

Inventor： Sean G. Trapp ,  Michael R. Leadbetter ,  Daniel D. Long ,  Lan Jiang ,  Sabine Axt

IPC: A61K31/44 ,  A61K31/275 ,  A61K31/195 ,  A61K31/17 ,  A61K31/18 ,  C07C237/48 ,  C07C233/36 ,  C07C233/37 ,  C07C233/40 ,  C07C233/62 ,  C07C233/78 ,  C07C235/10 ,  C07C255/24 ,  C07C275/14 ,  C07C275/18 ,  C07C275/24 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07C311/05 ,  C07C311/14 ,  C07C311/16 ,  C07C311/18 ,  C07C311/46 ,  C07C317/44 ,  C07C335/08 ,  C07C335/12 ,  C07C335/16 ,  C07D203/02 ,  C07D203/26

CPC classification number: C07C237/48 ,  C07C233/36 ,  C07C233/37 ,  C07C233/40 ,  C07C233/62 ,  C07C233/78 ,  C07C235/10 ,  C07C255/24 ,  C07C275/14 ,  C07C275/18 ,  C07C275/24 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07C311/05 ,  C07C311/14 ,  C07C311/16 ,  C07C311/18 ,  C07C311/46 ,  C07C317/44 ,  C07C335/08 ,  C07C335/12 ,  C07C335/16 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2602/10 ,  C07D203/02 ,  C07D203/26

Abstract: The invention provides amino- and amido-aminotetralin compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, and n are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Abstract translation: 本发明提供式（I）的氨基 - 和酰氨基 - 氨基四氢化萘化合物：其中R1，R2，R3，R4，R5，R6，R7和n在本说明书中定义，或其药学上可接受的盐，其为拮抗剂 在μ阿片受体。 本发明还提供包含这些化合物的药物组合物，使用这些化合物治疗与阿片样物质受体活性相关的病症的方法，以及可用于制备这些化合物的方法和中间体。

公开(公告)号：US08664274B2

公开(公告)日：2014-03-04

申请号：US13176866

申请日：2011-07-06

Applicant: Dongcheng Dai ,  Tove Bolken ,  Dennis E. Hruby ,  Thomas R. Bailey

Inventor： Dongcheng Dai ,  Tove Bolken ,  Dennis E. Hruby ,  Thomas R. Bailey

IPC: A61K31/166 ,  C07C233/64

CPC classification number: A61K31/175 ,  A61K31/18 ,  A61K31/277 ,  A61K31/40 ,  A61K31/415 ,  A61K31/433 ,  A61K31/5377 ,  A61K31/538 ,  A61K31/675 ,  C07C275/30 ,  C07C275/34 ,  C07C275/38 ,  C07C275/42 ,  C07C281/06 ,  C07C311/49 ,  C07D213/70 ,  C07D233/84 ,  C07D261/10 ,  C07D277/36 ,  C07D285/06 ,  C07D295/20 ,  C07D295/22 ,  C07D317/66 ,  C07D319/18

Abstract: Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel sulfonyl semicarbazides, carbonyl semicarbazides, semicarbazides, ureas and related compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, Pinchinde, and VSV), Filoviridae (ebola and Marburg viruses), Flaviviridae (yellow fever, omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

Abstract translation: 公开了通过以治疗有效量施用某些新型磺酰氨基脲，羰基氨基脲，氨基脲，脲和相关化合物来治疗病毒感染的化合物，方法和药物组合物。 还公开了制备化合物的方法和使用该化合物的方法及其药物组合物。 具体地，公开了治疗和预防由出血热病毒引起的病毒感染，即，包括但不限于：金杆菌科（Junin，Machupo，Guanarito，Sabia，Lassa，Tacaribe，Pinchinde和VSV），丝状病毒科 埃博拉病毒和马尔堡病毒），黄病毒科（黄热病，o疮出血热和Kyasanur森林病毒病毒）和布亚病毒科（裂谷热）。

公开(公告)号：US20140038980A1

公开(公告)日：2014-02-06

申请号：US14042891

申请日：2013-10-01

Applicant: Alan D. Snow ,  Beth Nguyen ,  Gerardo Castillo ,  Virginia Sanders ,  Thomas Lake

Inventor： Alan D. Snow ,  Beth Nguyen ,  Gerardo Castillo ,  Virginia Sanders ,  Thomas Lake

IPC: C07D213/30 ,  C07D213/69 ,  C07D295/096

CPC classification number: C07C49/248 ,  A61K31/047 ,  C07C39/15 ,  C07C39/16 ,  C07C39/17 ,  C07C45/62 ,  C07C45/64 ,  C07C49/83 ,  C07C49/835 ,  C07C69/017 ,  C07C215/50 ,  C07C231/02 ,  C07C235/34 ,  C07C235/38 ,  C07C235/48 ,  C07C235/54 ,  C07C235/56 ,  C07C237/22 ,  C07C275/34 ,  C07D207/16 ,  C07D211/74 ,  C07D213/30 ,  C07D213/69 ,  C07D213/85 ,  C07D221/08 ,  C07D221/18 ,  C07D231/06 ,  C07D241/08 ,  C07D263/38 ,  C07D265/38 ,  C07D295/096 ,  C07D295/192 ,  C07D311/60 ,  C07D317/50 ,  C07D317/54 ,  C07D317/58 ,  C07D317/60 ,  C07D317/66 ,  C07D317/68 ,  C07D333/16 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  C07D451/06 ,  C07D471/04 ,  C07D487/08 ,  C07D491/08

Abstract: Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

Abstract translation: 双 - 和三 - 二羟基芳基化合物及其亚甲二氧基类似物和药学上可接受的酯，其合成，含有它们的药物组合物及其在治疗淀粉样蛋白病，尤其是Aβ淀粉样变性中的用途，例如在阿尔茨海默病，IAPP淀粉样变性 在2型糖尿病中观察到，以及突触核蛋白病，例如在帕金森病中观察到的，以及用于这种治疗的药物的制造。