ЖИДКОФАЗНЫЕ ПУТИ ДЛЯ ГЕКСАПЕПТИДОВ WNT

Настоящее изобретение относится к области биотехнологии, конкретно к области синтеза полипептидов. Изобретение раскрывает новый подход к жидкофазному синтезу гексапептида WNT Foxy-5, а также к его защищенным производным и пептидным фрагментам, позволяя получить более высокие выходы целевого продукта. 3 н. и 3 з.п. ф-лы, 16 пр., 8 ил.

ПРОЛЕКАРСТВА СОПРЯЖЕННО-БИЦИКЛИЧЕСКИХ АНТАГОНИСТОВ C5aR

Группа изобретений относится к фармацевтической химии и включает соединения формул (IB), (IC), (IIA) или (IIB) или их фармацевтически приемлемые соли, фармацевтическую композицию и способ лечения на их основе. В формулах (IB), (IC), (IIA) или (IIB) член цикла a представляет собой C(R2c), член цикла b представляет собой C(R2d) и член цикла e представляет собой C(R2e); X1 выбран из группы, состоящей из связи и C1-8алкилена; R1 выбран из: a) 6-членного гетероарила, содержащего в качестве вершин кольца(ец) 1-4 гетероатома, выбранных из N, O и S; b) C6-10арила; группа -X1-R1 является незамещенной или замещена 1-5 заместителями Rx; R2aи R2e каждый независимо представляет собой C1-6алкил; R2b, R2c и R2d каждый независимо представляет собой атом водорода; каждый R3 представляет собой C1-4алкил; R4 представляет собой -NHC(O)NHP1; каждый R5 представляет собой галоген; R5’представляет собойатом водорода; R6 выбран из группы, состоящей из C1-6алкокси и галогена; R7 представляет собой P1; и R8 представляет ...

ПЯТИЧЛЕННЫЕ ГЕТЕРОЦИКЛИЧЕСКИЕ АМИДИНЫ, ОБЛАДАЮЩИЕ СВОЙСТВАМИ ИНГИБИТОРОВ ТРОМБИНА, СОЕДИНЕНИЯ, СОДЕРЖАЩИЕ ПРОИЗВОДНЫЕ ПЯТИЧЛЕННОГО ГЕТЕРОЦИКЛИЧЕСКОГО АМИДИНА, В КАЧЕСТВЕ СОСТАВНОЙ ЧАСТИ ИНГИБИТОРОВ СЕРИНПРОТЕАЗЫ И ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ

Описываются новые пятичленные гетероциклические амидины формулы (I), где А, В, D и Е имеют следующие значения: А формулы (II), где m = n = 0,1 или 2; R1 - группы: гидроксил, карбоксил, С1-6-алкил-ООС; R2 = R3 - водород, алкил с 1-4 атомами углерода; В формулы (III), где R4 - водород, алкил с 1-4 атомами углерода или R1 - (СН)m - (при этом R1 и m имеют вышеуказанные значения); Р - 0 или 1; R5 - водород или алкил с 1-4 атомами углерода; R6 - водород, алкил с 1-6 атомами углерода, циклоалкил с 3-8 атомами углерода; R4 и R6 вместе могут означать этиленовую группу; R7 - водород, алкил с 1-8 атомами углерода; R8 - водород, алкил с 1-4 атомами углерода; Е формулы (IV), где q - 0 или 1; D формул (Va), (Vb), (Cc), где R9 - водород, алкил с 1-3 атомами углерода; R10 = R11 - водород, алкил с 1-4 атомами углерода; Х - кислород, сера, NR12 (R12 = водород, алкил с 1-6 атомами углерода), Y - азот = или -CR13 = (R13 = водород, алкил с 1-4 атомами углерода); Z - азот = или -CR13=, где R13 имеет вышеуказанное ...

СОЕДИНЕННЫЕ С ЖЕЛЧНЫМИ КИСЛОТАМИ ПРОИЗВОДНЫЕ ПРОПАНОЛАМИНА, ЛЕКАРСТВЕННОЕ СРЕДСТВО

Изобретение относится к замещенным производным пропаноламина с желчными кислотами формулы I и их фармацевтически приемлемым солям и физиологически функциональным производным, где GS - группа желчной кислоты формулы II, R1 – связь с X, ОН, R2 – связь с X, ОН, -О-(C1-С6)алкил, -NH-(С2-С6)-алкил-SO3Н, -NH-(С1-С6)-алкил-СООН, R1 и R2 одновременно не означают связь с Х, Х – l, m, n – 0,1; L – (C1-C6)-алкил, AA1, АА2 независимо аминокислотный остаток, возможно одно- или многократно замещенный аминогруппой. Соединения I пригодны в качестве гиполипидемических средств. 2 н. и 7 з.п. ф-лы, 1 табл. I ...

ПЕПТИДНЫЕ ЭПОКСИКЕТОНЫ ДЛЯ ИНГИБИРОВАНИЯ ПРОТЕАСОМЫ

Изобретение относится к соединению, имеющему структуру формулы (I), или его фармацевтически приемлемой соли, ! ! где указанные радикалы являются такими, как представлено в описании, а также относится к соединению, представляющему собой ! ! или его фармацевтически приемлемой соли. В настоящем изобретении заявляется фармацевтическая композиция, обладающая ингибирующей активностью в отношении 20S протеасомы, содержащая фармацевтически приемлемый носитель или разбавитель и терапевтически эффективное количество соединения, а также изобретение относится к способам лечения заболеваний, относящихся к иммунным, таким как воспалительное заболевание кишечника, к лечению рака, к лечению инфекции, к лечению пролиферативного заболевания, к лечению нейродегенеративного заболевания или лечению астмы, 18 н. и 16 з.п. ф-лы, 21 пр., 2 ил.

БЕНЗИЛАМИНОВЫЕ ПРОИЗВОДНЫЕ КАК ИНГИБИТОРЫ КАЛЛИКРЕИНА ПЛАЗМЫ

Настоящее изобретение относится к соединениям формулы (I), композициям, содержащим такие соединения; применению таких соединений в терапии для лечения или предотвращения заболеваний или состояний, при которых предполагается активность калликреина плазмы; и способам лечения пациентов с помощью таких соединений; где Rвыбирают из Н, алкила, -СОалкила, -СОарила, -СОгетероарила, -(СН)ОН, -(СН)COOR, -(СН)CONH, -SOалкила, -SОарила, -SO(СН)R, -СО(СН)R, -СОциклоалкила, -COCH=CHR, -СО(СН)NHCO(СН)kRи -CONRR; Rвыбирают из Н и алкила; Rвыбирают из алкила, -(СН)арила, -(СН)гетероарила, (СН)циклоалкила, -СН(циклоалкила)и -(СН)арил-O-(СН)-арила; Rи Rнезависимо выбирают из Н и алкила; Rвыбирают из Н и ОН; или Rи R, вместе с атомами, к которым они присоединены, могут связываться с образованием 5- или 6-членной азациклоалкильной структуры; Rвыбран из Н и галогена; Rвыбран из Н, алкила, галогена и CF; Rпредставляет собой арил или гетероарил; Rпредставляет собой Н или алкил; а, b, с, d, е, f, g, h, i, j, l ...

АГЕНТ ДЛЯ ПРИДАНИЯ КОКУМИ

Изобретение относится к области биотехнологии, конкретно к агенту для придания кокуми, и может быть использовано в пищевой промышленности. Изобретение относится также к пищевой композиции, содержащей травы и/или специи, полученные из растений, принадлежащих к Labiatae, «мисо» или томат, способу получения пищевого продукта, включающему стадию добавления агента для придания кокуми к пищевым ингредиентам, пищевому продукту, полученному вышеуказанным способом, и способу усиления вкуса и/или запаха пищевого продукта с использованием агента для придания кокуми. Изобретение позволяет получить агент для придания кокуми γ-Glu-Nva, который проявляет повышенную активность CASR по сравнению с известными аналогами и обладает улучшенным эффектом придания кокуми. 7 н. и 13 з.п. ф-лы, 1 ил., 6 табл., 4 пр.

ПРОИЗВОДНЫЕ ЛАНТИОНИНА

Изобретение относится к соединению общей формулы (I) или к его пищевой соли:, где каждый R1 и R2 независимо представляет собой атом водорода или низшую алкильную группу, содержащую от 1 до 3 углеродных атомов; А представляет собой метиленовую группу или оксигруппу; и X представляет собой алкиленовую группу, содержащую от 1 до 5 углеродных атомов, при условии, что одна из метиленовых групп, присутствующих в алкиленовой группе, может быть заменена на тиогруппу, оксигруппу, и что алкиленовая группа может быть дополнительно замещена 1-6 алкильными группами, каждая из которых содержит от 1 до 3 углеродных атомов. Изобретение также относится к пищевой композиции, обеспечивающей эффект кокуми, на основе указанного соединения и к промежуточному соединению для получения соединения формулы (I). Технический результат: получено новое соединение и композиция на его основе, которые могут найти применение в пищевой промышленности в качестве придающего кокуми средства. 4 н. и 7 з.п. ф-лы, 4 табл., 28 пр ...

НОВЫЕ ПЕПТИДЫ КАК ИНГИБИТОРЫ NS3-СЕРИНПРОТЕАЗЫ ВИРУСА ГЕПАТИТА C

Изобретение относится к новым пептидным соединениям, которые обладают способностью ингибировать протеазу вируса гепатита С (HCV), их фармацевтическим композициям и применению соединений для получения лекарственного средства для лечения заболеваний, связанных с HCV. 10 н. и 38 з.п. ф-лы, 6 табл.

НОВЫЕ ХРОМОГЕННЫЕ СУБСТРАТЫ И ИХ ПРИМЕНЕНИЕ ДЛЯ КОЛИЧЕСТВЕННОГО ОПРЕДЕЛЕНИЯ АКТИВНОСТИ КАРБОКСИПЕПТИДАЗ

... 1. Соединение, соответствующее следующей формуле (I) в которой А представляет собой или или или или R1, R2 представляет собой Н, -СН3, -СН(СН3)2, -ОСН3, -Cl, CF3, -OCF3, -SCH3; R3 представляет собой аминокислотный остаток, который может быть отщеплен карбоксипептидазой А; R4 представляет собой остаток основной аминокислоты. 2. Соединение по п.1, соответствующее следующей формуле (I) в которой А представляет собой или или или или R1, R2 представляет собой Н, -СН3, -СН(СН3)2, -ОСН3, -Cl, -CF3, -OCF3, -SCH3; R3 представляет собой остаток гидрофобной аминокислоты; R4 представляет собой остаток аргинина или лизина. 3. Соединение по п.1, отличающееся тем, что R3 представляет собой остаток одной из следующих аминокислот: тирозин, фенилаланин, аланин, валин, лейцин, изолейцин, фенилглицин. 4. Соединение по п.1, отличающееся тем, что R3 представляет собой остаток фенилаланина. 5. Соединение по п.1, отличающееся тем, что R3 представляет собой остаток фенилаланина или тирозина, a R4 представляет собой ...

ПЕПТИДЫ, СВЯЗЫВАЮЩИЕ CD44

ИНГИБИТОРЫ ВИРУСА ГЕПАТИТА С (HCV)

... 1. Соединение Формулы I ! ! его фармацевтически приемлемые соли или стереоизомеры; ! в которой ! x представляет собой 0 или 1; ! y представляет собой 0 или 1; ! R1, R2, R4, R5, R6, W, R13 и V каждый, независимо, выбраны из водорода или из группы, состоящей из алкила, аралкила, гетероалкила, гетероциклила, гетероарила, арилгетероарила, алкилгетероарила, циклоалкила, алкилокси, аралкилокси, арилокси, гетероарилокси, гетероциклилокси, циклоалкилокси, амино, моно- или ди-алкиламино, ариламино, аралкиламино, гетероариламино, циклоалкиламино, карбоксиалкиламино, арилалкилокси или гетероциклиламино; каждый из которых может быть дополнительно независимо замещен один или несколько раз группой Х1 или Х2; где Х1 представляет собой алкил, алкенил, алкинил, циклоалкил, циклоалкилалкил, гетероциклил, гетероциклилалкил, арил, алкиларил, арилалкил, арилгетероарил, гетероарил, гетероциклиламино, алкилгетероарил или гетероарилалкил; где Х1 может быть независимо замещен одной или несколькими группами Х2, ...

ДИПЕПТИДНЫЕ МИМЕТИКИ НЕЙРОТРОФИНОВ NGF И BDNF

... 1. Соединения общей формулы (R-CH2-CO-A-B-NH-R')n (I), представляющие собой замещенные линейные дипептиды, последовательность которых соответствует последовательности экспонированных в растворитель участков петель 1 или 4 нейротрофических факторов, при этом по крайней мере один аминокислотный остаток или его биоизостер входят в состав бета-изгиба петли, обладающие полной или частичной агонистической или антагонистической активностью. ! 2. Соединения по п.1, где нейротрофический фактор представляет собой фактор роста нервов (NGF) или мозговой нейротрофический фактор (BDNF). ! 3. Соединения по п.1, где ! А и В - аминокислотные остатки дипептидной последовательности АВ; ! R= боковой радикал аминокислотного остатка, предшествующего дипептидному фрагменту АВ в последовательности нейротрофина, Н или бивалентный радикал -R-, в частности, -(СН2)m-; ! R'= боковой радикал аминокислотного остатка, следующего за дипептидным фрагментом АВ в последовательности нейротрофина, Н или бивалентный радикал ...

СОЕДИНЕНИЯ И КОМПОЗИЦИИ В КАЧЕСТВЕ ИНГИБИТОРОВ ПРОТЕАЗЫ, АКТИВИРУЮЩЕЙ КАНАЛЫ

... 1. Соединение формулы (1): ! ! и его фармацевтически приемлемые соли, гидраты, сольваты и стереоизомеры, где !J представляет собой 5-12-членное моноциклическое или конденсированное ! карбоциклическое кольцо, арил, гетероарил или гетероциклическое кольцо, ! содержащее N, О и/или S; ! R1 представляет собой -(CR2)1-NR2, -(CR2)1-NRC(=NR)-NR2, -(CR2)1-C(=NR)-NR2 или 5-7-членное азотсодержащее неароматическое гетероциклическое кольцо; ! W-R2 представляет собой заместитель в любом положении кольца А; ! W представляет собой -O(CR2)k-, -S(CR2)k-, -S(O)(CR2)k-, -SO2(CR2)k- или -OC(O)(CR2)k-; ! R2 представляет собой C1-6 алкил, С2-6 алкенил, С2-6 алкинил, R6, -CR9=CR9-R6 или, где кольцо Е представляет собой необязательно замещенный 5-7-членное моноциклическое или конденсированное карбоциклическое или гетероциклическое кольцо; или W-R2 вместе образуют C1-6 алкил, 5-7-членный арил или -OC(O)NR7R8; ! R3 представляет собой NR7R8 или R6; !R4 и R5 независимо представляют собой Н, C1-6 алкил, ОН или C1-6 ...

ПРОЛЕКАРСТВА ДЕЙСТВУЮЩИХ ВЕЩЕСТВ ГЕТЕРОЦИКЛИЧЕСКИМИ ЛИНКЕРАМИ

... 1. Соединение формулы:где X выбран из:остатка кетон-содержащего действующего вещества, где атом водорода соответствующей гидроксильной группы енольного таутомера кетона замещен ковалентной связью с -C(O)-N[(цикл A)-Y]-(CRR)-NH-C(O)-CH(R)-N(R)-[C(O)-CH(R)-N(R)]-R;остатка фенольного действующего вещества, где атом водорода соответствующей фенольной гидроксильной группы замещен ковалентной связью с -C(O)-N[(цикл A)-Y]-(CRR)-NH-C(O)-CH(R)-N(R)-[C(O)-CH(R)-N(R)]-R; иостатка амид-содержащего действующего вещества, где -C(O)-N[(цикл A)-Y]-(CRR)-NH-C(O)-CH(R)-N(R)-[C(O)-CH(R)-N(R)]-Rсвязан с амид-содержащим действующим веществом через кислород амидной группы, где амидная группа преобразована в амидо-енол или иминный таутомер;цикл A представляет собой гетероциклическое кольцо с 5-12 членами;каждый Y независимо выбран из алкила, замещенного алкила, алкенила, замещенного алкенила, алкинила, замещенного алкинила, арила, замещенного арила, ацила, замещенного ацила, карбоксила, алкоксикарбонила, замещенного ...

СОЕДИНЕНИЯ ДЛЯ ИНГИБИРОВАНИЯ ФЕРМЕНТА

... 1. Соединение, имеющее структуру формулы (I) или его фармацевтически приемлемая соль ! ! в которой L выбран из С=О, C=S и SO2; ! Х выбран из О, S, NH и N-C1-6-алкила; ! Z отсутствует или представляет собой С1-6-алкил или С1-6-алкоксигруппу; ! каждый из R1, R2 и R3 независимо друг от друга выбран из водорода, С1-6-алкила, ! С1-6-алкенила, С1-6-алкинила, С1-6-гидроксиалкила, С1-6-алкоксиалкила, арила, С1-6-аралкила, гетероарила, гетероциклила, С1-6-гетероциклоалкила, С1-6-гетероаралкила, карбоциклила и С1-6-карбоциклоалкила; ! R4 выбран из водорода, С1-6-аралкила и С1-6-алкила; ! R5 представляет собой гетероарил и ! R6 и R7 независимо друг от друга выбраны из водорода, С1-6-алкила и С1-6-аралкила. ! 2. Соединение по п.1, в котором Z отсутствует. ! 3. Соединение по п.1, в котором R4, R6 и R7 независимо друг от друга выбраны из водорода и метила. ! 4. Соединение по п.1, в котором L представляет собой С=О. ! 5. Соединение по п.1, в котором L представляет собой SO2. ! 6. Соединение по п.1, в ...

СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ ЛИЗОБАКТИНА

... 1. Способ получения циклических депсипептидов следующей формулы (I) ! ! в которой R1 обозначает Н или CH3, ! в которой R2 обозначает водород, C3-C6-циклоалкил, C5-C6-циклоалкенил, C3-C6-циклоалкилметил, 5-7-членный гетероциклилметил, метил, этил, н-пропил, изопропил, 1-метилпроп-1-ил, 2-метилпроп-1-ил, 2,2-диметилпроп-1-ил, 1,1-диметилпроп-1-ил, 1-этилпроп-1-ил, 1-этил-1-метилпроп-1-ил, н-бутил, 2-метилбут-1-ил, 3-метилбут-1-ил, 1-этилбут-1-ил, трет-бутил, 4-метилпент-1-ил, н-гексил, алкенил или арил, ! в которой R2 могут содержать 0, 1, 2 или 3 заместителя, независимо друг от друга выбранных из группы, включающей галоген, гидроксигруппу, аминогруппу, цианогруппу, триметилсилил, алкил, алкоксигруппу, бензилоксигруппу, C3-C6-циклоалкил, арил, 5-10-членный гетероарил, алкиламиногруппу, ариламиногруппу, алкилкарбониламиногруппу, арилкарбониламиногруппу, алкилкарбонил, алкоксикарбонил, арилкарбонил и бензилоксикарбониламиногруппу, ! где арил и гетероарил, в свою очередь, могут содержать 0, ...

АГЕНТ ДЛЯ ПРИДАНИЯ КОКУМИ

... 1. Агент для придания кокуми, состоящий в основном из γ-Glu-Nva.2. Комплексный агент для придания кокуми, содержащий, в комбинации,(а) γ-Glu-Nva; и(b) одну или по меньшей мере две аминокислоты или пептида, выбранных из группы, состоящей из γ-Glu-X-Gly, где X представляет собой аминокислоту или производное аминокислоты, γ-Glu-Val-Y, где Y представляет собой аминокислоту или производное аминокислоты, γ-Glu-Abu, γ-Glu-Ala, γ-Glu-Gly, γ-Glu-Cys, γ-Glu-Met, γ-Glu-Thr, γ-Glu-Val, γ-Glu-Orn, Asp-Gly, Cys-Gly, Cys-Met, Glu-Cys, Gly-Cys, Leu-Asp, D-Cys, γ-Glu-Met (О), γ-Glu-γ-Glu-Val, γ-Glu-Val-NH, γ-Glu-Val-ола, γ-Glu-Ser, γ-Glu-Tau, γ-Glu-Cys (S-Me) (О), γ-Glu-Leu, y-Glu-Ile, γ-Glu-t-Leu и γ-Glu-Cys (S-Me).3. Пищевая композиция, содержащая γ-Glu-Nva в количестве в диапазоне от 0,1 млр.д. (миллиардных долей) до 99,9 вес.%.4. Пищевая композиция по п.3, содержащая от 0,005 до 30 м.д. (миллионных долей) γ-Glu-Nva; от 0,01 до 10 вес.% трав и/или специй, полученных из растений, принадлежащих к; и любые ...

ПЕПТИДЫ ДЛЯ ОМОЛОЖЕНИЯ КОЖИ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

АМИДНЫЕ ПРОИЗВОДНЫЕ N-КАРБАМИД-ЗАМЕЩЕННЫХ АМИНОКИСЛОТ КАК МОДУЛЯТОРЫ ФОРМИЛПЕПТИДНОГО РЕЦЕПТОРА-1 (FPRL-1)

... 1. Соединение, представленное Формулой II, его энантиомеры, диастереоизомеры, таутомеры, гидраты, сольваты или фармацевтически приемлемые соли,,где:a равен 1, и b равен 0;a равен 0, и b равен 1;a равен 1, и b равен 1;Rпредставляет собой необязательно замещенный Cалкил, необязательно замещенный Cциклоалкил, необязательно замещенный гетероцикл, необязательно замещенный Cциклоалкил, необязательно замещенный Cарил, необязательно замещенный Cциклоалкенил, -NRRили OR;Rпредставляет собой необязательно замещенный Cалкил или необязательно замещенный Cарил;Rпредставляет собой водород, необязательно замещенный Cалкил, галоген, -COOR, -OR, NRR, NO, необязательно замещенный гетероцикл, необязательно замещенный Cциклоалкил, необязательно замещенный Cарил или необязательно замещенный Cциклоалкенил;Rпредставляет собой водород, необязательно замещенный Cалкил, галоген, -COOR, -OR, NRR, NO, необязательно замещенный гетероцикл, необязательно замещенный Cциклоалкил, необязательно замещенный Cарил или необязательно ...

METHOD FOR OBTAINING DERIVATIVES OF DIPEPTIDES OR THEIR PHARMACOLOGICALLY ACCEPTABLE SALTS

METHOD FOR OBTAINING DERIVATIVES OF DIPEPTIDES OR THEIR PHARMACEUTICALLY ACCEPTABLE SALTS

NEUARTIGE ANTIKOAGULIERENDE PEPTIDDERIVATE UND ARZNEIMITTEL DIE SOLCHE ENTHALTEN SO WIE ENTSPRECHENDES HERSTELLUNGSVERFAHREN

AMIDE DER GE 2270-ANTIBIOTIKA.

Herstellung von alpha-1-Aspartyl-1-phenylalanin-methylester mit geschütztem Stickstoffatom.

CARBOXYALKYL DIPEPTIDES, PROCESSES FOR THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

HERSTELLUNG VON GROSSEN KRISTALLEN VON N-BENZYLOXY-CARBONYL-L-ASPARAGINSAEURE

PEPTIDES

Crystallizing N-benzyloxycarbonyl-L-aspartic acid

N-Benzyloxycarbonyl-L-aspartic acid (Z-Asp) crystals several times larger than those obtained by conventional crystallization are prepared by acidifying an alkaline aqueous solution of a metal salt of Z-Asp at high temperatures of between about 20 DEG to 45 DEG C. The resulting large crystals contain less moisture and less impurities such as sodium chloride, dipeptide and benzyl alcohol, etc. than those crystals obtained at lower temperatures and they are easily processed for preparing aspartame.

A-HALOMETHYLAMINO COMPOUNDS AND THEIR PREPARATION

PHARMACOLOGICALLY ACTIVE COMPOUNDS

Poly-pyrrolecarboxamidonaphthalenic acid derivatives

Modulators of pharmacokinetic properties of therapeutics

Prodrug of an ice inhibitor

Dipeptide compounds which are growth hormone secretegoques.

This invention is directed to compounds of the formula and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretogogues and wnich increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recover/ of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis when used in combination with; a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally ...

Tartrate salt of a substituted dipeptide.

This invention relates to (L)-(-f-)-tartaric acid salt of the compound of Formula I Which is a growth hormone secretagogue and as such is useful for increasing the level of endogenous growth hormone.

Dipeptide compounds which are growth hormone secretagoques.

This invention is directed to compounds of the formula and the pharmaceulically-acceptable salts thereof, where the subslituents are as defined in the Specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this Invention are useful for (the treatment and prevention of osleoporosis. congestive heart failure, frailly associated with aging, obesity; accelerating bone fracture repair, attenuating .protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance of skin thickness, metabolic homeoslasis or renal homeostasis. The compounds of (he present invention are also useful in treating osleoporosis when used in combination with: a bisphosphonale compound such as alendronale; estrogen. premarin, and optionally ...

Crystalline forms of EtO2C-CH2-(R)Cgl-Aze-Pab-OH

There is provided EtO2C-CH2-(R)Cgl-Aze-Pab-OH, or pharmaceutically-acceptable salt thereof, in a form which is substantially crystalline. It has been found that crystalline forms of Et02C-CH2-(R)Cgl-Aze-Pab-OH have a high chemical and solid state stability when compared to amorphous forms of the compound.

Novel octahydro-6,10-dioxo-6h-pyridazino/1,2-a/1,2/diazepine-1-carboxylic acid derivatives preparation method and use for preparing therapeutically active compounds

Tartrate salt of a substituted dipeptide

Dipeptide compounds which are growth hormone secretagogues

Antiparisitic dihydroazole compounds and compositions comprising same

Crystalline forms of et02c-ch2(r)cgl-aze-pab-oh

Prodrug of an ice inhibitor.

This invention described an ice inhibitor prodrug (i)having good bioavaialability. Compound of formula (i)is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ trnasplant rejection, osteoarthritis, asthama, psoriasis, alzheimer's disese, mycardial infarction, congestive heart failure, huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.

Heterocyclic compounds

SMAC MIMETIC

Modulators of pharmacokinetic properties of therapeutics

Modulators of pharmacokinetic properties of therapeutics

Antiparistic dihydroazole compounds and compositions comprising same.

Smac mimetic.

Novel octahydro-6, 10-dioxo-6h-pyridazino/1,2-a/ /1,2/diazepin-1-carboxylic acid derivatives, preparation method and use for preparing therapeutically active compounds.

The invention concerns compounds of formula (I) in SR configuration or in the form of a SR + SS mixture, wherein R represents a hydrogen atom, an alkyl or aralkyl radical containing up to 18 carbon atoms, the amine function being free or protected. The compounds can be used for preparing active principles for medicines.

Smac mimetic.

Prodrug of an ice inhibitor

Smac mimetic.

Antiparistic dihydroazole compounds and compositions comprising same.

Modulators of pharmacokinetic properties of therapeutics

Antiparistic dihydroazole compounds and compositions comprising same.

THE TARTRATSALZ OF A SUBSTITUTED DIPEPTIDES FOR THE PROMOTION OF THE SECRETION OF GROWTH HORMONE

PROCEDURE FOR MANUFACTURING LYSOBACTIN DERIVATIVES

PEPTIDE AS HEMMER THE SERINPROTEASE THE HEPATITIS OF C VIRUS

PROCEDURE FOR the PRODUCTION OF NEW N2 ARYLSULFONYL L ARGININAMIDEN AND THEIR SALTS

PROCEDURE FOR the PRODUCTION OF NEW N2 ARYLSULFONYL L ARGININAMIDEN AND THEIR SALTS

PROCEDURE FOR THE CRYSTALLIZATION OF ALPHA L OF ASPARTYL L PHENYLALANINMETHYLESTER

AMIDINOPHENYLALANINDERIVATE, PROCEDURE FOR THEIR PRODUCTION, THEIR USE AND THESE CONTAINING MEANS AS ANTIKOAGULANTIEN.

PEPTID ANALOGUES WITH RENININHIBIERENDER ACTIVITY.

STRONGLY SUESSE L-ASPARTYL-3 (BICYCLOALKYL) - LALANINALKYLESTER.

2-AMINOACETAMIDDERIVATE.

SUESSSTOFFE DERIVED FROM IN ACCORDANCE WITH DIAMINOALKAN.

HETERO-CYCLIC ACYLAMINODIOL BETA AMINO ACID OF DERIVATIVES.

PHENYLAMIDINDERIVATE AS PANEL AGGREGATION INHIBITORS.

AMIDES GE 2270-ANTIBIOTIKA.

FIBRINOGEN RECEPTOR ANTAGONIST.

PEPTIDE WITH ENDOTHELIN ANTAGONISTIC ACTIVITY, THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS

CARBOXYALKYL DIPEPTIDE ONE, PROCEDURE FOR YOUR PRODUCTION AND THESE CONTAINING DRUGS.

AMINOACETYLMERCAPTOACETYLAMID DERIVATIVES WITH ENKEPHALINASE ONES AND ACE HEMMWIRKUNG

PROCEDURE FOR THE SEPARATION FROM METHYLESTER FROM ALPHA L-ASPARTYL-L-PHENYLALANINEN

NEW CHROMOGENEN OF SUBSTRATES AND THEIR USE FOR THE PROOF OF THE EFFECT OF CARBOXYPEPTIDASEN

MIMETIKA FROM BETA FOLDING SHEET AND PROCEDURE TO THE USE OF IT

A STORABLE AQUEOUS SOLUTION TO THE INFUSION SOME THROMBININHIBITOR CONTAINS

BORONSÄURE AND ESTERVERBINDUNGEN, THEIR SYSTHESE AND USES

BIOLOGICAL PROCEDURE FOR THE PRODUCTION OF CONNECTIONS ON THE BASIS THAT DIPEPTIDEN

TETRAPEPTIDE DERIVATIVE

N (3,3-DIMETHYLBUTYL) - L-ASPAREGINSÄURE-D-ALPHA AMINOALKENSÄURE-1-PHENYL-1-ALKANAMIDE, AS SÜSSTOFF USABLE

Amide derivatives of N-urea substituted amino acids as formyl peptide receptor like-1 (FPRL-1) receptor modulators

AMIDE DERIVATIVES OF N-UREA SUBSTITUTED AMINO ACIDS AS FORMYL PEPTIDE RECEPTOR LIKE-1 (FPRL-1) RECEPTOR MODULATORS Abstract The present invention relates to novel amide derivatives of N-urea substituted amino acids, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

METHOD FOR PRODUCING READILY SOLUBLE CRYSTALLINE ALPHA-L-ASPARTYL-L-PHENYLALANINE METHYL ESTER

PREPARATION OF N-ALKYLATED DIPEPTIDES

Inhibitors of cancer cell, T-cell and keratinocyte proliferation

The invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, wherein Y is -NRR, -NRC=ONRR -NRC=SNRR, -NRC=NRNR, heterocycle, - C=ONRR, heterocycle, or aryl; n is O to 8; m is 0, or 1 ; r is 0 to 3; t is O to 3; X is O or N; Z is CH, C=O, C=S or a single bond; Z is CO-R, CS-R, (CH)-R or the side-chain of a naturally occuring amino acid; , Z is CO-R , CS-R or (CH)-R or the side-chain of a naturally occuring amino acid; Z is CO-R, CS-R or (CH)-R or the side-chain of a naturally occuring amino acid; Zis H, alkyl, alkoxy, or cycloalkyl; R, R, R, and R are independently from each other H, OH, SH, NH, CN, NO, alkyl, cycloalkyl, heterocycloalkyl, haloalkyl, alkylthio, haloalkyloxy, hydroxyalkyl, hydroxyalkylarnino, alkylamino, alkylaryl, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxyalkyl, alkoxy, aryloxy, heteroaryl, aryl, or halogen.

Alpha-helix mimetics and method relating to the treatment of cancer stem cells

Prodrugs

The present invention relates to a prodrug comprising at least one cytostatic agent, wherein said prodrug is cleavable by prostate-specific antigen (PSA), a process for preparing said prodrug and a pharmaceutical composition containing said prodrug in a pharmaceutically effective amount, for use in the treatment of cancer.

Lipoyl compounds and their use for treating ischemic injury

The present invention relates, in various embodiments, to a compound represented by Structural Formula (I), pharmaceutically acceptable salts or prodrugs thereof, and compositions comprising said compounds, or pharmaceutically acceptable salts or prodrugs thereof. Methods of using compounds of Structural Formulas (I) and (la) or compositions comprising compounds of Structural Formulas (I) and (la), or pharmaceutically acceptable salts or prodrugs thereof, to treat ischemia or ischemia-reperfusion injury are also disclosed.

Pharmaceutical compositions of growth hormone secretagogue receptor ligands

The present invention relates to improvements in compositions containing peptides that are ligands of the GHS receptor, or pharmaceutically acceptable salts thereof, methods for preparing such compositions, and methods of using such compositions to treat mammals. In particular, the present invention relates to a pharmaceutical composition comprising a pamoate salt of H-Inp-D-Bal-D-Trp-Phe-Apc-NH2, which is a ligand of the GHS receptor and in which, after subcutaneous or intramuscular administration to a subject, the peptide forms an depot at physiological pH that is slowly dissolved and released into the body fluid and bloodstream. The present invention may further comprise an organic component such as dimethylacetamide (DMA) or polyethylene glycol with an average molecular weight of lower than 1000.

AMINO ACID DERIVATIVES

Peptides for skin rejuvenation and methods of using the same

The invention provides compositions for stimulating the formation of one or more extracellular matrix components that contain a lipoaminoacid derivative of the tripeptide carnosine such as N-Octanoyl Carnosine. Also provided are compositions containing N-Octanoyl Carnosine in combination with selected tripeptide and/or tetrapeptides as well as pharmaceutical and/or cosmetic compositions containing such compositions. The invention further provides methods of using the compositions and compositions of the invention to treat, alleviate, and/or ameliorate a symptom, condition, disorder, or disease of the skin or mucosa, wherein the symptom, condition, disorder, or disease is associated with changes in extracellular matrix components.

Tyrosine based linkers for the releasable connection of peptides

The invention relates to novel tyrosine based linkers that allow the releasable connection of peptides or proteins with other molecular entities, e.g. polyethylene glycol, to processes for their preparation and their use for preparing medicaments for the treatment and/or prophylaxis of diseases.

Immunoconjugates, compositions containing them, and methods of making and use

An immunoconjugate in which a phosphate-prodrugged DNA minor groove binding agent of formula (I), where X is a nucleophilically displaceable leaving group, is conjugated to an antibody or an antigen binding fragment of an antibody, and compounds that can be used for making such immunoconjugates, and uses of such immunoconjugates.

Sulfonamide-containing linkage systems for drug conjugates

Sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates. The conjugates have the formula of [(P)-(L)]m-(T), wherein (P) is a payload compound, (L) is a linker, (T) is a targeting moiety and m is an integer from 1- to 10. Also provided are pharmaceutical compositions comprising such conjugates and there use in treating cancer.

CD44 binding peptides

The present invention relates to a protein which binds to the domain encoded by exon 9 of human CD44 (CD44ex9), to fusion proteins and conjugates of said protein and especially to nanoparticles conjugated to said protein. The invention further relates to a method of production for the protein and the respective conjugated nanoparticles and the use of the protein of the invention for treatment and diagnosis of cancer diseases.

Conformationally restricted mimetics of beta turns and beta bulges and peptides containing the same

Novel octahydro-6,10-dioxo-6h-pyridazino/1,2-a/ /1,2/diazepin-1-carboxylic acid derivatives, preparation method and use for preparing therapeutically active compounds

PEPTIDES

Tumor necrosis factor inhibiting peptides and uses thereof

The present invention relates to Tumor Necrosis Factor-alpha (TNF-alpha or TNF-α) inhibiting peptides and process for the preparation thereof. The present invention further relates to a pharmaceutical composition comprising TNF-alpha inhibiting peptides of the present invention and uses thereof in treating TNF-alpha mediated inflammatory disorders.

Collagen peptide composition having good ability to enter the blood and food or beverage containing the same

An object of the present invention is to elucidate a collagen peptide effective for causing dipeptides or tripeptides serving as the active component to enter the blood, and thus to reduce the required intake thereof. According to the present invention, a collagen peptide composition obtained by digesting collagen or gelatin with protease is provided, wherein: (a) the ratio of hydroxyproline to total of amino acid residues at the second position from the N terminus of the peptides in the composition is 2 mol % or more and 20 mol % or less, and the ratio of glycine to total of amino acid residues at the third position from the N terminus of the peptides in the composition is 20 mol % or more and 50 mol % or less; and (b) the average molecular weight is 500 or more and 2000 or less.

Substrate peptide sequences for plague plasminogen activator and uses thereof

The present invention is directed to peptide sequences that were identified from combinatorial libraries and could serve as substrates of plague plasminogen activator (Pla). Another aspect of the present invention is drawn to peptides derived from the substrates for Pla as a result of chemical modifications leading to specific inactivation of the proteolytic activity of Pla. Additionally, the present invention is directed to the use of the substrates identified herein in the detection of bacteria expressing omptin family of proteases which includes Y. pestis . Furthermore, the present invention is also directed to the use of the inhibitors identified herein in the prevention and treatment of infection caused by these bacteria.

Peptidomimetic protease inhibitors

The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

Use of Toll-like receptor-9 agonists, Toll-like receptor-4 antagonists, and/or nuclear oligomerization domain-2 agonists for the treatment or prevention of Toll-like receptor-4-associated disorders

The present invention relates to the use of a TLR9 agonist and/or a TLR4 antagonist and/or a NOD2 agonist for treatment or prevention of disorders involving TLR4 activation, such as systemic sepsis and necrotizing enterocolitis.

Inhibitors of protein tyrosine phosphatases

Disclosed herein are compounds that selectively inhibit members of the PTP family of enzymes. Synthesized compounds demonstrated selective inhibition of TC-PTP. Also provided are methods of using the compounds and formulations containing the compounds. Also described is a fluorescence-tagged combinatorial library synthesis and screening method. And methods of using these compounds to effect enzyme activity both in cells and in vitro as well as method of using these compounds to treat diseases in human and animals.

Compounds for enzyme inhibition

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

Smac mimetec

A SMAC mimetic and pharmaceutical compositions thereof and methods of use.

IAP BIR domain binding compounds

Disclosed herein is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I: or a prodrug, or a pharmaceutically acceptable salt, or labeled with a detectable label or an affinity tag thereof; wherein R 1 , R 1a , R 100 , R 100a , R 2 , R 200 , W, B, and W 1 are defined herein. Also disclosed are methods of using compounds of Formula I to treat proliferative disorders such as cancer.

Age Inhibitors

The invention relates to a compound having general formula I, wherein: X represents CH 2 , C═O, C═S or CHOH, R 1 represents an amino acid optionally substituted by one or more halogen atoms, or by one or more CF 3 groups and n=0.1 or 2, or R 1 represents a peptide containing two amino acids, each amino acid being optionally substituted by one or more halogen atoms, or by one or more CF 3 groups and n=0 or 1, or XR 1 represent PO 3 H or SO 3 H and n=0.1 or 2; R 2 represents H, XR 1 , an alkyl group at C 1 -C 6 , an aralkyl group at C 1 -C 6 or an aryl group, whereby the alkyl, aralkyl and aryl groups can be substituted by an amine NH 2 , a carboxylic group COOH, one or more halogen atoms.

Acidic extracts and beverages containing 2,5-piperazinedione,3,6-bis(phenylmethyl)-(3s,6s)-

The present invention aims to provide extracts available for use in acidic beverage production and containing 2,5-piperazinedione,3,6-bis(phenylmethyl)-,(3S,6S)-, which is a useful substance with an improving effect on learning motivation. When an acid treatment step is included in the production of extracts containing 2,5-piperazinedione,3,6-bis(phenylmethyl)-,(3S,6S)-, it is possible to obtain acidic extracts which cause no sedimentation even when added to beverages. The extracts of the present invention can be added to beverages and so on without impairing the taste inherent to foods and beverages, and can be used for production of acidic beverages preferred by most consumers.

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.

Cross-linkers and their uses

Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.

SMAC Mimetic

A SMAC mimetic and pharmaceutical compositions thereof and methods of use.

Novel maytansinoid derivatives with peptide linker and conjugates thereof

The invention relates to novel cell-binding agent-cytotoxic agent conjugate having a peptide linkers and more specifically to conjugates of formula (I). The invention also provides novel cytotoxic agents of formula (II), linker compounds represented by formula (III), and drug-linker compounds represented by formula (IV). The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

Crystalline d-isoglutamyl-d-tryptophan and the mono ammonium slat of d-isoglutamyl-d-tryptophan

A process for making pure crystalline D-isoglutamyl-D-tryptophan is provided which includes the step of deprotecting essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan or its diester to yield essentially pure D-isoglutamyl-D-tryptophan. A process is also provided for the preparation of pure mono ammonium salt of D-isoglutamyl-D-tryptophan from essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan. D-isoglutamyl-D-tryptophan, ammonium salt (1:1) is a stable pharmaceutical solid.

Crystalline d-isoglutamyl-d-tryptophan and the mono ammonium slat of d-isoglutamyl-d-tryptophan

A process for making pure crystalline D-isoglutamyl-D-tryptophan is provided which includes the step of deprotecting essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan or its diester to yield essentially pure D-isoglutamyl-D-tryptophan. A process is also provided for the preparation of pure mono ammonium salt of D-isoglutamyl-D-tryptophan from essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan. D-isoglutamyl-D-tryptophan, ammonium salt ( 1:1 ) is a stable pharmaceutical solid.

Compounds (cystein based lipopeptides) and compositions as tlr2 agonists used for treating infections, inflammations, respiratory diseases etc.

The invention provides a novel class of compounds viz. generally lipopeptides like Pam3CSK4, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 2. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness a vaccine.

5,5-FUSED ARYLENE OR HETEROARYLENE HEPATITIS C VIRUS INHIBITORS

Provided herein are 5,5-fused heteroarylene hepatitis C virus inhibitor compounds, for example, of Formula I, IA, or IB, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof. 6. The method of claim 1 , wherein Uis S.7. The method of claim 1 , wherein Wis S.8. The method of claim 1 , wherein Wis O.9. The method of claim 1 , wherein Wis N.10. The method of claim 1 , wherein U claim 1 , W claim 1 , Xand Xare C claim 1 , and Vand Vare each independently CR.17. The method of claim 1 , wherein u is 1.18. The method of claim 1 , wherein u is 2.26. The method of claim 1 , wherein Ris —C(O)R claim 1 , —C(O)CH(NRR)R claim 1 , —C(O)CH[N(C(O)R)R]R claim 1 , —C(O)CH[N(C(O)OR)R]R claim 1 , or —C(O)CH[N(C(O)NRR)R]R.27. The method of claim 26 , wherein Ris —C(O)CH[N(C(O)OR)R]R.28. The method of claim 1 , wherein Ris —C(O)R claim 1 , —C(O)CH(NRR)R claim 1 , —C(O)CH[N(C(O)R)R]R claim 1 , —C(O)CH[N(C(O)OR)R]R claim 1 , or —C(O)CH[N(C(O)NRR)R]R.29. The method of claim 28 , wherein Ris —C(O)CH[N(C(O)OR)R]R.30. The method of claim 3 , wherein each Ris independently hydrogen or —C(O)OR.31. The method of claim 1 , wherein each Ris independently hydrogen claim 1 , methyl claim 1 , isopropyl claim 1 , 2-methylpropyl claim 1 , 1-methylpropyl claim 1 , 2-methylthioethyl claim 1 , phenyl claim 1 , benzyl claim 1 , 3-indolylmethyl claim 1 , hydroxymethyl claim 1 , 1-hydroxyethyl claim 1 , sulfhydrylmethyl claim 1 , 4-hydroxybenzyl claim 1 , aminocarbonylmethyl claim 1 , 2-(aminocarbonyl)ethyl claim 1 , carboxymethyl claim 1 , 2-carboxyethyl claim 1 , 4-aminobutyl claim 1 , 3-guanidinopropyl claim 1 , or 5-imidazolylmethyl.32. The method of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , or butyl.33. The method of claim 1 , wherein Ris hydrogen.34. The method of claim 1 , wherein Rand Rtogether with the C and N atoms to which they ...

Sulfur-Containing Amino Acid Derivative

The present invention provides a method of measuring an endogenous low-molecular-weight compound specifically and conveniently with high sensitivity. Using the particular sulfur-containing amino acid derivative, a method of measuring an endogenous low-molecular-weight compound specifically and conveniently with high sensitivity can be provided. 2. The derivative according to claim 1 , wherein Y is a group bound to an endogenous low-molecular-weight compound claim 1 , and Z is selected from the group consisting of a hydrogen atom and a high-molecular-weight-imparting group.3. The derivative according to claim 1 , wherein Y is an endogenous low-molecular-weight compound reactive group claim 1 , and Z is a labeling compound modifying group.4. The derivative according to claim 1 , wherein the immunoresponsive hydrophobic group has a cyclic structure.5. The derivative according to claim 4 , wherein the immunoresponsive hydrophobic group is selected from the group consisting of a 9-fluorenylmethyloxycarbonyl (Fmoc) group and a quinolinylaminocarbonyl group.6. The derivative according to claim 1 , wherein the endogenous low-molecular-weight compound reactive group is selected from the group consisting of an aldehyde group claim 1 , an N-succinimidyl group claim 1 , a halogen group claim 1 , an isothiocyanate group claim 1 , and a maleimido group.7. The derivative according to claim 1 , wherein the high-molecular-weight-imparting group or labeling compound modifying group is bound via a linker.8. A reagent for measuring an endogenous low-molecular-weight compound claim 1 , which comprises the sulfur-containing amino acid derivative according to .9. The reagent according to claim 8 , wherein the endogenous low-molecular-weight compound is an amino acid.10. A method of producing an antibody which is able to recognize an endogenous low-molecular-weight compound claim 2 , comprising immunizing an animal with an antigen comprising the sulfur-containing amino acid derivative ...

Macrocyclic Inhibitors Of Hepatitis C Virus

Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R 1 is —OR 7 , —NH—SO 2 R 8 ; R 2 is hydrogen, and where X is C or CH, R 2 may also be C 1-6 alkyl; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, C 3-7 cycloalkyl; R 4 is aryl or Het; n is 3, 4, 5, or 6; R 5 is halo, C 1-6 alkyl, hydroxy, C 1-6 alkoxy, phenyl, or Het; R 6 is C 1-6 alkoxy, or dimethylamino; R 7 is hydrogen; aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; R 8 is aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

Growth Hormone Releasing Peptides

Disclosed are peptide and peptidomimetic compounds generally according to formula (I) that are useful as GHRP analogs: R 1 -A 1 -A 2 -A 3 -A 4 -A 5 -R 2   (I) wherein: A 1 is Aib, Apc or Inp; A 2 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A 3 is D-Bal, D-Bip, D-Bpa, D-Dip, D-1Nal, D-2Nal, D-Ser(Bzl), or D-Trp; A 4 is 2Fua, Orn, 2Pal, 3Pal, 4Pal, Pff, Phe, Pim, Taz, 2Thi, 3Thi, Thr(Bzl); A 5 is Apc, Dab, Dap, Lys, Orn, or deleted; R 1 is hydrogen, (C1-6)alkyl, (C5-14)aryl, (C1-6)alkyl(C5-14)aryl, (C3-8)cycloakyl, or (C2-10)acyl; and R 2 is OH or NH 2 ; and pharmaceutical compositions and methods of use thereof.

CATIONIC LIPIDS, METHODS FOR PREPARING THE SAME, AND DELIVERY SYSTEMS HAVING ABILITY TO TRANSITION INTO CELLS COMPRISING THE SAME

The present invention provides cationic lipids, methods for preparing the same, and delivery systems comprising the same. The present invention can provide cationic lipids which enhance the efficiency of intracellular or in vivo delivery of multiple-anionic target compounds such as drugs, anticancer agents, nucleic acids, etc., have no intracellular toxicity, but show increased stability, methods for preparing the same, and delivery systems comprising the same. 2. The cationic lipid according to claim 1 , wherein each of Rand Ris independently saturated or unsaturated hydrocarbon chain derived from stearate claim 1 , laurate claim 1 , myristate claim 1 , palmitate claim 1 , or oleate.3. The cationic lipid according to claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , or benzyl.4. The cationic lipid of claim 1 , wherein the ligand is mPEG (methoxy end-capped polyethylene glycol) claim 1 , polypropylene glycol claim 1 , or polyoxyethylene.5. The cationic lipid of claim 1 , wherein the ligand is at least one sugar selected from the group consisting of mannitol claim 1 , sorbitol claim 1 , xylitol claim 1 , glucitol claim 1 , dulcitol claim 1 , inositol claim 1 , arabinitol claim 1 , arabitol claim 1 , galactitol claim 1 , iditol claim 1 , alitol claim 1 , fructose claim 1 , sorbose claim 1 , glucose claim 1 , mannose claim 1 , xylose claim 1 , trehalose claim 1 , allose claim 1 , dextrose claim 1 , altrose claim 1 , gulose claim 1 , idose claim 1 , galactose claim 1 , talose claim 1 , ribose claim 1 , arabinose claim 1 , lyxose claim 1 , sucrose claim 1 , maltose claim 1 , lactose claim 1 , lactulose claim 1 , fucose claim 1 , rhamnose claim 1 , melezitose claim 1 , maltotriose claim 1 , and raffinose.7. The delivery system according to claim 6 , wherein each of Rand Ris independently saturated or unsaturated hydrocarbon chain derived from stearate claim 6 , laurate claim 6 , myristate claim 6 , palmitate ...

DIPEPTIDE DERIVATIVE FOR THE TREATMENT OF CANCER

This invention relates to purified compound of formula (1). The invention includes all isomeric forms and all tautomeric forms of the compound of formula (1) and pharmaceutically acceptable salts thereof. The present invention further relates to processes for the production of the compound of formula (1) by fermentation of the fungal strain of sterile mycelium (PM0509732/MTCC5544) and to pharmaceutical compositions containing the compound as active ingredient and its use in medicines for treatment of cancer. 2. The compound of formula (1) as claimed in characterised by:(a) molecular weight of 418.16,{'sub': 18', '30', '2', '5', '2, '(b) molecular formula CHNOS,'}{'sup': '−1', '(c) IR (KBr) spectrum 3345, 1646, 1671, 1715, 1459, 1399 cm,'}{'sup': '1', 'sub': '6', 'figref': {'@idref': 'DRAWINGS', 'FIG. 1'}, '(d) H NMR spectrum (500 MHz, DMSO-d): δ 8.8 (bs, 1H), 8.1 (bs, 1H), 4.9 (bs, 1H), 4.8 (bs, 1H), 4.5 (bs, 1H), 4.0 (s, 1H), 3.9 (s, 1H), 3.6 (m, 2H), 3.2 (m, 1H), 3.1 (d, 1H), 1.6-1.0 (m, 16H, methylene groups), 0.8 (t, 3H) (also depicted in ), and'}{'sup': '13', '(e) C NMR spectrum (75 MHz, DMSO-d6): δ 174.17, 173.91, 169.42, 74.50, 70.30, 52.07, 51.26, 43.25, 42.10, 36.20, 35.60, 34.30, 32.90, 27.90, 26.70, 22.00, 18.30, 13.70.'}3. A process for the production of the compound of formula (1) as claimed in claim 1 , comprising the steps of:(a) cultivating the microorganism belonging to Endophytic fungal strain (PM0509732/MTCC5544) or one of its variants or mutants under submerged aerobic conditions in a nutrient medium containing sources of carbon and nitrogen to produce the compound of formula (1),(b) isolating the compound of formula (1) from the fermented broth, and(c) purifying the compound of formula (1).4. The process as claimed in claim 3 , further comprising the step of converting the compound of formula (1) to its pharmaceutically acceptable salt.5. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (1) as ...

AZIRIDINE MEDIATED NATIVE CHEMICAL LIGATION

Improved methods of native chemical ligation are provided. The methods involve reacting a thioacid (e.g. a peptide thioacid) with an aziridinyl compound (e.g. an aziridinyl peptide) under mild conditions without the use of protecting groups, and without requiring that a cysteine residue be present in the ligation product. Initial coupling of the thioacid and the aziridinyl compound yields a ligation product which contains an aziridinyl ring. Subsequent opening of the aziridinyl ring (e.g. via a nucleophilic attack) produces a linearized and modified ligation product. 1. A method of forming a ligation product , comprising the steps ofi) reacting a thioacid with a compound that comprises an aziridine ring under conditions that form a ligation product that comprises an aziridine ring; andii) exposing said ligation product that comprises an aziridine ring to conditions which cause opening of said aziridinyl ring, thereby forming said ligation product.2. The method of claim 1 , wherein said thioacid has a general formula RC(O)SH and Ris selected from the group consisting of an amino acid claim 1 , a peptide claim 1 , a polymer claim 1 , an organic group claim 1 , a prodrug and a detection agent.3. The method of claim 2 , wherein said Rdoes not comprise a protecting group.4. The method of claim 1 , wherein said compound that comprises an aziridine ring has a general formula aziridinyl-2-COR-3-R claim 1 , wherein Ris selected from the group consisting of an amino acid side chain claim 1 , a peptide claim 1 , a polymer claim 1 , a detection agent and a prodrug claim 1 , and Ris selected from the group consisting of a peptide claim 1 , a polymer claim 1 , a prodrug and a detection agent.5. The method of claim 4 , wherein at least one of said Rand said Rdo not comprise a protecting group.6. The method of claim 1 , wherein said ligation product that comprises an aziridine ring has a formula aziridinyl-1-COR-2-COR-3-R.7. The method of claim 1 , wherein said conditions which ...

Method for producing peptide

Peptides may be produced by using (A) a first amino acid or peptide, which is converted into its ionic liquid form through the formation of an ionic bond, as a substance serving as both a reaction solvent and a reaction starting material; and reacting the first amino acid or peptide with (B) an ester of second amino acid or peptide, in the absence of any peptide hydrolase or any condensation agent, in the presence of water in an amount of not more than 20% by mass relative to the total mass of the reaction system to form a peptide bond between the first amino acid or peptide and the second amino acid or peptide. By means of this process, it is possible to synthesize a peptide at a high concentration and at a high yield, and this method is excellent for producing peptides on an industrial scale.

BORONATE ESTER COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases. 3. The compound of claim 2 , wherein each of Rand Rindependently is hydrogen claim 2 , Caliphatic claim 2 , or —(CH)—COH;and p is 0, 1, or 2.4. The compound of wherein P is R—C(O)— claim 3 , R—O—C(O)— claim 3 , R—N(R)—C(O)— claim 3 , R—S(O)— claim 3 , or R—N(R)—S(O)—;{'sup': c', 'D', '1', 'D', '1', '2c, 'sub': 1-6', '1-6, 'claim-text': [{'sup': 1', '3a', '3b', '5', '5, 'sub': '1-6', 'Tis a Calkylene chain substituted with 0-2 independently selected Ror R, wherein the alkylene chain optionally is interrupted by —C(R)═C(R)—, —C≡C—, or —O—;'}, {'sup': 'D', 'Ris a substituted or unsubstituted mono- or bicyclic ring system;'}, {'sup': 2c', '5', '6', '6', '6', '4', '4', '4', '5', '4', '4', '4', '6', '4', '6', '4', '4', '5', '4', '5', '5', '4, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'Ris halo, —ORe, —SR, —S(O)R, —SOR, —SON(R), —N(R), —NRC(O)R, —NRC(O)—N(R), —NRCOR, —N(R)SOR, —N(R)SON(R), —O—C(O)R, —OC(O)N(R), —C(O)—R, —COR, or —C(O)N(R);'}, {'sup': 3a', '4, 'sub': 1-4', '2', '1-4', '2', '2', '1-4', '2', '1-4, 'each Rindependently is selected from the group consisting of —F, —OH, —O(Calkyl), —CN, —N(R), —C(O)(Calkyl), —COH, —CO(Calkyl), —C(O)NH, and —C(O)—NH(Calkyl);'}, {'sup': 3b', '3a', '7', '3b, 'sub': '1-3', 'each Rindependently is a Caliphatic substituted or unsubstituted with Ror R; or two substituents Ron the same carbon atom, taken together with the carbon atom to which they are attached, form a 3- to 6-membered cycloaliphatic ring;'}, {'sup': '7', 'each Ris a substituted or unsubstituted aromatic group; and'}], 'Ris selected from the group consisting of Caliphatic, Cfluoroaliphatic, —R, -T-R, and -T-R;'}{'sup': '4c', 'sub': 1-4', '1-4', '6-10', '1-4, 'Ris hydrogen, Calkyl, Cfluoroalkyl, or ...

Cysteine protease inhibitors

Compounds of the formula I wherein R 2a and R 2b are independently H, halo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy, or R 2a and R 2b together with the carbon atom to which they are attached form a C 3 -C 6 cycloalkyl; R 3 is a C 5 -C 10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; or R 3 is a C 2 -C 4 alkyl chain with at least 2 chloro or 3 fluoro substituents; or R 3 is C 3 -C 7 cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; R 4 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino or; R 4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents R 4 is Het, carbocyclyl, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 haloalkoxy; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

Inhibitors of Serine Proteases

This invention relates to compounds of formula I: or a pharmaceutically acceptable salt or mixtures thereof wherein C* represents a diastereomeric carbon comprising a mixture of R and S isomers wherein the R isomer is greater than 50% of the mixture.

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1 comprising administering to a subject in need thereof a compound described here. 2. The compound of claim 1 , wherein Ris 3-fluorophenyl.3. The compound of or claim 1 , wherein:{'sup': '1', 'Ris selected from cyclohexyl, cyclopentyl, cycloheptyl, 3,3-difluorocyclobutyl, 4,4,-difluorocyclohexyl, and bicyclo[2.2.1]heptanyl; and'}{'sup': '4', 'Ris selected from 1-(methylmethoxycarbonylamino)ethyl, 1,2,3,4-tetrahydroquinolin-1-yl, 1-ethoxycarbonylpiperidin-2-yl, 1-ethoxycarbonylpyrrolidin-2-yl, 1H-benzimidazol-1-ylmethyl, 1H-indazol-3-ylmethyl, indolin-1-ylmethyl, 1H-indol-3-ylmethyl, 1H-indol-5-ylmethyl, 1H-pyrrolo[2,3-b]pyridine-3-ylmethyl, 1H-pyrrolo[3,2-b]pyridin-3-ylmethyl, 1-methoxycarbonylpiperidin-2-yl, 1-methoxycarbonylpyrrolidin-2-yl, 2-fluoropyridin-3-ylaminomethyl, 2-imino-4-fluoropyridin-1-ylmethyl, 2-methoxyphenylaminomethyl, 2-methyl-1H-benzimidazol-1-ylmethyl, 2-methylimidazol-1-ylmethyl, 2-trifluoromethyl-1H-imidazol-1-yl, 3-cyanophenylaminomethyl, 3-fluoropyridin-2-ylaminomethyl, 3-methoxyphenylaminomethyl, 4-(1,3,4-oxadiazole-2-yl)phenylaminomethyl, 4-(dimethylaminocarbonyloxy)phenylmethyl, 4,5-dichloroimidazol-1-ylmethyl, 4-cyanophenylaminomethyl, 4-fluorophenylaminomethyl, 4-fluoropyridin-2-ylaminomethyl, 4-hydroxyphenylmethyl, 4-methoxycarbonylmorpholin-3-yl, 4-methoxycarbonylpiperazin-1-ylmethyl, 4-methoxyphenylaminomethyl, 4-methylcarbonyloxyphenylmethyl, 5-fluoropyridin-2-aminomethyl, 5-fluoropyridin-2-oxymethyl, 6-fluoropyridin-3-ylaminomethyl, benzomorpholin-4-ylmethyl, methoxycarbonylaminomethyl, methylmethoxycarbonylaminomethyl, methylphenylaminomethyl, phenylaminomethyl, pyridin-2-oxymethyl, pyridin-2-ylaminomethyl, pyridin-2-yloxymethyl, pyridin-3-oxymethyl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, thiazol-4-ylmethyl, and thien-2-ylmethyl.'}4. The compound of claim 1 , wherein the compound is selected from any one of Compound numbers 104 claim ...

Modulations of protease activated receptors

The present invention provides novel compounds of the Formula (1), pharmaceutical compositions comprising such compounds and methods for using such compounds as tools for biological studies or as agents or drugs for modulating Protease Activated Receptor-2 (PAR2) and for treating a subject at risk of—or susceptible to—a disease or disorder, or having a disease or disorder associated with undesirable PAR2 activity.

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here. 2. The compound of claim 1 , wherein:{'sup': 1', '7, 'sub': 4', '6, 'Ris C-Ccarbocyclyl optionally substituted with one to three Rgroups;'}{'sup': 2', '3', '7, 'each Rand Ris independently selected from aryl or heteroaryl, wherein said aryl or heteroaryl is independently optionally substituted with one to three Rgroups;'}{'sup': 4', '7, 'Ris alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, wherein said aryl, heteroaryl, aralkyl, and heteroaralkyl are each independently optionally substituted with one to three Rgroups;'}{'sup': '5', 'ring A is 4-6 membered non-aromatic ring having 0-1 additional heteroatoms selected from N, O or S, wherein ring A is optionally substituted with one or two Rgroups;'}{'sup': 5', '7', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6, 'sub': 3', '2', '1', '4', '1', '4', '1', '4', '2', '1', '4', '2', '2', '2', '1-4', '2', '1', '4', '2', '3', '5', '3', '6', '1', '4', '1', '4', '1', '4, 'each Rand Ris independently halo; —CF; —CN; —OR; —N(R); —C(O)C-Calkyl; C-Chaloalkyl; C-Calkyl optionally substituted with —ORor —N(R); —O—C-Calkyl optionally substituted with halo, —ORor —N(R); —SON(R); —S(O)—Calkyl; —SO(C-Calkyl); —NRSOR; C-Ccarbocyclyl optionally substituted with one or two Rgroups; —O—(C-Ccarbocyclyl optionally substituted with one or two Rgroups); 5-6 membered heteroaryl; —C-Calkyl-C(O)O—C-Calkyl; or —C(O)O—C-Calkyl; or'}{'sup': '6', 'sub': 1', '4, 'each Ris independently H or C-Calkyl.'}3. The compound of or claim 1 , wherein each Rand Ris independently aryl optionally substituted with one to three Rgroups.54. The compound of any one of - claims 1 , wherein Ris Cor Ccycloalkyl optionally substituted with one to two Rgroups and Rassociated with Ris halo.9. The compound of claim 7 , wherein Ris aryl or heteroaryl claim 7 , each aryl or heteroaryl is ...

Mglu 2/3 agonists

The present invention provides novel mGlu2/3 agonists useful in the treatment of neurological or psychiatric disorders.

INHIBITORS OF HCV NS5A

Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C. 14. The compound of wherein each Ris independently —CN claim 1 , —OCHF claim 1 , —OCF claim 1 , —CF claim 1 , or —F.15. The compound of wherein one or both of Y and Y′ are N.16. The compound of wherein Z and Z′ are each 1-3 amino acids.17. The compound of wherein the amino acids are in the D configuration.18. The compound of wherein Z and Z′ are each independently selected from the group consisting of —[U—(CR)—NR—(CR)]—U—(CR)—NR—(CR)—R claim 1 , —U—(CR)—Rand —[U—(CR)—NR—(CR)]—U—(CR)—O—(CR)—R.19. A pharmaceutical composition comprising the compound of .20. A method of treating hepatitis C comprising administering to a subject in need thereof claim 1 , a therapeutically effective amount of the compound of . This application claims the benefit of and priority to U.S. Application 61/347,788 filed May 24, 2010 which is hereby incorporated by reference in its entirety for all purposes.The invention relates to compounds useful for inhibiting hepatitis C virus (“HCV”) replication, particularly functions of the non-structural 5A (“NS5A”) protein of HCV.HCV is a single-stranded RNA virus that is a member of the Flaviviridae family. The virus shows extensive genetic heterogeneity as there are currently seven identified genotypes and more than 50 identified subtypes. In HCV infected cells, viral RNA is translated into a polyprotein that is cleaved into ten individual proteins. At the amino terminus are structural proteins: the core (C) protein and the envelope glycoproteins, E1 and E2. p7, an integral membrane protein, follows E1 and E2. Additionally, there are six non-structural proteins, NS2, NS3, NS4A, NS4B, NS5A and NS5B, which play a functional role in the HCV lifecycle. (see, for example, Lindenbach, B. D. and C. M. Rice, 436:933-938, 2005).Infection by HCV is a serious health issue. It is estimated that 170 million people worldwide are chronically infected ...

Pharmaceutical Compositions of Growth Hormone Secretagogue Receptor Ligands

The present invention relates to improvements in compositions containing peptides that are ligands of the GHS receptor, or pharmaceutically acceptable salts thereof, methods for preparing such compositions, and methods of using such compositions to treat mammals. In particular, the present invention relates to a pharmaceutical composition comprising a pamoate salt of H-Inp-D-Bal-D-Trp-Phe-Apc-NH2, which is a ligand of the GHS receptor and in which, after subcutaneous or intramuscular administration to a subject, the peptide forms an in situ depot at physiological pH that is slowly dissolved and released into the body fluid and bloodstream. The present invention may further comprise an organic component such as dimethylacetamide (DMA) or polyethylene glycol with an average molecular weight of lower than 1000.

Compositions Comprising Enzyme-Cleavable Prodrugs of Active Agents and Inhibitors Thereof

The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.

IBAT INHIBITORS FOR THE TREATMENT OF LIVER DISEASES

The present invention regards specific IBAT inhibitors useful in the prophylaxis and/or treatment of a liver disease. It also relates to compositions comprising these IBAT inhibitors, a method for treatment of the disorders and a kit comprising the substances or the compositions. 2. A compound according to claim 1 , chosen from1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-(carboxymethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N′—((S)-1-carboxyethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxypropyl) carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((R)-1-carboxy-2-methylthioethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxypropyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((R)-1-carboxy-2-methylthio-ethyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine; 1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxy-2-methylpropyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxy-2-(R)-hydroxypropyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxybutyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxyethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1- ...

Dipeptide analogs for treating conditions associated with amyloid fibril formation

Dipeptide analogs comprising a tryptophan (Trp) moiety coupled to a beta-sheet breaker moiety derived from alpha-aminoisobutyric acid (Aib) are disclosed. The dipeptide analogs exhibit an improved performance in inhibiting amyloid fibril formation, as compared to previously described dipeptides. Compositions containing the dipeptide analogs and uses thereof in treating amyloid-associated diseases and disorders are also disclosed.

AMINIOTHIAZOLES AND THEIR USES

The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases particularly bacterial infections. 2. The compound of claim 1 , wherein R claim 1 , Rand Rare H claim 1 , and Ris CH.3. The compound of claim 1 , wherein R claim 1 , Rand Rare H claim 1 , Ris CH claim 1 , and Ris CH—O—CH.6. The compound of claim 5 , wherein R claim 5 , Rand Rare H claim 5 , and Ris CH.7. The compound of claim 5 , wherein R claim 5 , Rand Rare H claim 5 , Ris CH claim 5 , and Ris CH—O—CH.11. The compound of claim 10 , wherein R claim 10 , Rand Rare H claim 10 , and Ris CH.12. The compound of claim 10 , wherein R claim 10 , Rand Rare H claim 10 , Ris CH claim 10 , and Ris CH—O—CH.15. The compound of claim 1 , wherein Ris OH or OAc.19. A method of treating a bacterial infection comprising administering to a subject in need thereof a pharmaceutically acceptable amount of a compound of claim 1 , such that the bacterial infection is treated.20. A method of treating an EF-Tu associated-state comprising administering to a subject in need thereof a pharmaceutically acceptable amount of a compound of claim 1 , such that the EF-Tu associated state is treated.21. A method of treating claim 1 , inhibiting or preventing the activity of EF-Tu in a subject in need thereof claim 1 , comprising administering to the subject a pharmaceutically acceptable amount of a compound of .22. The method of claim 20 , wherein a bacterial infection is treated in a subject in need thereof.23. A method of treating claim 1 , inhibiting or preventing the activity of bacteria in a subject in need thereof claim 1 , comprising administering to the subject a pharmaceutically acceptable amount of a compound of claim 1 , wherein the compound interacts with any target in the life cycle of the bacteria.24. The method of claim 22 , wherein the target is EF-Tu.25. A method of treating a bacterial infection in a subject claim 1 , comprising administering to a subject ...

Lipoyl Compounds And Their Use for Treating Ischemic Injury

The present invention relates, in various embodiments, to a compound represented by Structural Formula (I), pharmaceutically acceptable salts or prodrugs thereof, and compositions comprising said compounds, or pharmaceutically acceptable salts or prodrugs thereof. Methods of using compounds of Structural Formulas (I) and (la) or compositions comprising compounds of Structural Formulas (I) and (la), or pharmaceutically acceptable salts or prodrugs thereof, to treat ischemia or ischemia-reperfusion injury are also disclosed.

Synthetic Ion Channels

Provided herein are self-assembling compounds that can form ion channels in lipid bilayers or cell membranes and ion-channel-forming compositions comprising the self-assembling compounds. Also provided are methods of making and using the ion channels formed from a plurality of molecules of the self-assembling compounds. Further, provided are methods of treating or preventing conditions and diseases that are related to the dysfunction of ion channels, including chloride channels. 2. The self-assembling compound of claim 1 , wherein Y is a monovalent claim 1 , divalent claim 1 , trivalent claim 1 , tetravalent claim 1 , pentavalent or hexavalent linking group formed by removing one claim 1 , two claim 1 , three claim 1 , four claim 1 , five and six hydrogen atoms respectively from an unsubstituted or substituted hydrocarbon or carbocycle.3. The self-assembling compound of claim 1 , wherein at least one of Zor Zis S or NR'.4. The self-assembling compound of claim 1 , wherein at least one of A claim 1 , B claim 1 , and D is O or S.5. The self-assembling compound of claim 1 , wherein each of A and D is a bond.6. The self-assembling compound of claim 1 , wherein each of B claim 1 , B claim 1 , and Bis independently NH.7. The self-assembling compound of claim 1 , wherein X is hydrocarbyl or substituted hydrocarbyl.10. The self-assembling compound of claim 9 , wherein at least one of Zor Zis S or NR.11. The self-assembling compound of claim 9 , wherein at least one of A claim 9 , B claim 9 , C claim 9 , and D is O or S.12. The self-assembling compound of claim 9 , wherein each of B claim 9 , B claim 9 , and Bis independently NH.13. A composition claim 9 , comprising a cell membrane and a plurality of molecules of the self-assembling compound of .14. The composition of claim 13 , wherein the cell membrane comprises a lipid bilayer.15. The composition of claim 14 , wherein the plurality of molecules self-assemble to form an anion channel across the thickness of the lipid ...

LISSENCEPHALY THERAPEUTIC AGENT

An object of the present invention is to provide a medicament and method for treating lissencephaly patients. The present invention provides a lissencephaly therapeutic or preventive agent comprising a compound represented by the general formula (I): 4. The lissencephaly therapeutic or preventive agent according to claim 1 , wherein the heterocyclic group that is a substituent for the lower alkyl represented by Ris pyridyl optionally having lower alkyl.5. The lissencephaly therapeutic or preventive agent according to claim 1 , wherein the heteroatom of the heterocyclic group represented by Ris oxygen.6. The lissencephaly therapeutic or preventive agent according to claim 1 , wherein the lower alkyl represented by Ris cyclopropyl.7. The lissencephaly therapeutic or preventive agent according to claim 1 , wherein the compound represented by the general formula (I) is ((1S)-1-((((1S)-1-benzyl-2 claim 1 ,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 2-methoxyethyl ester claim 1 , ((1S)-1-((((1S)-1-benzyl-2 claim 1 ,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester claim 1 , ((1S)-1-((((1S)-1-benzyl-2 claim 1 ,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 8-methoxy-3 claim 1 ,6-dioxaoctyl ester claim 1 , ((1S)-1-((((1S)-1-benzyl-2 claim 1 ,3-dioxo-3-(cyclopropylamino)propyl)amino)carbonyl)-3-methylbutyl)carbamic acid 11-methoxy-3 claim 1 ,6 claim 1 ,9-trioxaundecanyl ester claim 1 , or ((1S)-1-((((1S)-1-benzyl-3-(cyclopropylamino)-2 claim 1 ,3-dioxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 2-(pyridin-2-yl)ethyl ester.8. The lissencephaly therapeutic or preventive agent according to claim 1 , which is an oral preparation claim 1 , injection claim 1 , or intravenous drip.9. The lissencephaly therapeutic or preventive agent according to claim 1 , wherein the compound represented by the general formula (I) is used such that 50 to 1 claim 1 ,200 ...

SERINE PROTEASE INHIBITORS

The invention provides methods of making and using compounds of the formula shown, which are inhibitors of human plasmin and plasma kallikrein. (Formula I) The compounds are useful for the prevention of blood loss, and as components of fibrin adhesives. 2. A compound according to claim 1 , wherein Ris a CHgroup bearing an aryl group.5. A pharmaceutical composition comprising one or more compounds according to claim 1 , further comprising one or more pharmaceutically acceptable carriers or excipients.6. A method for therapeutic modulation of the blood coagulation cascade or fibrinolysis claim 1 , for treating a hyperfibrinolytic condition in a patient claim 1 , or for controlling blood loss in a patient claim 1 , said method comprising administering to a patient in need thereof an effective amount of one or more compounds according to .78-. (canceled)9. The method of claim 6 , wherein said method is to control blood loss in a patient and said patient is undergoing an organ transplant or cardiac surgical procedure or said patient is undergoing a surgical procedure with cardiopulmonary bypass.10. (canceled)11. A method for inhibiting plasmin alone claim 1 , or plasmin and plasma kallikrein claim 1 , in a patient claim 1 , comprising administering to said patient an effective amount of one or more compounds according to .1216-. (canceled)17. A compound according to for use as a medicament for the inhibition of plasmin alone claim 1 , or for the inhibition of plasmin and plasma kallikrein.18. A fibrin adhesive comprising at least one compound according to .19. A compound according to for use as a component of a fibrin adhesive.2023-. (canceled) This application claims benefit of U.S. Provisional Patent Application No. 61/362,127, filed Jul. 7, 2010, which is hereby incorporated by reference in its entirety.The invention relates to the fields of organic chemistry, serine proteases (particularly plasmin and plasma kallikrein), hemostasis, and fibrinolysis.Plasmin (EC 3.4. ...

NOVEL LIPID DIPEPTIDE AND GEL

There is provided a gelator that is capable of forming a gel by an extremely small amount of addition in a wide pH range from acidic to alkaline regions, and a gel having high environmental compatibility, biocompatibility, and biodegradability. A gelator comprising: a lipid peptide of Formula (1) wherein Ris a Caliphatic group, Ris a hydrogen atom or a Calkyl group optionally having a Cbranched chain, Ris a —(CH)—X group, n is a number from 1 to 4, and X is an amino group, a guanidino group, a —CONHgroup, or a 5-membered ring optionally having 1 to 3 nitrogen atoms, a 6-membered ring optionally having 1 to 3 nitrogen atoms, or a fused heterocycle including a 5-membered ring and a 6-membered ring that optionally has 1 to 3 nitrogen atoms); or a pharmaceutically usable salt of the lipid peptide. 2. The fiber according to claim 1 , further comprising a surfactant.3. The fiber according to claim 2 , wherein the surfactant is an anionic surfactant claim 2 , a nonionic surfactant claim 2 , or a cationic surfactant.4. A gel comprising the fiber of claim 1 , and a solvent.5. The gel according to claim 4 , wherein the fiber adheres to or includes a low-molecular weight compound.6. The gel according to claim 4 , wherein the solvent is water claim 4 , an alcohol claim 4 , an aqueous solution claim 4 , an alcoholic solution claim 4 , a hydrophilic organic solution claim 4 , a higher alcohol claim 4 , a fatty acid claim 4 , higher fatty acid esters claim 4 , a glyceride claim 4 , a hydrophobic organic solution claim 4 , or a miscible mixed solvent thereof.7. The gel according to claim 6 , wherein the solvent is water claim 6 , an alcohol claim 6 , an aqueous solution claim 6 , an alcoholic solution claim 6 , a hydrophilic organic solution claim 6 , a higher alcohol claim 6 , a hydrophobic organic solution claim 6 , or a miscible mixed solvent thereof.8. The gel according to claim 6 , wherein the alcoholic solution is a mixed solution of at least one alcohol selected from a group ...

NOVEL LIPID DIPEPTIDE AND GEL

There is provided a gelator that is capable of forming a gel by an extremely small amount of addition in a wide pH range from acidic to alkaline regions, and a gel having high environmental compatibility, biocompatibility, and biodegradability. A gelator comprising: a lipid peptide of Formula (1) wherein Ris a Caliphatic group, Ris a hydrogen atom or a Calkyl group optionally having a Cbranched chain, Ris a —(CH)—X group, n is a number from 1 to 4, and X is an amino group, a guanidino group, a —CONHgroup, or a 5-membered ring optionally having 1 to 3 nitrogen atoms, a 6-membered ring optionally having 1 to 3 nitrogen atoms, or a fused heterocycle including a 5-membered ring and a 6-membered ring that optionally has 1 to 3 nitrogen atoms); or a pharmaceutically usable salt of the lipid peptide. 2. A gel comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the lipid peptide or the pharmaceutically usable salt of the lipid peptide as claimed in ; and a solvent.'}3. The gel according to claim 2 , wherein the solvent is water claim 2 , an alcohol claim 2 , an aqueous solution claim 2 , an alcoholic solution claim 2 , a hydrophilic organic solution claim 2 , a higher alcohol claim 2 , a fatty acid claim 2 , higher fatty acid esters claim 2 , a glyceride claim 2 , a hydrophobic organic solution claim 2 , or a miscible mixed solvent thereof.4. The gel according to claim 3 , wherein the solvent is water claim 3 , an alcohol claim 3 , an aqueous solution claim 3 , an alcoholic solution claim 3 , a hydrophilic organic solution claim 3 , a higher alcohol claim 3 , a hydrophobic organic solution claim 3 , or a miscible mixed solvent thereof.5. The gel according to claim 3 , wherein the alcoholic solution is a mixed solution of at least one alcohol selected from a group consisting of methanol claim 3 , ethanol claim 3 , 2-propanol claim 3 , and i-butanol and water.6. The gel according to claim 3 , wherein the hydrophilic organic solution is a mixed solution of at least ...

Hepatitis C Virus Inhibitors

Hepatitis C virus inhibitors are disclosed having the general formula: This Divisional application claims the benefit of U.S. Ser. No. 13/597,381 filed Aug. 29, 2012, now allowed, which in turn is a continuation application which claims the benefit of U.S. Ser. No. 12/966,175 filed Dec. 13, 2010, now U.S. Pat. No. 8,299,094, which in turn is a continuation application which claims the benefit of U.S. Ser. No. 12/202,603 filed Sep. 2, 2008, now U.S. Pat. No. 7,915,291, which in turn is a continuation application which claims the benefit of U.S. Ser. No. 11/295,914, filed Dec. 7, 2005, now U.S. Pat. No. 7,449,479, which in turn is a continuation application which claims the benefit of U.S. Ser. No. 10/441,657, filed May 20, 2003, now U.S. Pat. No. 6,995,174, which in turn claims the benefit of provisional application U.S. Ser. No. 60/382,055, filed May 20, 2002, now expired.The present invention is generally directed to antiviral compounds, and more specifically directed to compounds which inhibit the functioning of the NS3 protease encoded by Hepatitis C virus (HCV), compositions comprising such compounds and methods for inhibiting the functioning of the NS3 protease.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).Presently, the most effective HCV therapy employs a combination of alpha-interferon and ribavirin, leading to sustained efficacy in 40% of patients. (Poynard, T. et al. (1998), 352, 1426-1432). Recent clinical results demonstrate that pegylated alpha-interferon is superior to unmodified alpha-interferon as monotherapy (Zeuzem, S. et al. . (2000), 343, 1666-1672). However, even with experimental therapeutic regimens involving combinations of ...

Therapeutic or Preventive Agent for Diabetes

A collagen peptide mixture containing three or more kinds selected from Glu-Hyp-Gly, Glu-Hyp, Leu-Hyp-Gly, Pro-Ala, Ser-Hyp, Ala-Hyp-Gly, chemically-modified substances thereof and pharmaceutically acceptable salts thereof, and at least one peptide selected from the group consisting of Glu-Hyp-Gly, Glu-Hyp, Leu-Hyp-Gly, Pro-Ala, Ser-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, Ser-Hyp-Gly, Gly-Pro-Hyp, (Pro-Hyp-Gly) 5 , Pro-Hyp, Hyp-Gly, Pro-Gly, Pro-Pro and Ala-Hyp or a chemically-modified substance thereof or a pharmaceutically acceptable salt thereof have DPPTV inhibitory activity and/or GLP-1 secretion accelerating activity, and hence are effective as a therapeutic or preventive agent or the like for diabetes.

DIMERIC IAP INHIBITORS

The present invention provides compounds of formula M-L-M′ (where M and M′ are each independently a monomeric moiety of Formula (I) and L is a linker). The dimeric compounds have been found to be effective in promoting apoptosis in rapidly dividing cells. (I) 5. A compound selected from the group consisting of(S,S,S)-N,N′-(propane-1,3-diyl)bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);(S,S,S)-N,N′-(4,7,10,13,16-pentaoxanonadecane-1,19-diyl)bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);(S,S,S)-N,N′-(3,3′-(2,2′-oxybis(ethane-2,1-diyl)bis(oxy))bis(propane-3,1-diyl))bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)-butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);(S,S,S)-N,N′-(2,2′-(ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);(S,S,S)-N,N′-(3,3′-(ethane-1,2-diylbis(oxy))bis(propane-3,1-diyl))bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);(S,S,S)-N,N′-(ethane-1,2-diyl)bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);(S,S,S)-N,N′-(biphenyl-4,4′-diylbis(methylene))bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);(S,S,S)-N,N′-(undecane-1,1′-diyl)bis(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamide);1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)-propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-N-(3-(3-(1-(5-((S)-1-((S)-3-methyl-2-((S)-2-(methylamino)-propanamido)butanoyl)pyrrolidin-2-yl)pyridin-3-yl)-1H-indole-3-carboxamido)-propoxy)propyl)-1H- ...

NOVEL SELECTIVE INHIBITORS OF PROLYLCARBOXYPEPTIDASE

The present invention relates to compounds of the formulae: 2. A pharmaceutical composition comprising at least one compound according to or an isostere or salt thereof and a pharmaceutically acceptable carrier.3. A method of treating a subject in need of anorexigenic and anti-inflammatory treatment comprising administering to the subject in need of the treatment an effective amount of at least one compound or an isostere or salt thereof according to .4. A method of treating a subject in need of anorexigenic and anti-inflammatory treatment comprising administering to the subject in need of the treatment an effective amount of the pharmaceutical composition according to .5. An anorexigenic and anti-inflammatory composition comprising at least one compound according to or an isostere or salt thereof.6. An anorexigenic and anti-inflammatory pharmaceutical composition comprising at least one compound according to or an isostere or salt thereof and a pharmaceutically acceptable carrier.7. A method of treating obesity comprising administering to a subject in need of the treatment an effective amount of at least one compound according to or an isostere or salt thereof.8. A method of treating obesity comprising administering to the subject in need of the treatment an effective amount of the pharmaceutical composition according to .9. The compound of claim 1 , wherein R is Calkyl.10. The pharmaceutical composition of claim 2 , where R is Calkyl.11. The method of claim 3 , where R is Calkyl.12. The anorexigenic and anti-inflammatory composition of claim 5 , where R is Calkyl.13. The method of treating obesity according to claim 7 , where R is Calkyl. This is a §371 National Stage Application of International Application No. PCT/US2011/062889 filed 1 Dec. 2011 (1 Dec. 2010), pending, which claims priority of U.S. Provisional Application No. 61/418,708 filed 1 Dec. 2010 (1 Dec. 2010), the entire contents of which are incorporated herein by reference in their entirety.This ...

Boron containing polybasic bacterial efflux pump inhibitors and therapeutic uses thereof

Disclosed herein are polybasic bacterial efflux pump inhibitors containing boronic acid functionality and their methods of synthesis, methods of use, and pharmaceutical compositions. Some embodiments include methods of treating or preventing a bacterial infection by co-administering to a subject infected with bacteria or at risk of infection with bacteria the efflux pump inhibitor with another anti-bacterial agent.

Methods of Treating Depression and Other Related Diseases

The invention relates to methods for treating depression, anxiety, and other related diseases by administering a peptide NMDAR partial agonist.

Branched Linker for Protein Drug Conjugates

The present invention relates to method for connecting a protein and a drug to a protein drug conjugate, wherein the drug is linked to the protein through a specific branched linker, said branched linker comprises a peptide chain and is derived from o-hydroxy p-amino benzylic alcohol, wherein the peptide chain is connected to the phenyl ring via the p-amino group, the drug is connected to the phenyl ring via the benzylic alcohol moiety, and the protein is connected to the phenyl ring via the o-hydroxy group; further to a process for the preparation of said protein-drug-conjugates via various intermediates, to the pharmaceutical use of such protein drug conjugates, such as methods of controlling the growth of undesirable cells, to pharmaceutical compositions comprising such protein drug conjugates, and to intermediates of the preparation of the protein drug conjugates. 7. A compound of formula (I) claim 2 , with compound of formula (I) as defined in .9. A compound of formula (II) claim 3 , with compound of formula (II) as defined in .11. A compound selected from the group consisting ofcompound of formula (IIc), compound of formula (III), compound of formula (IV), compound of formula (IV-IIa), compound of formula (V), compound of formula (Va), compound of formula (III0-IIa), compound of formula (III0), compound of formula (IV0), compound of formula (IV0a), compound of formula (V0) and compound of formula (III0-I-IVa);with{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, 'compound of formula (IIc), compound of formula (III), compound of formula (IV), compound of formula (IV-IIa), compound of formula (V), compound of formula (Va), compound of formula compound of formula (III0), compound of formula (IV0), compound of formula (IV0a), compound of formula (V0) and compound of formula (III0-I-IVa) as defined in .'}13. A compound of formula (VI) claim 5 , with compound of formula (VI) as defined in .15. Use of the compound of formula (I) claim 2 , the compound of formula (I) ...

SMALL MOLECULE INHIBITORS OF AGBL2

Small molecule inhibitors of AGBL2 are provided, as well as methods of using the inhibitors to treat or prevent cancer and neurologic disorders. 2. The compound of claim 1 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.6. The compound of claim 5 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.1110. A composition comprising a compound of any of - and a pharmaceutically acceptable carrier.13. The method of claim 12 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.17. The method of claim 16 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.2322. The method of any of - claims 1 , further comprising administering a second therapeutic agent to the subject.24. The method of claim 23 , wherein the second therapeutic agent is a chemotherapeutic agent.26. The method of claim 25 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.30. The method of claim 29 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.3635. The method of any of - claims 25 , further comprising administering a second therapeutic agent to the subject.37. The method of claim 36 , wherein the second therapeutic agent is an anti-depressant or an anxiolytic. This application claims priority to U.S. Provisional Application No. 61/443,069, filed Feb. 15, 2011, which is incorporated herein by reference in its entirety.The removal of the C-terminal tyrosine of α-tubulin to form detyrosinated α-tubulin is involved in several aspects of microtubule function, including kinesin interactions, spindle dynamics, mitosis, and neuronal specification. Microtubules containing large amounts of detyrosinated α-tubulin are more stable and resistant to depolymerization by destabilizing agents. Further, detyrosinated α-tubulin has been shown to be elevated in aggressive breast and prostate cancers.Provided herein are small molecule inhibitors of ATP/GTP binding protein ...

PEPTIDES AND METHODS USING SAME FOR DIAGNOSIS AND TREATMENT OF AMYLOID-ASSOCIATED DISEASE

Peptides having at least 2 amino acids and no more than 15 amino acids are provided. The peptides comprise amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine. Also provided are pharmaceutical compositions and kits including such peptides as well as methods using same for diagnosing and treating amyloid associated diseases. 2. The method of claim 1 , wherein the amyloid-associated disease is Alzheimer's disease.3. The method of wherein said systemically administering comprises parenteral administration.4. The method of claim 1 , wherein said systemically administering is by oral administration claim 1 , rectal administration claim 1 , transmucosal administration claim 1 , transnasal administration claim 1 , intramuscular administration claim 1 , subcutaneous administration claim 1 , intramedullar injection claim 1 , intrathecal administration claim 1 , direct intraventricular administration claim 1 , intravenous administration claim 1 , intraperitoneal administration and intranasal injection.5. The method of claim 1 , wherein Ris methyl or alkyl substituted by halo.6. The method of claim 5 , wherein Rand Rare each hydrogen and Ris hydroxy.7. The method of claim 1 , wherein said dipeptide is as set forth in SEQ ID NO: 145.9. The method of claim 8 , wherein said peptide is an active ingredient of a pharmaceutical composition which also includes a physiologically acceptable carrier.10. The method of claim 8 , wherein the amyloid-associated disease is Alzheimer's disease.11. The method of claim 8 , wherein Ris methyl or alkyl substituted by halo.12. The method of claim 11 , wherein Rand Rare each hydrogen and Ris hydroxy.13. The method of claim 8 , wherein said dipeptide is as set forth in SEQ ID NO: 145. This application is a division of U.S. patent application Ser. No. 12/654,461 filed on Dec. 22, 2009, which is a division of U.S. patent application Ser. No. 10/562,852 filed on Apr. 19, 2006, now abandoned, ...

Peptide deformylase inhibitors

The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.

SUBSTITUTED ADIPIC ACID AMIDES AND USES THEREOF

The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein A is a five to eight membered monocyclic or a nine to twelve membered bicyclic heterocyclic ring, as further defined herein; Y is S, CH, or CH; Z is CH or N; Rand Rare hydrogen or (C-C)alkyl; Ris (C-C)alkoxy, OH, CN, (C-C)alkyl, halogen, or CF; r and s are 0, 1, or 2; and Rand Rare as further defined herein. These compounds are agonists, partial agonists and/or modulators of the NPY4 receptor and may be used for the treatment and prophylaxis of obesity, food intake, and other diseases and conditions modulated by the NPY4 receptor. 7. The compound according to claim 6 , wherein:X is S;{'sup': 5', '6, 'sub': 'm', 'Q is (CRR);'}{'sup': '1', 'sub': 2', '1', '3', '1', '4, 'Ris —CH-phenyl, wherein the phenyl is optionally substituted with halogen, (C-C)alkyl, and (C-C)alkoxyl;'}{'sup': 3a', '4a, 'sub': '3', 'Rand Rare independently hydrogen or COOCH;'}{'sup': 3b', '4b, 'sub': '3', 'Rand Rare each either hydrogen or CF;'}{'sup': 5', '6, 'sub': '3', 'Rand Rare each hydrogen or CH;'}m is 2; andt is 1.9. The compound according to claim 8 , wherein:{'sup': '1', 'sub': 2', '1', '3', '1', '4, 'Ris —CH-phenyl, wherein the phenyl is optionally substituted with one of halogen, (C-C)alkyl, or (C-C)alkoxyl;'}{'sup': '3a', 'sub': '3', 'Ris independently hydrogen or CF;'}{'sup': '3b', 'sub': '3', 'Ris independently hydrogen or CF; and'}{'sup': '10', 'sub': '3', 'Ris phenyl optionally substituted with —OCH.'}12. The compound according to claim 11 , wherein:{'sup': '3a', 'sub': 3', '3', '2', '3', '3, 'Ris hydrogen, CN, CF, CH,CHCH, propylene, or COOCH; and'}{'sup': '10', 'sub': 3', '3, 'Ris isobutyl, phenyl, or benzyl, wherein the phenyl or benzyl optionally are substituted ortho with —CHor —OCH.'}1312. A pharmaceutical composition comprising one or more compounds according to any one of through claims 1 , and a pharmaceutically acceptable carrier.14. Use of a composition ...

Angiotensin converting enzyme inhibitory peptide

To provide ACE inhibitory peptides which can effectively inhibit ACE by a small amount of ingestion and have no fear of causing side effects and which can be orally ingested easily during daily life by persons having high blood pressure, and compositions comprising the peptides. The peptides represented by the following structural formulae (1) to (9), and salts thereof are provided. (1) Asp-Arg-Pro, (2) Asn-Trp, (3) Val-Gly-Leu, (4) Ile-Gly-Val, (5) Gly-Val-Pro, (6) Ile-Pro-Tyr, (7) pyroGlu-Pro, (8) Tyr-Thr, (9) Pro-Trp

BORONATE ESTER COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases. 3. The compound of claim 2 , wherein each of Rand Rindependently is hydrogen claim 2 , Caliphatic claim 2 , or —(CH)—COH;and p is 0, 1, or 2.4. The compound of wherein P is R—C(O)— claim 3 , R—O—C(O)— claim 3 , R—N(R)—C(O)— claim 3 , R—S(O)— claim 3 , or R—N(R)—S(O)—;{'sup': c', 'D', '1', 'D', '1', '2c, 'sub': 1-6', '1-6, 'claim-text': [{'sup': 1', '3a', '3b', '5', '5, 'sub': '1-6', 'Tis a Calkylene chain substituted with 0-2 independently selected Ror R, wherein the alkylene chain optionally is interrupted by —C(R)═C(R)—, —C≡C—, or —O—;'}, {'sup': 'D', 'Ris a substituted or unsubstituted mono- or bicyclic ring system;'}, {'sup': 2c', '5', '6', '6', '6', '4', '4', '4', '5', '4', '4', '4', '6', '4', '6', '4', '4', '5', '4', '5', '5', '4, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'Ris halo, —OR, —SR, —S(O)R, —SOR, —SON(R), —N(R), —NRC(O)R, —NRC(O)—N(R), —NRCOR, —N(R)SOR, —N(R)SON(R), —O—C(O)R, —OC(O)N(R), —C(O)—R, —COR, or —C(O)N(R);'}, {'sup': 3a', '4, 'sub': 1-4', '2', '1-4', '2', '2', '1-4', '2', '1-4, 'each Rindependently is selected from the group consisting of —F, —OH, —O(Calkyl), —CN, —N(R), —C(O)(Calkyl), —COH, —CO(Calkyl), —C(O)NH, and —C(O)—NH(Calkyl);'}, {'sup': 3b', '3a', '7', '3b, 'sub': '1-3', 'each Rindependently is a Caliphatic substituted or unsubstituted with Ror R; or two substituents Ron the same carbon atom, taken together with the carbon atom to which they are attached, form a 3- to 6-membered cycloaliphatic ring;'}, {'sup': '7', 'each Ris a substituted or unsubstituted aromatic group; and'}], 'Ris selected from the group consisting of Caliphatic, Cfluoroaliphatic, —R, -T-R, and -T-R;'}{'sup': '4c', 'sub': 1-4', '1-4', '6-10', '1-4, 'Ris hydrogen, Calkyl, Cfluoroalkyl, or ...

3-Amino-2-Hydroxy-4-Phenylbutanoyl-Valyl-Isoleucine, Preparation and Use Thereof

The present invention relates to a novel compound, 3-amino-2-hydroxy-4-phenylbutanoyl-valyl-isoleucine with structure showed below. 110-. (canceled)12. A method of preparing the compound of comprising:{'i': 'Streptomyces parvus', 'a) transferring a stock culture of CGMCC No. 4027 into a slant culture medium and incubating;'}b) transferred the slant culture into a sterilized seed culture medium and cultivating;c) fermenting the seed culture in a fermentation medium comprising a carbon source and a nitrogen source;d) isolating and purifying a fraction from the fermentation medium containing a target compound; and{'claim-ref': {'@idref': 'CLM-00011', 'claim 11'}, 'e) identifying the compound of from the fraction.'}13. The method of claim 12 , wherein said slant culture medium comprises Gaise's synthetic agar.14. The method of claim 12 , wherein said seed culture comprises a combination of glucose claim 12 , glycerol claim 12 , soluble starch claim 12 , soybean meal claim 12 , KHPO claim 12 , and MgSOwith an initial pH of about 7.3-7.5.15. The method of claim 12 , wherein said fermentation medium comprises soybean meal claim 12 , dextrin claim 12 , glucose claim 12 , Fe(NH)(SO)with an initial pH of about 7.3-7.5.16. The method of claim 12 , wherein said isolation and purification step comprises chromatography or HPLC for eluting the fraction containing target compound.17. The method of claim 16 , wherein said eluted fraction target compound is further concentrated and dried for obtaining the purified compound.18. The method of claim 16 , wherein said compound of is identified by high resolution MS analysis.19. The method of claim 12 , wherein said compound is an aminopeptidase inhibitor.20. The method of claim 19 , wherein said aminopeptidase inhibitor is an aminopeptidase N inhibitor.21. A method for a cancer treatment claim 11 , a cancer adjuvant treatment claim 11 , or an immunoenhancement comprising administering to a subject in need an effective amount of the ...

Methods of Producing Anamorelin Hydrochloride Having Controlled Chloride Content

The present invention relates to particulate forms of anamorelin monohydrochloride or a composition comprising anamorelin monohydrochloride having controlled chloride content, preferably isolated in an amorphous and/or fine particulate state, processes for making the particulate forms, and pharmaceutical compositions comprising the particulate forms.

PEPTIDE NANOSTRUCTURES AND METHODS OF GENERATING AND USING THE SAME

A tubular or spherical nanostructure composed of a plurality of peptides, wherein each of the plurality of peptides includes no more than 4 amino acids and whereas at least one of the 4 amino acids is an aromatic amino acid. 1. A composition comprising:(i) a tubular or spherical nanostructure being composed of a plurality of peptides, wherein each of said plurality of peptides includes aromatic homodipeptides or wherein each of said plurality of peptides includes no more than 4 amino acids and comprises Phe-Phe; and(ii) an agent being attached to said tubular or spherical nanostructure.2. The composition of claim 1 , wherein said agent is selected from the group consisting of a drug claim 1 , a nucleic acid molecule and a polypeptide.3. The composition of claim 1 , wherein said agent is capable of being slowly released from said nanostructure.4. The composition of claim 1 , wherein said aromatic moiety is selected from the group consisting of substituted or unsubstituted naphthalenyl and substituted or unsubstituted phenyl.5. The composition of wherein said substituted phenyl is selected from the group consisting of pentafluoro phenyl claim 1 , iodophenyl claim 1 , biphenyl and nitrophenyl.6. The composition of claim 1 , wherein said homodipeptide is selected from the group consisting of naphthylalanine-naphthylalanine dipeptide claim 1 , (pentafluoro-phenylalanine)-(pentafluoro-phenylalanine)dipeptide claim 1 , (iodo-phenylalanine)-(iodo-phenylalanine)dipeptide claim 1 , (4-phenyl phenylalanine)-(4-phenyl phenylalanine)dipeptide and (p-nitro-phenylalanine)-(p-nitro-phenylalanine)dipeptide.7. A composition comprising a matrix and a plurality of nanostructures dispersed throughout said matrix claim 1 , said nanostructure being composed of a plurality of peptides claim 1 , wherein each of said plurality of peptides includes aromatic homodipeptides or wherein each of said plurality of peptides includes no more than 4 amino acids and comprises Phe-Phe.8. The composition ...

Macrocyclic inhibitors of flaviviridae viruses

Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Compounds for enzyme inhibition

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

Macrocyclic Compounds and Methods for Their Production

There is provided inter alia compounds of formula (I): 2. A compound according to wherein n represents a single bond.3. A compound according to claim 1 , wherein Rrepresents OH.4. A compound according to wherein Xrepresents C.5. A compound according to wherein Xrepresents C.6. A compound according to wherein Xrepresents C.7. A compound according to wherein Xrepresents C.8. A compound according to wherein Xrepresents C.9. A compound according to wherein Rrepresents H.10. A compound according to wherein Rrepresents H.11. A compound according to wherein Rrepresents OH.12. A compound according to wherein Rrepresents H claim 1 , Me or F.13. A compound according to wherein Rrepresents H or F.14. A compound according to wherein Rand/or Rrepresents F.15. A compound according to wherein Xrepresents NRR.16. A compound according to wherein Rrepresents alkyl claim 15 , alkenyl claim 15 , cycloalkyl claim 15 , cycloalkenyl claim 15 , alkylcycloalkyl claim 15 , alkylcycloalkenyl claim 15 , alkenylcycloalkyl claim 15 , alkenylcycloalkenyl claim 15 , aryl claim 15 , heteroaryl claim 15 , alkylaryl claim 15 , alkylheteroaryl claim 15 , alkenylaryl or alkenylheteroaryl and Rrepresents H claim 15 , alkyl claim 15 , alkenyl or —Oalkyl.19. (canceled)20. (canceled)21. A pharmaceutical composition comprising a compound according to together with a pharmaceutically acceptable diluent or carrier.22. A pharmaceutical composition comprising a compound according to together with a pharmaceutically acceptable diluent or carrier further comprising a second or subsequent active ingredient.23. A method of treatment of viral infections such as HCV or HIV infection or for use as an immunosuppressant or an anti-inflammatory agent which comprises administering to a subject a therapeutically effective amount of a compound according to . The present invention relates to sanglifehrin analogues, that are useful both as cyclophilin inhibitors, e.g. in the treatment of viral infection by viruses such as ...

Selective Cysteine Protease Inhibitors and Uses Thereof

The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease). 2. The compound according to claim 1 , in which A is H.3. The compound according to claim 1 , in which A is selected from the group consisting of PhCHOC(O)— claim 1 , Qunoline-C(O)— claim 1 , and (4-amino-3-chlorobenzene)-C(O)—.4. The compound according to claim 1 , in which Z is CORand Ris selected from the group consisting of OH claim 1 , OCH claim 1 , and CHCH5. The compound according to claim 1 , in which Z is CORand Ris OH.6. The compound according to claim 1 , in which a and b are both 0.7. The compound according to claim 1 , in which a is 0 and b is 1.8. (canceled)9. The compound according to claim 1 , in which a is 0 claim 1 , b is 0 and c is 0.10. The compound according to claim 1 , in which a is 0 claim 1 , b is 0 claim 1 , c is 0 and d is 0.11. The compound according to claim 1 , in which Ris in the trans configuration.12. The compound according to claim 1 , wherein Ris{'sub': '2', 'sup': '5', '1) SOR,'}{'sub': '3', 'sup': '5', '2) SOR,'}{'sup': '5', '3) SOR,'}{'sub': '2', 'sup': '5', '4) CORor'}{'sup': '5', '5) COR'}{'sup': '5', 'sub': 1', '6, 'wherein Ris H, C-Calkyl, aryl, or a heterocylyl.'}13. The compound according to claim 1 , in which Ris1) H,2) halogen,3 ...

Beta Amino Acid Derivatives as Integrin Antagonists

Disclosed herein are novel pharmaceutical agents which are useful as integrin receptor antagonists that mediate the pathologic processes of angiogenesis and fibrosis and as such are useful in pharmaceutical compositions and in methods for treating conditions mediated by these integrins by inhibiting or antagonizing these integrins. The novel pharmaceutical agents include those of the formula: 37.-. (canceled)9. The compound of claim 1 , wherein A is C—OH.10. (canceled)11. The compound of claim 1 , wherein X is halo.1213.-. (canceled)14. The compound of claim 1 , wherein X is alkylor substituted alkyl.1517.-. (canceled)18. The compound of claim 1 , wherein X is cyano.19. The compound of claim 1 , wherein X is heteroaryl.2021.-. (canceled)22. The compound of claim 1 , wherein L is hydrogen.23. The compound of claim 1 , wherein Y is t-butyl.24. The compound claim 1 , wherein Y is 2-hydroxy-isopropyl.2639.-. (canceled)4153.-. (canceled)54. The compound of claim 1 , wherein Z is hydrogen.5558.-. (canceled)59. The compound of claim 1 , wherein R′ is hydrogen.6082.-. (canceled)85. (canceled)86. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) the compound of ; and'}b) an excipient.87. A method of treating and/or preventing a disease or a disorder in a patient in need thereof claim 1 , comprising administering to the patient a compound of in an amount sufficient to treat and/or prevent the disease or disorder.88125.-. (canceled)127196.-. (canceled) This application claims the benefit of U.S. Provisional Applications Nos. 61/673,058 filed Jul. 18, 2012 and 61/764,443 filed Feb. 13, 2013, both of which are incorporated herein by reference in their entirely.I. Field of the InventionThe present invention relates to the fields of pharmaceuticals, medicine and cell biology. More specifically, it relates to pharmaceutical agents (compounds) which are useful as integrin receptor antagonists, with particularly exceptional biological ...

Compounds for enzyme inhibition

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

Hepatocyte Growth Factor Mimics as Therapeutic Agents

Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia (e.g. Alzheimer's) and Parkinson's disease. 2. The method of claim 1 , wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.3. The method of claim 1 , wherein said dementia is Alzheimer's disease dementia.5. The method of wherein said step of administering is performed multiple times over a period of time.6. The method of further comprising the steps of testing cognition of said subject during said period of time claim 5 , and adjusting an amount of said one or more HGF mimics administered based on test results.7. The method of claim 4 , wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.9. The method of wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.11. The method of claim 1 , wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide. 1. Field of the InventionThe invention generally relates to methods of using hepatocyte growth factor (HGF) mimics to treat dementia and Parkinson's disease.2. Background of the InventionThere are approximately 10 million diagnosed dementia patients in the United States alone and that number continues to grow every year as the population ages. The costs of treatment and care of these patients are in excess of $70 billion annually and are increasing rapidly. Unfortunately, the current treatment options for the management of dementia are severely limited and largely ineffective. The lack of treatment options for a burgeoning health problem of this magnitude necessitates that new and innovative therapeutic approaches be developed as quickly as possible.At its core dementia results from a combination of diminished synaptic connectivity ...

Binding ligand linked drug delivery conjugates of tubulysins

Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations. The compounds described herein include conjugates of tubulysins and vitamin receptor binding ligands. The conjugates also include a releasable bivalent linker.

TRYPSIN-LIKE SERINE PROTEASE INHIBITORS, AND THEIR PREPARATION AND USE

The invention provides compounds that are effective as inhibitors of human plasmin and plasma kallikrein, and that are useful for the prevention of blood loss and as components of fibrin adhesives. The invention further provides methods of making and using the compounds. 2. The method according to claim 1 , wherein n is 2 or 3.3. The method according to claim 1 , wherein R is selected from the group consisting of phenyl claim 1 , 4-pyridyl claim 1 , 4-pyridyl N-oxide and 4-piperidinyl.4. The method according to claim 3 , wherein R is selected from the group consisting of unsubstituted phenyl claim 3 , unsubstituted 4-pyridyl claim 3 , unsubstituted 4-pyridyl N-oxide and unsubstituted 4-piperidinyl.5. The method according to claim 1 , wherein n is 0 and R is phenyl.6. The method according to claim 1 , wherein n is 2 or 3 and R is 4-piperidinyl; wherein the nitrogen of said piperidinyl bears a substituent selected from the group consisting of C(═O)R′ claim 1 , C(═O)CHOR′ claim 1 , COR′ claim 1 , C(═O)NHR′ claim 1 , and C(═O)NR′.7. The method according to claim 1 , wherein a pharmaceutical composition is administered to the patient claim 1 , wherein the pharmaceutical composition comprises one or more of the compounds of claim 1 , and one or more pharmaceutically acceptable carriers or excipients.12. A pharmaceutical composition comprising a compound of in combination with one or more pharmaceutically acceptable carriers or excipients.14. A pharmaceutical composition comprising a compound of in combination with one or more pharmaceutically acceptable carriers or excipients. The invention relates to the fields of organic chemistry, serine proteases (particularly plasmin and plasma kallikrein), and hemostasis, and to therapeutic modulation of the blood coagulation cascade and fibrinolysis.Plasmin (EC 3.4.21.7, fibrinolysin) is a trypsin-like serine protease which effects protein cleavage at arginine or lysine residues; its principal substrates are fibrin and ...

COMPOUNDS FOR ENZYME INHIBITION

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention. 1. (canceled)3. The method of claim 2 , wherein the immune-related disease is autoimmune disease claim 2 , inflammatory bowel disease claim 2 , diabetes claim 2 , Sjogren's syndrome claim 2 , lupus claim 2 , multiple sclerosis claim 2 , myositis claim 2 , psoriasis claim 2 , rheumatoid arthritis claim 2 , allergies claim 2 , asthma claim 2 , atopic dermatitis claim 2 , scleroderma claim 2 , ankylosing spondylitis claim 2 , dermatomyositis claim 2 , tissue/organ transplant rejection claim 2 , graft versus host disease claim 2 , IgA deficiency claim 2 , severe combined immunodeficiency claim 2 , thymic dysplasia claim 2 , chronic granulomatous claim 2 , acquired immunodeficiency syndrome claim 2 , human immunodeficiency virus claim 2 , drug-induced immunodeficiency.4. The method of claim 3 , wherein the inflammatory bowel disease is selected from Crohn's disease and ulcerative colitis.5. The method of claim 2 , wherein L is C═O claim 2 , Q is absent claim 2 , M is Calkyl and Ris heterocyclylM- and the heterocyclyl moiety is morpholino.7. The method of claim 6 , wherein the cancer is selected from the group consisting of: selected from leukemia claim 6 , lymphoma multiple myeloma claim 6 , solid tumors claim 6 , head and neck squamous cell carcinoma claim 6 , cervical carcinoma claim 6 , and small cell lung carcinoma.8. The method of claim 7 , wherein the cancer is multiple myeloma.9. The method of claim 6 , wherein L is C═O claim 6 , Q is absent claim 6 , M is Calkyl and Ris heterocyclylM- and the heterocyclyl moiety is morpholino.11. The method of claim 10 , ...

BIS(FLUOROALKYL)-1,4-BENZODIAZEPINONE COMPOUNDS AND PRODRUGS THEREOF

Disclosed are compounds of Formula (I) and/or salts thereof: 2. The compound according to and/or at least one salt thereof claim 1 , wherein:Ring A is phenyl;{'sub': '3', 'Ris H; and'}z is 1 or 2.3. The compound according to and/or at least one salt thereof claim 1 , wherein:{'sub': 2', '2', '2', '3, 'Ris —CHCHCF;'}Ring A is phenyl; andz is 1 or 2.4. The compound according to and/or at least one salt thereof claim 1 , wherein:{'sub': 2', '2', '2', '3, 'Ris —CHCHCF;'}Ring A is phenyl;{'sub': a', '1-3', '2, 'Ris Calkyl or —CHOH;'}{'sub': 'b', 'each Ris independently F and/or Cl;'}y is 1; andz is 1 or 2.7. The compound according to selected from: (2R claim 1 ,3S)—N-((3S)-5-(3-fluorophenyl)-9-methyl-2-oxo-2 claim 1 ,3-dihydro-1H-1 claim 1 ,4-benzodiazepin-3-yl)-2 claim 1 ,3-bis(3 claim 1 ,3 claim 1 ,3-trifluoropropyl)succinamide (1); (2R claim 1 ,3S)—N-((3S)-5-(3-chlorophenyl)-9-ethyl-2-oxo-2 claim 1 ,3-dihydro-1H-1 claim 1 ,4-benzodiazepin-3-yl)-2 claim 1 ,3-bis(3 claim 1 ,3 claim 1 ,3-trifluoropropyl)succinamide (2); (2R claim 1 ,3S)—N-((3S)-5-(3-chlorophenyl)-9-isopropyl-2-oxo-2 claim 1 ,3-dihydro-1H-1 claim 1 ,4-benzodiazepin-3-yl)-2 claim 1 ,3-bis(3 claim 1 ,3 claim 1 ,3-trifluoropropyl)succinamide (3); (2R claim 1 ,3S)—N-(9-chloro-5-(3 claim 1 ,4-dimethylphenyl)-2-oxo-2 claim 1 ,3-dihydro-1H-1 claim 1 ,4-benzodiazepin-3-yl)-3-(4 claim 1 ,4 claim 1 ,4-trifluorobutyl)-2-(3 claim 1 ,3 claim 1 ,3-trifluoropropyl)succinamide (4); (2R claim 1 ,3S)—N-(9-chloro-5-(3 claim 1 ,5-dimethylphenyl)-2-oxo-2 claim 1 ,3-dihydro-1H-1 claim 1 ,4-benzodiazepin-3-yl)-3-(4 claim 1 ,4 claim 1 ,4-trifluorobutyl)-2-(3 claim 1 ,3 claim 1 ,3-trifluoropropyl)succinamide (5); (2R claim 1 ,3S)—N-((3S)-9-ethyl-5-(3-methylphenyl)-2-oxo-2 claim 1 ,3-dihydro-1H-1 claim 1 ,4-benzodiazepin-3-yl)-2 claim 1 ,3-bis(3 claim 1 ,3 claim 1 ,3-trifluoropropyl)succinamide (6); (2R claim 1 ,3S)—N-((3S)-5-(3-chlorophenyl)-9-methyl-2-oxo-2 claim 1 ,3-dihydro-1H-1 claim 1 ,4-benzodiazepin-3-yl)-2 claim 1 ,3-bis( ...

HYDROGEL-FORMING MATERIAL

There is provided a hydrogel-forming material from which a hydrogel can be formed with a simpler method and under milder conditions. A hydrogel-forming material comprising a lipid peptide-type gelator that is formed of at least one selected from compound of the following formula (1): 2. The hydrogel-forming material according to claim 1 , whereinthe additive is an additive including either an organic acid or an organic acid salt which has a pH of 6.5 to 9.3 or a pH of 1.8 to 2.5.3. The hydrogel-forming material according to claim 2 , whereinthe additive is at least one organic acid selected from a group consisting of acetic acid, lactic acid, succinic acid, tartaric acid, citric acid, trimellitic acid, malic acid, and phosphoric acid, or is at least one organic acid salt selected from a group consisting of an acetate, a lactate, a succinate, a tartrate, a citrate, a trimellitate, a maleate, and a phosphate.4. A gel which is formed of the hydrogel-forming material according to .5. A gel which is formed of the hydrogel-forming material according to .6. A gel which is formed of the hydrogel-forming material according to . The present invention relates to a hydrogel-forming material, specifically, to a hydrogel-forming material from which a hydrogel can be formed with a simple operation; and a hydrogel obtained from the hydrogel-forming material.As a material including water as a medium and having high biocompatibility, a hydrogel is used in a wide range of fields, and various kinds of hydrogels including a hydrogel formed of a high molecular weight compound and a hydrogel formed by the self-assembly of a low molecular weight compound have been studied.Among these, recently, regarding a low molecular weight hydrogelator formed of a low molecular weight compound, the functionality thereof has attracted much attention and the study thereof has been vigorously carried out although it is difficult to elucidate a mechanism for the self-organization of a low molecular weight ...

Mitotic kinesin inhibitors and methods of use thereof

This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders.

COMPOUNDS FOR ENZYME INHIBITION

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention. 1. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/646,510, filed Oct. 5, 2012, which is a continuation of U.S. patent application Ser. No. 13/328,909, filed Dec. 16, 2011, issued as U.S. Pat. No. 8,357,683 on Jan. 22, 2013, which is a continuation of U.S. patent application Ser. No. 12/708,753, filed Feb. 19, 2010, issued as U.S. Pat. No. 8,080,545 on Dec. 20, 2011, which is a continuation of U.S. patent application Ser. No. 11/820,490, filed Jun. 19, 2007, issued as U.S. Pat. No. 7,691,852 on Apr. 6, 2010, which claims the benefit of U.S. Provisional Application No. 60/815,218, filed Jun. 19, 2006. The contents of these applications are incorporated herein by reference in their entirety.In eukaryotes, protein degradation is predominately mediated through the ubiquitin pathway in which proteins targeted for destruction are ligated to the 76 amino acid polypeptide ubiquitin. Once targeted, ubiquitinated proteins then serve as substrates for the 26S proteasome, a multicatalytic protease, which cleaves proteins into short peptides through the action of its three major proteolytic activities. While having a general function in intracellular protein turnover, proteasome-mediated degradation also plays a key role in many processes such as major histocompatibility complex (MHC) class I presentation, apoptosis and cell viability, antigen processing, NF-κB activation, and transduction of pro-inflammatory signals.The 20S proteasome is a 700 kDa cylindrical-shaped multicatalytic protease complex comprised of 28 subunits, classified ...

Flavor compositions and screening methods for identifying the same

The presently disclosed subject matter relates to peptides and flavor compositions that include at least one, two, three, four, five or more peptide compounds, and screening methods for identifying the same. The flavor compositions can be used to enhance or modify the taste and/or flavor of various edible compositions such as human food products and pet food products.

METHODS OF PRODUCING ANAMORELIN HYDROCHLORIDE HAVING CONTROLLED CHLORIDE CONTENT

The present invention relates to particulate forms of anamorelin monohydrochloride or a composition comprising anamorelin monohydrochloride having controlled chloride content, preferably isolated in an amorphous and/or fine particulate state, processes for making the particulate forms, and pharmaceutical compositions comprising the particulate forms. 123-. (canceled)24) A process for preparing amorphous anamorelin monohydrochloride comprising:a) dissolving anamorelin free base in an organic solvent to form a solution; i) react said anamorelin free base with said hydrochloric acid, and', 'ii) form an organic phase and an aqueous phase;, 'b) mixing said solution with water and hydrochloric acid for a time sufficient toc) separating the aqueous phase from the organic phase; andd) isolating said amorphous anamorelin monohydrochloride from said aqueous phase.25) A process for preparing amorphous anamorelin monohydrochloride comprising:a) dissolving anamorelin free base in an organic solvent to form a solution; i) react said anamorelin free base with said hydrochloric acid, and', 'ii) form an organic phase and an aqueous phase;, 'b) mixing said solution with water and hydrochloric acid for a time sufficient toc) separating the aqueous phase from the organic phase;d) removing residual organic solvent from said aqueous phase via distillation; ande) isolating said amorphous anamorelin monohydrochloride from said aqueous phase; wherein (i) anamorelin free base is more soluble in the organic solvent than in water, and (ii) amorphous anamorelin monohydrochloride is more soluble in water than the organic solvent.26) A process for preparing amorphous anamorelin monohydrochloride comprising:a) dissolving anamorelin free base in isopropyl acetate to form a solution; i) react said anamorelin free base with said hydrochloric acid, and', 'ii) form an organic phase and an aqueous phase;, 'b) mixing said solution with water and hydrochloric acid for a time sufficient toc) separating the ...

Active Agent Prodrugs with Heterocyclic Linkers

The embodiments provide prodrug compounds of Formulae I-XVII. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug compound of Formulae I-XVII that provides controlled release of an active agent. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of an active agent from the prodrug so as to attenuate enzymatic cleavage of the prodrug. 64. The compound of any of - claims 2 , wherein X is selected from acetylmorphone claims 2 , hydrocodone claims 2 , hydromorphone claims 2 , ketobemidone claims 2 , methadone claims 2 , naloxone claims 2 , naltrexone claims 2 , N-methylnaloxone claims 2 , N-methylnaltrexone claims 2 , oxycodone claims 2 , oxymorphone claims 2 , and pentamorphone.74. The compound of any of - claims 2 , wherein X is selected from hydrocodone and oxycodone.8. The compound of claim 3 , wherein Ris a side chain of an L-amino acid selected from L-alanine claim 3 , L-arginine claim 3 , L-asparagine claim 3 , L-aspartic acid claim 3 , L-cysteine claim 3 , L-glutamic acid claim 3 , L-glutamine claim 3 , glycine claim 3 , L-histidine claim 3 , L-isoleucine claim 3 , L-leucine claim 3 , L-lysine claim 3 , L-methionine claim 3 , L-phenylalanine claim 3 , L-proline claim 3 , L-serine claim 3 , L-threonine claim 3 , L-tryptophan claim 3 , L-tyrosine claim 3 , L-valine claim 3 , L-homoarginine claim 3 , L-homolysine claim 3 , L-ornithine claim 3 , L-arginine mimic claim 3 , L-arginine homologue claim 3 , L-arginine truncate claim 3 , L-arginine with varying oxidation states claim 3 , L-lysine mimic claim 3 , L-lysine homologue claim 3 , L-lysine truncate claim 3 , and L-lysine with varying oxidation states.9. The compound of claim 7 , wherein Ris a side chain of an L-amino acid selected from L-alanine claim 7 , L-arginine claim 7 , L-asparagine claim 7 , L-aspartic acid claim 7 , L-cysteine claim 7 , L-glutamic acid claim 7 , ...

NOVEL THERAPEUTICS FOR THE TREATMENT OF GLAUCOMA

The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a KATP channel to reduce an intraocular pressure. 1. A pharmaceutical composition comprising a benzothiadiazine or chroman derivative disposed in an ophthalmically acceptable aqueous carrier.4. A unit dose container comprising the pharmaceutical composition according to .5. The unit dose container according to claim 4 , wherein the unit dose container is an eye drop dispenser.8. A pharmaceutical composition of claim 6 , wherein the benzothiadiazine or chroman derivative is comprise a 3S claim 6 ,4R stereo chemistry or a 3R claim 6 ,4S stereo chemistry.9. The pharmaceutical composition of claim 6 , wherein the compound is administered by topical application to the eye or administered by injection into the anterior chamber.10. The pharmaceutical composition of claim 6 , wherein the compound is administered using an ocular insert.11. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is a prodrug that is activated by removing one or more groups from the pharmaceutical composition.13. A composition as in claim 12 , wherein the R2 is a 2-pyrrolidinone group; R4 and R5 are —CH; and R6 claim 12 , R7 and R8 are —H. The present invention relates generally to benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives and methods for treating glaucoma and reducing intraocular pressure. It also relates to a process for their preparation and pharmaceutical compositions in which they are present.Without limiting the scope of the ...

NOVEL ULTRASHORT HYDROPHOBIC PEPTIDES THAT SELF-ASSEMBLE INTO NANOFIBROUS HYDROGELS AND THEIR USES

The present invention relates to hydrophobic peptides and/or peptidomimetics capable of forming a (nanofibrous) hydrogel and hydrogels comprising said hydrophobic peptides and/or peptidomimetics and to various uses, such as in regenerative medicine, injectable therapies, delivery of bioactive moieties, wound healing, 2D and 3D synthetic cell culture substrate, biosensor development, biofunctionalized surfaces, and biofabrication. 1. A hydrophobic peptide and/or peptidomimetic capable of forming a hydrogel , the hydrophobic peptide and/or peptidomimetic having the general formula:{'br': None, 'sub': a', 'b, 'Z—(X)—Z′'}whereinZ is an N-terminal protecting group;X is, at each occurrence, independently selected from the group consisting of aliphatic D- or L-amino acids and aliphatic D- or L-amino acid derivatives, and wherein the overall hydrophobicity decreases from N- to C-terminus;a is an integer selected from 2 to 7, preferably 2 to 6;Z′ is a C-terminal group; andb is 0 or 1.23.-. (canceled)4. The hydrophobic peptide and/or peptidomimetic according to claim 1 , wherein all or a portion of said aliphatic amino acids are arranged in an order of decreasing amino acid size in the direction from N- to C-terminus claim 1 , wherein the size of the aliphatic amino acids is defined as I=L>V>A>G.5. The hydrophobic peptide and/or peptidomimetic according to claim 1 , wherein the first N-terminal amino acid of said aliphatic amino acids is G claim 1 , V or A.6. (canceled)8. (canceled)9. The hydrophobic peptide and/or peptidomimetic according to claim 1 , wherein said N-terminal protecting group Z has the general formula —C(O)—R claim 1 , wherein R is selected from the group consisting of H claim 1 , unsubstituted or substituted alkyls claim 1 , and unsubstituted or substituted aryls claim 1 ,wherein R is preferably selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl and isobutyl.1011-. (canceled)12. The hydrophobic peptide and/or peptidomimetic ...

Derivatives of Xanthone Compounds

The present invention relates to xanthone analogs. Such compounds may be used in the treatment of bacterial infections. 136.-. (canceled)40. The compound of claim 39 , wherein each occurrence of Rin Formula (IIa-2) is independently optionally substituted alkyl.41. The compound of claim 40 , wherein Rindependently for each occurrence is —N(H)(C═NH)NH.42. The compound of claim 37 , wherein Ris hydrogen claim 37 , and Ris alkyl.46. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 37 , or a pharmaceutically acceptable salt thereof claim 37 , and a pharmaceutically acceptable excipient.47. The pharmaceutical composition of claim 46 , further comprising one or more additional therapeutic agents.48. A method for treating a microbial infection in a patient in need thereof claim 37 , the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 37 , or a pharmaceutically acceptable salt thereof.49. The method of claim 48 , wherein the microbial infection is a Gram negative bacterial infection or a Gram positive bacterial infection.50StreptococcusStaphylococcusBacillusCarynebacteriumClostridiumListeriaEnterococcus. The method of claim 49 , wherein the Gram positive bacteria is selected from the group consisting of spp. claim 49 , spp. claim 49 , spp. claim 49 , spp. claim 49 , spp. claim 49 , spp. claim 49 , and spp.51Staphylococcus aureus.. The method of claim 50 , wherein the Gram positive bacteria is52Staphylococcus aureusStaphylococcus aureus.. The method of claim 51 , wherein the is Methicillin resistant53. The method of claim 48 , the method further comprising administering one or more additional therapeutic agents.55. The compound of claim 54 , wherein Ris hydrogen claim 54 , and Ris alkyl.60. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 54 , or a pharmaceutically acceptable salt thereof claim ...

DELIVERY SYSTEMS FOR CONTROLLED DRUG RELEASE

The present invention provides a compound having the structure of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, for the controlled delivery and release of Agent. 16. The compound according to any one of claims - , wherein Agent is selected from the group consisting of N-nitrosoureas; doxorubicin , 2-pyrrolpyrrolinoanthracycline , morpholinoanthracycline , diacetatoxyalkylanthracycline , daunorubicin , epirubicin , idarubicin , nemorubicin , PNU-159682 , mitoxantrone; ametantrone; chlorambucil , bendamustine , melphalan , oxazaphosphorines; 5-fluorouracil , 5′-deoxy-5-fluorocytidine , 2′-deoxy-5-fluoridine , cytarabine , cladribine , fludarabine , pentostatine , gemcitabine , 4-amino-1-(((2S ,3R ,4S ,5R)-3 ,4-dihydroxy-5-methyltetrahydrofuran-2-yl)methyl)-5-fluoropyrimidin-2(1H)-one , thioguanine; methotrexate , raltitrexed , pemetrexed , plevitrexed; paclitaxel , docetaxel; topotecan , irinotecan , SN-38 , 10-hydroxycamptothecin , GG211 , lurtotecan , 9-aminocamptothecin , camptothecin , 7-formylcamptothecin , 7-acetylcamptothecin , 9-formylcamptothecin , 9-acetylcamptothecin , 9-formyl-10-hydroxycamptothecin , 10-formylcamptothecin , 10-acetylcamptothecin , 7-butyl-10-aminocamptothecin , 7-butyl-9-amino-10 ,11 ,-methylenedioxocamptothecin; vinblastine , vincristine , vindesine , vinorelbine; calicheamicins; maytansine , maytansinol; auristatin (including but not limited to auristatin D , auristatin E , auristatin F , monomethyl auristatin D , monomethyl auristatin E , monomethyl auristatin F , monomethyl auristatin F methylester , auristatin PYE auristatin PHE , the related natural product dolastatin 10 , and derivatives thereof); amatoxins (including but not limited to α-amanitin , β-amanitin , γ-amanitin , ε-amanitin , amanin , amaninamide , amanullin , and amanullinic acid and derivatives thereof); duocarmycin A , duocarmycin B1 , duocarmycin B2 , duocarmycin C , duocarmycin SA , CC1065 , adozelesin , bizelesin , ...

Dipeptide Comprising a Non-Proteogenic Amino Acid

Described is a dipeptide comprising a non-proteogenic amino acid, methods of making such and methods of using said dipeptide in a process of making a polypeptide or protein comprising one or more non-proteogenic amino acids. 2. The method according to claim 1 , wherein the amino protecting group is selected from the group consisting of: tert-Butoxycarbonyl (Boc) claim 1 , Triphenylmethyl (Trt) claim 1 , 2-(p-biphenylyl)-2-propyloxycarbonyl (Bpoc) claim 1 , 9-fluorenylmethyloxycarbonyl (Fmoc) claim 1 , 2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) claim 1 , Benzyloxycarbonyl (Cbz) claim 1 , Allyloxycarbonyl (Alloc) claim 1 , o-Nitrobenzenesulfonyl (oNBS) claim 1 , p-Nitrobenzenesulfonyl (pNBS) claim 1 , 2 claim 1 ,4-Dinitrobenzenesulfonyl (dNBS) claim 1 , 1-(4 claim 1 ,4-Dimethyl-2 claim 1 ,6-dioxocyclo-Hexylidene)-3-methylbutyl (ivDde) and o- or p-Nitrophenylsulfenyl (Nps).3. The method according to claim 1 , wherein the removable alkyl group is selected from the group consisting of Benzyl and tert-Butyl.4. The method according to claim 1 , wherein R1 and R2 jointly form a ring is selected from the group consisting of Phatalimide and 1 claim 1 ,3 claim 1 ,5-dioxazine.5. The method according to claim 1 , wherein(i) R1 is H or an amino protecting group selected from the group consisting of Boc, Trt, Bpoc, Fmoc, Nsc, Cbz, Alloc, oNBS, pNBS, dNBS, ivDde and Nps, and R2 is an amino protecting group selected from the group consisting of Boc, Trt, Bpoc, Fmoc, Nsc, Cbz, Alloc, oNBS, pNBS, dNBS, ivDde, and Nps; orR1 is a removable alkyl group selected from the group consisting of Benzyl and tert-Butyl, and R2 is H or a removable alkyl group selected from the group consisting of Benzyl and tert-Butyl; orR1 and R2 jointly form a ring selected from the group consisting of Phatalimide and 1,3,5-dioxazine;(ii) R3 is selected from the group consisting of H, a secondary ammonium cation, a tertiary ammonium cation, an alkali metal cation, and an alkaline earth metal cation forming a ...

Boronate ester compounds and pharmaceutical compositions thereof

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

BORONATE ESTER COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases. 2. The process of claim 1 , wherein the reaction of step (1) or step (3) or both is conducted in the presence of a peptide coupling reagent.3. The process of claim 2 , wherein the peptide coupling reagent is selected from the group consisting of a carbodiimide reagent claim 2 , phosphonium reagent claim 2 , and uronium reagent.4. The process of claim 3 , wherein the peptide coupling reagent is selected from one or more of the group consisting of dicyclohexylcarbodiimide (DCC) claim 3 , 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) claim 3 , benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) claim 3 , and O-(1H-benzotriazol-1-yl)-N claim 3 ,N claim 3 ,N′ claim 3 ,N′-tetramethyluronium tetrafluoroborate (TBTU).5. The process of claim 1 , further comprising converting the carboxylic acid moiety of compound (i) to an activated ester or acid halide prior to the reaction of step (1).6. The process of claim 5 , wherein said activated ester or acid halide is an O—(N-hydroxysuccinimide) ester.7. The process of claim 1 , wherein the reaction of step (3) is conducted in the presence of a solvent.8. The process of claim 7 , wherein the solvent is tetrahydrofuran.9. The process of claim 1 , wherein the reaction of step (4) is conducted in the presence of an aqueous mineral acid.10. The process of claim 9 , wherein the mineral acid is hydrochloric acid.11. The process of claim 1 , wherein the reaction of step (4) is conducted in the presence of an organic boronic acid acceptor.12. The process of claim 11 , wherein the organic boronic acid acceptor is i-BuB(OH).13. The process of claim 1 , wherein the reaction of step (5) is conducted in the presence of a solvent selected from the group consisting of ...

Peptide-based proteasome inhibitors for treating conditions mediated by senescent cells and for treating cancer

The proteasome inhibitors of this invention include peptide-based compounds with a short linear sequence of amino acids. An oxo or thio group is attached to the N-terminal amino acid. A protein-reactive electrophilic group such as an epoxyketone, an aziridinylketone, or a beta-lactone is attached to the C-terminal amino acid. Upon contact with a proteasome complex in a target cell, the electrophilic group reacts with a functional group in or near a binding pocket or active site of the proteasome, forming a covalent bond and thereby inactivating the proteasome. These and other proteasome inhibitors can be screened for binding affinity and an ability to selectively eliminate senescent cells or cancer cells. Compounds that selectively remove senescent cells can be developed for the treatment of conditions such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. 117.-. (canceled)1920.-. (canceled)23. The method of claim 18 , wherein Z is selected from aldehyde claim 18 , epoxyketone claim 18 , aziridinylketone claim 18 , boronate claim 18 , boronate ester and beta-lactone.25. The method of claim 18 , wherein:X is O or S;{'sup': 0', '10', '10, 'R- is R- or R-Q-;'}{'sup': 11', '11, 'Q is selected from ethylene glycol, polyethylene glycol, —C(═O)—, —NRC(═O)—, —OC(═O)—, —C(═S)—, —NRC(═S)—, —OC(═S)— and —OC(═S)—; and'}{'sup': 10', '11, 'Rand Rare independently selected from H, alkyl and substituted alkyl.'}28. The method of claim 26 , wherein:{'sup': '1', 'sub': (1-6)', '(1-6)', '(1-6)', '(1-6)', '(1-6), 'Ris selected from Calkyl, aryl-Calkyl, substituted aryl-Calkyl, cycloalkyl-Calkyl and substituted cycloalkyl-Calkyl;'}{'sup': 2', '4, 'sub': (1-6)', '(1-6)', '(1-6)', '(1-6)', '(1-6)', '(1-6)', '(1-6)', '(1-6), 'Rand Rare selected from Calkyl, substituted Calkyl, Calkoxy-Calkyl, substituted Calkoxy-Calkyl, Chydroxyalkyl and substituted Chydroxyalkyl; and'}{'sup': '3', 'sub': (1-6)', '(1-6)', '(1-6)', '(1-6)', '(1-6)', '(1-6), 'Ris selected from ...

Method for manufacturing oxytocin by liquid-phase polypeptide synthesis

The present disclosure discloses a liquid-phase synthesis method of oxytocin under mild conditions for the first time, which is characterized in that three oxytocin fragments which include Boc-Cys(Acm)-Tyr(tBu)-OH, H-Ile-Gln(Trt)-Asn(Trt)-Cys(Acm)-Pro-OMe and H-Leu-Gly-NHare synthesized for the first time, the fragments are assembled to synthesize an all-protected oxytocin amino acid sequence, iodine is used to remove Acm while cyclization is performed to form a disulfide bond to obtain protected cyclic oxytocin, trifluoroacetic acid is used to remove residual protecting groups to obtain crude oxytocin, ethyl acetate is used to perform recrystallization, and reversed-phase chromatography purification is performed to reach high-purity (crude product purity reaches 95%) and high biological value of oxytocin (588 IU/mg). In the present invention, a Boc-polypeptide synthesis and Fmoc-polypeptide synthesis combined method is provided, wherein, all the reactions are carried out under mild conditions without using the ammonia-sodium-method decapping reaction which is reported by literature referring to oxytocin liquid-phase synthesis domestically and abroad. Furthermore, the liquid-phase synthesis method of oxytocin is first performed without highly toxic reagents and unsafe reaction conditions, thus greatly reducing the cost of oxytocin synthesis and providing access to industrial production of oxytocin. 19-. (canceled)10. A method for manufacturing oxytocin by liquid-phase polypeptide synthesis , which comprises the following steps:(1) synthesizing fragment 1: Boc-Cys(Acm)-Tyr(tBu)-OH;(2) synthesizing fragment 2: H-Ile-Gln(Trt)-Asn(Trt)-Cys(Acm)-Pro-OMe;{'sub': '2', '(3) synthesizing fragment 3: H-Leu-Gly-NH;'}(4) synthesizing compound 4: Boc-Cys(Acm)-Tyr(tBu)-Ile-Gln(Trt)-Asn(Trt)-Cys(Acm)-Pro-OMe;(5) synthesizing compound 5: Boc-Cys(Acm)-Tyr(tBu)-Ile-Gln(Trt)-Asn(Trt)-Cys(Acm)-Pro-OH;{'sub': '2', '(6) synthesizing compound 6: Boc-Cys(Acm)-Tyr(tBu)-Ile-Gln(Trt)-Asn(Trt ...

PROTEASE-ACTIVATED CONTRAST AGENTS FOR IN VIVO IMAGING

Compounds useful as contrast agents in image-guided surgery are provided. The compounds comprise a latent cationic lysosomotropic fragment that is detectable upon cleavage by lysosomal proteases within treated tissues, particularly within tumors and other diseased tissues. Also provided are compositions comprising the compounds and methods for using the compounds, for example in dynamically monitoring protease activity in vivo during image-guided tumor resection surgery. 2. The compound of claim 1 , wherein the fluorescent label is a fluorescein claim 1 , an Oregon green claim 1 , a bora-diaza-indecene claim 1 , a rhodamine claim 1 , or a cyanine label.34-. (canceled)5. The compound of claim 1 , wherein the fluorescent label is a near infrared fluorescent label.67-. (canceled)8. The compound of claim 1 , wherein AAis an aralkyl amino acid side chain claim 1 , optionally substituted with 1 to 3 A groups.9. The compound of claim 1 , wherein U is O.10. The compound of claim 1 , wherein Land Lis each independently an optionally substituted alkyl linker claim 1 , wherein each carbon atom is optionally replaced with a heteroatom.1112-. (canceled)13. The compound of claim 1 , wherein Q is a QSY quencher.1415-. (canceled)16. The compound of claim 1 , wherein Q is QC-1.1819-. (canceled)22. The compound of claim 21 , wherein D comprises a fluorescent label and T comprises a quencher.23. The compound of claim 22 , wherein the fluorescent label is a fluorescein claim 22 , an Oregon green claim 22 , a bora-diaza-indecene claim 22 , a rhodamine claim 22 , or a cyanine label.2428-. (canceled)29. The compound of claim 21 , wherein D comprises a radioactive substance.30. The compound of claim 21 , wherein Lis an optionally substituted alkyl linker claim 21 , wherein each carbon atom is optionally replaced with a heteroatom.3135-. (canceled)36. The compound of claim 21 , wherein T is a peptidic targeting element.37. (canceled)38. The compound of claim 21 , wherein T is a cathepsin ...

SUBSTRATE-MIMETIC AKT INHIBITOR

Disclosed herein is a species of peptide and non-peptide inhibitors of Akt, an oncogenic protein. Beginning with a residue of Akt target substrate GSK-3, the functional domains of the GSK-3 residue were characterized. Functionally homologous non-peptide groups were substituted for the amino acids of the GSK-3 creating a hybrid peptide-non-peptide and non-peptide compounds capable of binding to Akt. The non-peptide compounds show increased stability and rigidity compared to peptide counterparts and are less susceptible to degradation. The bound non-peptide compounds exhibit an inhibitory effect on Akt, similar to peptide-based Akt inhibitors. 25.-. (canceled)6. The method of claim 1 , wherein the inhibitor has a p-amino benzoic acid or 4-aminobenzoic acid next to a valanine. This application is a divisional application of Ser. No. 12/480,329, entitled “Substrate-Mimetic AKT Inhibitor”, filed on Jun. 8, 2009, which claims priority to prior-filed International Application, Serial Number PCT/US2007/086751 filed Dec. 7, 2007, which claims priority to U.S. provisional patent application No. 60/868,989 filed Dec. 7, 2006, the contents of which are hereby incorporated by reference into this disclosure.This invention was made with Government support under Grant No. 1R01 CA107078-01, awarded by the National Institutes of Health. The Government may therefore have certain rights in the invention.This invention relates to oncogenic prevention and treatment. Specifically, the invention relates to using substrate inhibitors to block the effects of Akt, also known as protein kinase B (PKB).Akt/protein kinase B (PKB) has been shown to be a widely expressed Ser/Thr protein kinase whose persistent activation leads to human oncogenesis. Its role in cancer and chemoresistance is accomplished by the concomitant promotion of cell growth, migration, and angiogenesis as well as the suppression of the apoptotic pathway. There has been significant interest in Akt for its structural and ...

BORONATE ESTER COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases. 2. The process of claim 1 , wherein the reaction of step (1) or step (3) or both is conducted in the presence of a peptide coupling reagent.3. The process of claim 2 , wherein the peptide coupling reagent is selected from the group consisting of a carbodiimide reagent claim 2 , phosphonium reagent claim 2 , and uronium reagent.4. The process of claim 3 , wherein the peptide coupling reagent is selected from one or more of the group consisting of dicyclohexylcarbodiimide (DCC) claim 3 , l-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) claim 3 , benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) claim 3 , and O-(1H-benzotriazol-1-yl)-N claim 3 , N claim 3 , N′N′-tetramethyluronium tetrafluoroborate (TBTU).5. The process of claim 1 , further comprising converting the carboxylic acid moiety of compound (ii) to an activated ester or acid halide prior to the reaction of step (1).6. The process of claim 5 , wherein said activated ester or acid halide is an O—(N-hydroxysuccinnimide) ester.7. The process of claim 1 , wherein the reaction of step (3) is conducted in the presence of a solvent.8. The process of claim 7 , wherein the solvent is tetrahydrofuran.9. The process of claim 1 , wherein the reaction of step (4) is conducted in the presence of an aqueous mineral acid.10. The process of claim 9 , wherein the mineral acid is hydrochloric acid.11. The process of claim 1 , wherein the reaction of step (4) is conducted in the presence of an organic boronic acid acceptor.12. The process of claim 11 , wherein the organic boronic acid acceptor is t-BuB(OH).13. The process of claim 1 , wherein the reaction of step (5) is conducted in the presence of a solvent selected from the group consisting of ethyl ...

TRANSITION METAL CHELATING BEADS

The present invention relates to a complex comprising a transition metal cation (i); a ligand (ii) comprising at least one chelating group, preferably from 1 to 4 chelating groups, more preferred 2 or 3 chelating groups, wherein the chelating group(s) is/are selected from hydroxamate group —N(O″)—C(═O)—R, catechol ate group, carboxyl ate group, partly or totally protonated forms of these chelating groups and mixtures of these chelating groups and/or their partly or totally protonated forms, wherein R is hydrogen or a C1 to C5 alkyl group; and a magnetic bead (iii); wherein the magnetic bead (iii) and the ligand (ii) are covalently bonded. The invention also relates to the use of the complex for reduction of the content of at least one phosphor-oxy-substance, which preferably comprises a structural element —O—P(O″)(═O)—O— within its structure, in a fluid sample, as well as to a method for decreasing the content of at least one phosphor-oxy-substance, preferably a phospholipid, in a fluid sample, comprising a step of adding the complex. The invention further relates to a supernatant obtained or obtainable from this method and to the use of a supernatant obtained or obtainable from the method for qualitative and/or quantitative determination of at least one analyte in said supernatant. Furthermore, the invention relates to a method for qualitative and/or quantitative determination of at least one analyte in a fluid sample and to a method for determining the kind and/or amount of at least one phosphor-oxy-substance in a fluid sample. 1. A complex comprisingi) a transition metal cation;{'sup': '−', 'ii) a ligand comprising at least one chelating group, wherein the chelating group(s) is/are selected from hydroxamate group N(O)—C(═O)—R, partly or totally protonated forms of hydroxamate groups and mixtures of hydroxamate groups and their partly or totally protonated forms, wherein R is hydrogen or a C1 to C5 alkyl group;'}iii) a magnetic bead;wherein the magnetic bead (iii) ...

GEMINOID LIPOPEPTIDE COMPOUNDS AND THEIR USES

Disclosed are geminoid peptide-like compound according to Formula I: 118-. (canceled)19. A method of treatment or prophylaxis of a disease selected from the group consisting of viral infection , inflammation , and ADAM17-mediated diseases , the method comprising administering , to a subject in need thereof , a therapeutically or prophylactically effective amount of a compound according to Formula (I):{'br': None, 'sup': 1', '3', '2, 'sub': 'n', 'R—C(═O)—Z—NR-R\u2003\u2003(I);'}or a salt or solvate thereof,{'sup': 1', '2', '1', '2', '3, 'sub': 1', '6, 'in which Rand Rare each independently saturated, partly saturated or unsaturated, straight, branched or cyclic alkyl chains, wherein Rhas a number of C atoms of 11 to 19, and Rhas a number of C atoms of 12 to 20; Ris hydrogen or C-Calkyl;'}n is an integer from 1 to 15;{'sub': 'n', 'sup': '3', 'each Z independently is an amino acid residue, wherein Zcomprises an N-terminus attached to C(═O) and a C-terminus that is attached to NR.'}20. The method according to claim 19 , wherein R—C(═O) and Reach independently have a number of carbon atoms of 14 to 20.21. The method according to claim 20 , wherein R—C(═O) and Reach independently have a number of carbon atoms of 16 to 18.22. The method according to claim 19 , wherein the amino acid residue Z is a residue of an amino acid chosen from the group of natural amino acids claim 19 , beta-alanine (bAla) claim 19 , 4-aminomethyl phenylalanine (Amf) claim 19 , 4-guanidine phenylalanine (Gnf) claim 19 , 4-aminomethyl-N-isopropyl phenylalanine (Iaf) claim 19 , 3-pyridyl alanine (Pya) claim 19 , 4-piperidyl alanine (Ppa) claim 19 , 4-aminomethyl cyclohexyl alanine (Ama) claim 19 , 4-aminocyclohexyl alanine (Aca) claim 19 , ornithine (Orn) claim 19 , citrulline claim 19 , hydroxylysine (Hyl) claim 19 , allo-hydroxylysine (aHyl) claim 19 , 6-N-methyllysine (MeLys) claim 19 , desmosine (Des) claim 19 , isodesmosine (Ide) claim 19 , 2-aminoadipic acid (Aad) claim 19 , 3-aminoadipic acid ( ...

Contemporaneous, heterogeneously-oriented, multi-targeted therapeutic modification and/or modulation of disease by administration of sulfur-containing, amino acid-specific small molecules

The present invention discloses and claims novel pharmaceutical compositions, methods, and kits used for the contemporaneous, heterogeneously-oriented, multi-targeted therapeutic modification and/or modulation of cellular metabolic anomalies or other undesirable physiological conditions, including cancer, where the normal cellular biochemical function and/or the expression levels of various proteins/enzymes (i.e., the target molecules) are abnormal and must be modified and/or modulated in order to treat these metabolic anomalies or other undesirable physiological conditions, including cancer. The aforementioned target molecules, by way of non-limiting example, include: anaplastic lymphoma kinase (ALK), mesenchymal epithelial transition (MET) kinase, the receptor tyrosine kinase (ROS1), epidermal growth factor receptor (EGFR), peroxiredoxin (Prx), excision repair cross-complementing protein 1 (ERCC1), insulin growth factor 1 receptor (IGF1R), ribonucleotide reductase (RNR), tubulin, farnesyltransferase, and various other classes of proteins/enzymes. Additionally, the present invention discloses and claims methods and kits for (a) the selection of subjects for treatment; (b) the determination of the most effective medicinal agent(s) to be administered in combination with the administration of the sulfur-containing, amino acid-specific small molecules of the present invention; (c) the dosage of the medicinal agent(s) to be administered; (d) the determination of the length and/or number of treatment cycles; (e) the adjustment of the specific medicinal agent(s) used and the dosage administered during treatment; and/or (f) ascertaining the potential treatment responsiveness of the specific disease to the medicinal agents (s) selected for administration to a subject suffering from one or more types of: (i) cancer or (ii) metabolic anomalies or other undesirable physiological conditions by quantitatively determining the level of the abnormal biochemical activity and/or ...

PEPTIDOMIMETICS FOR THE TREATMENT OF CORONAVIRUS AND PICORNAVIRUS INFECTIONS

Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.

BRANCHED CHAIN-CONTAINING AROMATIC COMPOUND

The present invention provides a particular branched chain-containing aromatic compound. The branched chain-containing aromatic compound of the present invention is easily-soluble in isopropyl acetate superior in liquid-separation operability, and can be used for a production method of peptide and the like, which provides a final product simply by extraction separation, without crystallization and isolation of each intermediate in each step. 125-. (canceled)2831-. (canceled) The present invention relates to an aromatic compound containing a particular branched chain. The present invention further relates to a protecting reagent containing the compound or an adduct thereof. The present invention also relates to a production method of peptide by using the compound, and further relates to an organic synthesis method including the production method of the peptide.The production methods of peptide are generally divided into solid phase methods and liquid phase methods. The solid phase methods are advantageous since isolation and purification after reaction can be performed by only washing resin. However, they are associated with problems in that the reaction is essentially that of heterogeneous phases, reaction agents and reagents need to be used in excess to compensate for the low reactivity, and tracing of reaction and analysis of reaction product supported by carrier are difficult. On the other hand, the liquid phase method is advantage since it shows good reactivity, and intermediate peptide can be purified by extraction and washing, isolation and the like after condensation reaction. However, the method is associated with problems since the production step is complicated due to an extraction and washing step with a nonpolar organic solvent and an acidic or basic aqueous solution to remove residual reagents and/or byproducts in each step of coupling reaction and deprotection, and/or an isolation and purification step such as crystallization and the like, and the like ...

PLANT VIRUS PARTICLES FOR DELIVERY OF ANTIMITOTIC AGENTS

Anti-lymphoma plant virus particles are described. The anti-lymphoma plant virus particles include a filamentous or rod-shaped plant virus particle linked to an antimitotic agent. A therapeutically effective amount of an anti-lymphoma plant virus particle can be administered to a subject to provide a method of treating lymphoma. 1. An anti-lymphoma virus particle , comprising a filamentous or rod-shaped plant virus particle linked to an antimitotic agent.2. The anti-lymphoma virus particle of claim 1 , wherein the plant virus particle is a filamentous plant virus particle.3. The anti-lymphoma virus particle of claim 2 , wherein the filamentous plant virus particle the Alphaflexiviridae family.4. The anti-lymphoma virus particle of claim 1 , wherein the plant virus particle is a rod-shaped plant virus particle.5. The anti-lymphoma virus particle of claim 4 , wherein the plant virus particle is a member of the Virgaviridae family.6. The anti-lymphoma virus particle of claim 4 , wherein the plant virus particle is a tobacco mosaic virus.7. The anti-lymphoma virus particle of claim 1 , wherein the exterior surface of the plant virus particle has been PEGylated.8. The anti-lymphoma virus particle of claim 1 , wherein the antimitotic agent is a dolastatin.9. The anti-lymphoma virus particle of claim 8 , wherein the dolastatin is monomethyl auristatin E (MMAE).10. The anti-lymphoma virus particle of claim 8 , wherein the dolastatin is valine-citrulline monomethyl auristatin E (vcMMAE).11. The anti-lymphoma virus particle of claim 1 , wherein the antimitotic agent is covalently conjugated to the exterior of the plant virus particle.12. The anti-lymphoma virus particle of claim 1 , wherein a targeting ligand is attached to the exterior of the plant virus particle.13. A method of treating lymphoma in a subject by administering to the subject a therapeutically effective amount of an anti-lymphoma virus particle claim 1 , comprising a filamentous or rod-shaped plant virus ...

METHODS, COMPOUNDS, COMPOSITIONS AND VEHICLES FOR DELIVERING 3-AMINO-1-PROPANESULFONIC ACID

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compound that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to the prevention and treatment of Alzheimer's disease 5. A method for treating Alzheimer's disease claim 1 , mild cognitive impairment claim 1 , Down's syndrome claim 1 , Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type claim 1 , cerebral amyloid angiopathy claim 1 , a degenerative dementia claim 1 , a dementia of mixed vascular and degenerative origin claim 1 , dementia associated with Parkinson's disease claim 1 , dementia associated with progressive supranuclear palsy claim 1 , dementia associated with cortical basal degeneration claim 1 , or diffuse Lewy body type of Alzheimer's disease claim 1 , comprising administering a therapeutically effective amount of a compound of to a human subject in need thereof.6. The method of claim 5 , which is for treating Alzheimer's disease claim 5 , mild cognitive impairment claim 5 , cerebral amyloid angiopathy claim 5 , or degenerative dementia.7. The method of claim 6 , which is for treating Alzheimer's disease.8. The method of wherein the compound is administered intratracheally claim 5 , intranasally claim 5 , ontologically claim 5 , rectally claim 5 , vaginally claim 5 , or orally.9. A pharmaceutical composition comprising a compound of together with a pharmaceutically acceptable carrier.10. The pharmaceutical composition of which is suitable for oral administration.11. The pharmaceutical composition of claim 9 , which is in the form of a hard shell gelatin capsule claim 9 , soft shell gelatin capsule claim 9 , cachet claim 9 , pill claim 9 , tablet claim 9 , lozenge claim 9 , powder claim 9 , granule claim 9 , pellet claim 9 , dragee claim 9 , which is ...

PEPTIDE MOLECULAR MATERIALS

This invention provides a novel peptide molecular material, wherein the molecular structure of the material is a combination of halogen-substituted or unsubstituted aryl and a peptide molecular. This material can self-assemble to form a nanofiber and form a hydrogel. The hydrogel has various properties, including low cytotoxicity, the promotion of cell growth and migration as well as being stable under a physiological condition and a human body temperature. 2. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from a hydrogen atom and C-Caralkyl; x is 1; and y is 1.3. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare independently selected from a hydrogen atom; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl claim 1 , C-Caralkyl and C-Chydroxyaralkyl; x is 1; and y is 2.4. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare independently selected from a hydrogen atom; Rand Rare independently selected from the group consisting of a hydrogen atom and C-Caralkyl; x is 1; and y is 3.5. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl and C-Caminoalkyl; x is 1; and y is 5.6. The peptide molecular material according to claim 1 , wherein A is phenyl; Rand Rare hydrogen atoms; Rand Rare independently selected from a hydrogen atom claim 1 , C-Calkyl and C-Caminoalkyl; x is 0 to 2; and y is 5.7. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl claim 1 , C-Caralkyl and C ...

Selective caspase inhibitors and uses thereof

The present invention relates to compounds of Formula I, IA, II, HA, III, or IHA and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more caspases. Also described are methods where the compounds of Formula I, IA, II, IIA, III, or IIIA are used in the prevention and/or treatment of various diseases and conditions in subjects, including caspase-mediated diseases such as sepsis, myocardial infarction, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative disease (e.g. multiple sclerosis (MS) and Alzheimer's, Parkinson's, and Huntington's diseases).

Heteroaryl pyridone and aza-pyridone amide compounds

Heteroaryl pyridone and aza-pyridone amide compounds of Formula I are provided, and various substituents including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk, and for treating cancer and immune disorders such as inflammation mediated by Btk. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.