СПОСОБ ПОЛУЧЕНИЯ ИНГИБИТОРОВ ATR КИНАЗЫ (ВАРИАНТЫ)

Изобретение относится к способу получения соединения формулы I-1, включающему стадии: a) взаимодействия соединения формулы 6a* с соединением формулы 27 при соответствующих условиях образования амидной связи, где соответствующие условия для образования амидной связи включают взаимодействие соединения формулы 6a* с соединением формулы 27 в апротонном растворителе при нагреве, с образованием соединения формулы 28; b) очистки соединения формулы 28 с использованием соответствующего хелатирующего агента для палладия, выбранного из пропан-1,2-диамина; этан-1,2-диамина; этан-1,2-диамина; пропан-1,3-диамина; тетраметилэтилендиамина; этиленгликоля; 1,3-бис(дифенилфосфанил)пропана; 1,4-бис(дифенилфосфанил)бутана и 1,2-бис(дифенилфосфанил)этан/Pr-1,2-диамина; c) взаимодействия соединения формулы 28 при соответствующих условиях снятия защиты, где соответствующие условия снятия защиты включают взаимодействие соединения формулы 28 с кислотой в присутствии растворителя, с образованием соединения формулы ...

НАБОР ДЛЯ МЕЧЕНИЯ РАДИОАКТИВНЫМИ ИЗОТОПАМИ

Группа изобретений относится к мечению нацеливающего агента галлием-68. Раскрыт набор для мечения функционализированного хелатом нацеливающего агента радиоактивным изотопом, содержащий подходящее количество ацетатной соли или ацетатного солевого буфера для нейтрализации элюата с кислым pH из генератора галлия-68 до значения pH в диапазоне от 3 до 5, когда указанный генератор элюируют; функционализированный хелатом нацеливающий агент, причем указанная хелатная функциональная группа способна хелатировать галлий-68 при условиях мечения радиоактивным изотопом; и ингибитор металлов, способный дезактивировать металлические примеси без препятствования хелатированию между галлием-68 и указанным функционализированным хелатом нацеливающим агентом при условиях реакции мечения радиоактивным изотопом, причем указанный ингибитор металлов выбран из группы, содержащей: DOTA, DTPA, моносахариды и дисахариды. Также раскрыты применение указанного набора для мечения функционализированного хелатом нацеливающего ...

ПРОНИЦАЕМЫЕ ИНГИБИТОРЫ ГЛИКОЗИДАЗЫ И ИХ ПРИМЕНЕНИЯ

Настоящее изобретение относится к соединениям и их фармацевтически приемлемым солям, которые раскрыты в формуле изобретения. Соединения по изобретению являются полезными в качестве ингибиторов O-связанной N-ацетилглюкозаминидазы (O-GlcNAc-дазы) и могут быть полезными для лечения некоторых расстройств, таких как болезнь Альцгеймера. 2 н. и 5 з.п. ф-лы, 4 табл., 120 пр.

ДЕЙТЕРИРОВАННЫЕ ПРОИЗВОДНЫЕ ТИЕНОПИПЕРИДИНА, СПОСОБ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ

Изобретение относится к дейтерированным производным тиенопиперидина со структурой формулы (I) или их фармацевтически приемлемым солямФормула (I),где X представляет собой P или S; m равняется 0 или 1; n равняется 0 или 1; Rвыбран из водорода, линейного или разветвленного C1-C4алкила, замещенного или незамещенного галогеном или фенилом; Rне замещен или выбран из водорода, линейного или разветвленного C1-C4алкила, замещенного или незамещенного галогеном или фенилом, при этом если Rне замещен, то X и O образуют двойную связь, а также к способу их получения и применению для лечения и предупреждения сердечно-сосудистых и цереброваскулярных заболеваний. 4 н. и 5 з.п. ф-лы, 2 ил., 4 табл., 12 пр.

АГЕНТЫ, СВЯЗЫВАЮЩИЕСЯ С PSMA, И ИХ ПРИМЕНЕНИЕ

Изобретение описывает связывающиеся с простата-специфическим мембранным антигеном (PSMA) соединения, имеющие структуругде, Z представляет собой тетразол или COQ; каждый Q независимо выбран из водорода или защитной группы; и где (A) m имеет значение 0, 1, 2, 3, 4, 5 или 6; R представляет собой пиридиновое кольцо, выбранное из группы, включающей,игде Х представляет собой фтор, йод, радиоизотоп фтора, радиоизотоп йода, хлор, бром, радиоизотоп брома, радиоизотоп астата, NO, NH, N(R), Sn(R), Si(R), Hg(R), В(ОН), -NHNH, -NHN=CHR, -NHNH-CHR; n имеет значение 1, 2, 3, 4 или 5; Y представляет собой О, S, N(R'), C(O), NR'C(O), C(O)N(R), OC(O), C(O)O, NR'C(O)NR, NR'C(S)NR', NR'S(O), S(CH), NR'(CH), O(CH), OC(O)CHRNHC(O), NHC(O)CHRNHC(O) или ковалентную связь; где р имеет значение 1, 2 или 3, R' представляет собой Н или C-Салкил, и Rпредставляет собой водород, алкил, арил или гетероарил, каждый из которых может быть замещен; Rпредставляет собой C-Салкил; и Rпредставляет собой алкил, алкенил, алкинил ...

МЕЧЕНЫЕ МОЛЕКУЛЯРНЫЕ ВИЗУАЛИЗИРУЮЩИЕ АГЕНТЫ, СПОСОБЫ ПОЛУЧЕНИЯ И СПОСОБЫ ПРИМЕНЕНИЯ

Изобретение относится к визуализирующему агенту для визуализации клеточного окислительного стресса in vivo и к соединению-предшественнику для синтеза визуализирующего агента. Агент содержит меченое цистиновое соединение, имеющее структуру I:где один из R и R′ содержит метку, выбранную из флуоресцентной метки, представляющей собой Bodipy, или радиоизотопной метки, выбранной изС,N,O,F,F,Br,Br,I,I,I иBr, а другой из R и R′ представляет собой водород. Также изобретение относится к способу визуализации биологического образца, имеющего цистин/глутаматный транспортер, причем способ включает введение указанного выше визуализирующего агента в указанный биологический образец через цистин/глутаматный транспортер. Изобретение также предусматривает способ обнаружения окислительного стресса in vivo в апоптотических клетках посредством введения визуализирующего агента в цистин/глутаматный антипортер клеток. 5 н. и 9 з.п. ф-лы, 10 ил., 6 пр.

СПОСОБ ПОЛУЧЕНИЯ РАДИОАКТИВНОГО, МЕЧЕННОГО ФТОРОМ ОРГАНИЧЕСКОГО СОЕДИНЕНИЯ

Предложен способ получения радиоактивного, меченного фтором, органического соединения формулы (2), включающий стадию нагревания при температуре 40-90°C соединения формулы (1) (где Rозначает линейный или разветвленный алкил с 1-10 атомами углерода или ароматический заместитель; Rозначает линейный или разветвленный галогеналкилсульфокислотный заместитель с 1-10 атомами углерода, линейный или разветвленный алкилсульфокислотный заместитель с 1-10 атомами углерода, фторсульфокислотный заместитель или ароматический сульфокислотный заместитель, и Rозначает защитную группу) при перемешивании в инертном органическом растворителе в присутствии катализатора межфазного переноса, ионовF и ионов калия для осуществления мечения радиоактивным фтором, и концентрация катализатора межфазного переноса в инертном органическом растворителе составляет не менее 70 ммоль/л. Предложенный способ позволяет улучшить выход при радиоактивном фторировании. 4 з.п. ф-лы, 43 пр., 5 табл., 6 ил.

ИНГИБИТОРЫ ПРОТЕИНКИНАЗ, ИХ СПОСОБ ПОЛУЧЕНИЯ И МЕДИЦИНСКОЕ ПРИМЕНЕНИЕ

Изобретение относится к соединениям формулы I, их дейтерированным производным и фармацевтически приемлемым солям, где в формуле I R1представляет собой атом водорода или C1-C6алкил; R2и R3представляют собой C1-C6алкил или R2и R3вместе с атомом C, к которому они присоединены, образуют C3-C6циклоалкил; R4и R5независимо выбраны из водорода и галогена, и по меньшей мере один из R4и R5представляет собой галоген; R6выбран из атома водорода или C1-C6алкила; R7представляет собой, Z представляет собой O или, и n равен целому числу от 0 до 4; каждый из W и Y независимо представляет собой C или N, но оба W и Y не могут одновременно представлять собой C, и если Z представляет собой O, W представляет собой C; R10, R11, R12и R13независимо выбраны из атома водорода, C1-C6алкила, C1-C6гидроксиалкила или циклопропилметила, или R6и R7вместе с атомами C, к которым они присоединены, образуют 6-членный гетероцикл, содержащий один атом N, который замещен; R8представляет собой C1-C6гидроксиалкил. Также изобретение ...

ПРОЛЕКАРСТВА КЕТАМИНА, ЕГО КОМПОЗИЦИИ И ПРИМЕНЕНИЯ

Изобретение относится к соединениям или к их фармацевтически приемлемым солям, являющимся пролекарствами кетамина, которые выбраны из следующих структур:Изобретение также относится к фармацевтической композиции, модулирующей противодействие рецептора NMDA, на основе указанных соединений. Технический результат – получены новые соединения и фармацевтическая композиция на их основе, которые могут найти применение в медицине для лечения заболеваний, связанных с рецептором NMDA, включая депрессию и боль. 8 н. и 7 з.п. ф-лы, 6 табл., 109 пр.

ПолученныеF-меченных соединений, включающее стадию гидролитического снятия защиты и твердофазную экстракцию

... 1. Способ, включающий:(1) введение в защищенное соединение-предшественник меткиF;(2) снятие защиты сF-меченного соединения, полученного на стадии (1), путем гидролиза;(3) разбавление водой незащищенногоF-меченного соединения, полученного на стадии (2);(4) захват незащищенногоF-меченного соединения на колонке для твердофазной экстракции (SPE) путем пропускания разбавленного раствора, полученного на стадии (3), через указанную колонку;(5) элюирование незащищенногоF-меченного соединения из колонки для SPE;при условии, что после стадии снятия защиты не осуществляют стадию нейтрализации.2. Способ по п. 1, где указанную стадию снятия защиты (2) осуществляют кислотным гидролизом.3. Способ по п. 1, где указанноеF-меченное соединение представляет собойF-фтордезоксиглюкозу (F-FDG), 6-[F]-L-фтор-ДОФА ([F]-фтордигидроксифенилаланин,F-FDOPA),F-фтортимидин (F-FLT),F-фтормизонидазол (F-FMISO),F-1-(5-фтор-5-дезокси-α-арабинофуранозил)-2-нитроимидазол (F-FAZA), 16-α-[F]-фторэстрадиол (F-FES) или 6-[F]-фторметараминол ...

АНАЛОГИ ХОЛИНА В КАЧЕСТВЕ РАДИОАКТИВНОГО ИНДИКАТОРА

... 1. Соединение формулы (I):где:каждый из R, R, Rи Rнезависимо представляет собой водород или дейтерий (D);каждый из R, Rи Rнезависимо представляет собой водород, R, -(CH)R, -(CD)R, -(CF)R, -CH(R)или -CD(R);Rпредставляет собой независимо водород, -OH, -CH, -CF, -CHOH, -CHF, -CHCl, -CHBr, -CHI, -CD, -CDOH, -CDF, CDCl, CDBr, CDI или -CH;m означает целое число от 1 до 4;каждый из X и Y независимо представляет собой водород, дейтерий (D) или F;Z представляет собой галоген, выбранный из F, Cl, Br и I, или радиоактивный изотоп; иQ означает анионный противоион;при условии, что указанное соединение формулы (I) не является фторметилхолином, фторметил-этил-холином, фторметил-пропил-холином, фторметил-бутил-холином, фторметил-пентил-холином, фторметил-изопропил-холином, фторметил-изобутил-холином, фторметил-втор-бутил-холином, фторметил-диэтил-холином, фторметил-диэтанол-холином, фторметил-бензил-холином, фторметил-триэтанол-холином, 1,1-дидейтерофторметилхолином, 1,1-дидейтерофторметил-этил-холином ...

РАДИОАКТИВНО-МЕЧЕНЫЕ СОЕДИНЕНИЯ

СПОСОБЫ И ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ ДЛЯ ПОЛУЧЕНИЯ СТЕРИЧЕСКИХ СОЕДИНЕНИЙ

... 1. Способ получения оптически обогащенного соединения формулы 1 ! ! где атомы углерода альфа и бета относительно карбоксигруппы являются стереоцентрами; ! R1 и R'1, каждый независимо представляет собой H, необязательно замещенную алифатическую группу, необязательно замещенную циклоалифатическую группу, необязательно замещенную арилалифатическую группу, необязательно замещенную гетероалифатическую группу или необязательно замещенную гетероарилалифатическую группу; ! R'2 представляет собой -NHR2 или -OE; ! R2 представляет собой H, необязательно замещенную алифатическую группу, необязательно замещенную циклоалифатическую группу, необязательно замещенную арилалифатическую группу, необязательно замещенную гетероалифатическую группу или необязательно замещенную гетероарилалифатическую группу; и ! E представляет собой C1-C6 алкил или бензил; ! включающий следующие стадии: ! a) образование соли соединения формулы 1 ! b) кристаллизация указанной соли с получением соединения с больше чем 55% энантиомерным ...

ИНГИБИТОРЫ ПРОТЕИНКИНАЗ, ИХ СПОСОБ ПОЛУЧЕНИЯ И МЕДИЦИНСКОЕ ПРИМЕНЕНИЕ

СПОСОБЫ И РЕАКТИВЫ ДЛЯ ВВЕДЕНИЯ РАДИОАКТИВНОЙ МЕТКИ

СПОСОБЫ ПОЛУЧЕНИЯ СОЕДИНЕНИЙ, КОТОРЫЕ МОЖНО ИСПОЛЬЗОВАТЬ В КАЧЕСТВЕ ИНГИБИТОРОВ КИНАЗЫ ATR

... 1. Способ получения соединения формулы 4:из соединения формулы 3:в подходящих условиях образования оксима;гдеRпредставляет собой C-алкил;Rпредставляет собой C-алкил;или Rи Rвместе с атомами кислорода, к которым они прикреплены, образуют необязательно замещенное 5- или 6-членное насыщенное гетероциклическое кольцо, имеющее два атома кислорода;Rпредставляет собой водород, C-алкил или 3-6-членный насыщенный или частично ненасыщенный гетероциклил, имеющий 1-2 гетероатома, выбранных из группы, состоящей из кислорода, азота и серы; причем гетероциклил необязательно замещен 1 экземпляром галогена или C-алкила;Jпредставляет собой H, галоген, C-алкил или C-алкокси;PG представляет собой защитную группу карбамата.2. Способ по п. 1, используемый для получения соединения формулы I:гдеRпредставляет собой;Jпредставляет собой галоген, C-алкил или C-алкокси;Q представляет собой фенил, пиридил или N-алкилированный пиридин;Jпредставляет собой галоген; CN; фенил; оксазолил; или C-алифатическую группу, где ...

ДЕЙТРИРОВАННЫЕ ГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ СРЕДСТВ ВИЗУАЛИЗАЦИИ

6-Хлор-3-(фенил-d5)-инден-1-он и его применение

2-АМИНО-3-ФТОР-3-(ФТОРМЕТИЛ)-6-МЕТИЛ-6-ФЕНИЛ-3,4,5,6-ТЕТРАГИДРОПИРИДИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ BACE1

ПОЛУЧЕНИЕ N-МОНОФТОРАЛКИЛТРОПАНОВ

... 1. Способ получения N-монофторалкилтропана формулы (IIIA):(IIIA)включающий:(1) предоставление предшественника, который содержит амин формулы (III):(2) алкилирование указанного предшественника алкилирующим агентом формулы F-(CH)X в присутствии основания и возможно в присутствии йодидной соли в подходящем растворителе с получением N-монофторалкилтропана формулы (IIIA),где:m равно 2, 3 или 4; иX представляет собой I или -OSOR, где Rпредставляет собой Cалкил, Сперфторалкил или Сарил.2. Способ по п.1, где X представляет собой -OSoR, и Rвыбран из -СН, -CFили СНСН.3. Способ по п.1, где X представляет собой I.4. Способ по п.3, где m равно 3, и алкилирующий агент представляет собой F-(CH)-I.5. Способ получения содержащего триалкилолово предшественника для радиойодинирования формулы IV:включающий:(1) осуществление способа по любому из п.п.1-4 с получением N-монофторалкиламинного продукта формулы (IIIA);(2) взаимодействие соединения формулы (IIIA) со стадии (1) с SnR в присутствии подходящего катализатора ...

СО-КРИСТАЛЛЫ И СОДЕРЖАЩИЕ ИХ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ

СПОСОБ РАДИОАКТИВНОГО КОНЬЮГИРОВАНИЯ

... 1. Способ мечения радиоизотопом молекулы, обеспечивающей направленную доставку к биомишени, при котором:(1) берут защищенное соединение Формулы (IA) или (IB)(2) удаляют защиту с защищенного соединения Формулы (IA) или (IB) стадии (1) с получением аминооксисоединения Формулы (IIA) или (IIB) соответственно;(3) осуществляют конденсацию:(а) либо аминооксисоединения Формулы (IIA) с карбонильным соединением Формулы (IIIA)(б) либо аминооксисоединения Формулы (IIB) с карбонильным соединением Формулы (IIIB)с получением меченого радиоизотопом конъюгата Формулы (IVA) или (IVB) соответственно:где [ВТМ] представляет собой молекулу, обеспечивающую направленную доставку к биомишени;Xпредставляет собой защищенную аминооксигруппу формулыгде Rи Rнезависимо выбраны из Салкила, Cфторалкила или Cарила;Q представляет собой группу, которая содержит радиоизотоп, подходящий для in vivo визуализации PET (позитронно-эмиссионной томографии) или SPECT (однофотонной эмиссионной компьютерной томографии);Yпредставляет ...

ФАРМАЦЕВТИЧЕСКИЕ СОЕДИНЕНИЯ

... 1. Соединение формулы (1):или соль, N-оксид, таутомер или стереоизомер указанного соединения, где:А представляет собой СН или азот;Е представляет собой СН или азот;Rвыбран из следующего:- ациклическая Cуглеводородная группа, возможно содержащая один или два заместителя R, причем один атом углерода в ациклической Cуглеводородной группе может быть необязательно заменен гетероатомом или группой, выбранными из О, S, NR, S(O) и SO, или два соседних атома углерода в ациклической d.углеводородной группе могут быть необязательно заменены группой, выбранной из CONR, NRCO, NRSOи SONR, при условии, что в каждом случае в ациклической Cуглеводородной группе сохраняется по меньшей мере один атом углерода; и- моноциклическая карбоциклическая или гетероциклическая группа, содержащая от 3 до 7 членов кольца, из которых 0, 1, 2, 3 или 4 членов кольца являются гетероатомами, выбранными из О, N и S, причем указанная карбоциклическая или гетероциклическая группа возможно содержит один или два заместителя R; ...

ЛИГАНДЫ ДЛЯ ВИЗУАЛИЗАЦИИ ИННЕРВАЦИИ СЕРДЦА

... 1. Соединение, имеющее формулу Delta: ! ! где связывающие группы В, D, Е, F и G независимо выбраны из группы, состоящей из связи, алкила (C1-C5, предпочтительно С2), арила, аралкила, алкиларила, гетероарила, алкокси, алкиламино, арилокси и алкоксиалкила; ! R8-R14 независимо выбраны из группы, состоящей из Н, OR3, F, Cl, Br, I, CH2F, OCH2CH2F, (C1-С4)алкила, арила, гетероарила, С(=O)R3, CO2R3 и Im; ! R3, R4, R5 и R6 независимо выбраны из группы, состоящей из Н, алкила, арила, аралкила, гетероарила, алкиламино, алкилокси и арилокси. ! и, возможно, любые два радикала из R4, R5, R6, R13 и R14 могут образовывать циклическую структуру, выбранную из группы, состоящей из связи, -CH2-, -CH2 - CH2-, -CH2-CH2-CH2-, -СН=СН-, -Х=СН- и -Х-СН=СН-, где Х выбран из группы, состоящей из О, NH, N=и NR7, и R7 выбран из группы, состоящей из алкила, арила и гетероарила; и указанный визуализирующий фрагмент Im может быть выбран из группы, состоящей из 18F, 76Br, 124I, 131I, 99mTc, 153Gd и 111In. !2. Соединение ...

СПОСОБЫ ПОЛУЧЕНИЯ (S)-1-(3-ЭТОКСИ-4-МЕТОКСИФЕНИЛ)-2- МЕТАНСУЛЬФОНИЛЭТИЛАМИНА

... 1. Способ получения соединения формулы (I):или его фармацевтически приемлемой соли, гидрата, сольвата или полиморфа, в которой:R представляет собой -СН(С-Салкил)Ar или водород,Rпредставляет собой С-Салкил,каждый из R, R, R, Rи Rв каждом случае независимо представляет собой водород, галоген, С-Салкил, С-Салкокси, -CF, -CN или -NO, иAr представляет собой арил,включающий:(a) сочетание необязательно замещенного бензонитрила с диалкилсульфоном,(b) гидролиз продукта сочетания с получением бета-кетосульфона,(c) взаимодействие бета-кетосульфона с хиральным вспомогательным реагентом с получением хирального енамина,(d) восстановление хирального енамина с получением N-защищенного аминосульфона и(е) необязательное снятие защиты с N-защищенного аминосульфона.2. Способ по п. 1, в котором R представляет собой Н, Rпредставляет собой -СН, Rпредставляет собой Н, Rпредставляет собой Н, Rпредставляет собой -ОСН, Rпредставляет собой -ОСНСНи Rпредставляет собой Н.3. Способ по п. 1, в котором R представляет собой ...

ДЕЙТЕРИРОВАННЫЕ ТИАЗОЛИДИНОНОВЫЕ АНАЛОГИ В КАЧЕСТВЕ АГОНИСТОВ РЕЦЕПТОРА ФОЛЛИКУЛОСТИМУЛИРУЮЩЕГО ГОРМОНА

... 1. Дейтерированное тиазолидиноновое производное в соответствии с формулой (I)(I),где каждый Y независимо друг от друга выбирают из группы, состоящей из водорода (H), дейтерия (D);X выбирают из группы, состоящей из S, сульфоксида;R, Rнезависимо друг от друга выбирают из группы, состоящей из водорода (H), дейтерия (D), метила, CHD, CHD, CD, этила, CHDCH, CHDCHD, CHDCHD, CHDCD, CDCH, CDCHD, CDCHD, CDCD;при условии, что, по меньшей мере, один Y представляет собой дейтерий (D), или, по меньшей мере, один из R, Rсодержит, по меньшей мере, один дейтерий (D);необязательно, по меньшей мере, один атом углерода независимо друг от друга замененC;и его физиологически приемлемые соли, сольваты, таутомеры и стереоизомеры, включая их смеси во всех соотношениях.2. Дейтерированное тиазолидиноновое производное по п. 1, где,по меньшей мере, один атом углерода замененC;и его физиологически приемлемые соли, сольваты, таутомеры и стереоизомеры, включая их смеси во всех соотношениях.3. Дейтерированное тиазолидиноновое ...

SPEZIFISCH MARKIERTE PROTEINE, AMINOSÄURE UND BIOCHEMISCHE VORLÄUFER

VERFAHREN UND VORRICHTUNG ZUR SYNTHESE MARKIERTER VERBINDUNGEN.

Deuterierte Pyrazolopyrimidinone sowie diese Verbindungen enthaltende Arzneimittel

Die Erfindung betrifft deuterierte Pyrazolopyrimidinone sowie diese Verbindungen enthaltende Arzneimittel. DOLLAR A Weiterhin betrifft die Erfindung die Verwendung deuterierter Pyrazolopyrimidinone zur Hemmung der Thrombozyten-Adhäsion und -Aggregation, zur Langzeitsteigerung der Gedächtnisleistung und Lernfähigkeit sowie zur Behandlung von Herz- und Kreislauferkrankungen, Hypertonie, pulmonaler Hypertonie, erektiler Dysfunktion und obstruktiven Atemwegserkrankungen wie z. B. Asthma bronchiale. DOLLAR A Außerdem offenbart die Erfindung pharmazeutische Zusammensetzungen deuterierter Pyrazolopyrimidinone sowie deren physiologisch verträglichen Salze zur Hemmung der Thrombozyten-Adhäsion und -Aggregation, zur Langzeitsteigerung der Gedächtnisleistung und Lernfähigkeit sowie zur Behandlung von Herz- und Kreislauferkrankungen, Hypertonie, pulmonaler Hypertonie, erektiler Dysfunktion und obstruktiven Atemwegserkrankungen wie z. B. Asthma bronchiale neben pharmazeutisch verträglichen Hilfs- und ...

Methods

Compound

Novel process and catalyst

Improved radiosynthesis method

CYCLOVITAMIN D COMPOUNDS AND VITAMIN D COMPOUNDS ISOTOPICALLY SUBSTITUTED AT CARBON 6

Compounds for use as radioligands

Compounds

1, 3, 4-THIADIAZOLE COMPOUNDS AND THEIR USE IN TREATING CANCER

Fused benzoxazepinones as ion modulators

Deuterated 1-piperazino-3-phenyl indanes for treatment of schizophrenia

AZETIDINYLOXYPHENYLPYRROLIDINE COMPOUNDS

Modulators of pharmacokinetic properties of therapeutics

Modulators of pharmacokinetic properties of therapeutics

4-Aryl-N-phenyl-1,3,5,-triazin-2-amines containinga sulfoximine group

SUBSTITUTED DIHYDROISOQUINOLINONE COMPOUNDS

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

AZETIDINYLOXYPHENYLPYRROLIDINE COMPOUNDS

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Modulators of pharmacokinetic properties of therapeutics

Modulators of pharmacokinetic properties of therapeutics

NOVEL HETEROCYCLIC DERIVATIVES AND THEIR USE IN THE TREATMENT OF NEUROLOGICAL DISORDERS

4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group

SUBSTITUTED OXOPYRIDINE DERIVATIVES AND USE THEREOF IN THE TREATMENT OF CARDIOVASCULAR DISORDERS

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

1, 3, 4-THIADIAZOLE COMPOUNDS AND THEIR USE IN TREATING CANCER

Biaryl amide compounds as kinase inhibitors

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Novel heterocyclic derivatives and their use in the treatment of neurological disorders

Fused benzoxazepinones as ion modulators

Modulators of pharmacokinetic properties of therapeutics

Deuterated 1-piperazino-3-phenyl indanes for treatment of schizophrenia

Deuterated 1-piperazino-3-phenyl indanes for treatment of schizophrenia

Modulators of pharmacokinetic properties of therapeutics

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Novel heterocyclic derivatives and their use in the treatment of neurological disorders

Deuterated 1-piperazino-3-phenyl indanes for treatment of schizophrenia

SUBSTITUTED OXOPYRIDINE DERIVATIVES AND USE THEREOF IN THE TREATMENT OF CARDIOVASCULAR DISORDERS

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Fused benzoxazepinones as ion modulators

SUBSTITUTED DIHYDROISOQUINOLINONE COMPOUNDS

SUBSTITUTED OXOPYRIDINE DERIVATIVES AND USE THEREOF IN THE TREATMENT OF CARDIOVASCULAR DISORDERS

1, 3, 4-THIADIAZOLE COMPOUNDS AND THEIR USE IN TREATING CANCER

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Modulators of pharmacokinetic properties of therapeutics

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

4-Aryl-N-phenyl-1,3,5,-triazin-2-amines containinga sulfoximine group

Modulators of pharmacokinetic properties of therapeutics

Novel heterocyclic derivatives and their use in the treatment of neurological disorders

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Biaryl amide compounds as kinase inhibitors

SUBSTITUTED DIHYDROISOQUINOLINONE COMPOUNDS

4-Aryl-N-phenyl-1,3,5,-triazin-2-amines containinga sulfoximine group

AZETIDINYLOXYPHENYLPYRROLIDINE COMPOUNDS

RADIO LIGAND AND CONNECTION ASSAY

CARBOBORANE METALLOPHTHALOCYANINE, THEIR PRODUCTION, PHARMACEUTICAL PRODUCTS AND MEDICAL USES

VERFAHREN ZUR HERSTELLUNG VON NEUEM 2-DEUTERO-3-FLUOR-DL-ALANIN

Diacylethylenediamine compound

[Problem] A compound which is useful as an anti-obesity agent is provided. [Means for Solution] The present inventors have investigated a compound having a DGAT1 inhibitory action, which is promising as an active ingredient of a pharmaceutical composition for treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases, and as a result, they have found that the diacylethylenediamine compound of the present invention has an excellent DGAT1 inhibitory action, thereby completing the present invention. That is, the diacylethylenediamine compound of the present invention has a DGAT1 inhibitory action, and can be therefore used as an agent for preventing and/or treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases.

Isotopologues of thalidomide

Provided herein are thalidomide, which is enriched with isotopes such as deuterium. Pharmaceutical compositions comprising the isotopes-enriched compounds, and methods of using such compounds are also provided.

No-Carrier-Added Nucleophilic [F-18] Fluorination of Aromatic Compounds

Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No-carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F-18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F-18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F-18]fluoro-L-dopa.

Trihydroxy polyunsaturated eicosanoid derivatives

The invention features methods for the preparation of naturally occurring trihydroxy polyunsaturated eicosanoids and their structural analogs. The invention further provides new derivatives and analogs of trihydroxy polyunsaturated eicosanoids that can be prepared according to these methods. The invention also provides compositions and methods using trihydroxy polyunsaturated eicosanoid derivatives for the prevention, amelioration and treatment of a variety of diseases or conditions associated with inflammation or inflammatory response, autoimmune diseases, rheumatoid arthritis, cardiovascular diseases, or abnormal cell proliferation or cancer.

Compounds and their use as BACE Inhibitors

The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.

Iodine radiolabelling method

The present invention provides a novel method of labelling biological targeting molecules (BTMs) of interest with radioiodine. Also provided are novel radioiodinated BTMs prepared using the method, as well as radiopharmaceutical compositions comprising such radioiodinated BTMs. The invention also provides radioiodinated intermediates useful in the method, as well as in vivo imaging methods using the radioiodinated BTMs.

Method for Obtaining Novel Derivatives of Naphthalene for the In Vivo Diagnosis of Alzheimer's Disease

This invention relates to a chemistry branch, particularly to the field of compounds' organic synthesis that belongs to the aromatic bicyclic or naphthalene category, used in the detection of amyloid sheets. These new naphthalene derivatives have a general formula: Wherein R represents mutually independent groups. In I: R 1 :-alkylenyl-C(O)NH-alkylenyl-R 3 , -alkylenyl-C(O)O—R 4 , R 3 :—COOH, —OH, —SH, —NH 2 , -alkyl-NH-alkyl-N-dithiocarbamate alkaline earth metal salts, R 4 : H, succinimidyl group, R 2 : —H,-alkyl. In II: R 1 : -alkyl, -alkylenyl-halide-alkylenyl-hydroxyl-alkylenyl-O-aryl, —O-alkylsulfonate alkylenyl, R 2 : -halide-alkylenyl-O-aryl, -alkylenyl-O-alkylsulfonate, -alkylenyl-halide-, —CH(O), —HC═C(CN) 2 , —HC═CHNO 2 , -alkylenyl-NH 2 , -alkylenyl-NH-alkyl, -alkylenyl-alkyl-N-dithiocarbamate alkaline salts. The terms “alkyl” and “alkylenyl” refer to linear or branched aliphatic chains, preferably from 1 to 4 carbon atoms and the term halide to fluorine, bromine or iodine. These compounds are neutral, lipophilic and have low molecular weight and therefore they cross the blood brain barrier and attach to the amyloid sheets. The present invention provides procedures for obtaining naphthalene derivatives with good yields, which can be practical, economical and adapted to a larger-scale manufacturing. We are unaware whether the compounds presented in this invention have been previously reported.

Deuterated compounds useful for treating neurodegenerative diseases

The present application is related to deuterated compounds which are novel neurotrophin mimetics. The application also discloses the treatment of disorders involving degradation or dysfunction of cells expressing p75 in a mammal by administering an effective amount of such deuterated compounds.

4-hydroxybutyric acid analogs

This invention relates to novel derivatives of 4-hydroxybutyric acid and prodrugs thereof, and pharmaceutically acceptable salts of the foregoing. This invention also provides pharmaceutical compositions comprising a compound of this invention and the use of such compositions in methods of treating narcolepsy, fibromyalgia, other disorders or conditions that are beneficially treated by improving nocturnal sleep or by administering sodium oxybate.

Styryl-based compound, composition containing styryl-based compound, and organic light emitting diode including styryl-based compound

A styryl-based compound represented by Formula 1, a composition containing the styryl-based compound, and an organic light-emitting diode (OLED) including the styryl-based compound: The styryl-based compound may exhibit high heat resistance and thus an OLED including the same may have low driving voltage, high brightness, high efficiency, and long lifetime.

Production of renewable aromatic compounds

The invention provides a process for producing a variety renewable aromatic compounds such as benzene, toluene, xylenes, and cumene, as well as compounds derived from these including, for example, aniline, benzoic acid, cresol, cyclohexane, cyclohexanone, phenol and bisphenol A, toluene di-isocyanate, isophthalic acid, phthalic anhydride, terephthalic acid and dimethyl terephthalate. The invention also provides for renewable forms of these aromatic compounds.

Device for the synthesis of radio-labeled compounds

The invention relates to a device for the synthesis of radio-labeled compounds, which comprises a reaction vessel for reacting a precursor compound having protective groups with a radioactive isotope to obtain a first reaction product; a first cartridge for hydrolyzing the protective groups of the first reaction product to obtain a second reaction product; and a second cartridge for purifying the second reaction product, wherein the reaction vessel, the first cartridge, and the second cartridge are connected to each other via pipelines. Here it is provided that the first cartridge contains 801 to 1200 mg of a solid carrier and/or the reaction vessel is a reaction vessel made of a temperature-resistant plastic with the plastic having a temperature resistance of at least 120° C.

Method of preparing ethacrynic amide derivatives and application thereof

The present invention provides a method for preparing [ 18 F]—N-(4-fluorobutyl)ethacrynic amide which is prepared from radiofluorination and deprotection of the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)-butyl)ethacrynic amide], obtained from ethacrynic acid via 6-step synthesis in 39% yield, in a radiochemical yield of 44%, aspecific activity of 48 GBq/μmol and radiochemical purity of 98%. The present invention further provides a composition for positron emission tomography (PET) of an animal models of a tumor liver or a liver disease, comprising [ 18 F]—N-(4-fluorobutyl)ethacrynic amide and a pharmaceutically acceptable carrier.

Processes for Making Compounds Useful as Inhibitors of ATR Kinase

The present invention relates to processes and intermediates for preparing compounds useful as inhibitors of ATR kinase, such as aminopyrazine-isoxazole derivatives and related molecules. The present invention also relates to compounds useful as inhibitors of ATR protein kinase. The invention relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and solid forms of the compounds of this invention. The compounds of this invention have formula I or II: wherein the variables are as defined herein.

Compositions and Methods for Imaging

The present disclosure provides compositions for in vivo imaging of hydrogen peroxide; and methods for detecting hydrogen peroxide in vivo. The compositions and methods find use in various diagnostic applications, which are also provided.

Organic electroluminescent element, compounds and materials used for the organic electroluminescent element, and light-emitting, display and illuminating devices using the elements

An organic electroluminescent element is provided that has high luminous efficiency, and a slow luminance deterioration rate in the initial stage of lighting. The organic electroluminescent element includes a substrate; a pair of electrodes including an anode and a cathode, disposed on the substrate; and at least one organic layer including a light emitting layer, disposed between the electrodes, wherein at least one organic layer includes a compound represented by the general formula (1). (R 11 to R 15 represent hydrogen atoms, alkyl groups, or silyl groups, and any one of R 21 to R 24 represents a group represented by general formula (1A) or (1B). Ph 4 represents a p-phenylene group, and at least one of Ph 4a and Ph 4b represents a p-phenylene group.)

Compound for organic light-emitting diode and organic light-emitting diode including the same

A compound represented by Formula 1 below may be used in an organic light emitting diode.

Fluorinated 2-Amino-4-(Benzylamino)Phenylcarbamate Derivatives

The invention relates to fluorinated compounds and their use as anti-epileptic, muscle-relaxing, fever-reducing and peripherally analgesically acting medications and as imaging agents. Novel fluorinated 2-amino-4-(benzylamino)phenyl carbamate derivatives of ezogabine and pharmaceutically acceptable salts or solvates thereof and their use are described.

Benzoquinoline inhibitors of vesicular monoamine transporter 2

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

Ligands for imaging cardiac innervation

Novel compounds that find use as imaging agents within nuclear medicine applications (PET imaging) for imaging of cardiac innervation are disclosed. These PET based radiotracers may exhibit increased stability, decreased NE release (thereby reducing side effects), improved quantitative data, and/or high affinity for VMAT over prior radiotracers. Methods of using the compounds to image cardiac innervation are also provided. In some instances the compounds are developed by derivatizing certain compounds with 18F in a variety of positions: aryl, alkyl, a keto, benzylic, beta-alkylethers, gamma-propylalkylethers and beta-proplylalkylethers. Alternatively or additionally, a methyl group a is added to the amine, and/or the catechol functionality is either eliminated or masked as a way of making these compounds more stable.

Isotopically enriched arylsulfonamide ccr3 antagonists

Provided herein are isotopically enriched arylsulfonamides, for example, of Formula I, that are useful for modulating CCR3 activity, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CCR3-mediated disease, disorder, or condition.

Deuterated cftr potentiators

This invention relates to compounds of Formula I: and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator.

Transition-metal free reductive cleavage of aromatic c-o, c-n, and c-s bonds by activated silanes

The present invention describes chemical systems and methods for reducing C—O, C—N, and C—S bonds, said system comprising a mixture of (a) at least one organosilane and (b) at least one strong base, said system being substantially free of a transition-metal compound, and said system optionally comprising at least one molecular hydrogen donor compound, molecular hydrogen, or both.

DEUTERIUM-ENRICHED PIOGLITAZONE

The present application describes deuterium-enriched pioglitazone, pharmaceutically acceptable salt forms thereof, and methods of treating using the same. 120-. (canceled)22. The method of claim 21 , wherein the abundance of deuterium in Ris at least 50% and the abundance of deuterium in Ris at least 50%.23. The method of claim 21 , wherein the abundance of deuterium in Ris at least 50% and the abundance of deuterium in Ris at least 90%.24. The method of claim 21 , wherein Ris D.25. The method of claim 21 , wherein the deuterium enriched compound is administered as a pharmaceutical composition claim 21 , the pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the deuterium enriched compound or a pharmaceutically acceptable salt form thereof.27. The method of claim 26 , wherein Ris H.28. The method of claim 26 , wherein Ris D.29. The method of claim 26 , wherein the deuterium enriched compound is administered as a pharmaceutical composition claim 26 , the pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the deuterium enriched compound or a pharmaceutically acceptable salt form thereof. The present application is a divisional of U.S. patent application Ser. No. 12/233,751, filed on Sep. 19, 2008, which claims priority to U.S. Provisional Patent Application Ser. No. 60/975,193, filed Sep. 26, 2007; the disclosure of each of which is hereby incorporated by reference.This invention relates generally to deuterium-enriched pioglitazone, pharmaceutical compositions containing the same, and methods of using the same.Pioglitazone, shown below, is a well known thiazolidinedione.Since pioglitazone is a known and useful pharmaceutical, it is desirable to discover novel derivatives thereof. Pioglitazone is described in U.S. Pat. No. 4,687,777; the contents of which are incorporated herein by reference.Accordingly, one object of the present ...

Cd8 imaging constructs and methods of use thereof

Antigen binding constructs that bind to CD8, as well as formulations and methods of using them, are described herein.

RADIOACTIVE IODINE LABELED PYRIDO[1,2-a]BENZOIMIDAZOLE DERIVATIVE COMPOUND

The present invention relates to a radioactive iodine-labeled pyrido[1,2-a]benzimidazole derivative compound represented by a definite general formula or a salt thereof, or a radiopharmaceutical comprising the same. 2. The radioactive iodine-labeled compound or a salt thereof according to claim 1 , wherein the radioactive iodophenyl group is a substituent having a phenyl group which hydrogen atom at position 4 is substituted with a radioactive iodine atom.3. The radioactive iodine-labeled compound or a salt thereof according to claim 1 , wherein the radioactive iodine atom is I claim 1 , I claim 1 , I claim 1 , or I.4. A radiopharmaceutical comprising a radioactive iodine-labeled compound or a salt thereof according to .5. The radiopharmaceutical according to claim 4 , which is for use in single photon emission computed tomography (SPECT).6. A diagnostic agent for Alzheimer's disease comprising a radioactive iodine-labeled compound or a salt thereof according to . The present invention relates to a radioactive iodine-labeled pyrido[1,2-a]benzimidazole derivative compound or a salt thereof, and a radiopharmaceutical comprising the same.Accumulation of senile plaque (SP) composed mainly of amyloid β protein (Aβ) and neurofibrillary tangle (NFT) composed mainly of tau protein is found in the brain with Alzheimer's disease (AD). Since the accumulation of NFT exhibits high correlation with clinical symptoms, as compared with SP, development of radioactive molecule imaging probes for nuclear medicine diagnosis targeting the tau protein has received attention recently.For example, Patent Document 1 describes radioactive iodine-labeled compounds comprising rhodanine and thiohydantoin derivatives having affinity for the tau protein.Also, Patent Documents 2 and 3 describe compounds having binding activity against both of the Aβ and the tau protein. Specifically, Patent Document 2 describes a radioactive iodine-labeled compound having styrylbenzimidazole as a nucleus, and ...

Terephthalate derivatives and compositions thereof

The present invention provides dimethylterephthalate in which two of the aromatic ring carbons are derived from ethanol. The present invention also provides bis (2-hydroxyethyl) terephthalate, wherein two to six carbon atoms in a molecule can be derived from ethanol.

INDAZOLES AND USE THEREOF

In one aspect, the present disclosure provides indazoles of Formula I: (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R, R, R, R, Z, Z, Z, and G are defined as set forth in the specification. Further, the present disclosure also provides compounds of Formulae II and IA, and the pharmaceutically acceptable salts and solvates thereof. The present disclosure is also directed to the use of compounds of Formulae I, II, and IA, and the pharmaceutically acceptable salts and solvates thereof, to treat a disorder responsive to the blockade of sodium channels. In one embodiment, compounds of the present disclosure are especially useful for treating pain. 2. The compound of claim 1 , wherein G is dihydroxyalkyl claim 1 , or a pharmaceutically acceptable salt or solvate thereof.4. (canceled)6. The compound of claim 5 , wherein:{'sup': '2', 'Zis selected from the group consisting of N and CH;'}{'sup': '3', 'Ris selected from the group consisting of hydrogen and alkyl; and'}{'sup': '4', 'Ris selected from the group consisting of hydrogen, halogen, alkyl, and haloalkyl,'}or a pharmaceutically acceptable salt or solvate thereof.7. The compound of claim 1 , wherein Ris hydrogen claim 1 , and Zis N claim 1 , or a pharmaceutically acceptable salt or solvate thereof.89-. (canceled)10. The compound of claim 1 , wherein G is —(CHR)—C═O)E claim 1 , E is —NRR claim 1 , and Rand Rare hydrogen claim 1 , or a pharmaceutically acceptable salt or solvate thereof.11. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , hydroxyalkyl claim 1 , and —X—R claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. The compound of claim 11 , wherein Ris hydrogen claim 11 , or a pharmaceutically acceptable salt or solvate thereof.13. (canceled)15. The compound of claim 11 , wherein Ris —X—R claim 11 , wherein X is —O— or —NH— claim 11 , or a pharmaceutically acceptable salt or solvate thereof.1619-. (canceled)21. The ...

2',6'-DIOXO-3'-DEUTERO-PIPERDIN-3-YL-ISOINDOLINE COMPOUNDS

The present application describes 2-(2′,6′-dioxo-3′-deutero-piperidin-3′-yl)isoindoles, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treating using the same. 13-. (canceled)524-. (canceled)25. The deuterium-enriched compound of claim 4 , wherein X is C═O.26. The deuterium-enriched compound of claim 4 , wherein Ris aryl.27. The deuterium-enriched compound of claim 25 , wherein Ris aryl.28. The deuterium-enriched compound of claim 26 , wherein said aryl is phenyl.29. The deuterium-enriched compound of claim 27 , wherein said aryl is phenyl.30. The deuterium-enriched compound of claim 27 , wherein Ris (CH).31. The deuterium-enriched compound of claim 29 , wherein Ris (CH).32. The deuterium-enriched compound of claim 27 , wherein Ris (C-C)heterocycloalkyl.33. The deuterium-enriched compound of claim 30 , wherein Ris (C-C)heterocycloalkyl.34. The deuterium-enriched compound of claim 31 , wherein Ris (C-C)heterocycloalkyl.35. The deuterium-enriched compound of claim 33 , wherein (C-C)heterocycloalkyl is morpholinyl.36. The deuterium-enriched compound of claim 34 , wherein (C-C)heterocycloalkyl is morpholinyl.37. The deuterium-enriched compound of claim 33 , wherein the abundance of deuterium in Z is at least 90%.38. The deuterium-enriched compound of claim 34 , wherein the abundance of deuterium in Z is at least 90%.39. The deuterium-enriched compound of claim 36 , wherein the abundance of deuterium in Z is at least 90%.40. The deuterium-enriched compound of claim 33 , wherein R-Rare H claim 33 , and Ris H.41. The deuterium-enriched compound of claim 34 , wherein R-Rare H claim 34 , and Ris H.42. The deuterium-enriched compound of claim 36 , wherein R-Rare H claim 36 , and Ris H.43. The deuterium-enriched compound of claim 39 , wherein R-Rare H claim 39 , and Ris H.441. A pharmaceutical composition comprising a deuterium-enriched compound of claim and one or more excipients.45. A pharmaceutical ...

Purification method

The invention provides a method for the purification of complexed 227Th from a mixture comprising complexed 227Th and 223Ra (complexed or in solution), said method comprising: i) preparing a first solution comprising a mixture of complexed 227Th ions and 223Ra ions in a first aqueous buffer; ii) loading said first solution onto a separation material; iii) eluting complexed 227Th from said separation material whereby to generate a second solution comprising complexed 227Th; iv) Optionally rinsing said separation material using a first aqueous washing medium; The invention additionally provides a purified 227Th solution, a pharmaceutical product and its use in treatment of disease such as cancer and a kit for generation of such a product.

CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR

The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof. 2. The compound or salt thereof of wherein each position represented as D has deuterium enrichment of no less than about 50%.3. The compound or salt thereof of wherein each position represented as D has deuterium enrichment of no less than about 90%.4. The compound or salt thereof of wherein each position represented as D has deuterium enrichment of no less than about 98%.5. A method of treating a P2Y12 receptor-mediated disorder comprising administering to a patient in need thereof claim 1 , a therapeutically effective amount of a compound or salt thereof as recited in .6. The method of claim 5 , wherein said disorder is arterial thrombosis or coronary artery disease.7. The method of claim 5 , further comprising administering an additional therapeutic agent.8. The method of wherein said additional therapeutic agent is an alpha adrenergic receptor antagonist claim 7 , a beta adrenergic receptor antagonist claim 7 , an angiotensin II receptor antagonist claim 7 , an angiotensin-converting enzyme inhibitor claim 7 , an anti-arrhythmic claim 7 , an antithrombotic claim 7 , an antiplatelet agent claim 7 , a calcium channel blocker claim 7 , a fibrate claim 7 , or a HMG-CoA reductase inhibitor.9. The method of wherein said alpha adrenergic receptor antagonist is abanoquil claim 8 , adimolol claim 8 , ajmalicine claim 8 , alfuzosin claim 8 , amosulalol claim 8 , arotinolol claim 8 , atiprosin claim 8 , benoxathian claim 8 , buflomedil claim 8 , bunazosin claim 8 , carvedilol claim 8 , CI-926 claim 8 , corynanthine claim 8 , dapiprazole claim 8 , DL-017 claim 8 , domesticine claim 8 , doxazosin claim 8 , eugenodilol claim 8 , fenspiride claim 8 , GYKI-12 claim 8 ,743 claim 8 , GYKI-16 claim 8 ,084 claim 8 , indoramin claim 8 , ketanserin claim 8 , L-765 claim 8 ,314 claim 8 , labetalol claim 8 , mephendioxan claim 8 , ...

Compositions for binding sphingosine-1-phosphate receptor 1 (s1p1), imaging of s1p1, and methods of use thereof

Among the various aspects of the present disclosure is the provision of a compositions for binding sphingosine-1-phosphate receptor 1 (S1P1), imaging of S1P1, and methods of use thereof. Provided are imaging agents for imaging S1P1 and S1P1 associated diseases, disorders, and conditions. Also provided are therapeutic compositions and methods for the treatment of S1P1 associated diseases, disorders, and conditions.

AZETIDINYLOXYPHENYLPYRROLIDINE COMPOUNDS

The invention provides certain azetidinyloxyphenylpyrrolidine compounds, particularly compounds of formula I, and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I to treat overactive bladder. 4. The compound or salt of wherein Ris Cl.6. The compound which is (2S)-3-[(3S claim 3 ,4S)-3-[(1R)-1-hydroxyethyl]-4-(4-methoxy-3-{[1-(5-chloropyridin-2-yl)azetidin-3-yl]oxy}phenyl)-3-methylpyrrolidin-1-yl]-3-oxopropane-1 claim 3 ,2-diol.8. A pharmaceutical composition comprising a compound of or claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , and a pharmaceutically acceptable carrier claim 3 , diluent or excipient.9. A method of treating overactive bladder comprising administrating to a patient in need thereof an effective amount of a compound of or claim 3 , or a pharmaceutically acceptable salt thereof.10. A method of treating overactive bladder comprising administrating to a patient in need thereof an effective amount of a compound of or claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , in combination with an effective amount of tadalafil.11. (canceled)12. (canceled)13. (canceled) The invention provides certain azetidinyloxyphenylpyrrolidine compounds, pharmaceutical compositions thereof, methods of using the same, and processes for preparing the same.Overactive bladder (OAB) is a symptomatically defined medical condition referring to the symptoms of urinary frequency and urgency, with or without urge incontinence. OAB is a condition that adversely affects the quality of life and social functioning of approximately 17 percent of the adult population. In spite of progress made for OAB treatment, many patients suffer with OAB for years without resolution. The first-line treatment for OAB are antimuscarinic drugs which have a good initial response, but experience diminishing patient compliance over the long term due to adverse effects and decreasing efficacy. There remains a ...

Creatine prodrugs, compositions and methods of use thereof

The present disclosure provides creatine prodrug analogs and their compositions useful for the treatment of creatine deficiencies.

ANTIBACTERIAL AGENTS: O-ALKYL-DEUTERATED PYRONINS

The invention provides compounds of formula Ia, Ib, Ic, or as well as compositions comprising a compound of formula Ia-Id, methods of making such compounds, and methods of using such compounds, e.g., as inhibitors of bacterial RNA polymerase and as antibacterial agents. 3. The compound of claim 1 , which is a compound of formula Ia claim 1 , or a salt thereof.4. The compound of claim 1 , which is a compound of formula Ib claim 1 , or a salt thereof.5. The compound of claim 1 , which is a compound of formula Ic claim 1 , or a salt thereof.6. The compound of claim 1 , which is a compound of formula Id claim 1 , or a salt thereof.7. The compound or salt of claim 1 , wherein Ris H.8. The compound or salt of claim 1 , wherein Ris methyl.9. The compound or salt of claim 8 , wherein Ris methyl and where the compound is a mixture of the R and S stereoisomers.10. The compound or salt of claim 8 , wherein Ris methyl and wherein the compound claim 8 , or a salt thereof claim 8 , is predominantly the R stereoisomer claim 8 , preferably at least 90% of the R isomer.12. The compound or salt of wherin Ris methyl that is enriched in deuterium by at least 10-times the natural abundance of deuterium.1516-. (canceled)17. A composition comprising the compound or salt of claim 1 , and water claim 1 , that is suitable for intravenous administration.18. The composition of claim 17 , which is free of co-solvents and surfactants.1925-. (canceled)26. A method of inhibiting a bacterial RNA polymerase claim 1 , comprising contacting a bacterial RNA polymerase with a compound or salt of .27. A method of treating a bacterial infection in a mammal claim 1 , comprising administering to the mammal a therapeutically effective amount of a compound or salt of .2829-. (canceled)30. An antibacterial composition comprising the compound or salt of .31. The antibacterial composition of claim 30 , that 1) comprises water claim 30 , 2) is suitable for intravenous administration claim 30 , 3) is free of co- ...

COMPOUNDS, COMPOSITIONS, AND METHODS

The present disclosure relates generally to LRRK2 inhibitors, or a pharmaceutically acceptable salt, deuterated analog, prodrug, tautomer, stereoisomer, or mixture of stereoisomers thereof, and methods of making and using thereof. 131.-. (canceled)33. The method of claim 32 , wherein Rand Rare methyl.34. The method of claim 32 , wherein at least one of Rand Ris hydrogen.35. The method of claim 34 , wherein both Rand Rare hydrogen.36. The method of claim 32 , wherein Ris optionally substituted cyclopropyl or optionally substituted cyclobutyl.37. The method of claim 36 , wherein Ris cyclopropyl independently substituted with one or more halo claim 36 , hydroxy claim 36 , cyano claim 36 , or heteroaryl.38. The method of claim 36 , wherein Ris cyclopropyl claim 36 , cyclobutyl claim 36 , hydroxycylobut-3-yl claim 36 , cyanocylobut-3-yl claim 36 , triazol-2yl-cyclobut-3-yl claim 36 , triazol-1-yl-cyclobut-3-yl claim 36 , or fluorocyclobut-3-yl.39. The method of claim 32 , wherein Ris CD claim 32 , ethyl claim 32 , prop-2-yl claim 32 , or methyl optionally substituted with halo.40. The method of claim 32 , wherein Ris halo claim 32 , cyano claim 32 , or Calkyl optionally substituted with one or more halo.41. The method of claim 40 , wherein Ris bromo.42. The method of claim 40 , wherein Ris —CF.43. The method of claim 32 , wherein Ris optionally substituted cycloalkyl claim 32 , optionally substituted Calkoxy claim 32 , or —N(R)(R).44. The method of claim 43 , wherein Ris optionally substituted Calkyl.45. The method of claim 43 , wherein Ris H and Ris ethyl.46. The method of claim 32 , wherein Ris cyclopropyl claim 32 , methoxy claim 32 , 1 claim 32 ,1-difluoroeth-2-ylamino claim 32 , cyclopropylamino claim 32 , —NH(CH) claim 32 , or —NH(CHCH).47. The method of claim 32 , wherein Ris hydrogen.48. The method of claim 32 , wherein Ris cycloalkyl independently substituted with one or more hydroxy claim 32 , cyano claim 32 , or heteroaryl; Ris halo or Chaloalkyl; Ris —N(R)(R) ...

SULPHONYL UREA DERIVATIVES AS NLRP3 INFLAMMASOME MODULATORS

The present disclosure relates to compounds of Formula (I): 2. The compound of any one of the preceding claims , wherein Ris C-Cbicyclic cycloalkyl.6. The compound of any one of the preceding claims , wherein Ris C-Ctricyclic cycloalkyl.9. The compound of any one of the preceding claims , wherein , Ris C-Caryl optionally substituted by one or more R.10. The compound of any one of the preceding claims , wherein Ris phenyl is substituted by one , two , or three R.15. The compound of any one of the preceding claims , wherein Ris cyclopentyl , cyclohexyl , or cycloheptyl , wherein the cyclopentyl , cyclohexyl , or cycloheptyl is optionally substituted by one or more R.17. The compound of any one of the preceding claims , wherein at least one Ris methyl , ethyl , isopropyl , isobutyl , secbutyl , methoxy , ethoxy , —CF , —OCF , —OCHCF , F , or Cl.18. The compound of any one of the preceding claims , wherein Ris —R.19. The compound of any one of the preceding claims , wherein Ris —(CXX)—R.20. The compound of any one of the preceding claims , wherein Ris —(CXX)—R.21. The compound of any one of the preceding claims , wherein each Xis H.22. In some embodiments , at least one Xis C-Calkyl , C-Calkenyl , or C-Calkynyl , wherein the C-Calkyl , C-Calkenyl , or C-Calkynyl is optionally substituted with one or more halo , —CN , —OH , —O(C-Calkyl) , —NH , —NH(C-Calkyl) , —N(C-Calkyl) , or oxo.23. The compound of any one of the preceding claims , wherein Ris 4- to 8-membered heterocycloalkyl optionally substituted with one or more C-Calkyl , C-Calkenyl , C-Calkynyl , C-Chaloalkyl , halo , —CN , —OH , —O(C-Calkyl) , —NH , —NH(C-Calkyl) , —N(C-Calkyl) , or oxo.24. The compound of any one of the preceding claims , wherein Ris 4- to 8-membered heterocycloalkyl.25. The compound of any one of the preceding claims , wherein Ris 5- to 8-membered heterocycloalkyl.26. The compound of any one of the preceding claims , wherein Ris 5- to 7-membered heterocycloalkyl.27. The compound of any one of ...

Antibacterial agents: soluble salts and aqueous formulations of pyronins

The invention provides salts of formula Ia, Ib, Ic, or Id: wherein variables are as described in the specification, as well as compositions comprising a salt of formula Ia-Id, methods of making such salts, and methods of using such salts as, e.g., inhibitors of bacterial RNA polymerase and as antibacterial agents.

Deuterated compounds, compositions, and methods of use

Deuterated polyunsaturated fatty acid (“PUFA”) compounds, compositions, and uses of the compounds for reducing lipid autooxidation and the treatment of various diseases and conditions are provided.

PSILOCIN DERIVATIVES AS SEROTONERGIC PSYCHEDELIC AGENTS FOR THE TREATMENT OF CNS DISORDERS

The present application relates to psilocin derivatives of Formula (1), to processes for their preparation, to compositions comprising them and to their use in activation of a serotonin receptor in a cell, as well as to treating diseases, disorders or conditions by activation of a serotonin receptor in a cell. 2. The compound of claim 1 , wherein Ris selected from S(O)Rand SOR claim 1 , wherein all available hydrogen atoms are optionally substituted with a halogen atom and/or all available atoms are optionally substituted with an alternate isotope thereof.3. The compound of claim 1 , wherein Ris selected from hydrogen claim 1 , C-Calkyl claim 1 , C(O)R claim 1 , CORand C(O)N(R) claim 1 , wherein all available hydrogen atoms are optionally substituted with a halogen atom and/or all available atoms are optionally substituted with an alternate isotope thereof.4. The compound of claim 3 , wherein Ris selected from hydrogen claim 3 , deuterium claim 3 , CH claim 3 , CFand CD.5. The compound of claim 1 , wherein Ris selected from hydrogen claim 1 , CH claim 1 , CHCH claim 1 , CH(CH)and C(CH) claim 1 , wherein all available hydrogen atoms are optionally substituted with a halogen atom and/or all available atoms are optionally substituted with an alternate isotope thereof.6. The compound of claim 5 , wherein Ris selected from hydrogen and deuterium.7. The compound of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare independently selected from hydrogen and C-Calkyl claim 1 , wherein at least one of R claim 1 , R claim 1 , Rand Ris deuterium or at least one of R claim 1 , R claim 1 , Rand Rcomprises deuterium and wherein all available hydrogen atoms are optionally substituted with a halogen atom and/or all available atoms are optionally substituted with an alternate isotope thereof.8. The compound of claim 7 , wherein R claim 7 , R claim 7 , Rand Rare independently selected from hydrogen claim 7 , deuterium claim 7 , CHand CD claim 7 , wherein at least one of R claim 7 , R ...

CYCLIC PEROXIDES AS PRODRUGS FOR SELECTIVE DELIVERY OF AGENTS

Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5] decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier. 24.-. (canceled)622.-. (canceled)23. The compound of claim 1 , wherein each Lis independently selected from a bond or substituted or unsubstituted arylene.24. (canceled)25. The compound of claim 1 , wherein each Lis independently selected from a bond claim 1 , substituted or unsubstituted alkylene claim 1 , or substituted or unsubstituted heteroalkylene.26. (canceled)27. The compound of claim 1 , wherein each -L-L- is independently a bond claim 1 , -Ph-(CH)— or -Ph(CH)—OC(O)—; and w is an integer 1 to 4.2831.-. (canceled)32. The compound of claim 1 , wherein the drug moiety is independently a monovalent radical of an anti-infective agent.33. The compound of claim 32 , wherein the anti-infective agent is an anti-parasitic agent.34. The compound of claim 32 , wherein the anti-infective agent is an anti-malarial drug.35. The compound of claim 32 , wherein the anti-infective agent is an anti-bacterial drug.36. The compound of claim 1 , wherein the drug moiety is independently a monovalent radical of an anti-cancer drug.37. The compound of claim 1 , wherein the detectable moiety is independently a monovalent radical of a fluorophore.38. The compound of claim 1 , wherein the protein moiety is independently a monovalent radical of an antibody.39. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of .40. A method of treating a disease in a patient in need of such treatment claim 1 , said method comprising administering a therapeutically effective amount of a compound of to said patient.41. (canceled)42. The method of claim 40 , wherein ...

HEATSEAL

The present invention relates to systems and methods to facilitate replacement between runs of a kit or cassette from an automated radiosynthesis device located in a hot cell. The method and apparatus of the invention enable automated disconnection of the outlet line by sealing the tubing hermetically by means of heat and by cutting the tubing where it is sealed in such a way that there is no risk of environmental contamination with radioactive material. The invention enables disconnection of the outlet line without manual intervention before opening the shielded enclosure. 1. A method comprising:(i) providing a kit that can be fitted to an automated radiosynthesis device in order to synthesise a positron emission tomography (PET) tracer and one or more sections of thermoplastic tubing;(ii) fitting said kit and said one or more sections of thermoplastic tubing to the automated radiosynthesis device;(iii) introducing a PET isotope into said kit to carry out a radiochemical process to form a radiolabelled product;(iv) transferring said radiolabelled product from said kit to a product collection device and/or a product processing device; and,(v) heat sealing and cutting said one or more sections of thermoplastic tubing.2. The method as defined in wherein said product collection device is a product collection vial.3. The method as defined in wherein said product processing device is a chromatography device claim 2 , a dispensing device or a quality control device.4. The method as defined in wherein each of said radiosynthesis device claim 3 , product collection device and product processing device is contained within a shielded enclosure.5. The method as defined in wherein said shielded enclosure is a hot cell.6. The method as defined in wherein said automated radiosynthesis device is contained within a first shielded enclosure and said product collection device and/or said product processing device are contained within a second shielded enclosure.7. The method as ...

OXINDOLE DERIVATIVES CARRYING A PIPERIDYL-SUBSTITUTED AZETIDINYL SUBSTITUENT AND USE THEREOF FOR TREATING VASOPRESSINE-RELATED DISEASES

The present invention relates to novel substituted oxindole derivatives of formula (I) wherein the variables are as defined in the claims and description; to pharmaceutical compositions comprising them, and to their use for treatment of vasopressin-related disorders. 2. The compound of claim 1 , wherein at least one hydrogen atom has been replaced by a deuterium atom.3. The compound of claim 1 , wherein Xis C—Rand R claim 1 , Rand R claim 1 , independently of each other claim 1 , are selected from the group consisting of hydrogen claim 1 , halogen claim 1 , C-C-alkyl claim 1 , fluorinated C-C-alkyl claim 1 , C-C-alkoxy and fluorinated C-C-alkoxy.4. The compound of claim 3 , wherein R claim 3 , Rand R claim 3 , independently of each other claim 3 , are selected from the group consisting of hydrogen claim 3 , fluorine and methoxy.5. The compound of claim 4 , wherein Ris selected from hydrogen claim 4 , fluorine and methoxy.6. The compound of claim 4 , wherein Ris selected from the group consisting of hydrogen claim 4 , fluorine and methoxy.7. The compound of claim 4 , wherein Ris hydrogen or fluorine.8. The compound of claim 1 , wherein Xis N and Rand R claim 1 , independently of each other claim 1 , are selected from the group consisting of hydrogen claim 1 , halogen claim 1 , C-C-alkyl claim 1 , fluorinated C-C-alkyl claim 1 , C-C-alkoxy and fluorinated C-C-alkoxy.9. The compound of claim 8 , wherein Ris selected from the group consisting of hydrogen claim 8 , fluorine and methoxy.10. The compound of claim 8 , wherein Ris selected from the group consisting of hydrogen claim 8 , fluorine and methoxy.11. The compound of claim 1 , wherein Ris selected from the group consisting of methoxy and ethoxy.12. The compound of claim 1 , wherein Ris hydrogen or methoxy.13. The compound of claim 1 , wherein Ris selected from the group consisting of cyano claim 1 , fluorine and chlorine.14. The compound of claim 1 , wherein Ris hydrogen or fluorine.15. The compound of claim 1 , ...

PYRIDINES AND PYRIMIDINES AND USE THEREOF

The present disclosure provides pyridines and pyrimidines of Formula I and pharmaceutically acceptable salts and solvates thereof: wherein A, G, W, W, W, and Rare defined as set forth in the specification. The present disclosure also provides uses of the compounds of Formula I and pharmaceutically acceptable salts and solvates thereof. In certain embodiments, Compounds of the present disclosure are useful for treating pain. In another embodiment, Compounds of the present disclosure are useful for treating a disorder responsive to blockade of sodium channels, or alleviating symptoms of the disorder. 36-. (canceled)910-. (canceled)11. The compound of claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , optionally substituted cycloalkyl claim 1 , optionally substituted heterocyclo claim 1 , optionally substituted aryl claim 1 , optionally substituted heteroaryl claim 1 , and —SOR claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. The compound of claim 11 , wherein Ris optionally substituted phenyl or (C-C)alkyl claim 11 , or a pharmaceutically acceptable salt or solvate thereof.13. (canceled)1517-. (canceled)18. The compound of claim 1 , wherein Wis N claim 1 , Wis CH claim 1 , and Wis CH claim 1 , or a pharmaceutically acceptable salt or solvate thereof.19. The compound of claim 1 , wherein Wis N claim 1 , Wis N claim 1 , and Wis CH claim 1 , or a pharmaceutically acceptable salt or solvate thereof.20. (canceled)22. The compound of claim 1 , wherein G is —C(═O)E claim 1 , or a pharmaceutically acceptable salt or solvate thereof.23. (canceled)2530-. (canceled)31. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , hydroxyalkyl claim 1 , and —X—R claim 1 , or a pharmaceutically acceptable salt or solvate thereof.32. (canceled)3438-. (canceled)40. The compound of selected from the group consisting of:6-(1-(4-(Trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)picolinamide ...

Cot modulators and methods of use thereof

The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.

Piercing Device

The present invention provides a system for the production of a radiopharmaceutical including a radiosynthesis apparatus and a disposable cassette. The system of the invention includes a device that enables a position on the cassette to be freed for inclusion of an additional reagent vial. With the system of the invention a broader range of radiochemical syntheses can be envisaged using the cassette. 1. A system for the production of a radiopharmaceutical comprising:(i) a cassette comprising all the reagents required to produce two batches of said radiopharmaceutical when a radioisotope is introduced into said cassette, wherein each of said reagents is contained in a stoppered reagent vial that is pierced by a spike by automated movement of said stoppered reagent vial and/or said spike;(ii) an automated radiosynthesiser onto which said cassette removably fits and which comprises moving parts that control operation of the cassette, wherein one such moving part is a device to facilitate the automated piercing of one of said stoppered reagent vials wherein said device is attached to the outside of said automated radiosynthesiser and comprises a support and a substantially rigid rod housed within said support.2. The system as defined in claim 1 , wherein said support comprises a support body and a rod fixing means.3. The system as defined in claim 2 , wherein said rod fixing means comprises a bore in said support body wherein said bore has cross-sectional dimensions substantially similar to the cross-sectional dimensions of said rod but allowing said rod to be securely contained within said bore.4. The system as defined in claim 1 , wherein said support is held in place on the outside of said automated radiosynthesiser by co-operative engagement of a support fixing element and an automated radiosynthesiser fixing element.5. The system as defined in claim 1 , wherein said rod is made from rigid plastic.6. The system as defined in claim 1 , wherein said device further ...

Radiosynthesiser Add-On Device

The present invention relates to an automated radiosynthesis device adapted for the addition of multiple additional components. The automated radiosynthesis device of the invention enables a wider range of radiochemical synthetic processes to be carried out in an automated fashion. 1. An automated radiosynthesis device comprising:(i) a plurality of connectors for removably attaching a disposable kit;(ii) a plurality of actuators to selectively control moving parts of said disposable kit;(iii) a control unit for directing the selective control of the moving parts of said disposable kit by said plurality of actuators;(iv) a reaction vessel heating well;(v) an inert gas conduit;(vi) a vacuum conduit;(vii) a radioisotope conduit;(viii) means to fix add-on devices onto the radiosynthesis device at various locations.2. The automated radiosynthesis device as defined in claim 1 , wherein said plurality of connectors is selected from the group comprising fasteners and fluidic connectors.3. The automated radiosynthesis device as defined in claim 2 , wherein said fluidic connectors are selected from the group comprising push-on type connectors claim 2 , luer slip connectors or luer screw connectors.4. The automated radiosynthesis device as defined in claim 1 , wherein said disposable kit is suitable for the synthesis of a radiotracer compound.5. The automated radiosynthesis device as defined in claim 4 , wherein said radiotracer compound is a positron-emission tomography (PET) tracer.6. The automated radiosynthesis device as defined in claim 5 , wherein said radiotracer compound is an F-labelled PET tracer.7. The automated radiosynthesis device as defined in claim 1 , wherein said disposable kit is a single-use cassette.8. The automated radiosynthesis device as defined in claim 1 , wherein said plurality of actuators is selected from the group comprising rotatable arms for stopcocks of valves claim 1 , linear actuators claim 1 , arms that press onto reagent vials and pinch ...

DEUTERIUM-ENRICHED PIOGLITAZONE

The present application describes deuterium-enriched pioglitazone, pharmaceutically acceptable salt forms thereof, and methods of treating using the same. 2. The method of claim 1 , wherein Rand R-Rare H.4. The method of claim 3 , wherein Rand R-Rare H.6. The method of claim 5 , wherein Rand R-Rare H.9. The method of claim 8 , wherein Rand R-Rare H.1120-. (canceled) The present application is a divisional of U.S. patent application Ser. No. 12/233,751, filed on Sep. 19, 2008, which claims priority to U.S. Provisional Patent Application Ser. No. 60/975,193, filed Sep. 26, 2007; the disclosure of each of which is hereby incorporated by reference.This invention relates generally to deuterium-enriched pioglitazone, pharmaceutical compositions containing the same, and methods of using the same.Pioglitazone, shown below, is a well known thiazolidinedione.Since pioglitazone is a known and useful pharmaceutical, it is desirable to discover novel derivatives thereof. Pioglitazone is described in U.S. Pat. No. 4,687,777; the contents of which are incorporated herein by reference.Accordingly, one object of the present invention is to provide deuterium-enriched pioglitazone or a pharmaceutically acceptable salt thereof.It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the deuterium-enriched compounds of the present invention or a pharmaceutically acceptable salt thereof.It is another object of the present invention to provide a method for treating a disease selected from diabetes mellitus type 2 and/or non-alcoholic steatohepatitis, comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the deuterium-enriched compounds of the present invention or a pharmaceutically acceptable salt thereof.It is another object of the present invention to provide a novel deuterium-enriched ...

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. Also disclosed are methods of making the compounds. 1. A pharmaceutical composition , comprising:a means for inhibiting a Janus kinase (JAK); anda pharmaceutically acceptable excipient.2. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is a liquid carrier.3. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is a solid carrier.4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration claim 1 , parenteral administration claim 1 , inhalation spray nasal administration claim 1 , vaginal administration claim 1 , rectal administration claim 1 , sublingual administration claim 1 , urethral administration claim 1 , or topical administration.5. The pharmaceutical composition of claim 4 , wherein parenteral administration is selected from intramuscular claim 4 , intraperitoneal claim 4 , intravenous claim 4 , ICV claim 4 , intracisternal injection or infusion claim 4 , subcutaneous injection claim 4 , or implant administration.6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a gel claim 1 , ointment claim 1 , cream claim 1 , aerosol claim 1 , a semi-solid claim 1 , a solid claim 1 , a powder claim 1 , a tablet claim 1 , a suppository claim 1 , a pill claim 1 , a soft elastic capsule claim 1 , a jelly claim 1 , a hard gelatin capsule claim 1 , a solution claim 1 , a suspension claim 1 , or a combination thereof.7. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is selected from binding agents claim 1 , fillers claim 1 , lubricants claim 1 , disintegrants claim 1 , ...

Preparation method for deuterated macrocyclic compound

Provided are a compound as represented by formula (D) and a preparation method therefor, where X2 is a halogen, Pg is selected from H and an amino protecting group, such as Cbz, Boc, Fmoc, Alloc, Teoc, methoxycarbonyl or ethoxycarbonyl. Also provided are a synthesized intermediate compound of the formula (D) compound and a preparation method for the intermediate compound.

Process for Making Biologically Active Compounds and Intermediates Thereof

A process of manufacturing biologically active compounds, their analogs, pharmaceutically acceptable salts, solvates, polymorphs, isotopic variants, and intermediates thereof. Notably, the compounds of the formula IA, 1B, 1C. 1D. 1E, 1F and IG for which novel processes have been disclosed, selectively act on the cannabinoid receptors, and with high affinity. The processes for the preparation of the compounds enable the syntheses of cannabinoid modulators on a large-scale that are eco-friendly and economically viable. Additionally, the processes disclosed enable the synthesis of cannabinoid modulators with high purity and in high yield for their use in making drug substance and drug products. 8. The process of claim 1 , wherein X1 is —SO2- claim 1 , —O— or —CH2-.9. The process of claim 7 , wherein X1 is —SO2- claim 7 , —O— or —CH2-. The present invention relates to a chemical process for the preparation of compounds of one of Formulae I, IA, IB, IC, ID, IE, 1F. and 1G. and IV, IVA, IVB, IVC, V and VI and intermediates thereof.More specifically, the invention relates to a chemical process for the preparation of 5-[4-(4-cyano-1-butyn-1-yl)phenyl]-1-(2,4-dichlorophenyl)-N-(1,1-dioxido-4-thiomorpholinyl)-4-methyl-1H-pyrazole-3-carboxamide and 5-(4-(4-cyanobut-1-yn-1-yl)phenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-morpholino-1H-pyrazole-3-carboxamide and their analogs, solvates, polymorphs and isotopic variations thereof.Compounds of this class with unique pharmacological properties and therapeutic value have been disclosed in WO200674445, WO2008154015 and WO2010104488.Disclosed herein are processes for the preparation of compounds comprising, reacting a compound of Formula II with a compound of Formula III to provide a compound of Formula VII, second by reacting a compound of Formula VII with an alkyne in the presence of a palladium reagent and copper (I) iodide, in a basic medium and in an aprotic solvent to obtain a product of Formula I, third by hydrolysis of a compound ...

Deuterium-Substituted 7-Substituted-2-(Benzylamino)-6-Ozopurine Compounds and Uses Thereof

The invention relates to compounds of formula (I): The compounds are useful as antibacterial agents, especially again -associated diseases. 2. The compound of claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Y claim 1 , and Yis deuterium.4. The compound of claim 2 , wherein the level of deuterium incorporation at each of Y claim 2 , Y claim 2 , Y claim 2 , and Ydesignated as deuterium is at least 52.5% claim 2 , at least 75% claim 2 , at least 82.5% claim 2 , at least 90% claim 2 , at least 95% claim 2 , at least 97% claim 2 , at least 98% claim 2 , or at least 99%.5. The compound of claim 1 , wherein at least one of least one of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Yand Yis deuterium.7. The compound of claim 5 , wherein the level of deuterium incorporation at each of Y Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Yand Ydesignated as deuterium is at least 52.5% claim 5 , at least 75% claim 5 , at least 82.5% claim 5 , at least 90% claim 5 , at least 95% claim 5 , at least 97% claim 5 , at least 98% claim 5 , or at least 99%.8. The compound of claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Yand Yis deuterium.10. The compound of claim 8 , wherein the level of deuterium incorporation at each of Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Yand Ydesignated as deuterium is at least 52.5% claim 8 , at least 75% claim 8 , at least 82.5% claim 8 , at least 90% claim 8 , at least 95% claim 8 , at least 97% claim 8 , at least 98% claim 8 , or at least 99%.12. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.13Clostridium difficileClostridium difficile. A method of inhibiting ...

Novel organic compounds for organic light-emitting diode and organic light-emitting diode including the same

The present invention relates to a compound for organic light-emitting diodes that can operate organic light-emitting diodes at a low driving voltage and an organic light-emitting diode comprising the same and, more particularly, to a compound for use as a fluorescent host in organic light-emitting diodes, which can bring about excellent diode properties by operating organic light-emitting diodes at a low driving voltage, and an organic light-emitting diode comprising the same. 3. The organic luminescent compound as set forth in claim 1 , wherein at least one of the substituents R1 to R5 in Chemical Formula A contains a deuterium.4. The organic luminescent compound as set forth in claim 4 , wherein R1 is a deuterium and k is 5.5. The organic luminescent compound as set forth in claim 3 , wherein R2 and/or R3 is a deuterium claim 3 , and l is 2 or greater claim 3 , or m is 2 or greater.6. The organic luminescent compound as set forth in claim 3 , wherein R4 and/or R5 is a deuterium claim 3 , and n is 2 or greater or o is 2 or greater.8. An organic light-emitting diode comprising:a first electrode;a second electrode facing the first electrode; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'an organic layer interposed therebetween, wherein the organic layer contains at least one organic luminescent compound of any one of .'}9. The organic light-emitting diode as set forth in claim 8 , wherein the organic layer comprises at least one of a hole injecting layer claim 8 , a hole transport layer claim 8 , a functional layer capable of both hole injection and hole transport claim 8 , a light-emitting layer claim 8 , an electron transport layer claim 8 , and an electron injecting layer.10. The organic light-emitting diode as set forth in claim 9 , wherein the organic layer interposed between the first electrode and the second electrode is a light-emitting layer composed of a host and a dopant claim 9 , the organic luminescent compound serving as the host.11. The ...

Inhibitors of Cholesterol Ester Transfer Protein

The invention relates to novel oxazolidinones their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering cholesterol ester transfer protein inhibitors.

DEUTERATED ORGANIC COMPOUND, MIXTURE AND COMPOSITION CONTAINING SAID COMPOUND, AND ORGANIC ELECTRONIC DEVICE

The present disclosure discloses a deuterated organic compound and a formulation and an organic electronic device containing the same, wherein the deuterated organic compound has the following structural formula: 113-. (canceled)15. The organic compound according to claim 14 , wherein (S1-T1)≦0.25 eV.16. The organic compound according to claim 14 , wherein at least one H atom in at least one electron donor group D is substituted by deuterium.17. The organic compound according to claim 14 , wherein at least one H atom in at least one electron acceptor group A is substituted by deuterium.18. The organic compound according to claim 14 , wherein at least one H atom in Ar is substituted by deuterium.22. The organic compound according to claim 14 , wherein more than 20% of the H atoms are substituted by deuterium.24. A mixture comprising at least one organic compound according to and further an organic functional material selected from a hole-injection or hole-transport material claim 14 , a hole-blocking material claim 14 , an electron-injection or electron-transport material claim 14 , an electron-blocking material claim 14 , an organic host material claim 14 , a singlet emitter claim 14 , and a triplet emitter.26. The formulation according to claim 25 , wherein the organic solvent selecting from methanol claim 25 , ethanol claim 25 , 2-methoxyethanol claim 25 , dichloromethane claim 25 , trichloromethane claim 25 , chlorobenzene claim 25 , o-dichlorobenzene claim 25 , tetrahydrofuran claim 25 , anisole claim 25 , morpholine claim 25 , toluene claim 25 , o-xylene claim 25 , m-xylene claim 25 , p-xylene claim 25 , 1 claim 25 ,4-dioxahexane claim 25 , acetone claim 25 , methyl ethyl ketone claim 25 , 1 claim 25 ,2-dichloroethane claim 25 , 3-phenoxytoluene claim 25 , 1 claim 25 ,1 claim 25 ,1-trichloroethane claim 25 , 1 claim 25 ,1 claim 25 ,2 claim 25 ,2-tetrachloroethane claim 25 , ethyl acetate claim 25 , butyl acetate claim 25 , dimethylformamide claim 25 , ...

ORGANIC COMPOUNDS

The invention relates to particular deuterated substituted heterocycle fused gamma-carbolines, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HTreceptor, the serotonin transporter (SERT), pathways involving the dopamine Dand Dreceptor signaling system, and/or the μ-opioid receptor. 2. A compound according to claim 1 , wherein Z is O.3. A compound according to claim 1 , wherein Z is —C(O).4. A compound according to claim 1 , wherein Ris methyl.5. A compound according to claim 1 , wherein Ris H and Ris D.6. A compound according to claim 1 , wherein Ris D and Ris D.7. A compound according to claim 1 , wherein Ris H and Ris H.8. A compound according to claim 1 , wherein any one claim 1 , or any two claim 1 , or any three of Rto Ris D.9. A compound according to claim 1 , wherein any one claim 1 , or any two claim 1 , any three claim 1 , any four claim 1 , any five or any six of Rto Ris D.10. A compound according to claim 1 , wherein all four of Rto Ris D.11. A compound according to claim 1 , wherein all six of Rto Ris D.12. A compound according to claim 1 , in the form of a salt claim 1 , e.g. claim 1 , in the form of a pharmaceutically acceptable salt.13. A compound according to claim 1 , having greater than 50% incorporation of deuterium at one or more of the indicated positions of the structure (i.e. claim 1 , greater than 50 atom % D) claim 1 , e.g. claim 1 , greater than 60% claim 1 , or greater than 70% claim 1 , or greater than 80% claim 1 , or greater than 90% or greater than 95% claim 1 , or greater than 96% claim 1 , or greater than 97% claim 1 , or greater than 98% claim 1 , or greater than 99%.14. A pharmaceutical composition comprising a compound according to claim 1 , in free or pharmaceutically acceptable salt form claim 1 , in admixture with a pharmaceutically acceptable diluent or carrier.15. The ...

[18F] FMAU LABELING FOR PET IMAGING OF CANCER PATIENTS

Provided herein are methods and labeling kits for synthesizing 2′-deoxy-2′-[F]fluoro-5-methyl-1-beta-D-arabino-furanosyl-uracil in a one-pot reaction in compliance with CGMP. Also disclosed are labeling kits that can be assembled in an automated synthesis system to enable such a reaction. 1. A system for producing 2′-deoxy-2′-[F]fluoro-5-methyl-1-beta-D-arabinofuranosyl-uracil ([F]FMAU) comprising:2-trifluoromethane-sulfonyl-1,3,5-tri-O-benzoyl ribofuranose;2,4-bis-trimethylsilyl-5-methyl-uracil, a Friedel-Crafts catalyst, and hexamethyldisilizane;an eluent;{'sup': '18', 'an inlet for receiving [F]-fluoride fluoride produced via a cyclotron; and'}{'sup': '18', 'an [F]FMAU collection device.'}2. The system of claim 1 , wherein the Friedel-Crafts catalyst is trimethylsilyl trifluoromethanesulfonate.3. The system of claim 1 , wherein the system is configured for automated one-pot synthesis.4. The system of claim 1 , wherein the system is in compliance with CGPMs.5. The system of claim 1 , further comprising tetrabutylammonium fluoride and acetonitrile.6. The system of claim 1 , further comprising sodium methoxide and methanol.7. The system of claim 1 , further comprising a carrier claim 1 , excipient claim 1 , diluent claim 1 , or a combination thereof.8. An automated synthesis module (ASM) for synthesizing 2′-deoxy-2′[F]fluoro-5-methyl-1-beta-D-arabinofuranosyl-uracil ([F]FMAU) in compliance with CGMPs comprising:a first container for holding 2-trifluoromethane-sulfonyl-1,3,5-tri-O-benzoyl ribofuranose;a second container for holding 2,4-bis-trimethylsilyl-5-methyl-uracil, a Friedel-Crafts catalyst, and hexamethyldisilizane;a third container for holding an eluent;{'sup': '18', 'an inlet for receiving [F]-fluoride produced via a cyclotron; and'}{'sup': '18', 'a fourth container for collecting [F]FMAU.'}9. The ASM of claim 8 , wherein the Friedel-Crafts catalyst is trimethylsilyl trifluoromethanesulfonate.10. The ASM of claim 8 , wherein the system is configured for ...

POSITIVE ALLOSTERIC MODULATORS OF THE GLP-1 RECEPTOR

Described are positive allosteric modulators of the GLP-1 receptor, pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for diabetes mellitus type 2, obesity, depression, Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, cognitive dysfunction, learning disability, and asthma in a subject. 2. The compound of claim 1 , wherein W and Y are each CR.3. The compound of or claim 1 , wherein W claim 1 , X claim 1 , Y and Z are each CR.4. The compound of any one of - claim 1 , wherein R claim 1 , at each occurrence claim 1 , is independently selected from the group consisting of hydrogen claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , halogen claim 1 , C-Calkoxy claim 1 , C-Ccycloalkoxy claim 1 , cyano claim 1 , SOR claim 1 , NRR claim 1 , hydroxyl claim 1 , heterocycle claim 1 , heteroaryl claim 1 , and C-Chaloalkyl.5. The compound of any one of - claim 1 , wherein{'sup': '1', 'sub': 1', '3', '1', '3', '2', '2', '3, 'R, at each occurrence, is independently selected from the group consisting of hydrogen, C-Calkyl, halogen, C-Calkoxy, cyano, CFH, CFH, and CF.'}6. The compound of any one of - claim 1 , wherein{'sup': '1', 'R, at each occurrence, is independently selected from the group consisting of hydrogen and halogen.'}7. The compound of any one of - claim 1 , wherein{'sup': 2', 'a', 'b', 'c, 'sub': 1', '3', '2', '4', '3', '6', '1', '3', '3', '6', '2', '1', '3, 'Ris hydrogen, C-Calkyl, C-Calkenyl, C-Ccycloalkyl, halogen, C-Calkoxy, C-Ccycloalkoxy, cyano, SOR, NRR, hydroxyl, heterocycle, heteroaryl, or C-Chaloalkyl.'}8. The compound of any one of - claim 1 , wherein{'sup': '2', 'sub': 1', '3', '2', '4', '3', '6', '1', '3', '3', '6', '2', '2', '3, 'Ris hydrogen, C-Calkyl, C-Calkenyl, C-Ccycloalkyl, halogen, C-Calkoxy, C-Ccycloalkoxy, cyano, CFH, CFH, or CF.'}9. The compound of any one of - claim 1 , wherein{'sup': '2', 'sub': 1', '3', '2', '4', '1', '3', '3, 'Ris C-Calkyl, C-Calkenyl, halogen, C- ...

18/19F-LABELLED COMPOUNDS WHICH TARGET THE PROSTATE SPECIFIC MEMBRANE ANTIGEN

This disclosure relates to novel compounds comprising a zwitterionic trifluoroborate prosthetic group which target prostate-specific membrane antigen (PSMA), e.g. in prostate cancer. The compounds have Formula I, wherein each R1 is an anionic group, L is a linker and R2B-F3 is —N(R)CHBF, a pyridinium group substituted with BFor methyl BF, or an azole group substituted with methyl BF3. Methods and uses of imaging and treating PSMA-expressing cancers are also disclosed. 3. The compound of claim 1 , wherein Ris COH.7. The compound of claim 1 ,{'sup': '4', 'sub': 2', '2', '2', '2', '2', '2, 'wherein Ris absent, —CH—, —CHCH— or —CHCHCH.'}8. The compound of claim 1 ,{'sup': '5', 'wherein Ris —S—, —NHC(O)—, —C(O)—, —C(O)O— or —OC(O)—.'}13. The compound of claim 1 , in which at least one fluorine in the —BFmoiety is F.14. A method of imaging prostate specific membrane antigen (PSMA)-expressing cancer in a subject claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00013', 'claim 13'}, 'administering to the subject a composition comprising the compound of and a pharmaceutically acceptable excipient; and'}imaging tissue of the subject using positron emission tomography (PET).15. A method of treating prostate specific membrane antigen (PSMA)-expressing cancer in a subject claim 1 , the method comprising: administering to the subject a composition comprising the compound of and a pharmaceutically acceptable excipient.16. The method of claim 14 , wherein the cancer is prostate cancer claim 14 , renal cancer claim 14 , breast cancer claim 14 , thyroid cancer claim 14 , gastric cancer claim 14 , colorectal cancer claim 14 , bladder cancer claim 14 , pancreatic cancer claim 14 , lung cancer claim 14 , liver cancer claim 14 , brain tumor claim 14 , melanoma claim 14 , neuroendocrine tumor claim 14 , ovarian cancer or sarcoma. The present invention relates to novel fluorine-labeled compounds as well as uses/methods for these compounds, including but not limited to uses/ ...

PYRIDONE DERIVATIVES HAVING TETRAHYDROPYRANYLMETHYL GROUPS

The present disclosure provides novel compounds or salts thereof, or crystals of the compounds or the salts, which inhibit Axl and are useful in the treatment of a disease caused by hyperfunction of Axl, the treatment of a disease associated with hyperfunction of Axl, and/or the treatment of a disease involving hyperfunction of Axl. 2. The method of claim 1 , wherein the compound of formula (I) is administered to patient having lung cancer or non-small cell lung cancer.4. The method of claim 3 , wherein the cancer is lung cancer or non-small cell lung cancer.7. The method of claim 6 , wherein the compound of formula (I) is administered to patient having lung cancer or non-small cell lung cancer.9. The combination of claim 8 , wherein the compound of formula (I) claim 8 , or the pharmaceutically acceptable salt thereof claim 8 , and the tyrosine kinase inhibitor are separately contained in different formulations.10. The combination of claim 8 , wherein the compound of formula (I) claim 8 , or the pharmaceutically acceptable salt thereof claim 8 , and the tyrosine kinase inhibitor are contained in a single formulation.13. A methanesulfonate claim 11 , phosphate claim 11 , naphthalene-1 claim 11 ,5-disulfonate claim 11 , or sulfate of the compound of .15. The method of claim 14 , wherein the compound of formula (I) claim 14 , or the pharmaceutically acceptable salt thereof claim 14 , and the tyrosine kinase inhibitor are administered at the same time.16. The method of claim 14 , wherein the compound of formula (I) claim 14 , or the pharmaceutically acceptable salt thereof claim 14 , and the tyrosine kinase inhibitor are administered at different times.17. The method of claim 14 , wherein the cancer is lung cancer or non-small cell lung cancer. This application is a continuation of U.S. patent application Ser. No. 15/036,981, filed May 16, 2016, entitled “PYRIDONE DERIVATIVES HAVING TETRAHYDROPYRANYLMETHYL GROUPS,” which is a national stage application under 35 U.S.C. § ...

Cytotoxic Chemotherapy-Based Predictive Assays for Acute Myeloid Leukemia

The invention relates to methods, systems and kits for determining therapeutic effectiveness or toxicity of cancer-treating compounds that incorporate into or bind to DNA. In particular, the invention is directed to methods, systems and kits for predicting a patient's treatment outcome after administration of a microdose of therapeutic composition to the patient or a sample from the patient. The methods provides physicians with a diagnostic tool to segregate cancer patients into differential populations that have a higher or lower chance of responding to a particular therapeutic treatment.

Delivery System For Ayahuasca-Like Substances

Provided herein is a delivery device and vaporizable formulations that provide users or patients with the ability to safely, reliably, and conveniently obtain a high-quality, therapeutic vapor comprising an ayahuasca-like substance. The delivery device includes a chamber coupled to a power unit capable of providing power to vaporize the formulations for consumption of the substance in a consistently desirable and safe manner. Further included are kits and methods of treating psychological disorders using the delivery device and vaporizable formulations provided herein.

Process for producing Gallium-68 through the irradiation of a solution target

The present disclosure relates to a process for purifying and concentrating Ga isotope produced by the irradiation with an accelerated particle beam of a Zn target in solution. The process according to the present disclosure allows for the production of pure and concentrated Ga isotope in hydrochloric acid solution. The present disclosure also relates to a disposable cassette for performing the steps of purification and concentration of the process. 1. A process for producing and purifying Gallium radioisotope , the process comprising:irradiating a target containing a target solution comprising zinc using an accelerated particle beam;diluting the irradiated target solution with water;feeding the diluted target solution into a strong cation exchanger;washing the strong cation exchanger;eluting zinc isotopes from the strong cation exchanger with a zinc elution solution including acetone;washing the strong cation exchanger;{'sup': '68', 'eluting Gallium isotope from the strong cation exchanger with hydrochloric acid solution to obtain an eluted solution;'}feeding the eluted solution into a strong anion exchanger,washing the strong anion exchanger; and{'sup': '68', 'eluting Gallium isotope from the strong anion exchanger with hydrochloric acid solution to obtain a final solution'}wherein the irradiated target solution is diluted at least 5 volume times with water.2. The process according to claim 1 , wherein the irradiated target solution is diluted at least 10 volume times with water.3. The process according to claim 1 , further comprising:complementing the eluted solution with another hydrochloric acid solution to obtain a complemented solution, wherein the complementing is performed before feeding said the eluted solution into the strong anion exchanger.4. The process according to claim 3 , wherein the complemented solution includes a molarity in hydrochloric acid between 7 M and 10 M.5. The process according to claim 1 , wherein the accelerated particle beam is a ...

2'-HALOGENATED-4'-THIO-2'-DEOXY-5-AZACYTIDINE ANALOGS AND USE THEREOF

Halogenated analogs of 5-aza-2′-deoxycytidine, such as halogenated analogs of 5-aza-4′-thio-2′-deoxycytidine (5-aza-T-dCyd) are described. Pharmaceutical compositions including a halogenated analog and methods of using the halogenated analogs to inhibit neoplasia are described. In some examples, the halogenated analogs have a structure according to formula Ia, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof: 2. The compound of claim 1 , wherein:(i) X is F; or(ii) Y is hydrogen or F; or(iii) each R is hydrogen; or{'sup': 'a', '(iv) Ris hydrogen; or'}(v) any combination of (i), (ii), (iii), and (iv).7. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier.8. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is formulated for intravenous claim 7 , oral claim 7 , intraperitoneal claim 7 , subcutaneous claim 7 , rectal claim 7 , or buccal administration.9. A method of inhibiting a neoplasia claim 7 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting neoplastic cells with an effective amount of a compound according to .'}10. The method of claim 9 , wherein contacting the neoplastic cells with the effective amount of the compound reduces proliferation of the neoplastic cells.12. The method of claim 9 , wherein contacting the neoplastic cells with the effective amount of the compound comprises administering a therapeutically effective amount of the compound to a subject having or suspected of having a disease characterized at least in part by presence of neoplastic cells.13. The method of claim 12 , wherein the disease is a cancer.14. The method of claim 13 , wherein the cancer is a cancer of the kidney claim 13 , bladder claim 13 , breast claim 13 , colon claim 13 , endometrium claim 13 , skin claim 13 , blood claim 13 , pancreas claim 13 , prostate claim 13 , bone claim 13 , liver claim 13 , lung claim 13 , esophagus claim 13 , or central ...

N-(pyridin-2-ylsulfonyl)cyclopropanecarboxamide Derivatives and their Use in the Treatment of Disease

The invention relates to heterocyclic compounds of the formula (I), in which all of the variables are as defined in the specification; capable of modulating the activity of CFTR. The invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including Cystic fibrosis and related disorders. 4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof wherein:{'sup': '1', 'Yis N;'}{'sup': '2', 'Yis CH;'}{'sup': '3', 'sub': 9-10', '9-10', '3', '1-4', '1-4', '1-4', '1-4, 'Ris phenyl, pyridyl or Cheteroaryl, wherein said phenyl, pyridyl or Cheteroaryl, is optionally substituted with 1 to 4 substituents each independently selected from halogen, CD, Calkyl, Calkoxy, halo-substituted-Calkyl and halo-substituted-Calkoxy.'}5. The compound of claim 3 , or a pharmaceutically acceptable salt thereof wherein:{'sup': '1', 'Yis N;'}{'sup': '2', 'Yis CH;'}{'sup': '3', 'sub': 3-8', '4-7', '0-3', '3-8', '6-12', '5-6', '3-6', '3-8', '4-7', '6-12', '5-6', '3-6', '1-4', '1-4', '1-4', '1-4', '1-4, 'Ris Ccycloalkyl, Cheterocycloalkyl, —O—Calkyl-Ccycloalkyl, Cspirocycloalkyl, Cheterocycloalkene or Ccycloalkene, wherein said Ccycloalkyl, Cheterocycloalkyl, Cspirocycloalkyl, Cheterocycloalkene or Ccycloalkene, is optionally substituted with 1 to 4 substituents each independently selected from halogen, Calkyl, hydroxy, Calkoxy, halo-substituted-Calkyl, hydroxy-substituted-Calkyl and halo-substituted-Calkoxy.'}6. The compound of claim 3 , or a pharmaceutically acceptable salt thereof wherein:{'sup': '1', 'Yis N;'}{'sup': '2', 'Yis CH;'}{'sup': '3', 'sub': 1-4', '3', '1-4', '1-4', '1-4', '1-4', '1-4', '1-2, 'Ris Calkyl, CD, Calkoxy or Calkenyl, wherein said Calkyl, Calkenyl or Calkoxy is optionally substituted with 1 to 3 substituents each independently selected from ...

Vinylsulfone-based 18F-labeling Compositions and Methods and Uses Thereof

A thio-selective radioactive labeling agent has the following general formula:

DEUTERATED IBRUTINIB

The present invention in one embodiment provides a compound of Formula I: 2. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare each hydrogen.3. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare each deuterium.413.-. (canceled)14. The compound of claim 1 , wherein each Yis hydrogen and each Yis hydrogen.15. The compound of claim 1 , wherein each Yis deuterium and each Yis deuterium.17. (canceled)18. A pharmaceutical composition comprising the compound of or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.19. A method of inhibiting BTK in a cell claim 1 , comprising contacting the cell with a compound of .20. A method of treating a disease selected from the group consisting of chronic lymphocytic leukemia claim 1 , mantle cell lymphoma claim 1 , and multiple myeloma claim 1 , comprising administering to a subject in need of such treatment a compound of .21. The compound of claim 1 , wherein the deuterium incorporation at each designated deuterium atom is at least 95%.22. The compound of claim 1 , wherein the deuterium incorporation at each designated deuterium atom is at least 97%. This application is a continuation of U.S. application Ser. No. 14/418,831, which is the U.S. National Stage of International Application No. PCT/US2013/052721, which designated the United States and was filed on Jul. 30, 2013, published in English, which claims the benefit of U.S. Provisional Application No. 61/677,307, filed on Jul. 30, 2012. The entire teachings of the above applications are incorporated herein by reference.Many current medicines suffer from poor absorption, distribution, metabolism and/or excretion (ADME) properties that prevent their wider use or limit their use in certain indications. Poor ADME properties are also a major reason for the failure of drug candidates in clinical trials. While formulation technologies and prodrug strategies can be employed in some cases to improve certain ADME ...

METHOD FOR PRODUCING 4-BORONO-L-PHENYLALANINE HAVING 18F ATOM INTRODUCED THEREINTO, AND PRECURSOR OF 4-BORONO-L-PHENYLALANINE HAVING 18F ATOM INTRODUCED THEREINTO

F-labeled 4-boronophenylalanine (BPA) can be produced by preparing and further processing a precursor of F-labeled BPA represented by the following formula: 2. The compound according to claim 1 , wherein X represents F claim 1 , and M represents an alkali metal ion claim 1 , an ammonium ion claim 1 , a tetraalkylammonium ion claim 1 , a tetraarylammonium ion claim 1 , a tetraalkylphosphonium ion claim 1 , a tetraarylphosphonium ion claim 1 , or an imidazolium ion.5. The method for producing F-labeled BPA according to claim 4 , wherein X represents F claim 4 , and M represents an alkali metal ion claim 4 , an ammonium ion claim 4 , a tetraalkylammonium ion claim 4 , a tetraarylammonium ion claim 4 , a tetraalkylphosphonium ion claim 4 , a tetraarylphosphonium ion claim 4 , or an imidazolium ion. The present invention relates to a method for producing 4-borono-L-phenylalanine having 18F atom introduced thereinto (fluorinated BPA) (BPA:4-Boronophenylalanine), and precursors thereof.At present, attention has been paid to positron emission tomography (PET) as a technique that is high in sensitivity to be excellent in quantitatively determining performance and can form images easily in light of a principle thereof. This technique has widely been used. The half value period of PET diagnostic reagents (tracers) used for diagnoses is short, and the tracers are each administrated in a fine amount so that any living body is hardly exposed to radiation based thereon. Therefore, this inspecting method is a low invasive inspecting method, thus is greatly advantageous to PET. Furthermore, PET is highly sensitive even to tumors that are not easily determined by CT (computed tomography) or MRI (magnetic resonance imaging), and tumor tissues thereof can be evaluated according to images.18F-labeled BPA, in which a 18F-fluorine atom is introduced into BPA, which is a boronated amino acid used as a boron reagent for BNCT (boron neutron capture therapy), was developed as a molecular ...

LYSINE ISOTOPOLOGUES, COMPOSITIONS COMPRISING THE SAME AND METHODS OF SYNTHESIS

This invention relates to lysine isotopologues of Formulas I and 1-A, as described herein, and processes for synthesizing the same and derivatives and intermediates involved therein. In one aspect, described herein is a chemical compound comprising an isotopically labeled analog, i.e., an isotopologue of a standard or naturally occurring lysine. The lysine isotopologue is synthetically formed to have stable isotopes of elements incorporated at selected positions. As such, the lysine isotopologue has a molecular mass different from the mass of a standard or naturally occurring lysine. 2. The compound of claim 1 , wherein C claim 1 , Cand Care C.3. The compound of claim 1 , wherein at least four of C claim 1 , C claim 1 , C claim 1 , C claim 1 , Cand Care C.4. The compound of claim 1 , wherein C claim 1 , C claim 1 , Cand Care C.5. The compound of claim 1 , wherein C claim 1 , C claim 1 , Cand Care C.6. The compound of claim 1 , wherein at least five of C claim 1 , C claim 1 , C claim 1 , C claim 1 , Cand Care C.7. The compound of claim 1 , wherein C claim 1 , C claim 1 , C claim 1 , Cand Care C.8. The compound of claim 1 , wherein C claim 1 , C claim 1 , C claim 1 , Cand Care C.98. The compound of any one of - claims 1 , wherein at least two of H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , Hand Hare H.108. The compound of any one of - claims 1 , wherein Hand Hare H.118. The compound of any one of - claims 1 , wherein Hand Hare H.128. The compound of any one of - claims 1 , wherein at least four of H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , Hand Hare H.138. The compound of any one of - claims 1 , wherein H claims 1 , H claims 1 , Hand Hare H.148. The compound of any one of - claims 1 , wherein at least six of H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , H claims 1 , Hand Hare 2H.1514. The compound of any one of - claims 1 , wherein Nis N.1614. ...

DEUTERIUM-SUBSTITUTED OXADIAZOLES

Described are deuterated modulators of S1P1 receptors, pharmaceutical compositions thereof, and methods of use thereof. 156-. (canceled)58. The compound as recited in claim 57 , wherein Ris deuterium.59. The compound as recited in claim 57 , wherein R-Rare deuterium.60. The compound as recited in claim 57 , wherein R-Rare deuterium.61. The compound as recited in claim 57 , wherein Ris deuterium.62. The compound as recited in claim 57 , wherein Rand Rare deuterium.63. The compound as recited in claim 57 , wherein R-Rare deuterium.64. The compound as recited in claim 57 , wherein R-Rare deuterium.65. The compound as recited in claim 57 , wherein R-Rare deuterium.66. The compound as recited in claim 57 , wherein Rand R-Rare deuterium.67. The compound as recited in claim 57 , wherein R-Rand R-Rare deuterium.68. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 10%.73. The compound as recited in claim 72 , wherein each position represented as D has deuterium enrichment of no less than about 10%.74. The compound as recited in claim 73 , wherein each position represented as D has deuterium enrichment of no less than about 10%.75. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier.76. A method of treatment or prevention of a S1P1 receptor-mediated disorder comprising the administration claim 57 , to a patient in need thereof claim 57 , of a therapeutically effective amount of a compound as recited in . This application claims the benefit of U.S. Provisional Application No. 62/143,489, filed on Apr. 6, 2015, the disclosure of which is hereby incorporated by reference in its entirety.Disclosed herein are new oxadiazole compounds and compositions and their application as pharmaceuticals for the treatment or prevention of disorders. Methods of modulation of sphingosine-1-phosphate subtype 1 receptor (S1P1 receptor) activity in a subject are also ...

2-(2,4,5-SUBSTITUTED ANILINE) PYRIMIDINE DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE THEREOF

Disclosed are a 2-(2,4,5-substituted aniline) pyrimidine derivative, a pharmaceutical composition and a use thereof. The pharmaceutical composition comprises a therapeutically effective amount of the 2-(2,4,5-substituted aniline) pyrimidine derivative, a solvate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Also disclosed is a use of the 2-(2,4,5-substituted aniline) pyrimidine derivative, a solvate, or a pharmaceutically acceptable salt thereof in the preparation of drugs for treating cancers. The compounds of the present invention have a relatively high solubility in water and a relatively high permeability, and/or a relatively low binding ability to plasma proteins, and at the same time have a relatively low toxicity characteristic and a relatively high anti-tumor activity. 2. The 2-(2 claim 1 ,4 claim 1 ,5-substituted aniline)pyrimidine derivative represented by formula I claim 1 , or the solvate claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein claim 1 , the methyl substituted by 1 to 3 of deuterium atom(s) is a tri-deuterated methyl.3. The 2-(2 claim 1 ,4 claim 1 ,5-substituted aniline)pyrimidine derivative represented by formula I claim 1 , or the solvate claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , which is selected from the group consisting of{'sub': '3', 'N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-(D-methyl)indol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-dimethylaminoethyl-methylamino}-4-(D-methoxy)-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-dimethylaminoethyl-(D-methyl)amino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-di(D-methyl)aminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-[methyl(D-methyl)amino]ethyl- ...

Deuterated tic10

This invention relates to novel imidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one compounds, and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions alone or in combination with other therapeutics in the treatment of diseases and conditions that are beneficially treated by administering an inducer of the gene encoding tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) superfamily member 10.

DEUTERATED IDEBENONE

The present invention in one embodiment provides a compound of Formula I: 2. The compound of claim 1 , wherein each of R claim 1 , Rand Ris independently selected from CHand CD.3. The compound of claim 1 , wherein each Yis deuterium.4. The compound of claim 1 , wherein each Yis hydrogen.5. The compound of claim 1 , wherein each Yis hydrogen.6. The compound of claim 1 , wherein each Yis deuterium.7. The compound of claim 1 , wherein each Yis hydrogen.8. The compound of claim 1 , wherein each Yis deuterium.9. The compound of claim 1 , wherein Ris CH.10. The compound of claim 1 , wherein Ris CD.11. The compound of claim 1 , wherein Ris CH.12. The compound of claim 1 , wherein Ris CD.13. The compound of claim 1 , wherein Ris CH.14. The compound of claim 1 , wherein Ris CD.15. The compound of claim 1 , wherein each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; and each Yis deuterium.19. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.20. A pharmaceutical composition comprising the compound of or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.21. A method of reducing oxidative toxicity in mitochondria claim 1 , comprising contacting mitochondria with a compound of .22. A method of treating a condition that is Duchenne's muscular dystrophy or multiple sclerosis claim 1 , comprising administering to a subject in need of such treatment a compound of .23. The method of claim 22 , wherein the condition is primary progressive multiple sclerosis. This application is a continuation of U.S. application Ser. No. 14/414,039, filed on Jan. 9, 2015, which is the U.S. National Stage of International Application No. PCT/US2013/050302, filed on Jul. 12, 2013, published in English, which claims the benefit of U.S. Provisional Application No. 61/670,716, ...

ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION HAVING ANTICANCER ACTIVITY

The invention provides a compound of formula (I): 2. A compound according to claim 1 , or a tautomer or a solvate or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris:{'sub': 1-4', '2-4', '1-4, 'sup': '1', '(i) halogen, hydroxy, nitrile, Calkyl, Calkynyl, or Calkoxy, for example wherein n is 1 and Ris chloro or nitrile e.g. chloro; or'}{'sub': 1-4', '1-4', '1-4', '2-6', '1-4', '1-4', '2-4', '2', 'v', '2', '0,1', 'v', '2', '1-4', '2', 'v', '1-4', '2', '2', 'd', '1-6', 'd', 'd', '2, 'sup': x', 'y', 'x', '8, '(ii) hydroxy, halogen, nitrile, Calkyl, haloCalkyl, hydroxyCalkyl, Calkenyl, Calkoxy, haloCalkoxy, Calkynyl, —(CH)—COH, —O—(CRR)—COCalkyl, —(CH)—CON(Calkyl), —P(═O)(R), —S(O)—Calkyl, —S(O)-heterocyclic group with 3 to 6 ring members or —S(O)—N(R).'}36-. (canceled)7. A compound according to claim 1 , or a tautomer or a solvate or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris:{'sub': 1-4', '2-6', '1-4, '(i) hydrogen, Calkyl, Calkenyl, or hydroxyCalkyl; or'}{'sup': x', 'y, 'sub': u', '2', '2', '2', '2', '2', '3', '2', '3', '2', '2, '(ii) hydrogen or —(RR)—COH (e.g. —COOH, —CHCOOH, —CHCH—COH, —(CH(CH))—COH or —(C(CH)—COH).'}8. (canceled)9. A compound according to claim 1 , or a tautomer or a solvate or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 3', 'x', 'y, 'sub': t', 'q', '3-6, '(i) Ris -(A)-(CRR)—X and A is either a Ccycloalkyl group e.g. a cyclopropyl group or a heterocyclic group with 3 to 5 ring members e.g. a heterocyclic group with 5 ring members; or'}{'sup': 3', 'x', 'y, 'sub': t', 'q, '(ii) Ris -(A)-(CRR)—X and A is a heterocyclic group with 3 to 5 ring members e.g. a heterocyclic group with 5 ring members.'}10. (canceled)11. A compound according to claim 1 , or a tautomer or a solvate or a pharmaceutically acceptable salt thereof claim 1 , wherein s is 0 or 1.12. (canceled)13. A compound according to claim 1 , or a tautomer or a solvate or a pharmaceutically acceptable salt thereof claim 1 , wherein ...

STABILISED RADIOLABELLING REACTION

The present invention provides a method for the synthesis of an injectable composition comprising a [F]-labelled pyridaben derivative that is advantageous over prior methods. In particular, the method of the present invention comprises a method of radiosynthesis that permits a more facile purification using solid phase extraction (SPE). 1. A method comprising reacting a precursor compound with F-fluoride in the presence of (2 ,2 ,6 ,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) to obtain an F-labelled compound wherein: {'br': None, 'BTM-LINKER-LG \u2003\u2003(I)'}, 'said precursor compound is of Formula Iwherein:BTM is an analogue of pyridaben;LINKER is an alkylene or an alkoxyalkylene; and,LG is a sulfonate-containing leaving group; and{'sup': '18', 'claim-text': {'br': None, 'sup': '18', 'BTM-LINKER-F \u2003\u2003(II)'}, 'said F-labelled compound is of Formula IIwherein BTM and LINKER are as defined for Formula I.3. The method as defined in wherein Ris Calkyl.4. The method as defined in wherein Ris methyl claim 2 , ethyl claim 2 , propyl claim 2 , n-butyl claim 2 , s-butyl claim 2 , or t-butyl.5. The method as defined in wherein Ris halo.6. The method as defined in wherein Ris chloro.7. The method as defined in wherein W is heteroalkylene.8. The method as defined in wherein W is alkoxyalkylene.11. The method as defined in wherein LG is selected from mesylate claim 1 , tosylate claim 1 , triflate claim 1 , nosylate claim 1 , or 1 claim 1 ,2-cyclic sulfate.12. The method as defined in wherein LG is tosylate.13. The method as defined in wherein said precursor compound is dissolved in acetonitrile.14. The method as defined in wherein said TEMPO is present in a molar ratio to the precursor compound of between 0.01:1 and 5:1.15. The method as defined in wherein the starting radioactivity is at least 100 GBq.16. The method as defined in wherein the starting radioactivity is between 100-1000 GBq.17. The method as defined in wherein the starting radioactivity is between 100-750 ...

RADIOLABELING OF POLYPEPTIDES

Improved methods of radiolabeling antibodies using click chemistry are described. Also described are pharmaceutical compositions and uses related to the radiolabeled antibodies produced by the methods. 1. A method of labeling a polypeptide with a radiometal ion , the method comprising:a. providing a modified polypeptide comprising the polypeptide covalently linked to a first click reaction partner;b. providing a radiocomplex comprising the radiometal ion associated with a chelating moiety, wherein the chelating moiety comprises a chelant covalently linked to a second click reaction partner; andc. contacting the modified polypeptide with the radiocomplex under a condition to allow the first click reaction partner to react with the second click reaction partner to thereby label the polypeptide with the radiometal ion.2. The method of claim 1 , wherein one of the first and second click reaction partners comprises an alkyne group claim 1 , and the other click reaction partner comprises an azide claim 1 , or wherein one of the first and second click reaction partners comprises an alkene group claim 1 , and the other click reaction partner comprises a diene.3. The method of claim 1 , wherein the polypeptide is an antibody claim 1 , or an antigen binding fragment thereof.4. The method of claim 3 , wherein the antibody is an anti-PSMA monoclonal antibody.5. The method of claim 1 , wherein the radiometal ion is Ac claim 1 , In or Zr.6. The method of claim 1 , further comprising reacting an electrophile on a side chain with a sulfhydryl group covalently linked to the first click reaction partner to obtain the modified polypeptide.7. The method of claim 1 , wherein the modified polypeptide is a modified antibody or antigen binding fragment thereof obtained by a site-specific incorporation of the first click reaction partner.8. The method of claim 7 , wherein the modified antibody or antigen binding fragment thereof is obtained by a method comprising trimming an antibody or ...

DEUTERATED BENZIMIDAZOLE COMPOUND AND MEDICAL USE THEREOF

The present invention relates to a medicament for treating or preventing a disease involving Na channel, for example, neuropathic pain, nociceptive pain, inflammatory pain, small-fiber neuropathy, erythromelalgia, paroxysmal extreme pain disorder, dysuria, or multiple sclerosis, comprising a compound of formula (I) wherein R, R, R, and Rare hydrogen, halogen, cyano, Calkyl, Calkoxy, etc., provided that at least one of R, R, Rand Ris the above Caryl, Caryloxy, etc., Rand Rare hydrogen, Calkyl, Ccycloalkyl, etc., Ris hydrogen, Calkyl, Ccycloalkyl, etc., m is 0, 1, or 2, L is CRR, Rand Rare hydrogen, hydroxy group, Calkyl, Calkoxy, etc., or a pharmaceutically acceptable salt thereof. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1a', '1b', '1c', '1d, 'sub': 1-4', '1-4', '6-10', '6-10', '1-4', '1-4', '1-4, 'R, R, R, and Rare independently, hydrogen, halogen, cyano, Calkyl, Calkoxy (wherein the alkyl and the alkyl moiety in the alkoxy may be independently substituted with 1 to 3 the same or different halogen atoms), Caryl, Caryloxy, 5- to 12-membered heteroaryl, or 5- to 12-membered heteroaryloxy (wherein the aryl and the aryl moiety in the aryloxy, and the heteroaryl and the heteroaryl moiety in the heteroaryloxy may be independently substituted with 1 to 3 substituents selected independently from the group consisting of halogen, cyano, Calkyl optionally-substituted with 1 to 3 substituents selected independently from Substituent-group A, Calkoxy optionally-substituted with 1 to 3 substituents selected independently from Substituent-group A, and Calkylsulfonyl optionally-substituted with 1 to 3 substituents selected independently from Substituent-group A).'}3. The compound of or or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1a', '1b', '1c', '1d, 'sub': 6-10', '6-10', '1-4', '1-4, 'R, R, R, and Rare independently, hydrogen, Caryl, Caryloxy, 5- to 12-membered heteroaryl, or 5- to 12-membered ...

PET Imaging Agents

Preparation of novel 2-benzyl-5-methyl-2H-tetrazole derivatives of the formula (I) for use as PET imaging agents. The present invention relates to novel compounds of formula (I) their preparation and use as PET imaging agents for imaging techniques and diagnostics in the field of diseases and disorders mediated by or related to the enzyme autotaxin.

DEUTERATED sGC STIMULATORS

This invention relates to deuterated compounds of Formula I, and pharmaceutically acceptable salts thereof. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Yand Yis deuterium.3. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Yand Yis deuterium.4. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Yand Yis deuterium.5. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Yand Yis deuterium.6. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Y claim 1 , Y claim 1 , Yand Yare the same.7. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Yand Yare the same.8. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Yand Yare the same.9. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Yand Yare the same.10. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.11. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.12. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.13. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.14. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.15. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.18. The compound of claim 1 , wherein{'sup': 1', '2', '3', '4', '1', '2', '3', '4, 'when any one of Y, Y, Yand Yis deuterium, the level of deuterium incorporation at each of Y, Y, Yand Ydesignated as deuterium is at least 52.5%, at least 75%, at least 82.5%, at least 90%, at least 95%, at least 97%, at least 98%, or at least 99%;'}{'sup': 5a ...

DEUTERATED sGC STIMULATORS

This invention relates to deuterated compounds of Formula I, and pharmaceutically acceptable salts thereof. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Yand Yis deuterium.3. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Yand Yis deuterium.4. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Yand Yis deuterium.5. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Yand Yis deuterium.6. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one of Yand Yis deuterium.7. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Y claim 1 , Y claim 1 , Yand Yare the same.8. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Yand Yare the same.9. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Yand Yare the same.10. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein each of Yand Yare the same.11. (canceled)12. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.13. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.14. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.15. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium.16. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis deuterium or Yis deuterium.17. (canceled)20. The compound of claim 1 , wherein{'sup': 1', '2', '3', '4', '1', '2', '3', '4, 'when any one of Y, Y, Yand Yis deuterium, the level of deuterium incorporation at each of Y, Y, Yand Ydesignated as deuterium is at least 52.5%, at least 75%, at least 82.5%, at least 90%, at ...

METHODS AND REAGENTS FOR RADIOLABELING

The present invention provides methods for radiolabeling compounds useful as Hsp90 inhibitors. The present invention also provides intermediates useful in such methods, and compositions of radiolabeled compounds. The present invention provides, among other things novel methods for the synthesis of radiolabeled compounds. In certain embodiments, the present invention provides compounds of formula I. 190-. (canceled)93. The method of claim 92 , wherein Z claim 92 , Z claim 92 , and Zare —N—.94. The method of claim 93 , wherein Yis —CR—.95. The method of claim 94 , wherein Yis —CR—.96. The method of claim 95 , wherein each of Ris hydrogen.97. The method of claim 96 , wherein X is —CH— or —S—.98. The method of claim 97 , wherein X is —CH—.99. The method of claim 97 , wherein X is —S—.100. The method of claim 97 , wherein Ris hydrogen.101. The method of claim 97 , wherein Ris halogen.102. The method of claim 101 , wherein Ris fluoro.103. The method of claim 96 , wherein -L-Rcomprises a methylene that is replaced with —NH— to form a secondary amine.104. The method of claim 97 , wherein L is a Caliphatic group claim 97 , wherein a methylene of the aliphatic group is replaced with —NH— to form a secondary amine.105. The method of claim 104 , wherein L is a Caliphatic group claim 104 , wherein a methylene of the aliphatic group is replaced with —NH— to form a secondary amine.108. The method of claim 96 , wherein two Rgroups are taken together with their intervening atoms to form Ring A claim 96 , wherein Ring A is a 5- to 6-membered partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen claim 96 , nitrogen claim 96 , or sulfur claim 96 , 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen claim 96 , nitrogen claim 96 , or sulfur claim 96 , or 6-membered aryl.109. The method of claim 108 , wherein Ring A is a 5-membered partially unsaturated monocyclic heterocyclyl having 2 heteroatoms selected from oxygen.110. The method ...

Tracer Substances for SVC Analysis

The present invention relates to novel tracer substances useful in the analysis for semi-volatile organic contaminants (SVCs) such as PCBs (polychlorinated biphenyls). The invention also describes methods for establishing multilayered sealant barriers towards SVCs, which barriers contain said tracer substances, and methods for assessing the integrity of such barriers. 4. (canceled)5. A coating composition comprising the following three components: {'br': None, 'sub': 1', '2', '3, 'R—Si(OR)'}, '1. an epoxysiloxane of formula'} [{'sub': 1', '5', '30, 'Ris a Cto Calkyl group containing one or more epoxy groups and'}, {'sub': 2', '1', '6, 'Ris a Cto Calkyl group, and'}], 'wherein'} {'br': None, 'sub': 3', '4', '3, 'R—Si(OR)'}, '2. an aminosiloxane of formula'} [{'sub': 3', '5', '30, 'Ris a Cto Calkyl group containing one or more amino groups and'}, {'sub': 4', '1', '6, 'Ris a Cto Calkyl group, and'}], 'wherein'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '3. a compound of Formula I as defined in .'}6. A process for treating surfaces comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a. forming a first barrier over a surface, the first barrier comprising a first coating composition and a compound of Formula I as defined in a , and'}b. once the first barrier has cured, forming a second barrier over the first barrier, the second barrier comprising a second coating composition, andc. once the second barrier has cured, forming a third barrier over the second barrier, the third barrier comprising a third coating composition.7. A process for treating surfaces according to claim 6 , wherein the first coating composition is a coating composition comprising the following three components: {'br': None, 'sub': 1', '2', '3, 'R—Si(OR)'}, '1. an epoxysiloxane of formula'} [{'sub': 1', '5', '30, 'Ris a Cto Calkyl group containing one or more epoxy groups and'}, {'sub': 2', '1', '6, 'Ris a Cto Calkyl group, and'}], 'wherein'} {'br': None, 'sub': 3', '4', '3 ...

Disconnector Device

The present invention relates to an automated radiosynthesis device adapted for enhanced automatic disconnection of a disposable kit once a radiosynthesis has been carried out. The automated radiosynthesis device of the invention therefore reduces the time to remove the disposable kit from the radiosynthesis device and reduces radiation exposure to the operator. 21. The automated radiosynthesis device as defined in claim , wherein said plurality of connectors is selected from the group comprising fasteners , and fluidic connectors.3. The automated radiosynthesis device as defined in claim 2 , wherein said fluidic connectors are selected from the group comprising push-on type connectors luer slip connectors and luer screw connectors.41. The automated radiosynthesis device as defined in claim claim 2 , wherein said disposable kit is suitable for the synthesis of a radiotracer compound.5. The automated radiosynthesis device as defined in claim 4 , wherein said radiotracer compound is a positron-emission tomography (PET) tracer.6. The automated radiosynthesis device as defined in claim 5 , wherein said radiotracer compound is an F-labelled PET tracer.71. The automated radiosynthesis device as defined in claim claim 5 , wherein said disposable kit is a single-use cassette.81. The automated radiosynthesis device as defined in claim claim 5 , wherein said plurality of actuators is selected from the group comprising rotatable arms for stopcocks of valves claim 5 , linear actuators claim 5 , arms that press onto reagent vials and pinch valves.91. The automated radiosynthesis device as defined in claim claim 5 , wherein said moving parts of said disposable kit are selected from the group comprising reagent vials claim 5 , syringes and valves.101. The automated radiosynthesis device as defined in claim claim 5 , wherein said control unit includes software comprising instructions for a particular radiosynthesis method to be carried out on said disposable kit attached to said ...

HETEROBIARYL COMPOUNDS AND IMAGING AGENTS FOR IMAGING HUNTINGTIN PROTEIN

Provided herein are certain compounds and imaging agents useful for detecting a disease or condition associated with protein aggregation, compositions thereof, and methods of their use. 5. The compound of claim 1 , wherein Xis oxo-heterocyclyl.1012.-. (canceled)13. The compound of claim 1 , wherein Xis heteroaryl.14. (canceled)15. The compound of claim 1 , wherein Xis phenyl.16. (canceled)17. The compound of claim 1 , wherein Xis heteroaryl.18. (canceled)19. The compound of claim 1 , wherein Ris hydrogen.20. The compound of claim 1 , wherein Ris hydrogen.21. The compound of claim 1 , wherein Ris hydrogen.22. The compound of claim 1 , wherein each Ris independently halo claim 1 , cyano claim 1 , Calkyl claim 1 , or Calkoxy.23. The compound of claim 1 , wherein each Ris independently halo claim 1 , Calkyl claim 1 , or Calkoxy.24. The compound of claim 1 , wherein n is 0.25. The compound of claim 1 , wherein n is 1.26. The compound of claim 1 , wherein n is 1 and each Ris hydrogen.27. A compound selected from those in Table 1 claim 1 , or an isotopically enriched analog claim 1 , pharmaceutically acceptable salt claim 1 , prodrug claim 1 , tautomer claim 1 , stereoisomer claim 1 , or a mixture of stereoisomers thereof claim 1 , optionally wherein the compound is labeled with one or more radioactive isotopes.28. The compound of claim 2 , wherein the compound is labeled with one or more radioactive isotopes.29. The compound of claim 1 , wherein the compound contains one or more positron-emitting radioactive isotopes selected from C claim 1 , N claim 1 , O claim 1 , and F.30. An imaging agent comprising the compound of claim 29 , or an isotopically enriched analog claim 29 , pharmaceutically acceptable salt claim 29 , prodrug claim 29 , tautomer claim 29 , stereoisomer claim 29 , or a mixture of stereoisomers thereof.31. A method of generating diagnostic images in an individual comprising administering an effective amount of a compound of to an individual claim 1 , and ...

AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSES

Compounds having the following formula I: 2. A compound of claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris —C(O)R; or Calkyl claim 1 , Ccycloalkyl claim 1 , phenyl claim 1 , pyrazolyl claim 1 , thiazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyridazinyl claim 1 , pyrazinyl claim 1 , quinolinyl or pyrrolopyridinyl claim 1 , each group substituted by 0-4 groups selected from R.3. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein both Rand Rare hydrogen.5. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris pyrazolyl claim 1 , thiazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyridazinyl claim 1 , pyrazinyl or quinolinyl claim 1 , each group substituted with 0-3 R.6. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris —C(O)R; or Calkyl claim 1 , Ccycloalkyl or phenyl substituted with 0-3 R.8. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris phenyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , triazolyl claim 1 , oxadiazolyl claim 1 , pyrimidinyl claim 1 , tetrazolyl claim 1 , pyrazolyl claim 1 , thiazolyl claim 1 , furanyl claim 1 , or pyranyl claim 1 , each group substituted with 0-4 R. (Especially phenyl substituted with 0-4 R).9. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein:{'sup': 3a', 'b', '11', '11', 'b', 'c', 'b', 'c', 'b', 'a', 'a, 'sub': 2', '3', '2', '11', '11', 'p', 'p', '1-6, 'Rat each occurrence independently is hydrogen, Ph, CN, NH, OCF, OR, halo, cycloalkyl, C(O)NRR, S(O)NRR, C(O)R, SOR, NRSOR, NRC(O)R, haloalkyl, CN, 5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, S or O substituted with 0-3 Rand Calkyl substituted ...

OPIOID RECEPTOR MODULATING OXABICYCLO[2.2.2]OCTANE MORPHINANS

The application is directed to compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein R, R, Y, Z, and G are defined as set forth in the specification. The invention is also directed to use of compounds of Formula (I), and pharmaceutically acceptable salts and solvates thereof, to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. Certain compounds of the present invention are especially useful for treating pain. 4. The compound of any one of - , or a pharmaceutically acceptable salt or solvate thereof , wherein Ris hydrogen , hydroxy , halo , cyano , carboxy , or aminocarbonyl; or alkyl , alkenyl , alkynyl , alkoxy , alkenyloxy , or alkynyloxy , any of which is optionally substituted with 1 , 2 , or 3 substituents , each independently selected from the group consisting of hydroxy , halo , haloalkyl , amino , alkylamino , dialkylamino , carboxy , alkoxy , alkoxycarbonyl , aryl , heteroaryl , heterocyclo , cycloalkyl , and cycloalkenyl , wherein said aryl , heteroaryl , heterocyclo , cycloalkyl , and cycloalkenyl are optionally substituted with 1 , 2 , or 3 independently selected Rgroups.5. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein Ris hydroxy or unsubstituted Calkoxy claim 4 , preferably unsubstituted Calkoxy claim 4 , further preferably methoxy.6. The compound of any one of - claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein Ris —O-PG.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein PG is selected from the group consisting of alkyl claim 6 , arylalkyl claim 6 , heterocyclo claim 6 , (heterocyclo)alkyl claim 6 , acyl claim 6 , silyl claim 6 , and carbonate claim 6 , any of which is optionally substituted.8. The compound of claim 7 , or a pharmaceutically acceptable salt or solvate thereof claim 7 , wherein PG is selected from ...

CONDENSED 5-OXAZOLIDINONE DERIVATIVE

Provided are condensed 5-oxazolidinone derivatives and pharmaceutically permissible salts thereof, which have excellent anticoagulant effects, are well absorbed orally, and are useful as therapeutic drugs for thrombosis, etc. Compounds represented by formula (1) and pharmaceutically permissible salts thereof. [In the formula, L represents a C-Calkylene group that may be substituted; Rand Reach independently represent a hydrogen atom or C-Calkyl group, etc. that may be substituted; Xrepresents N or CR; Rand Reach independently represent a hydrogen atom, halogen atom, or C-Calkyl group; Rrepresents a C-Ccycloalkyl group, etc. that may be substituted; and Rrepresents a hydrogen atom, etc.] 3. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein L is a Calkylene group which may be optionally substituted by 1 to 3 fluorine atoms.7. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare each independently a hydrogen atom or a Calkyl group which may be optionally substituted by 1 to 3 identical or different halogen atoms.8. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rform claim 1 , together with the carbon atom bonded thereto claim 1 , a 4- to 7-membered cycloalkane ring or a 4- to 7-membered saturated heterocyclic ring wherein the 4- to 7-membered cycloalkane ring and the 4- to 7-membered saturated heterocyclic ring may be each optionally substituted by 1 to 4 identical or different groups selected from the group consisting of a halogen atom and Calkyl.9. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein L is a Calkylene group substituted by 1 to 3 fluorine atoms.14. The compound according to or a pharmaceutically acceptable salt thereof claim 10 , wherein Rand Rare each independently a hydrogen atom or a Calkyl group which may be optionally substituted by 1 to 3 identical or different halogen atoms. ...

ARYL SUBSTITUTED INDOLES AND THE USE THEREOF

The invention relates to aryl and heteroaryl substituted compounds of Formula (I), and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein G, R, and Z-Zare defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain. 160-. (canceled)62. (canceled)6474-. (canceled)75. A pharmaceutical composition claim 61 , comprising the compound of claim 61 , or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , and a pharmaceutically acceptable carrier.7679-. (canceled)80. A method for treating pain in a mammal claim 61 , comprising administering an effective amount of a compound as claimed in or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , to a mammal in need of such treatment.81. (canceled)82. The method of claim 80 , wherein the method is for preemptive or palliative treatment of pain.83. The method of claim 80 , wherein said pain is selected from the group consisting of chronic pain claim 80 , inflammatory pain claim 80 , neuropathic pain claim 80 , postsurgical pain claim 80 , acute pain claim 80 , and surgical pain.84. A method of modulating sodium channels in a mammal claim 61 , comprising administering to the mammal at least one compound as claimed in or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof claim 61 , wherein Na1.7 sodium channel is modulated.85. (canceled)86. A compound as claimed in claim 61 , wherein the compound is H claim 61 , C claim 61 , or C radiolabeled claim 61 , or a pharmaceutically acceptable salt claim 61 , prodrug or solvate thereof.8791-. (canceled)92. A pharmaceutical composition claim 63 , comprising the compound of claim 63 , or a pharmaceutically acceptable salt claim 63 , prodrug or solvate thereof claim 63 , and a pharmaceutically ...

ISOTOPOLOGUES OF 2-(TERT-BUTYLAMINO)-4-((1R,3R,4R)-3-HYDROXY-4-METHYLCYCLOHEXYLAMINO)-PYRIMIDINE-5-CARBOXAMIDE

Provided herein are isotopologues of Compound A, which are enriched with isotopes such as, for example, deuterium. Pharmaceutical compositions comprising the isotope-enriched compounds, and methods of using such compounds are also provided. Embodiments provided herein encompass isotopologues of Compound A and pharmaceutically acceptable salts, stereoisomers, tautomers, solid forms, polymorphs, hydrates, clathrates, and solvates thereof. 3. The compound of claim 1 , wherein the isotopologues are deuterium-enriched.5. The compound of claim 4 , wherein one of Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , and Yis isotopically enriched with deuterium claim 4 , and the others are non-enriched hydrogens.6. The compound of claim 4 , wherein two of Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , Y claim 4 , and Yare isotopically enriched with deuterium claim 4 , and the others are non-enriched hydrogens.8. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof.9. A method of treating claim 1 , managing or preventing a disease or disorder comprising administering to a patient a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein the disease or disorder is cancer claim 1 , cardiovascular disease claim 1 , inflammatory disease claim 1 , autoimmune disease or a metabolic disorder. This application claims the benefit of U.S. Provisional Application No. 62/109,096, filed Jan. 29, 2015, the entire content of which is incorporated herein by reference.Provided herein are isotopologues ...

NOVEL COMPOUNDS FOR THE TREATMENT OF HEPATITIS C

The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV. 3. A compound of where Ris deuterated alkyl or deuterated alkoxy.4. A compound of where Ris cyano.5. A compound of where Aris phenyl or pyridinyl substituted with 1 CON(R)(R) and also with 0-3 substituents selected from cyano claim 1 , halo claim 1 , deuterated alkyl claim 1 , and deuterated alkoxy.6. A compound of where Aris phenyl or pyridinyl substituted with 1 CON(R)(R) and with 1 deuterated alkoxy substituent.7. A compound of where Aris pyrimidinyl claim 1 , oxadiazolyl claim 1 , thiadiazolyl claim 1 , or imidazopyridinyl.11. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.12. A method of treating hepatitis C infection comprising administering a therapeutically effective amount of a compound of to a patient. This application claims priority to Provisional Patent Application U.S. Ser. No. 62/119,550 filed Feb. 23, 2015, hereby incorporated by reference in its entirety.The disclosure generally relates to the novel compounds of formula I, including their salts, which have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV. The disclosure also relates to compositions and methods of using these compounds.Hepatitis C virus (HCV) is a major human pathogen, infecting an estimated 170 million persons worldwide—roughly five times the number infected by human immunodeficiency virus type 1. A substantial fraction of these HCV infected individuals develop serious progressive liver disease, including cirrhosis and hepatocellular carcinoma (Lauer, G. M.; Walker, B. D. 2001, 345, 41-52).HCV is a positive-stranded RNA virus. Based on a comparison of the deduced amino acid sequence and the extensive ...

CARBOXYLIC ACID COMPOUND, METHOD FOR PREPARATION THEREOF, AND USE THEREOF

The present invention relates to the technical field of medicine, and specifically relates to the carboxylic acid compound represented by the chemical formula I or chemical formula II, and a pharmaceutically acceptable salt, a prodrug, and a solvate thereof, and a method for preparation thereof, as well as a pharmaceutical composition containing the described substances, and a use thereof. 116-. (canceled)27. A pharmaceutical composition comprising the carboxylic acid compound according to claim 17 , or a pharmaceutically acceptable salt thereof claim 17 , and a pharmaceutically acceptable carrier. The invention relates to pharmaceutical technical field, specifically, to carboxylic acid compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof and preparation methods thereof, and to pharmaceutical compositions comprising the same and uses thereof.Uric acid is the final metabolite of diet and purine in human body. In vivo environment (pH 7.4, 37 degrees), uric acid is present in blood mainly in the form of sodium salt of uric acid, the serum uric acid value of normal people is generally lower than 6 mg/dL. When uric acid in serum exceeds 7 mg/dL (Shi, et al., Nature 2003, 425: 516-523), sodium salt of uric acid will crystallize out and precipitate on joints and other parts of the body, and result in disorders such as gout, urinary stones, kidney stones, etc. Patients with gout are often accompanied with other complications, including hypertension, diabetes, hyperlipidemia, dyslipidemia, atherosclerosis, obesity, metabolic disease, nephropathy, cardiovascular disease, and respiratory disease, etc. (Rock, Et al., Nature Reviews Rheumatology 2013, 9: 13-23). In 2002, Japanese scientists Endou group reported that anion transport channel protein URAT1 is a major protein responsible for reabsorption of uric acid in kidney, they also found that the blood uric acid in people with URAT1 gene mutation (causing the synthesis of such protein being ...

9h-pyrrolo-dipyridine derivatives

The invention relates to 9H-pyrrolo-dipyridine derivatives of formula I, processes for preparing them, pharmaceutical compositions containing them and their use as radiopharmaceuticals in particular as imaging agents for the detection of Tau aggregates.

N-SUBSTITUTED 8-[(2,6-DIFLUOROBENZYL)OXY]-2,6-DIMETHYLIMIDAZO[1,2-A]PYRAZIN-3-CARBOXAMIDE DERIVATIVES AS STIMULATORS OF SOLUBLE GUANYLATE CYCLASE (SGC) FOR THE TREATMENT OF CARDIOVASCULAR DISEASES

The present application relates to novel substituted imidazo[1,2-a]pyrazine carboxamides, to processes for their preparation, to their use, alone or in combinations, for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders. 9. (canceled)10. (canceled)11. A medicament comprising the compound as defined in in combination with one or more inert claim 1 , nontoxic claim 1 , pharmaceutically suitable excipients.12. A medicament comprising the compound as defined in in combination with a further active compound selected from the group consisting of organic nitrates claim 1 , NO donors claim 1 , cGMP-PDE inhibitors claim 1 , antithrombotic agents claim 1 , hypotensive agents and lipid metabolism modifiers.13. (canceled)14. A method for the treatment and/or prophylaxis of heart failure claim 1 , angina pectoris claim 1 , hypertension claim 1 , pulmonary hypertension claim 1 , ischaemias claim 1 , vascular disorders claim 1 , renal insufficiency claim 1 , thromboembolic disorders claim 1 , arteriosclerosis claim 1 , dementia disorders and erectile dysfunction in humans and animals comprising administering an effective amount of at least one compound of to a human or animal in need thereof.15. A method for the treatment and/or prophylaxis of heart failure claim 2 , angina pectoris claim 2 , hypertension claim 2 , pulmonary hypertension claim 2 , ischaemias claim 2 , vascular disorders claim 2 , renal insufficiency claim 2 , thromboembolic disorders claim 2 , arteriosclerosis claim 2 , dementia disorders and erectile dysfunction in humans and animals comprising administering an effective amount of the compound of to a human or animal in need thereof.16. A method for the treatment and/or prophylaxis of heart failure claim 3 , angina pectoris claim 3 , hypertension claim 3 , pulmonary hypertension claim 3 , ...

Ether compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R 12 or R 13 on the A group is an ether (R 32 ) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

Compounds for Treatment of Complement Mediated Disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 7. The pharmaceutical composition of claim 6 , wherein Xis CRand Xis CR.8. The pharmaceutical composition of claim 7 , wherein Ris C-Calkyl.9. The pharmaceutical composition of claim 8 , wherein Ris hydrogen.10. The pharmaceutical composition of claim 8 , wherein C-Calkyl is methyl.11. The pharmaceutical composition of claim 10 , wherein Ris hydrogen.12. The pharmaceutical composition of claim 7 , wherein Rand Rare both hydrogen.17. The pharmaceutical composition of claim 1 , wherein the composition is suitable for delivery to a human.18. The pharmaceutical composition of claim 1 , wherein the composition is suitable for systemic delivery.19. The pharmaceutical composition of claim 1 , wherein the composition is suitable for topical delivery.20. The pharmaceutical composition of claim 1 , wherein the composition is suitable for ocular delivery.21. The pharmaceutical composition of claim 1 , wherein the composition is suitable for intravitreal delivery. This application is a continuation of U.S. application Ser. No. 14/631,828, filed Feb. 25, 2015, which claims the benefit of provisional U.S. Application No. 61/944,189 filed Feb. 25, 2014, provisional U.S. Application No. 62/022,916 filed Jul. 10, 2014, and provisional U.S. Application 62/046,783 filed Sep. 5, 2014. The entirety of each of ...

Radioactive phospholipid metal chelates for cancer imaging and therapy

Alkylphosphocholine analogs incorporating a chelating moiety that chelates a radioactive metal isotope are disclosed herein. The alkylphophocholine analogs, which can be used to treat or detect solid tumors, have the formula: R 1 includes a chelating agent that is chelated to a metal atom, wherein the metal atom is a positron or single photon emitting metal isotope with a half life of greater than or equal to 4 hours, or an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R 2 is —N + H 3 , —N + H 2 Z, —N + HZ 2 , or —N + Z 3 , wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2.

DEUTERATED CFTR POTENTIATORS

This invention relates to compounds of Formula I: 119.-. (canceled)21. The compound of claim 20 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.22. The compound of claim 20 , wherein the isotopic enrichment coefficient for each designated deuterium is at least 3500 claim 20 , wherein the isotopic enrichment coefficient refers to the ratio between the isotopic abundance and the natural abundance of a specified isotope.24. The salt of claim 23 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.25. The salt of claim 23 , wherein the isotopic enrichment coefficient for each designated deuterium is at least 3500 claim 23 , wherein the isotopic enrichment coefficient refers to the ratio between the isotopic abundance and the natural abundance of a specified isotope. This application is a continuation-in-part of International Application No. PCT/US12/38297, filed May 17, 2012, which claims the benefit of U.S. Provisional Application Ser. No. 61/487,497, filed May 18, 2011. This application also claims the benefit of U.S. Provisional Application Ser. No. 61/727,941, filed Nov. 19, 2012; U.S. Provisional Application Ser. No. 61/780,681, filed Mar. 13, 2013; and U.S. Provisional Application Ser. No. 61/860,602, filed Jul. 31, 2013. The contents of these applications are incorporated herein by reference in their entirety.Many current medicines suffer from poor absorption, distribution, metabolism and/or excretion (ADME) properties that prevent their wider use or limit their use in certain indications. Poor ADME properties are also a major reason for the failure of drug candidates in clinical trials. While formulation technologies and prodrug strategies can be employed in some cases to improve certain ADME properties, these approaches often fail to address the underlying ADME problems that exist for many drugs and drug candidates. One such problem is rapid metabolism that causes a number of ...

METHOD FOR SYNTHESIZING IODO- OR ASTATOARENES USING DIARYLIODONIUM SALTS

The present invention concerns a method of synthesizing a iodo- or astatoarene comprising the reaction of a diaryliodonium compound with a iodide or astatide salt, respectively. The invention also relates to said iodo- or astatoarene and diaryliodonium compound as such. The invention also concerns a method of synthesizing a iodo- or astatolabelled biomolecule and/or vector using said iodo- or astatoarene. 4. The method according to claim 1 , wherein the iodo- or astatoarene is of formula (I):{'br': None, 'Ar—X \u2003\u2003(I)'}wherein:X is I or At; and{'sub': 1', '2, 'Ar is Aror Ar.'}5. The method according to claim 1 , wherein the iodine or astatide salt is of formula (III):{'br': None, 'sup': +', '−, 'AX\u2003\u2003(III)'}wherein:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'X is as defined in ; and'}A is a monovalent cation selected among Na, K, Cs, tetraalkylammonium and tetraalkylphosphonium.6. The method according to claim 1 , wherein X is radioactive.7. The method according to claim 6 , wherein X is At.8. The method according to claim 6 , wherein X is I.9. The method according to claim 1 , wherein the reaction is carried out in a solvent selected from the group consisting of: acetonitrile claim 1 , an alcohol such as methanol claim 1 , dimethylformamide claim 1 , water claim 1 , and mixtures thereof.10. The method according to claim 1 , further comprising an astatide or iodide salt, and the diaryliodonium salt of formula (II) are insoluble, and', 'said iodo- or astatoarene is soluble., 'a purification step wherein a iodo- or astatoarene is extracted by a solvent in which11. The method of synthesizing an astatoarene according to claim 1 , previously comprising a step of reduction of astatine.12. A method of synthesizing a iodo- or astatolabeled biomolecule and/or vector comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(i) synthesizing a iodo- or astatoarene according to the method of ;'}(ii) reacting said iodo- or astatoarene ...

RADIOLABELED ERLOTINIB ANALOGS AND USES THEREOF

Radiolabeled compounds which are erlotinib analogs that feature a radioactive halogen and processes of preparing same are disclosed. Uses of these radiolabeled compounds in radioimaging, for identifying and monitoring a level, distribution and/or mutational status of deregulated EGFR, and/or in radiotherapy, are also disclosed. 147-. (canceled)49. The radiolabeled compound of claim 48 , wherein at least one of Yand Yis said Q.50. The radiolabeled compound of claim 49 , wherein Q is a saturated or unsaturated hydrocarbon chain of 2 to 20 carbon atoms claim 49 , optionally interrupted by one or more heteroatoms claim 49 , substituted by or terminating with said radioactive halogen claim 49 , and optionally substituted by one or more additional substituents.51. The radiolabeled compound of claim 49 , wherein Q is an alkylene chain or is or comprises an alkylene glycol or a derivative thereof claim 49 , each being substituted by or terminating with said radioactive halogen.52. The radiolabeled compound of claim 49 , wherein Q is represented by (CR′R″)nX claim 49 ,wherein R′ and R″ are each independently selected from hydrogen, alkyl, cycloalkyl, aryl, heteroalicyclic, heteroaryl, alkoxy, aryloxy, thioalkoxy, thioaryloxy, hydroxyl, halogen, trihaloalkyl, trihaloalkoxy, amine, cyano, nitro, carbonyl, thiocarbonyl, carboxylate, thioacarboxylate, amide, thioamide, carbamate, thiocarbamate, alkaryl, aralkyl, sulfinyl, sylfonyl, sulfonate, and sulfonamide;n is an integer of from 1 to 20; andX is said radioactive halogen.53. The radiolabeled compound of claim 52 , wherein each of R′ and R″ is hydrogen.54. The radiolabeled compound of claim 52 , wherein n is 2.55. The radiolabeled compound of claim 48 , wherein at least one of Yand Yis said radioactive halogen.56. The radiolabeled compound of claim 48 , wherein each of R-Ris hydrogen; and/or{'sub': 5', '12, 'each of R-Ris hydrogen; and/or'}{'sub': 17', '21, 'each of R-Ris hydrogen; and/or'}{'sub': 13', '16, 'each of R-Ris ...

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 2. The process of claim 1 , wherein Rand R are independently chosen from hydrogen claim 1 , halogen claim 1 , and C-Calkyl.3. The process of claim 1 , wherein Ris hydrogen.5. The process of claim 1 , wherein Ris hydrogen.6. The process of claim 1 , wherein B is —(C-Calkyl)(aryl) or —(C-Calkyl)(heteroaryl); each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.7. The process of claim 1 , wherein B is —(C-Calkyl)(heteroaryl) which is unsubstituted or substituted with one or more substituents independently chosen from Rand R.8. The process of claim 1 , wherein Ris selected from halogen and C-Calkyl.14. The process of claim 13 , wherein Rand R are independently chosen from hydrogen claim 13 , halogen claim 13 , and C-Calkyl.15. The process of claim 14 , wherein Ris C-Calkanoyl.16. The process of claim 15 , wherein B is —(C-Calkyl)(heteroaryl); each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R.17. The process of claim 16 , wherein Ris hydrogen.18. The process of claim 17 , wherein Ris selected from halogen and C-Calkyl. This application is a continuation of U.S ...