公开(公告)号：US12084455B2

公开(公告)日：2024-09-10

申请号：US17224557

申请日：2021-04-07

Applicant: Gilead Sciences, Inc.

Inventor： Elizabeth M. Bacon ,  Elbert Chin ,  Jeromy J. Cottell ,  Ashley Anne Katana ,  Darryl Kato ,  John O. Link ,  Nathan Shapiro ,  Teresa Alejandra Trejo Martin ,  Zheng-Yu Yang

IPC: C07D405/14 ,  A61K31/52 ,  A61K31/55 ,  A61K31/553 ,  A61K31/685 ,  A61K31/688 ,  A61K45/06 ,  A61P31/18 ,  C07C243/28 ,  C07C275/16 ,  C07D401/12 ,  C07D403/12 ,  C07D471/08 ,  C07D487/08 ,  C07D487/10 ,  C07D491/04

CPC classification number: C07D487/08 ,  A61K31/52 ,  A61K31/55 ,  A61K31/553 ,  A61K31/685 ,  A61K31/688 ,  A61K45/06 ,  A61P31/18 ,  C07C243/28 ,  C07C275/16 ,  C07D401/12 ,  C07D403/12 ,  C07D405/14 ,  C07D471/08 ,  C07D487/10 ,  C07D491/04

Abstract: The invention provides a compound of Formula I:






or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I.

公开(公告)号：US12070513B2

公开(公告)日：2024-08-27

申请号：US17237850

申请日：2021-04-22

Applicant: The Johns Hopkins University

Inventor： Martin G. Pomper ,  Ronnie Charles Mease ,  Ying Chen

IPC: A61K51/04 ,  A61K9/127 ,  C07C275/16 ,  C07C275/18 ,  C07D213/16 ,  C07D213/61 ,  C07D213/74 ,  C07D213/82 ,  C07F7/22

CPC classification number: A61K51/0455 ,  A61K9/127 ,  A61K51/0402 ,  C07C275/16 ,  C07C275/18 ,  C07D213/61 ,  C07D213/74 ,  C07D213/82 ,  C07F7/2208 ,  C07B2200/05 ,  Y02P20/55

Abstract: Prostate-specific membrane antigen (PSMA) binding compounds having radioisotope substituents are described, as well as chemical precursors thereof. Compounds include pyridine containing compounds, compounds having phenylhydrazine structures, and acylated lysine compounds. The compounds allow ready incorporation of radionuclides for single photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging, for example, prostate cancer cells and angiogenesis.

公开(公告)号：US20170267717A1

公开(公告)日：2017-09-21

申请号：US15506351

申请日：2015-08-24

Applicant: Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.

Inventor： Bernd NEUMAIER ,  Boris ZLATOPOLSKIY ,  Raphael RICHARZ ,  Phillip KRAPF

IPC: C07K5/062 ,  C07C275/16 ,  C07D237/24 ,  C07D241/24 ,  C07D213/82 ,  C07B59/00

CPC classification number: C07K5/06026 ,  C07B59/002 ,  C07B2200/05 ,  C07C275/16 ,  C07D213/82 ,  C07D237/24 ,  C07D241/24 ,  C07K1/13 ,  C07K5/06078

Abstract: Novel efficient, time-saving and reliable radiofluorination procedures for the production of 18F-labelled active esters via nucleophilic substitution of the corresponding onium precursors with 18F− are described. The active ester including [18F]F-Py-TFP and [18F]TFB produced by one of these methods was used to prepare PSMA-specific PET tracers such as [18F]DCFPyL. The key advantages of these inventive methods are efficiency, short time of preparation and excellent amenability to automation. A pharmaceutical composition containing at least one PSMA-specific PET tracers prepared by the inventive method is useful for positron emission tomography (PET) imaging, especially imaging prostate tumor.

公开(公告)号：US20170135961A1

公开(公告)日：2017-05-18

申请号：US15209352

申请日：2016-07-13

Applicant: The Johns Hopkins University

Inventor： Sachin S. Chandran ,  Sangeeta Ray ,  Martin G. Pomper ,  Samuel R. Denmeade ,  Ronnie C. Mease

IPC: A61K9/51

CPC classification number: A61K9/51 ,  C07C275/16 ,  Y10S977/773 ,  Y10S977/906 ,  Y10S977/911

Abstract: The invention provides a nanoparticle composition that is decorated with a urea-based small-molecule peptidomimetic inhibitor of prostate specific membrane antigen (PSMA), which is expressed by almost all solid tumors. This strategy takes advantage of both the avidity of the functionalized nanoparticle for binding to PSMA and the ability of the nanoparticle to be retained for longer periods of time in the tumor due to enhanced leakage via EPR into the tumor interstitium and poor clearance due to underdeveloped or non-existent lymphatics within the tumor.

公开(公告)号：US20170044098A1

公开(公告)日：2017-02-16

申请号：US15337867

申请日：2016-10-28

Applicant: Molecular Insight Pharmaceuticals, Inc.

Inventor： John W. Babich ,  Craig N. Zimmerman ,  Kevin P. Maresca

IPC: C07C275/16

CPC classification number: C07C275/16 ,  A61K39/385 ,  C07B59/001 ,  C07C275/24 ,  C07C275/30 ,  C07C311/19 ,  C07D213/38

Abstract: Compounds of Formula (Ia) wherein R is a C6-C12 substituted or unsubstituted aryl, a C6-C12 substituted or unsubstituted heteroaryl, a C1-C6 substituted or unsubstituted alkyl or —NR′R′, Q is C(O), O, NR′, S, S(O)2, C(O)2(CH2)p Y is C(O), O, NR′S, S(O)2, C(O)2(CH2)p Z is H or C1-C4 alkyl, R′ is H, C(O), S(O)2, C(O)2, a C6-C12 substituted or unsubstituted aryl, a C6-C12 substituted or unsubstituted heteroaryl or a C1-C6 substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C6-C12 heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition, Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.

Abstract translation: 式（Ia）化合物其中R是C 6 -C 12取代或未取代的芳基，C 6 -C 12取代或未取代的杂芳基，C 1 -C 6取代或未取代的烷基或-NR'R'，Q是 C（O），O，NR'，S，S（O）2，C（O）2（CH 2）p Y是C（O），O，NR'，S，S（O） ）2（CH 2）p Z是H或C 1 -C 4烷基，R'是H，C（O），S（O）2，C（O）2，C 6 -C 12取代或未取代的芳基， 当被取代，芳基，杂芳基和烷基被卤素，C 6 -C 12杂芳基，-NR'R'或COOZ取代时，C 6 -C 12取代或未取代的杂芳基或C 1 -C 6取代或未取代的烷基， 其具有诊断和治疗性质，例如前列腺癌的治疗和治疗以及与NAALADase抑制相关的其它疾病。 放射性标记可以通过各种通过碳或杂原子连接在X氨基酸侧链附着的假基团并入结构中。

公开(公告)号：US09458256B2

公开(公告)日：2016-10-04

申请号：US12513576

申请日：2007-11-07

Applicant: Aylvin Jorge Angelo Athanasius Dias ,  Bartholomeus Johannes Margretha Plum ,  Peter Jan Leonard Mario Quaedflieg ,  Roel Wim Wiertz

Inventor： Aylvin Jorge Angelo Athanasius Dias ,  Bartholomeus Johannes Margretha Plum ,  Peter Jan Leonard Mario Quaedflieg ,  Roel Wim Wiertz

IPC: C08F8/30

CPC classification number: C08F220/36 ,  A61K47/593 ,  A61L27/16 ,  A61L27/34 ,  A61L2300/606 ,  A61L2400/18 ,  A61L2420/02 ,  C07C275/16 ,  C08F8/30 ,  C08F2220/346 ,  C08F2220/365 ,  C09D133/14

Abstract: Compounds and polymers obtained from such compounds are provided, wherein the compounds have (a) at least two polymerizable moieties, (b) at least one amino acid residue of an amino acid comprising at least two amine groups of which at least two amine groups have formed a carbamate, a thiocarbamate or a carbamide group, and (c) a biomolecular moiety linked directly or via a spacer to the carboxylic acid moiety of the diamino acid residue or a carboxylic acid to which such moiety can be linked.

Abstract translation: 提供了由这些化合物获得的化合物和聚合物，其中所述化合物具有（a）至少两个可聚合部分，（b）氨基酸的至少一个氨基酸残基包含至少两个胺基，其中至少两个胺基具有 形成氨基甲酸酯，硫代氨基甲酸酯或脲基，和（c）直接或通过间隔基与二氨基酸残基的羧酸部分连接的生物分子部分或可连接该部分的羧酸。

公开(公告)号：US20160237212A1

公开(公告)日：2016-08-18

申请号：US15026069

申请日：2014-09-30

Applicant: MATTHEW BECKER ,  Fei Lin

Inventor： MATTHEW BECKER ,  Fei Lin

IPC: C08G71/02 ,  C07C247/04 ,  C07C227/18 ,  C07C229/34

CPC classification number: C08G71/02 ,  C07C227/18 ,  C07C229/34 ,  C07C247/04 ,  C07C275/16 ,  C08G2230/00 ,  C09D175/02

Abstract: Amino acid-based poly(ester urea)s (PEU) are emerging as a class of polymers that have shown promise in regenerative medicine applications. Embodiments of the invention relate to the synthesis of PEUs carrying pendent “clickable” groups on modified tyrosine amino acids. The pendent species include alkyne, azide, alkene, tyrosine-phenol, and ketone groups. PEUs with Mw exceeding 100k Da were obtained via interfacial polycondensation methods and the concentration of pendent groups was varied by copolymerization. The incorporation of derivatizable functionalities is demonstrated using 1H NMR and UV-Vis spectroscopy methods. Electrospinning was used to fabricate PEU nanofibers with a diameters ranging from 350 nm to 500 nm. The nanofiber matricies possess mechanical strengths suitable for tissue engineering (Young's modulus: 300±45 MPa; tensile stress: 8.5±1.2 MPa). A series of bioactive peptides and fluorescent molecules were conjugated to the surface of the nanofibers following electrospinning using bio-orthogonal reactions in aqueous media.

Abstract translation: 氨基酸基聚（酯尿素）（PEU）正在出现，这些聚合物在再生医学应用中已显示出希望。 本发明的实施方案涉及在修饰的酪氨酸氨基酸上携带侧面的“可点击”基团的PEU的合成。 悬挂物种包括炔烃，叠氮化物，烯烃，酪氨酸 - 苯酚和酮基团。 通过界面缩聚方法得到Mw超过100kDa的PEU，通过共聚改变侧基的浓度。 使用1 H NMR和UV-Vis光谱法证明可衍生化官能度的结合。 使用静电纺丝制造直径范围为350nm至500nm的PEU纳米纤维。 纳米纤维素材具有适用于组织工程的机械强度（杨氏模量：300±45MPa;拉伸应力：8.5±1.2MPa）。 在水性介质中使用生物正交反应进行静电纺丝后，将一系列生物活性肽和荧光分子缀合到纳米纤维的表面。

公开(公告)号：US09295727B2

公开(公告)日：2016-03-29

申请号：US14182557

申请日：2014-02-18

Applicant: BIND Therapeutics, Inc.

Inventor： Stephen E. Zale ,  Mir Mukkaram Ali

IPC: A61K9/00 ,  A61K9/51 ,  A61K31/74 ,  A61K47/34 ,  A61K31/197 ,  A61K31/337 ,  A61K47/48 ,  B82Y5/00 ,  C07C275/24 ,  C08G63/664 ,  C07C275/16 ,  C08G63/685 ,  C08G63/692 ,  A61K9/14

CPC classification number: A61K9/1647 ,  A61K9/146 ,  A61K9/5153 ,  A61K9/5192 ,  A61K31/136 ,  A61K31/197 ,  A61K31/337 ,  A61K31/704 ,  A61K47/34 ,  A61K47/542 ,  A61K47/60 ,  A61K47/6935 ,  A61K47/6937 ,  B82Y5/00 ,  C07C275/16 ,  C07C275/24 ,  C08G63/664 ,  C08G63/6852 ,  C08G63/6922 ,  Y10S977/904 ,  Y10S977/905 ,  Y10S977/906 ,  Y10S977/911 ,  Y10S977/915

Abstract: The present invention generally relates to polymers and macromolecules, in particular, to polymers useful in particles such as nanoparticles. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. In some cases, the nanoparticle may contain a drug. Other aspects of the invention are directed to methods using nanoparticle libraries.

公开(公告)号：US09272991B2

公开(公告)日：2016-03-01

申请号：US13144301

申请日：2010-01-13

Applicant: Wolf-Hagen Schunck ,  Gerd Wallukat ,  Robert Fischer ,  Cosima Arnold ,  Dominik N. Mueller ,  Narender Puli ,  John R. Falck

Inventor： Wolf-Hagen Schunck ,  Gerd Wallukat ,  Robert Fischer ,  Cosima Arnold ,  Dominik N. Mueller ,  Narender Puli ,  John R. Falck

IPC: C07C275/16 ,  C07C233/09 ,  C07C233/49 ,  C07C235/28 ,  C07C275/14 ,  C07C233/47 ,  C07D303/38

CPC classification number: C07D303/38 ,  C07C233/09 ,  C07C233/47 ,  C07C233/49 ,  C07C235/28 ,  C07C235/76 ,  C07C275/14 ,  C07C275/16 ,  C07C275/20

Abstract: The present invention provides compounds (n-3 PUFA derivatives) of formula (I) that modulate conditions associated with cardiac damage, especially cardiac arrhythmias.

Abstract translation: 本发明提供了调节与心脏损伤特别是心律失常相关的病症的式（I）化合物（n-3 PUFA衍生物）。

公开(公告)号：US09226981B2

公开(公告)日：2016-01-05

申请号：US14211683

申请日：2014-03-14

Applicant: THE JOHNS HOPKINS UNIVERSITY

Inventor： Martin G. Pomper ,  Ronnie Charles Mease ,  Ying Chen

IPC: A61K51/00 ,  C07C275/18 ,  A61K51/04 ,  A61K9/127 ,  C07C275/16 ,  C07D213/61 ,  C07D213/74 ,  C07D213/82 ,  C07F7/22

CPC classification number: A61K51/0455 ,  A61K9/127 ,  A61K51/0402 ,  C07B2200/05 ,  C07C275/16 ,  C07C275/18 ,  C07D213/61 ,  C07D213/74 ,  C07D213/82 ,  C07F7/2208 ,  Y02P20/55

Abstract: Prostate-specific membrane antigen (PSMA) binding compounds having radioisotope substituents are described, as well as chemical precursors thereof. Compounds include pyridine containing compounds, compounds having phenylhydrazine structures, and acylated lysine compounds. The compounds allow ready incorporation of radionuclides for single photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging, for example, prostate cancer cells and angiogenesis.

Abstract translation: 描述了具有放射性同位素取代基的前列腺特异性膜抗原（PSMA）结合化合物及其化学前体。 化合物包括含吡啶化合物，具有苯肼结构的化合物和酰化赖氨酸化合物。 化合物允许放射性核素用于单光子发射计算机断层摄影（SPECT）和正电子发射断层摄影（PET），用于成像，例如前列腺癌细胞和血管生成。