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91. 发明申请

US20180298054A1 TARGETED NITROXIDE AGENTS 审中-公开
公开(公告)号：US20180298054A1
公开(公告)日：2018-10-18
申请号：US15855598
申请日：2017-12-27
申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education
发明人： Peter Wipf , Marie-Celine Frantz
IPC分类号： C07K5/08 , C07D221/22 , C07D211/94 , C07D209/46 , C07C237/16 , A61K47/64 , A61K31/454 , C07D279/06 , C07D209/44 , C07D417/12 , C07D401/12 , C07D211/58 , C07D471/08
摘要： Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

92. 发明授权

US09890192B2 Targeted nitroxide agents 有权
公开(公告)号：US09890192B2
公开(公告)日：2018-02-13
申请号：US14943965
申请日：2015-11-17
申请人： University of Pittsburgh—of the Commonwealth System of Higher Education
发明人： Peter Wipf , Marie-Celine Frantz
IPC分类号： C07K5/08 , A61K31/454 , C07D211/58 , C07D401/12 , C07D417/12 , C07C237/16 , C07D209/46 , C07D211/94 , C07D221/22 , C07D209/44 , C07D279/06 , C07D471/08 , A61K47/64
CPC分类号： C07K5/08 , A61K31/454 , A61K47/64 , C07C237/16 , C07D209/44 , C07D209/46 , C07D211/58 , C07D211/94 , C07D221/22 , C07D279/06 , C07D401/12 , C07D417/12 , C07D471/08
摘要： Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

93. 发明授权

US09675446B2 Prosthetic implant for medialization thyroplasty 有权
公开(公告)号：US09675446B2
公开(公告)日：2017-06-13
申请号：US14772344
申请日：2014-03-04
申请人： University of Pittsburgh—Of the Commonwealth System of Higher Education , Loyola University Chicago
发明人： James J. Jaber , Steven Charous , Peter Wipf , Christopher Siviy , April J. Chambers
IPC分类号： A61F2/20 , A61M16/04
CPC分类号： A61F2/20 , A61F2210/0057 , A61F2220/0025 , A61M16/04
摘要： Systems and methods for medializing a paralyzed vocal cord are disclosed. In some embodiments, an apparatus includes a lateral portion, a medial portion, and a strut coupled to the lateral and the medial portions. Either the medial portion or the lateral portion can be adjustable in two dimensions which are not parallel to the length of the strut, which can also be adjustable. In some embodiments, the medial portion and/or the lateral portion can each comprise two adjustable arms and a base member which has a curvilinear configuration.

94. 发明申请

US20170107190A1 ANTIFIBROTIC EFFECTS OF OXETANYL SULFOXIDES 有权
公开(公告)号：US20170107190A1
公开(公告)日：2017-04-20
申请号：US15293107
申请日：2016-10-13
申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education , Medical University of South Carolina
发明人： Peter Wipf , Carol A. Feghali-Bostwick
IPC分类号： C07D305/08 , C07D305/06
CPC分类号： C07D305/08 , C07D305/06
摘要： A compound, or a pharmaceutically acceptable salt thereof, having a structure of wherein Z is aryl or substituted aryl, heteroaryl, or substituted heteroaryl; X is —S—, —S(O)—, or S(O)2—; R20 and R21 are each independently H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, or halogenated alkyl; one of R22, R23, and R24 is —O— and the others of R22, R23 and R24 are independently —CH2—, or —C(R13)— wherein R13 is alkyl, alkenyl, alkynyl, trialkylsilyl group, or —(CH2)mOR15, wherein R15 is alkyl or an aryl and m is an integer in the range of 1 to 10; and R25 is H, alkyl, substituted alkyl, halogen, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C1-C3 alkoxy, aryloxy, or —(CH2)qOR17, wherein R17 is alkyl an aryl and q is an integer in the range of 1 to 10.

95. 发明申请

US20170095493A1 NOVEL TLR4 INHIBITORS FOR THE TREATMENT OF HUMAN INFECTIOUS AND INFLAMMATORY DISORDERS 审中-公开
公开(公告)号：US20170095493A1
公开(公告)日：2017-04-06
申请号：US15383625
申请日：2016-12-19
申请人： University of Pittsburgh - of the Commonwealth System of Higher Education
发明人： Peter Wipf , Matthew D. Neal , Sodhi P. Chhinder , David J. Hackam
IPC分类号： A61K31/7028 , A61K31/351 , A61K31/7034
CPC分类号： A61K31/7028 , A61K31/351 , A61K31/7008 , A61K31/7024 , A61K31/7034
摘要： The present invention relates to methods of treating infectious, inflammatory and post-traumatic disorders by administering various compounds newly discovered to have TLR4 inhibitory activity. In addition to methods of treatment, the present invention further provides for pharmaceutical compositions comprising said compounds, together with a suitable pharmaceutical carrier. Because TLR4 is the most upstream receptor in the pro-inflammatory LPS signaling cascade, treatments of the invention, which inhibit or antagonize TLR4 action, may avoid the pitfalls associated with other cytokine inhibitors that act further down the pathway and accordingly play a less specific (and perhaps non-critical) role.

96. 发明申请

US20170095478A1 COMBINATION THERAPY TO ENHANCE THE ANTICANCER EFFICACY OF PLATINUM DRUGS 审中-公开
公开(公告)号：US20170095478A1
公开(公告)日：2017-04-06
申请号：US15380776
申请日：2016-12-15
申请人： University of Pittsburgh - of the Commonwealth System of Higher Education
发明人： WEI QIAN , Peter Wipf , Bennett Van Houten
IPC分类号： A61K31/517 , A61K33/24 , A61K31/428 , A61K31/4436 , A61K31/44 , A61K45/06 , A61K31/282
摘要： The present invention relates to compositions and methods for reducing cell proliferation and/or promoting cell death. It is based, at least in part, on the discovery that in platinum drug-resistant cell lines, certain compounds, together with a second antiproliferative agent (e.g., cisplatin), act synergistically to promote apoptosis. Accordingly, the present invention provides for novel anticancer strategies.

97. 发明授权

US09546144B2 Bifunctional compounds 有权
标题翻译：双功能化合物
公开(公告)号：US09546144B2
公开(公告)日：2017-01-17
申请号：US14880862
申请日：2015-10-12
申请人： University of Pittsburgh—of the Commonwealth System of Higher Education
发明人： Peter Wipf , Joel S. Greenberger , Michael W. Epperly , Melissa M. Sprachman , Julie Pamela Goff
IPC分类号： A61K38/06 , A61K38/07 , C07D305/06 , C07D405/14 , C07D405/12 , C07K5/087 , C07K5/065 , C07D205/04 , C07K5/097
CPC分类号： C07D305/06 , C07D205/04 , C07D405/12 , C07D405/14 , C07K5/06078 , C07K5/0812 , C07K5/0823
摘要： A compound having the formula: wherein X is S, SO or SO2; one of R1, R2, and R3 is O and the others of R1, R2 and R3 are independently, the same or different, CH2, or CR13 wherein, R13 is an alkyl group, an alkenyl group, an alkynyl group, a trialkylsilyl group, or —(CH2)mOR15, wherein R15 is an alkyl group or an aryl group and m is an integer in the range of 1 to 10, and one of R5, R6, and R7 is O and the others of R5, R6 and R7 are independently, the same or different, CH2, or CR14 wherein, R14 is an alkyl group, an alkenyl group, an alkynyl group, a trialkylsilyl group, or —(CH2)nOR16, wherein R16 is an alkyl group or an aryl group and n is an integer in the range of 1 to 10; R4 and R8 are independently, the same or different, H, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, a heteroaryl group, a C1-C3 alkoxy group, an aryloxy group, or —(CH2)qOR17, wherein R17 is an alkyl group or an aryl group and q is an integer in the range of 1 to 10, provided that R4 is not a C1-C3 alkoxy group or an aryloxy group when R1 or R3 is O and R8 is not a C1-C3 alkoxy group or an aryloxy group when R5 or R7 is O; R9, R10, R11 and R12 are independently, the same or different, H, an alkyl group, an alkenyl group, an alkynyl group, or an aryl group.
摘要翻译：具有下式的化合物：其中X是S，SO或SO 2; R 1，R 2和R 3中的一个为O，R 1，R 2和R 3中的一个独立地为相同或不同的CH 2或CR 13，其中R 13为烷基，烯基，炔基，三烷基甲硅烷基或 - （CH 2）m OR 15，其中R 15是烷基或芳基，m是1至10的整数，R 5，R 6和R 7中的一个是O，而其中R 5，R 6和 R7独立地相同或不同，CH2或CR14，其中R14是烷基，烯基，炔基，三烷基甲硅烷基或 - （CH2）nOR16，其中R16是烷基或芳基 n为1〜10的整数， R4和R8独立地相同或不同，为氢，烷基，烯基，炔基，芳基，杂芳基，C1-C3烷氧基，芳氧基或 - （CH2）qOR17 其中R 17为烷基或芳基，q为1〜10的整数，条件是当R 1或R 3为O时，R 4不为C 1 -C 3烷氧基或芳氧基，且R 8不为当R 5或R 7为O时，C 1 -C 3烷氧基或芳氧基; R 9，R 10，R 11和R 12独立地为相同或不同的H，烷基，烯基，炔基或芳基。

98. 发明申请

US20160257657A1 SMALL MOLECULE INHIBITORS OF THE NUCLEAR TRANSLOCATION OF ANDROGEN RECEPTOR FOR THE TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER 审中-公开
标题翻译：用于治疗耐药性前列腺癌的雄激素受体的核转录因子的小分子抑制剂
公开(公告)号：US20160257657A1
公开(公告)日：2016-09-08
申请号：US15080237
申请日：2016-03-24
申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education
发明人： Peter Wipf , James K. Johnson , Erin M. Skoda , Joel B. Nelson , Zhou Wang
IPC分类号： C07D261/08 , A61K31/4166 , A61K31/42 , A61K31/496 , A61K31/46 , A61K31/495 , C07D413/12 , A61K31/454 , C07D451/00 , A61K31/58 , C07D295/185
CPC分类号： C07D261/08 , A61K31/4166 , A61K31/42 , A61K31/454 , A61K31/46 , A61K31/495 , A61K31/496 , A61K31/58 , A61K45/06 , C07D295/185 , C07D413/12 , C07D451/00 , A61K2300/00
摘要： A compound, or a pharmaceutically acceptable salt or ester thereof, according to formula I: R20—(Z)b—(Y)c—(R21)a—(X)d—R22—R23 wherein R20 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; Z is alkanediyl, substituted alkanediyl, cycloalkanediyl, or substituted cycloalkanediyl; Y is S, O, S(═O), —S(═O)(═O)—, or NR10, wherein R10 is H or alkyl; R21 is alkanediyl, substituted alkanediyl, cycloalkanediyl, substituted cycloalkanediyl alkadienyl, substituted alkadienyl, alkatrienyl, substituted alkatrienyl; X is —C(═O)—, —S(═O)(═O)—, or —N(H)C(═O)—; R22 includes at least one divalent amino radical; R23 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.
摘要翻译：根据式I的化合物或其药学上可接受的盐或酯：R 20 - （Z）b - （Y）c - （R 21）a - （X）d -R 22 -R 23，其中R 20是芳基，取代的芳基，杂芳基，取代的杂芳基，杂环烷基，取代的杂环烷基，烷氧基，芳氧基，含硫基团或含硒基团; Z是烷二基，取代的烷二基，环烷二基或取代的环烷二基; Y是S，O，S（= O），-S（= O）（= O） - 或NR 10，其中R 10是H或烷基; R21是烷二基，取代的烷二基，环烷二基，取代的环烷二基亚二烯基，取代的链二烯基，亚烷基三烯基，取代的链三烯基; X是-C（= O） - ， - S（= O）（= O） - 或-N（H）C（= O） - ; R22包括至少一个二价氨基; R 23是芳基，取代的芳基，杂芳基，取代的杂芳基，杂环烷基，取代的杂环烷基，烷氧基，芳氧基，含硫基团或含硒基团; a，b，c和d独立地为0或1。

99. 发明授权

US09402839B2 Selective targeting agents for mitochondria 有权
标题翻译：线粒体选择性靶向剂
公开(公告)号：US09402839B2
公开(公告)日：2016-08-02
申请号：US14619680
申请日：2015-02-11
申请人： University of Pittsburgh—Of the Commonwealth System of Higher Education
发明人： Peter Wipf , Jingbo Xiao , Mitchell P. Fink , Valerian Kagan , Yulia Tyurina , Anthony J. Kanai
IPC分类号： A61K47/42 , A61K31/4468 , C07K7/06 , A61K31/555 , A61K31/7034 , A61K31/7048 , A61K47/48 , C07K5/08 , C07K5/10
CPC分类号： A61K31/4468 , A61K31/555 , A61K31/7034 , A61K31/7048 , A61K47/48023 , A61K47/481 , A61K47/48246 , A61K47/54 , A61K47/55 , A61K47/64 , C07K5/08 , C07K5/10 , C07K7/06
摘要： The present invention provides a composition and related methods for delivering cargo to a mitochondria which includes (a) a membrane active peptidyl fragment having a high affinity with the mitochondria and (b) cargo. The cargo may be selected from a wide variety of desired cargos which are to be delivered to the mitochondria for a specific purpose. Compositions and methods are disclosed for treating an illness that is caused or associated with cellular damage or dysfunction which is caused by excessive mitochondrial production of reaction oxygen species (ROS). Compositions which act as mitochondria-selective targeting agents using the structural signaling of the β-turn recognizable by cells as mitochondria) targeting sequences are discussed. Mitochondria and cell death by way of apoptosis is inhibited as a result of the ROS-scavenging activity, thereby increasing the survival rate of the patient.
摘要翻译：本发明提供了一种用于将货物运送到线粒体的组合物和相关方法，其包括（a）与线粒体具有高亲和力的膜活性肽基片段和（b）货物。货物可以选自将被输送到线粒体以用于特定目的的各种期望的货物。公开了用于治疗由反应氧物质（ROS）的过量线粒体产生引起的与细胞损伤或功能障碍相关的疾病的组合物和方法。讨论了使用由细胞作为线粒体识别的β-转角的结构信号传导作为线粒体选择性靶向剂的组合物靶向序列。作为ROS清除活性的结果，线粒体和凋亡细胞死亡被抑制，从而增加患者的存活率。

100. 发明申请

US20160151269A1 COMPOUNDS FOR THE TREATMENT OF PATHOLOGIES ASSOCIATED WITH AGING AND DEGENERATIVE DISORDERS 审中-公开
公开(公告)号：US20160151269A1
公开(公告)日：2016-06-02
申请号：US14956272
申请日：2015-12-01
申请人： University of Pittsburgh - of the Commonwealth System of Higher Education
发明人： Laura J. Niedernhofer , Paul D. Robbins , Peter Wipf
IPC分类号： A61K8/64 , A61Q19/08 , A61K38/06 , A61K8/49 , A61K31/4468 , A61K31/4545
摘要： The present invention relates to methods of inhibiting one or more signs of aging and/or degenerative disorder in a subject in need of such treatment, which comprise administering, to the subject, an effective amount of one or more of the compounds as set forth herein. “Inhibiting a sign of aging or degenerative disorder” means reducing the risk of occurrence, delaying the onset, slowing the progression, and/or reducing the severity and/or manifestation, of a sign of aging or degenerative disorder, and includes, but is not limited to, preventing the occurrence, development or progression of a sign of aging or degenerative disorder.

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