СУЛЬФОНАМИДНОЕ ПРОИЗВОДНОЕ И ЕГО МЕДИЦИНСКОЕ ПРИМЕНЕНИЕ

Изобретение относится к новым сульфонамидным производным общей формулы (1) или их фармацевтически приемлемым солям, обладающим свойствами ингибитора интегрина α4β7. Соединения могут найти применение для лечения или профилактики воспалительного заболевания, в котором патологическое состояние связано с опосредованным интегринами α4β7 процессом адгезии. В общей формуле (1)А обозначает группу, представленную общей формулой (2-1) или (2-2)где Arm представляет собой 5- или 6-членное ароматическое кольцо, содержащее 0, 1 или 2 гетероатома, выбранных из атомов азота, Rи R, каждый, независимо, представляет собой любой заместитель из атома водорода, атома галогена, низшей алкильной группы, низшей алкокси группы, моно- или ди-низшей алкиламино группы, R, Rи R, каждый, независимо, представляет собой любой заместитель из атома водорода, низшей алкильной группы, низшей алкокси группы, амино группы, низшей алкиламино группы, низшей ди(алкил)амино группы или (низший алкиламино)низшей алкильной группы, ...

СУЛЬФОНАМИДНОЕ ПРОИЗВОДНОЕ, ЛЕКАРСТВЕННОЕ СРЕДСТВО, СПОСОБЫ ЛЕЧЕНИЯ

Объектом изобретения является сульфонамидное соединение формулы I, обладающее действием, ингибирующим активность матриксной металлопротеиназы-13 и агликаназы, где R1- NHOH; R2 - группа -A-R6, где А - алкилен C1-С6; R6 - группа формулы II, где Х - группа -N(R10)-; R7и R8 , одинаковые или различные, - Н, C1-С6 алкил, СООН, низший алкокси, галоген, фенил или R7 и R8 вместе с атомами углерода, к которым они присоединены, образуют ненасыщенное С3-С7 кольцо, арил С6-С10, гетероарил С5-С7, содержащий 1 или 2 кольцевых атома азота или серы; R10 - Н, C1-6 алкил; R3 - Н, С1-6 алкил, возможно замещенный галогеном, фенилом, необязательно замещенным галогеном, или алкинил С3-10; R4 - фенилен; R5 - C1-6 алкил, необязательно замещенный по меньшей мере одним атомом галогена, 5- или 6-членный гетероарил, содержащий 1 или 2 атома N, фенил, необязательно замещенный по меньшей мере одним атомом галогена. Соединения I пригодны для лечения артрита или остеоартрита. 4 с. и 14 з.п. ф-лы, 11 табл.

ПРОИЗВОДНЫЕ КСАНТИНА С КОНЦЕВЫМИ АМИНИРОВАННЫМИ АЛКИНОЛЬНЫМИ БОКОВЫМИ ЦЕПЯМИ И ЛЕКАРСТВЕННОЕ СРЕДСТВО

Изобретение относится к новым производным ксантина с концевыми аминированными алкинольными боковыми цепями формулы I в форме индивидуальных стереоизомеров или в виде смесей стереоизомеров, обладающим нейрозащитным действием. Указанные соединения обладают большим терапевтическим потенциалом. В соединениях общей формулы I R1 и R3 означают алкинольный остаток формулы (Ia), R2 означает а) линейный или разветвленный (С1 -C5)-алкил, б) (С3-C6)-циклоалкил, в) (С4-C8)-циклоалкил-алкил, R4 означает водород или (C1-C3)-алкил, R5 и R6 независимо друг от друга означают а) атом водорода, б) (С1-C6)-алкил, в) фенил(С1-C5)-алкил, или R5 и R6 вместе с атомом азота, с которым они связаны, образуют 5-6-членный насыщенный цикл, или R5 и R6 вместе с атомом азота, с которым они связаны, образуют 5-6-членный насыщенный цикл, где одна -СН2-группа цикла заменена остатком из группы О, NR13, причем R13 означает атом водорода, (C1-C3)-алкилкарбонил, (С1-C4)-алкил, А означает неразветвленный или разветвленный (С1- ...

ПРОИЗВОДНОЕ КСАНТИНА

FIELD: chemistry.SUBSTANCE: invention relates to a xanthine derivative of formula (I),formula (I),where R is selected from;Ris selected from methoxycarbonyl; Ris selected from hydrogen and halogen atoms; each of X and Y is independently selected from C or N; n equals 0, 1, 2, 3 or 4, for treating diseases associated with dipeptidyl peptidase IV.EFFECT: disclosed is a xanthine derivative.8 cl, 6 dwg, 7 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 709 348 C2 (51) МПК C07D 473/06 (2006.01) A61K 31/522 (2006.01) A61P 3/10 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 473/06 (2019.05); A61K 31/522 (2019.05); A61P 3/10 (2019.05) (21)(22) Заявка: 2017145919, 26.05.2016 (24) Дата начала отсчета срока действия патента: R U 26.05.2016 (72) Автор(ы): ГАО Юйчже (CN), ВАН Гочэн (CN) (73) Патентообладатель(и): ЦЗЯНСУ ТАСЛИ ДИИ ФАРМАСЬЮТИКАЛ КО., ЛТД. (CN) Дата регистрации: 18.12.2019 29.05.2015 CN 201510290336.0 (43) Дата публикации заявки: 02.07.2019 Бюл. № 19 (56) Список документов, цитированных в отчете о поиске: DE 102004008112 A1, 01.09.2005. WO 2010043688 A1, 22.04.2010. EP 2540724 А1, 02.01.2013. WO 2005085246 A1, 15.09.2005. US 7501426 B2, 10.03.2009. EA 13411 B1, 30.04.2010. (45) Опубликовано: 18.12.2019 Бюл. № 35 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 29.12.2017 2 7 0 9 3 4 8 Приоритет(ы): (30) Конвенционный приоритет: CN 2016/083406 (26.05.2016) C 2 C 2 (86) Заявка PCT: (87) Публикация заявки PCT: Адрес для переписки: 123242, Москва, пл. Кудринская, д. 1, а/я 35, "Михайлюк, Сороколат и партнеры патентные поверенные" (54) ПРОИЗВОДНОЕ КСАНТИНА (57) Реферат: Изобретение относится к производному ксантина, представленному формулой (I), R выбран из R U 2 7 0 9 3 4 8 WO 2016/192559 (08.12.2016) ; R1 выбран из метоксикарбонила; R2 выбран из водорода и атомов галогена; каждый из X и Y независимо выбран из C или N; n равняется 0, 1, формула (I), где Стр.: 1 2, 3 или 4, для лечения ...

ПРОИЗВОДНЫЕ ПУРИНА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ИСПОСОБ ЛЕЧЕНИЯ

Изобретение относится к новым производным пурина формул I, II, III и IV, фармацевтической композиции на их основе и способу лечения болезненного состояния, характеризующегося тромботической активностью. В соединениях I, II, III и IV, в которых Z1 и Z2 каждый представляет -О-; R1 представляет водород или OR10; R2 представляет собой -C(NH)NH2; R3 представляет собой -С(О)N(R10)R11, (1,2)-тетрагидропиримидинил (необязательно замещенный алкилом), (1,2)-имидазолил (необязательно замещенный алкилом) или (1,2)-имидазолинил (необязательно замещенный алкилом); R4 представляет собой водород; R5 представляет собой алкил или аралкил; R6 представляет собой алкил, аралкил или (C(R7 )(R8)n)-R9; R7 представляет собой алкил, -R12-С(O)OR10, -R12-C(O)N(R10)R11, -R12-C(R10)(C(O)OR10)2, -R12-N(R10)R11, -R12-N(R10)C(NR10)R13, -R12-N(R10 )C(O)N(R10)R11, -R12-N(R10)C(NR10 )N(R10)R11, -R12-OR10, -R12-OP(O)(OR10 )2, -R12-SR10, -R12-S(O)2 R13 или R7 представляет собой аралкил (необязательно замещенный одним или более ...

[UNK]

ВУ” 2017145919” АЗ Дата публикации: 09.08.2019 Форма № 18 ИЗ,ПМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение ж 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2017145919/04(078570) 26.05.2016 РСТ/СМ№2016/083406 26.05.2016 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 201510290336.0 29.05.2015 СМ Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) ПРОИЗВОДНОЕ КСАНТИНА Заявитель: ЦЗЯНСУ ТАСЛИ ДИИ ФАРМАСЬЮТИКАЛ КО., ЛТД., СМ 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты (см. п см. Примечания [ ] приняты во внимание следующие пункты: р [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) (070 473/06 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) С07р 473/06, Аб1КЗ1/522, Аб1РЗ/10 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): РУ\УР1, ЕАРАТТУ, Езрасепе, боозе, РАТЕМТСОРЕ, РаеагсВ, РиБСвет, эСОРОЪ, Уапаех 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ПРЕДМЕТУ ПОИСКА Кате- Наименование документа с указанием (где необходимо) частей, Относится к гория* относящихся к предмету ...

ПРОИЗВОДНЫЕ КСАНТИНА ИЛИ ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ, СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ КСАНТИНА ИЛИ ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫХ СОЛЕЙ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Использование: в медицине для устранения состояний, где значительно ингибирование ФДЭ типа IV. Сущность изобретения: производные ксантина, в которых в пиримидиновом кольце заместитель атома азота в первом положении представлен алкилом (С3 - C6) c прямой или разветвленной целью, алкенилом или алкинилом, атом азота во втором положении замещен фенилом, имеющим в мета- и орто-положении заместители, которые могут быть одинаковы или различны и представлены водородом, галогеном, метил-, метокси-, нитро- или трифторметилгруппой или заместители вместе образуют метилендиокси- или этилендиоксигруппу при условии, что оба эти радикала одновременно не являются водородами, или их фармацевтически приемлемые соли. Производные получены обработкой соответствующего 6-аминоурацила нитритом натрия и муравьиной кислотой в избытке формамида и добавлением дитионита натрия для восстановления полученного 6-амино-5-нитрозоурацила до соответствующего амина, последний конденсируют с формамидом до получения производных ...

КСАНТИНОВЫЕ СОЕДИНЕНИЯ, ОБЛАДАЮЩИЕ ПОЛОЖИТЕЛЬНЫМ АЛЛОСТЕРИЧЕСКИМ МОДУЛЯТОРНЫМ ДЕЙСТВИЕМ В ОТНОШЕНИИ GABAB

... 1. Соединение общей формулы (I) ! ! а также его фармацевтически приемлемые соли; !где R1 выбран из галогена; C1-С10алкила; C1-С10алкокси; гидрокси-C1-С10алкила; C1-С10алкокси-C1-С10алкила; С3-С10циклоалкила; амино, замещенного одним или более чем одним C1-С10алкилом и C1-С10алкокси-C1-С10алкилом; и гетероциклила, незамещенного или замещенного одним или более чем одним C1-С10алкилом, C1-С10алкокси, C1-С10алкокси-C1-С10алкилом, ди-C1-С10алкиламино, оксо и гетероциклил-C1-С10алкилом; ! R2 выбран из бензила, замещенного одним или более чем одним галогеном; циано; C1-С10алкилом; C1-С10алкокси; ароилом; галогено-C1-С10алкилом; арил-C1-С10алкокси и C1-С10алкоксикарбонилом; 2-нафтилметила; 1-(4-хлорфенил)-5-(трифторметил)-1Н-пиразол-4-илметила; 2-(4-хлорфенил)этила; 2,1,3-бензотиадиазол-5-илметила; и 1-[5-(трифторметил)]-1,3-бензотиазол-2-илметила; ! R3 выбран из C1-С10алкила и арила, замещенного одним или более чем одним галогеном; ! R4 выбран из этила; изобутила; пропила; 3,3-диметилбутила; C1 ...

XANTHIN DERIVATE VERBINDUNGEN ZUR AKTIVIERUNG DER CHLORID-LEITUNG IN TIERZELLEN

XANTHIN DERIVATE VERBINDUNGEN ZUR AKTIVIERUNG DER CHLORID-LEITUNG IN TIERZELLEN

Verfahren zur Herstellung von Purinverbindungen

New bicyclic imidazole derivatives are dipeptidylpeptidase-IV inhibitors useful to treat e.g. arthritis, obesity, allograft transplantation and calcitonin-induced osteoporosis

Bicyclic imidazole derivatives (I) and their salts, tautomers, enantiomers and/or diastereomers are new. Bicyclic imidazole derivatives (I) and their salts, tautomers, enantiomers and/or diastereomers are new. R 1>(phenyl)pyridinyl, (pyridinylphenyl)carbonyl, (phenyl)quinolinyl, (phenyl)isoquinolinyl or phenanthridinyl (substituted by R 10>-R 12>) (where N atom is substituted by an O atom); R 10>H, F, Cl, Br, I, 1-4C alkyl, OH, 1-4C alkyloxy, NO 2, NH 2, 1-3C alkylamino, di-(1-3C alkyl)amino, pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl, 1-3C alkyl-carbonylamino, N-(1-3C alkyl)-1-3C alkyl-carbonylamino, 1-3C alkylsulfonylamino, N-(1-3C alkyl)-1-3C alkyl-sulfonylamino group, 1-3C alkyl-carbonyl, CN, aminocarbonyl, (1-3C alkylamino)carbonyl, [di-(1-3C alkyl)-amino]carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, CH 3, OCH 3 (substituted by 1-3F), 1-3C alkylsulfanyl, 1-3C alkylsulfinyl or 1-3C alkylsulfonyl, 2-4C alkenyl, 2-4C alkynyl, 3-4C alkenyloxy ...

VERFAHREN ZUR HERSTELLUNG VON 4(5)- AMINOIMIDAZOL-5(4)-CARBOXAMID AUS 4(5)-AMINOIMIDAZOL--5(4)-CARBONITRIL

PURIN-2,6-DIONE ALS INHIBITOREN DES ENZYMS DIPEPTIDYL-PEPTIDASE IV (DPP-IV)

New 8-substituted-xanthine derivatives, useful e.g. for treating diabetes and arthritis, act by inhibiting dipeptidylpeptidase-IV

... 8-substituted-xanthine derivatives (I), their tautomers, enantiomers, diastereomers or mixtures, and salts. 8-substituted xanthine derivatives of formula (I), their tautomers, enantiomers, diastereomers or mixtures, and salts, are new: R<1> = hydrogen; 1-8C alkyl; 3-8C alkenyl or alkynyl; 3-4C alkenyl substituted by 1-2C alkoxycarbonyl, aminocarbonyl (optionally substituted by 1 or 2 1-3C alkyl) or het-CO; 1-6C alkyl substituted by Ra; phenyl(1-6C)alkyl, optionally ring-substituted by R<10>-R<14>; phenyl(1-4C)alkyl, optionally substituted in alkyl by Rz and in the ring by R<10>-R<14>; R<10>-R<14>-substituted phenyl; phenyl(2-3C) alkenyl, phenyl (or naphthyl)-(CH2)m-(A or B)-(CH2)n, naphthyl(1-3C)alkyl or phenylcarbonylmethyl (all optionally ring-substituted by R<10>-R<14>); (1,4-napththoquinon-2-yl; chromen-4-on-3-yl; 1-oxo- or 1,3-dioxo-indan-2-yl; 2,3-dihydro-3-oxo-benzofuran-2-yl; heteroaryl-(CH2)m-(A or B)-(CH2)n; 1-6C alkyl-A-(CH2)n; 3-7C cycloalkyl-(CH2)m-A or B)-(CH2)n; R<21>-A-( ...

XANTHINDERIVATE ALS SELEKTIVE HM74A-AGONISTEN

Anticellulitic cosmetic compositions containing 1-(Hydroxyalkyl)Xanthines

A cosmetic composition suitable for use as an anticellulitic or slimming agent which comprises, as active ingredient, at least one 1-hydroxyalkylxanthine of formula:… …… [in which:… R1 is a C2-C5 ???-hydroxy-n-alkyl or C3-C5 (???-1) hydroxy-n-alkyl group;… R2 is a hydrogen atom or a methyl or ethyl group; and… R2 is a C1-C4 alkyl group, the number of carbon atoms in R1+R3 being from 4 to 9], or a salt thereof, in a cosmetically acceptable carrier and compounds of formula (I) per se.

Pharmaceutical compositions

The use of a compound of formula I in which R1, R2 and R3 are N or CH, X1 and X2 are hydrogen, hydroxy, or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group and Z1 and Z2 are hydrogen, hydroxy, keto (=O), or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group or one of Z1 and X1 and Z2 and X2 form a second bond of a double bond at the 1,6 or 2,3 positions with the proviso that at least one of the groupings R1 Z1 X1 R2 Z2 X2 and R1 X1 Z2 form a hydroxamate moiety (-N(OH)C(=O)- and B is a 5 or 6 membered ring of formula II or III in which R4, R5, R6, R7, R8, R9 and R10 are CH or N with the proviso that ring B cannot contain more than 3 ring members which are nitrogen and the ring B may optionally be substituted by one or more of hydroxy, keto (=O), and an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or heterocyclyl group or a salt thereof formed with a physiologically acceptable ...

Therapeutic compounds

Xanthine derivative

Xanthine derivatives of the general formula: wherein R<1> and R<3> each represent an alkyl group containing from 1 to 6 carbon atoms, and R<2> represents a cyclohexenyl furyl, tetrahydrofuryl or thienyl group, and pharmacologically- acceptable salts thereof formed with an alkali metal or a nitrogen-containing organic base, are useful in the treatment of respiratory and cardiovascular conditions. They are prepared by cyclisation of the appropriate 6-alkanoylamino- 6-amino uracil, or by reacting the appropriate substituted 5,6-diaminouracil with an anhydride of the acid R<3>-COOH. The preparation of the starting materials and corresponding 5-nitroso-6-aminouracils is described.

Ethynylxanthines, preparation and use as calcium ion channel modulators

The present invention relates to novel pharmaceutical compounds, which exhibit ability to act as calcium ion channel modulators, methods for their synthesis and the treatment and/or prevention of various diseases and disorders including deregulated calcium ion channel activity.

DUAL SELECTIVE PI3 DELTA AND GAMMA KINASE INHIBITORS

DUAL SELECTIVE PI3 DELTA AND GAMMA KINASE INHIBITORS

New derivatives of the xanthine, their methods of preparation and the compositions pharmaceutical containing them.

DUAL SELECTIVE PI3 DELTA AND GAMMA KINASE INHIBITORS

XANTHINDERIVATE USE AS DRUGS AS WELL AS THEIR PROCEDURES FOR THE THEIR PRODUCTION

XANTHIN PHOSPHODIESTERAS v INHIBITORS

8-Ä3-AMINO-PIPERIDIN-1-YLÜ-XANTHINE, THEIR PRODUCTION AND THEIR USE AS DPP-IV HEMMER

NARCOTINE CLEANING METHOD

MACROLID KONJUGATE ONE WITH ENTZÜNDUNGSHEMMENDER EFFECT

N-ALKYLATING QUARTÄRE NITROGENOUS ONE HETERO CYCLES, PROCEDURE FOR THEIR PRODUCTION AND THEIR USE IN DRUGS

TERTIARY HYDROXYALKYLXANTHINE, PROCEDURE FOR YOUR PRODUCTION, IT CONTAINING DRUGS AND YOUR USE.

PROCEDURE FOR the PRODUCTION OF 2-AMINO-6 HALOGENOPURIN AND SYNTHESIS OF ONE INTERMEDIATE CONNECTION

2-CYANO-3,5-DIHYDROXY-HEX-2-EN-CARBONSÄURE of AMIDE DERIVATIVES, PROCEDURES FOR YOUR PRODUCTION AND YOUR USE AS DRUGS

XANTHINDERIVATE, PROCEDURE FOR YOUR PRODUCTION AND YOUR PHARMACEUTICAL APPLICATION

BIZYKLISCH HEXAHYDROBENZ (E) ISOINDOLE WITH ALPHA-1-ADRENERG OF ANTAGONISTIC EFFECT SUBSTITUTED

SUBSTITUTED AMINOALKYLVERBINDUNGEN

XANTHIN OF DERIVATIVES CONNECTIONS TO THE ACTIVATION OF THE CHLORIDE LINE IN ANIMAL CELLS

NOVEL XANTHINE DERIVATIVES

Nitrogenated fused ring derivative, pharmaceutical composition comprising the same, and use of the same for medical purposes

... [PROBLEMS] To provide a compound useful as a prophylactic or therapeutic agent for a sex hormone-dependent disease or the like. [MEANS FOR SOLVING PROBLEMS] Disclosed are: a nitrogenated fused ring derivative represented by the general formula (I), or a prodrug, salt or the like thereof, which has a GnRH antagonistic activity; a pharmaceutical composition comprising the derivative or the prodrug, salt or the like thereof; use of the the derivative or the prodrug, salt or the like thereof for medical purposes; and others. In the general formula (I), the rings A and B independently represent an aryl or a heteroaryl; R and R independently represent a halogen, a cyano, an alkyl, an alkylsulfonyl, -OW, -SW, -COW, -NWW, -SONWW, an aryl or the like; R represents H or an alkyl; E represents an oxygen atom or the like; U represetns a single bond or an alkylene; and X represents Y, -CO-Y, -SO-Y, -S-(alkylene)-Y, -O-(alkylene)-Y, -SO-(alkylene)-Y or the like [wherein Y represents Z, an amino or the ...

Certain chemical entities, compositions and methods

Substituted aryl sulfone derivatives as calcium channel blockers

2,3-substituted fused bicyclic pyrimidin-4(3H)-ones which modulate the function of the vanilloid-1 receptor (VR1)

Compounds of formula (I) which are useful as therapeutic compounds, particularly in the treatment of pain and other conditions ameliorated by the modulation of the function of the vanilloid-1 receptor (VRl, also known as TRPVl).

XANTHINE DERIVATIVES, PRODUCTION THEREOF AND USE THEREOF AS MEDICINES

Inhibitors of PI3K-delta and methods of their use and manufacture

The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

Polymorph of Linagliptin benzoate

The present invention relates to a novel polymorph of Linagliptin benzoate and to methods for its preparation. Furthermore the present invention relates to the use of the novel polymorph for the preparation of a medicament. In addition the present invention relates to pharmaceutical compositions comprising an effective amount of the novel polymorph of Linagliptin benzoate.

Processes for preparing isoquinolinones and solid forms of isoquinolinones

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI 3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

Substituted xanthine derivatives

This invention relates to novel compounds that are substituted xanthine derivatives and pharmaceutically acceptable salts thereof. For example, this invention relates to novel substituted xanthine derivatives that are derivatives of pentoxifylline. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions for which pentoxifylline and related compounds are beneficial.

Heterocyclic compounds, which are inhibitors of the enzyme dpp-iv

Purine derivatives as liver x receptor agonists

PURINE DERIVATIVES AS LIVER X RECEPTOR AGONISTS

Xanthine derivative, production and use thereof as a medicament

Xanthine derivative, production and use thereof as a medicament

... -362 Abstract The present invention relates to substituted xanthines of general formula wherein R1 to R4 are defined as in claim 1, the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Xanthine compounds having terminally aminated alkynol side chains

8-phenyl-6,9-dihydro-[1,2,4]triazolo[3,4-i]purin-5-one derivatives

Xanthine compounds having terminally aminated alkynol side chains

METHOD FOR PRODUCTION OF 2-AMINO-6-HALOGENOPURINE AND SYNTHESIS INTERMEDIATE THEREFOR

Substituted oxazolines as antiproliferative agents

Bifunctional antagonists of cytokine-sensitive protein kinase activation cascades and methods for use as anti-inflammatory agents

XANTHINE DERIVATIVES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

The invention relates to substituted xanthines of general formula (I) wherein R1 - R4 are defined as cited in claim 1, the tautomers, stereoisomers, mixtures, prodrugs and salts thereof which exhibit valuable pharmacological properties, particularly an inhibitory effect on the activity of the dipeptidylpeptidase-IV enzyme.

A1 ADENOSINE RECEPTOR ANTAGONISTS

Compounds of the general formula (I) are described wherein A is a 5- or 6- membered aromatic or heteroaromatic ring. Compositions comprising such compounds and methods of use thereof are also described.

8-CHLORO-1,3-DISUBSTITUTED XANTHINE DERIVATIVES AS HM74A RECEPTOR MODULATORS

The present invention provides therapeutically active compounds which are xanthine derivatives, processes for the manufacture of said derivatives, pharmaceutical formulations containing the active compounds and the use of the compounds in therapy, particularly in the treatment of diseases where under- activation of the HM74A receptor contributes to the disease or where activation of the receptor will be beneficial, having the formula (II): wherein R1 is selected from: hydrogen and C1-4 alkyl which may be optionally substituted with one or more groups selected from CN and CF3, R2 is selected from: C2-10 unsubstituted alkyl, C1-10 alkyl substituted with one or more groups selected from fluorine and CN, C5 alkenyl, unbranched C4 alkenyl, and C1-4 alkyl substituted with cycloalkyl, and R3 is selected from halogen and CN.

PREPARATION OF NOVEL XANTHINE DERIVATIVES

PROCEDE DE PREPARATION DE NOUVEAUX DERIVES DE LA XANTHINE ADIR 22 RUE GARNIER F-92200 NEUILLY SUR SEINE De nouveaux dérivés de la xanthine utilisables comme médicaments, et répondant à la formule : < IMG > (I) dans laquelle : R1 est hydrogène ou alcoyle de C1 à C5 ; R2 est hydrogène ou alcoyle de C1 à C5 comportant éventuellement une double liaison, ou benzyle ; R3 est hydrogène ou méthyle ; A est -(CH2)n- (n étant un nombre entier de 1 à 4) éventuellement substitué, lorsque n est supérieur à 1, par un hydroxyle ; X est un azote ou < IMG > ; et les substituants R sont chacun alcoyle de C1 à C5 ou forment ensemble une chaine polyméthylénique de C4 à C6, comportant éventuellement un oxygène ou un soufre ; ont été préparés en condensant : soit : < IMG > soit : < IMG > les composés (I) et leurs sels physiologiquement tolérables peuvent être utilisés en thérapeutique notamment dans le traitement de la migraine et de l'asthénie.

2,5,6-SUBSTITUTED-N -ALKYLPYRIMIDINES

The synthesis and application of N(1)-n-alkyl-pyrimidinium-salts are described. These surfactants have a very small critical micelle concentration (CMC) in the order of 10-5 10-7 Mol/Liter. These N(1)-n-alkyl-pyrimidinium components have pharmacological activities and can act as antimetabolites.

PHARMACEUTICAL PREPARATIONS

A pharmaceutical preparation is disclosed which is made up of a micelle or a vesicle each consisting of a cationic tenside with a monovalent ion and a hydrophobic cyclic or linear peptide, dispersed in a solvent whose pH value lies between pH 7 - pH 8, the critical micellization concentration (cmc) lying in the range of 1.0 . 10-7 to 7.0 . 10-5 mol/litre. The preparations disclosed have in particular the advantage that by the increasing of the hydrophobicity of the alkyl or aryl chain or the radical at the N+ tenside both the membrane permeability is increased and furthermore the pharmaceutical active substance, in particular linear and cyclic tyrocidines (A - E), can be transferred actively into the cytosol. They thus act on the transcription level. In addition, linear and cyclic tyrocidines in particular have antiviral effects.

N-ALKYLATED QUATERNARY NITROGEN-CONTAINING HETEROCYCLES

The synthesis of 4-, 4-(1,1)- and 3,5- substituted N-alkyl-pyri-dinium salts as well as of 2-carboxamide substituted N(1,4)diazinium componunds are described. The N-surfactants obtained have a small critical micelle concentration (CMC) of 10-5 - 10-7 Mol/ Liter. These surfactants produce micells of different size and form depending on the nature of the anions. 4-(1,1)-substituted and 3,5-substituted N-alkyl-pyridinium components are capable of forming vesicles in equeous solutions of different forms and sizes. The N-surfactants synthesized can be used as pharmaceuticals.

PREPARATION OF NOVEL XANTHINE DERIVATIVES

BENZYLATED PDE4 INHIBITORS

XANTHINE PHOSPHODIESTERASE V INHIBITORS

A xanthine phosphodiesterase V inhibitor having the formula (I), where R4 is a C3-15 cycloalkyl group, with or without one or more substituents, C3-15 cycloalkenyl group, with or without one or more substituents, or a heterocycloalkyl group of 3 to 15 members, with or without one or more substituents; useful for treating male (erectile) and female sexual dysfunction and other physiological disorders. For example, a representative compound of the invention is formula (II).

SOLID FORMULATION

A solid pharmaceutical preparation which comprises crystalline cellulose and either a xanthine derivative represented by the formula (I): (I) (II) (wherein R1, R2, and R3 are the same or different and each represents hydrogen, lower alkyl, lower alkenyl, or lower alkynyl and R4 represents cycloalkyl, -(CH2)n- R5, or the formula (II) shown above) or a pharmacologically acceptable salt of the derivative. The preparation is excellent in properties (e.g., hardness, disintegrability, releasability, and stability).

SULFONAMIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING SAME

Provided is a compound having an integrin a4 inhibiting action. A sulfonamide derivative represented by general formula (I) or a pharmaceutically acceptable salt thereof. (In the formula, R1-R5, e-h, D, and B are as defined in the specification.) ...

XANTHINE DERIVATIVES AS SELECTIVE HM74A AGONISTS

The present invention relates to compounds 0f formula (I), which are xanthine derivatives, processes for the manufacture of said derivatives, pharmaceutical formulations containing the active compounds and the use of the compounds in therapy, for example, in the treatment of diseases where under-activation of the HM74A receptor contributes to the disease or where activation of the receptor will be beneficial.

2-PHENOXY PYRIMIDINONE ANALOGUES

... 2-Phenoxy pyrimidinone analogues are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

KW-3902 CONJUGATES THAT DO NOT CROSS THE BLOOD-BRAIN BARRIER

The present invention relates to certain compounds and to methods for the preparation of certain compounds that can be used in the fields of chemistr y and medicine. Specifically, described herein are methods for the preparati on of various compounds and intermediates, and the compounds and intermediat es themselves. More specifically, described herein are methods for synthesiz ing KW-3902 derivatives of Formula (I), (II), (HI), (IV), (V), and (VI). ...

NARCOTINE PURIFICATION PROCESS

A process for purifying Narcotine to remove color and impurities to form Noscapine. The process includes forming an aqueous isopropanol solution with the Narcotine product wherein the isopropanol concentration of the solution is about 20% to about 70% by volume; and adjusting the pH of the solution with a strong base to a pH of about 10 to about 14, wherein impurities are removed from the Narcotine product.

XANTHINE DERIVATIVES AS SELECTIVE HM74A AGONISTS

The present invention relates to compounds1 of formula (I) which are xanthine derivatives, processes for the manufacture of said derivatives, pharmaceutical formulations containing these, compounds and the use of the compounds in therapy, for example, in the treatment of diseases where under-activation of the HM74A receptor contributes to the disease or where activation of the receptor will be beneficial.

PROCESSES FOR PREPARING ISOQUINOLINONES AND SOLID FORMS OF ISOQUINOLINONES

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI 3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

A POLYMERIC FORM OF 1-((4-METHYL-QUINAZOLIN-2-YL)METHYL)-3-7-(2-BUTYN-1-YL)-8-(3-(R)-AMINOPIPERIDIN-1-YL)XANTHINE

The invention relates to polymorphic crystal modifications of 1-((4-methyl-quinazolin-2-yl)methyl)-3,7-(2-butyn-1-yl)-8-(3-(R)-aminopiperidin-1-yl)xanthine, their production and their use for the preparation of a medicament.

POLYMORPHS

... production and their use for the preparation of a drug. The invention relates to polymorphic crystal modifications of 1-((4-methyl-quinazolin-2-yl)methyl)-3,7-(2-butyn-1-yl)-8-(3-(R)-aminopiperidin-1-yl)xanthine, their ...

SUBSTITUTED QUINAZOLINES, THE PREPARATION THEREOF AND THE USE THEREOF IN PHARMACEUTICAL COMPOSITIONS

The present invention relates to a compound of formula (I) (see formula I) wherein X and Y are the same or different and are independently: (see formula II) (see formula III); in which each R is independently selected from R1 and R2, in which R1 and R2 are the same or different and are independently selected from 3-amino-piperidin-1-yl; or a stereoisomer, mixture or salt thereof. The compound has valuable pharmacological properties, particularly an inhibitory effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

CAFFEINATED COMPOUNDS AND COMPOSITIONS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES

Compounds and their pharmaceutically acceptable salts for treatment of ß-amyloid diseases, such as observed in Alzheimer's disease and synucleinopathies, such as Parkinson's disease.

SUBSTITUTED AMINO ALKYL COMPOUNDS

Compounds and pharmaceutical compositions thereof comprise the formula: (R)j - (core moiety), including resolved enantiomers and/or diastereomers, hydrates, salts, solvates and mixtures thereof, wherein j is an integer from one to three, the core moiety is non-cyclic or comprises at least one, five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino substituted or unsubstituted benzyl, alkyl (C1-6) or alkenyl (C1-6), and at least one R has formula (I), wherein n is an integer from four to eighteen; each R'1 and R'2 is independently hydrogen, alkyl (C1-4) or alkenyl (C1-4), the alkyl or alkenyl groups being preferably substituted by a halogen, hydroxyl, ketone or dimethylamino group and/or may be interrupted by an oxygen or hydrogen atom or an alkyl (C 1- 4) group; and each R'3 and R'4 is independently hydrogen or methyl. Preferably, n is an integer from six to ten, R'1 and R'2 are independently hydrogen or methyl and R'3 and ...

XANTHINE DERIVATIVES

There is provided a novel xanthine Compound(I) (see formula I) wherein R1 and R2 are the same or different and each represent hydroxy-substituted, oxo-substituted or unsubstituted lower alkyl, Y is a single bond or alkylene, and Q is (see formula II or see formula III) wherein R3 and R4 are the same or different and each represent hydrogen or hydroxy, n is 0 or 1; provided that when both of R3 and R4 are hydrogen, at least one of R1 and R2 is hydroxy-substituted or oxo-substituted lower alkyl; or a pharmaceutically acceptable salt thereof. The xanthine compound has adenosine A1 receptor antagonizing activity, and thus shows diuretic effect, renal-protecting effect, bronchodilatory effect, cerebral function improving effect and anti-dementia effect.

XANTHINE COMPOUND, METHOD FOR PREPARING THEREOF, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

A novel xanthine compound having bronchodilating and brain function improving activity represented by the following formula (I) and (II): ( I ) ( II ) wherein R1 represents a hydrogen atom, 4-methoxybenzyl group, a straight- or branched-chain alkyl group having 1 to 6 carbon atoms, or a cycloalkyl group having 3 to 6 carbon atoms; R2 represents a hydrogen atom, a straight- or branched-chain alkyl group having 1 to 6 carbon atoms, or a cycloalkyl group having 3 to 6 carbon atoms; n represents an integer of from 1 to 4; and A represents -COCH3 or C(OR3)(OR4)CH3 in which R3 and R4 independently represents an alkyl group having 1 to 3 carbon atoms or R3 together with R4 represents a polymethylene group having 2 to 4 carbon atoms is disclosed. Also 6 0 disclosed are a pharmacologically acceptable salt of the same, method for preparing the same, and a pharmaceutical composition for the treatment of respiratory tract disease or brain disfunction comprising the effective amount of same. 61 ...

2-CYANO-3, 5-DIHYDROXYHEX-2-ENECARBOXAMIDE DERIVATIVES

... 2-Cyano-3,5-dihydroxyhex-2-enecarboxamide derivatives (see fig.I) are suitable for the production of pharmaceuticals for the prophylaxis and thera py of diseases or disorders whose course involves increased connective tissue or cartilage degradation.

XANTHINE COMPOUNDS HAVING TERMINALLY AMINATED ALKYNOL SIDE CHAINS

Xanthine compounds having terminally aminated alkynol side chains Compounds of the formula I, (see fig.I) in which one of the radicals R1 and R3 is an alkynol residue of the formula Ia or Ib (see fig.Ia) (see fig.Ib) are suitable for producing pharmaceuticals having a neuroprotective effect.

SOLID DISPERSION AND SOLID DISPERSION DOSAGE FORM OF XANTHINE DERIVATIVE

The present invention relates to a solid dispersion and a solid dispersion dosage form which comprise a xanthine derivative represented by the following formula (I) or a pharmacologically allowable salt thereof and a polymer (see fig. I) (I) (In the above formula, R1 and R2 are the same or different, and represent substituted or unsubstituted lower alkyl groups, and Q represents a hydrogen atom or a hydroxyl group.) ...

Verfahren zur Herstellung eines 3,7-Dimethylxanthin-Doppelsalzes

Verfahren zur Herstellung neuer heterocyclischer Verbindungen

Verfahren zur Herstellung eines wasserlöslichen Theophyllinderivates

Verfahren zur Herstellung von Dialkylxanthinverbindungen

Verfahren zur Herstellung eines Theophyllinsalzes.

Verfahren zur Herstellung von 8-(2'-Oxy-3'-(2"-methoxy-phenoxy)-1'-propoxy)-xanthin oder dessen Substitutionsprodukten

Verfahren zur Herstellung von neuen substituierten Aminen und deren Verwendung

Sympathicomimetic amines - also showing cardiac and circulatory activity

Amines (I) and their acid salts- R1 = H, alkyl R2 = H, OH R3,4 = OH, opt. etherified, halogen, alkyl A = Th.CH2CHR5.CH2 or Th.CH2CH2, where Th = theobromine or theophylline and R5 = H or OH Z = A, H or alkyl; when H or alkyl, A = Th.CH2CHOH-CH2. nor-ephedrino-N-hydroxypropyltheophylline (II), nor-ephedrino-N-di-(hydroxypropyltheophylline), (beta-(beta'-phenyl-beta'-hydroxyethylamino)-hydroxypropyl) -theophylline, ephedrino-N-hydroxypropyltheophylline. The cpds. show marked sympathicomimetic action. Also cardiac and circulatory activity.

Procédé de préparation d'un nouveau dérivé de théophylline

VERFAHREN ZUR HERSTELLUNG VON SILBERVERBINDUNGEN VON PYRIMIDIN-, PURIN- UND 8-AZAPURINVERBINDUNGEN.

Procédé de préparation de 7-(p-diméthylamino-benzyl) théophylline

Procédé de préparation de 8-(p-diméthylamino-benzyl) théophylline

Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors

Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme.

Process for the preparation of linagliptin

The present invention relates to processes for the preparation of 8-(3R)-3-aminopiperidinyl)-7-butyn-2-yl-3 -methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione and novel intermediates useful in its synthesis.

8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions

The present invention relates to substituted xanthines of general formula wherein R 1 to R 3 are as defined herein, the tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions

The present invention relates to substituted xanthines of general formula wherein R 1 to R 4 are as defined herein, the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

A2B ADENOSINE RECEPTOR ANTAGONISTS

Disclosed are novel compounds that are Aadenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea. 2. The method of claim 1 , wherein the disease state is chosen from atherosclerosis claim 1 , and angiogenesis.39.-. (canceled)10. A method of treating a cardiovascular disease by inhibition of an adenosine receptor characterized as A claim 1 , comprising administering to a human in need thereof a therapeutically effective dose of the compound 3-ethyl-1-propyl-8-{1-[(3-trifluoromethylphenyl)methyl]pyrazol-4-yl}-1 claim 1 ,3 claim 1 ,7-trihydropurine-2 claim 1 ,6-dione.11. The method of claim 1 , wherein the disease state is chosen from atherosclerosis claim 1 , and angiogenesis.1218.-. (canceled) This application is a Continuation of U.S. patent application Ser. No. 11/950,740, filed Dec. 5, 2007, which is a Divisional of U.S. patent application Ser. No. 11/189,202, filed Jul. 25, 2005, now U.S. Pat. No. 7,317,017, which is a Continuation of U.S. patent application Ser. No. 10/431,167, filed May 6, 2003, now U.S. Pat. No. 6,977,300, which is a Continuation in Part of U.S. Non-Provisional patent application Ser. No. 10/290,921, filed Nov. 8, 2002, now U.S. Pat. No. 6,825,349, which claims the benefit of U.S. Provisional Patent Application Ser. No. 60/401,408, filed Aug. 5, 2002 and U.S. Provisional Patent Application Ser. No. 60/348,222, filed Nov. 9, 2001 the complete disclosure of which is hereby incorporated by reference.The present invention relates to Aadenosine receptor antagonists, and to their use in treating mammals for various disease states, such as gastrointestinal disorders, immunological disorders, neurological disorders, and cardiovascular diseases due to both cellular hyperproliferation and apoptosis, and the like. The invention also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.Adenosine is a naturally occurring nucleoside, which exerts its ...

SOLID STATE FORMS OF LINAGLIPTIN

The present invention provides solid state forms of Linagliptin, processes for preparing the solid state forms, and pharmaceutical compositions thereof. 1. Crystalline Form X of Linagliptin , characterized by data selected from: a powder XRD pattern having peaks at 8.3° , 9.6° , 13.0° , 17.6° , and 18.9°±0.2 degrees 2θ; a powder XRD pattern as shown in ; and any combinations thereof.2. The crystalline Form X according to claim 1 , characterized by a powder XRD pattern having peaks at 8.3° claim 1 , 9.6° claim 1 , 13.0° claim 1 , 17.6° claim 1 , and 18.9°±0.2 degrees 2θ claim 1 , further characterized by one claim 1 , two claim 1 , three claim 1 , four claim 1 , or five peaks selected from 8.8° claim 1 , 10.6 13.6° claim 1 , 16.2° claim 1 , and 17.0°±0.2 degrees 2θ.3. The crystalline Form X of any one of and claim 1 , which is anhydrous.4. The crystalline Form X of any one of to claim 1 , which is non-hygroscopic.5. Crystalline Form XXII of Linagliptin claim 1 , characterized by data selected from: a powder XRD pattern having peaks at 9.8° claim 1 , 10.6° claim 1 , 12.3° claim 1 , 20.1° claim 1 , and 23.7°±0.2 degrees 2θ; a powder XRD pattern as shown in ; and any combinations thereof.6. The crystalline Form XXII according to claim 5 , characterized by a powder XRD pattern having peaks at 9.8° claim 5 , 10.6° claim 5 , 12.3° claim 5 , 20.1° claim 5 , and 23.7°±0.2 degrees 2θ claim 5 , and further characterized by one or more powder XRD peaks selected from 7.1° claim 5 , 14.1° claim 5 , 15.7° claim 5 , 21.8° claim 5 , and 27.2°±0.2 degrees 2θ.7. The crystalline Form XXII of any one of and claim 5 , having a total solvent content of about 5000 ppm to about 20 ppm claim 5 , as measured by GC.8. The crystalline Form XXII of any one of to claim 5 , which is non-hygroscopic.98. The use of the solid state forms of Linagliptin according to any one of to for the preparation of a different solid state form of Linagliptin.108. The use of the solid state forms of Linagliptin ...

NOVEL HYPOGLYCEMIC COMPOUNDS

The present invention relates to novel hypoglycemic compounds of formula (1) and pharmaceutically acceptable salts thereof. The invention relates to novel amino acid derivatives of the formula (1), wherein, A is amino acid B is peptide bond R—NH— wherein R is defined in the specification 2. The compound of formula 1 as claimed in wherein the amino acid is selected from amino acid analogues.3. The compound of formula 1 as claimed in wherein the amino acid is selected from glycine claim 1 , alanine claim 1 , valine claim 1 , histidine claim 1 , serine claim 1 , leucine claim 1 , isoleucine claim 1 , phenylalanine claim 1 , methionine claim 1 , tryptophan claim 1 , lysine claim 1 , glutamine claim 1 , glutamic acid claim 1 , serine claim 1 , proline claim 1 , cysteine claim 1 , tyrosine claim 1 , histidine claim 1 , arginine claim 1 , asparagines claim 1 , aspartic acid claim 1 , threonine or mixtures of amino acid thereof.4. An amino acid analogue of 2-({6-[(3R)-3-substituted-aminopiperidin-1-yl]-3-methyl-2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydropyrimidin-1(2H)-yl}methyl)-benzonitrile and pharmaceutically acceptable salts thereof.5. An amino acid analogue of 1-[2-Amino-3 claim 1 ,3-bis-(4-fluoro-phenyl)-propionyl]-4-fluoro-pyrrolidine-2-carbonitrile and pharmaceutically acceptable salts thereof.6. An amino acid analogue of (2R)-4-oxo-4-[3-(trifluoromethyl)-5 claim 1 ,6-dihydro[1 claim 1 ,2 claim 1 ,4]triazolo[4 claim 1 ,3-a]pyrazin-7(8H)-yl]-1-(2 claim 1 ,4 claim 1 ,5-trifluorophenyl)butan-2-amine and pharmaceutically acceptable salts thereof.7. An amino acid analogue of 8-[(3R)-3-aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-3 claim 1 ,7-dihydro-1H-purine-2 claim 1 ,6-dione and pharmaceutically acceptable salts thereof.8. An amino acid analogue of (1S claim 1 ,3S claim 1 ,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo-[3.1.0]-hexane-3-carbonitrile and pharmaceutically acceptable salts thereof.9. An amino acid ...

Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions

The present invention relates to substituted quinazolines of formula (I): 2. The compound of formula (I) according to claim 1 , in whichR1 and R2 are the same or different and are independently selected from 3-(R)-amino-piperidin-1-yl, (2-amino-2-methyl-propyl)-methylamino and (2-(S)-amino-propyl)-methylamino;or a tautomer, enantiomer, diastereomer, mixture or salt thereof.3. The compound of formula (I) according to claim 1 , in which X and Y are the same claim 1 , or a tautomer claim 1 , enantiomer claim 1 , diastereomer claim 1 , mixture or salt thereof.6. Physiologically acceptable salt of the compound according to with an inorganic or organic acid or base.7. Pharmaceutical composition containing a compound of formula (I) according to claim 1 , or a physiologically acceptable salt thereof with an inorganic or organic acid or base claim 1 , optionally together with one or more pharmaceutically acceptable excipients.8. Use of a compound according to for preparing a pharmaceutical composition which is suitable for treating type II diabetes mellitus or obesity.9. Process for preparing a pharmaceutical composition according to claim 7 , characterised in that the compound of formula (I) or a physiologically acceptable salt thereof with an inorganic or organic acid or base is incorporated in one or more pharmaceutically acceptable excipients.10. A method of treating or preventing type II diabetes mellitus or obesity claim 1 , the method comprising administering the compound according to claim 1 , and optionally one or more other active substances claim 1 , to a patient.11. The method according to claim 10 , wherein the one or more other active substances is selected from metformin claim 10 , metformin; sulphonylureas claim 10 , nateglinide claim 10 , repaglinide claim 10 , thiazolidinediones (e.g. pioglitazone) claim 10 , PPAR-gamma agonists claim 10 , alpha-glucosidase blockers claim 10 , insulin or insulin analogues claim 10 , and GLP-1 and GLP-1 analogues.12. ...

COMPOUNDS AND COMPOSITIONS FOR TREATING CHEMICAL WARFARE AGENT-INDUCED INJURIES

Compounds and compositions for treating injuries caused by exposure to chemical warfare agents are described herein. 122-. (canceled)24. The compound of claim 23 , wherein{'sup': '2', 'sub': 1', '6, 'a. Ris H or C-Calkyl;'}{'sup': '6', 'b. L is C(O)NR;'}{'sup': 3', '7, 'sub': 4', '14, 'c. Ris C-Ccyclyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with R;'}{'sup': '6', 'd. each Ris H;'}{'sup': 7', '8, 'sub': 1', '6', '2', '6', '2', '6, 'e. Ris C-Calkyl, C-Calkenyl, C-Calkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halo, hydroxyl, alkoxy, thiol, alkylthio, aryloxy, arylalkoxy, amino, alkylamino, dialkylamino, thioyl, alkylthioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea, hydroxyl alkoxyl, alkoxy alkoxyl, acyl, nitro, or cyano, each of which is optionally substituted with 1-3 R;'}{'sup': '8', 'sub': 1', '6', '2', '6', '2', '6', '3, 'f. each Ris independently C-Calkyl, C-Calkenyl, or C-Calkynyl, halo, hydroxyl, alkoxy, thiol, alkylthio, aryloxy, amino, alkylamino, dialkylamino, thioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea acyl, nitro, cyano, cyclyl, heterocyclyl, aryl, or heteroaryl, wherein said heterocyclyl can be substituted at one or more positions with halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphate, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, —CF, and —CN;'}{'sup': '9', 'g. Ris H;'}{'sup': 11', '12', '8, 'sub': 1', '6', '2', '6', '2', '6, 'h. each of R-Ris, independently, H, C-Calkyl, C-Calkenyl, or C-Calkynyl, halo, hydroxyl, alkoxy, amino, alkylamino, thiol, alkylthiol, nitro, or cyano, each of which is optionally substituted with 1-2 R;'}i. m is 1 andj. n is 0.25. The compound of claim 24 , wherein{'sup': '2', 'sub': 1', '6, 'a. Ris C-Calkyl;'}{'sup': 3', '7, 'b. Ris aryl or heteroaryl, substituted with R;'}{'sup': 7', '8, 'c. Ris aryl or ...

XANTHINE DERIVATIVES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

The present invention relates to substituted xanthines of general formula 2. The Compound according to claim 1 , wherein{'sup': '1', 'claim-text': (1) a hydrogen atom,', {'sub': '1-6', '(2) a C-alkyl group,'}, {'sub': '3-6', '(3) a C-alkenyl group,'}, {'sub': 3-4', '1-2, '(4) a C-alkenyl group which is substituted by a C-alkyloxy-carbonyl group,'}, {'sub': '3-6', '(5) a C-alkynyl group,'}, {'sub': 3-6', '1-3, '(6) a C-cycloalkyl-C-alkyl group,'}, '(7) a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group,', {'sub': '1-4', 'sup': 10', '12, 'claim-text': [{'sup': '10', 'claim-text': (i) a hydrogen atom, a fluorine, chlorine or bromine atom,', {'sub': 1-4', '3-6, '(ii) a C-alkyl, trifluoromethyl, hydroxymethyl, C-cycloalkyl, ethynyl or phenyl group,'}, {'sub': 1-4', '1-2', '1-2', '1-3', '1-3', '1-3', '1-3', '1-2', '1-3', '1-2', '1-3', '1-3', '1-3', '1-3', '3-6', '3-6', '1-2, '(iii) a hydroxy, C-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C-alkyloxy, C-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C-alkyloxy, C-alkyloxy-carbonyl-C-alkyloxy, aminocarbonyl-C-alkyloxy, C-alkyl-aminocarbonyl-C-alkyloxy, di-(C-alkyl)aminocarbonyl-C-alkyloxy, pyrrolidin-1-yl-carbonyl-C-alkyloxy, piperidin-1-ylcarbonyl-C-alkyloxy, morpholin-4-ylcarbonyl-C-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsulphonylethoxy, C-cycloalkyloxy or C-cycloalkyl-C-alkyloxy group,'}, {'sub': 1-3', '1-3', '1-3', '1-3', '1-2', '1-2, '(iv) a carboxy, C-alkyloxycarbonyl, carboxy-C-alkyl, C-alkyloxy-carbonyl-C-alkyl, aminocarbonyl, C-alkylaminocarbonyl, di-(C-alkyl)aminocarbonyl or cyano group,'}, {'sub': 1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-3', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2, '(v) a nitro, amino, C-alkylamino, di-(C-alkyl)amino, cyano-C-alkylamino, [N-(cyano-C-alkyl)-N—C-alkyl-amino ...

Inhibitors of PI3K-Delta and Methods of Their Use and Manufacture

The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

Difluoromethylation Of Unsaturated Compounds

A reagent for carrying out a difluoromethylation reaction of unsaturated compounds and ring-nitrogen-containing aromatic compounds, a zinc difluoro-methanesulfinate, as well as a method for making the reagent and a method for its use are disclosed. 1. Zinc difluoromethanesulfinate.2. The zinc difluoromethanesulfinate according to present as a hydrate.3. The zinc difluoromethanesulfinate according to claim 2 , wherein said hydrate is a trihydrate.4. A method for difluoromethylating an unsaturated substrate compound that is other than a hydrocarbon compound comprising the steps of:a) reacting said unsaturated substrate compound with an excess of zinc difluoromethanesulfinate and an excess of tert-butyl hydroperoxide in a water-containing liquid reaction mixture at an initial temperature below about 10° C. under vigorous agitation; andb) permitting said reaction mixture to warm to ambient room temperature, while maintaining said agitation.5. The method according to claim 4 , wherein said unsaturated substrate compound and said excess of zinc difluoromethanesulfinate are admixed in a water-containing liquid reaction mixture at an initial temperature below about 10° C. under vigorous agitation prior to the addition of said tert-butyl hydroperoxide claim 4 , and said tert-butyl hydroperoxide is added slowly thereto.6. The method according to claim 4 , wherein said zinc difluoromethanesulfinate is a zinc difluoromethanesulfinate hydrate.7. The method according to claim 4 , wherein said reaction mixture is maintained until said unsaturated substrate compound is consumed.8. The method according to claim 4 , wherein said unsaturated substrate compound is a heteroaryl or an α claim 4 ,β-unsaturated compound.9. The method according to claim 4 , wherein said unsaturated substrate compound that is a heteroaryl compound.10. The method according to claim 9 , wherein said heteroaryl compound contains 1 to 5 nitrogen atoms in the aromatic ring system that is difluoromethylated.11. ...

PROCESS FOR THE PREPARATION OF CHIRAL 8-(3-AMINOPIPERIDIN-1-YL)-XANTHINES

The invention relates to an improved process for preparing enantiomerically pure 8-(3-aminopiperidin-1-yl)-xanthines. 3. The first compound according to claim 2 , wherein the phthalyl protecting group of the second compound is detached in the presence ethanolamine.4. The first compound according to claim 2 , wherein the phthalyl protecting group of the second compound is detached in the presence of i) ethanolamine and ii) in the presence of toluene or a mixture of tetrahydrofuran and water.5. The first compound according to claim 2 , further comprising crystallizing the first compound from ethanol or methanol.6. The first compound according to claim 2 , further comprising crystallizing the first compound from ethanol.7. The first compound according to in a form pure for medicament production.8. The first compound according to in a form pure for medicament production.10. A process for preparing a medicament comprising the first compound according to claim 1 , the process comprising combining the first compound with one or more inert carriers and/or diluents.11. A process for preparing a medicament comprising the first compound according to claim 2 , the process comprising combining the first compound with one or more inert carriers and/or diluents.12. A process for preparing a medicament comprising the first compound according to claim 9 , the process comprising combining the first compound with one or more inert carriers and/or diluents. The invention relates to an improved process for preparing chiral 8-(3-aminopiperidin-1-yl)-xanthines, their enantiomers and their physiologically tolerated salts.8-(3-aminopiperidin-1-yl)-xanthines of the following general structurein which Ris, for example, an optionally substituted arylmethyl group or an optionally substituted heteroarylmethyl group, Ris, for example, an alkyl group and Ris, for example, an optionally substituted benzyl group or a straight-chain or branched alkenyl or alkinyl group are already known from the ...

DUAL SELECTIVE PI3 DELTA AND GAMMA KINASE INHIBITORS

The present invention relates to dual delta (δ) and gamma (γ) PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of Pi3K kinase mediated diseases or disorders with them. 121-. (canceled)22. A method of treating T-cell lymphoma in a patient in need thereof , the method comprising administering to the patient an effective amount of 2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.23. A method of treating T-cell lymphoma in a patient in need thereof , the method comprising administering to the patient an effective amount of (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.24. A method of treating T-cell lymphoma in a patient in need thereof , the method comprising administering to the patient an effective amount of a compound that is (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof , wherein the compound contains less than about 5% by weight of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.25. The method of claim 24 , wherein the compound contains less than about 2.5% by weight of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.26. The method of claim 24 , wherein the compound contains less than about 1% by weight of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.27. The method of claim 24 , wherein the compound contains less than about 0.1% by weight of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one or a pharmaceutically acceptable salt thereof.28. The method of claim 22 , wherein the patient is a human patient.29. The ...

SULFONAMIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING SAME

Provided is a compound having α4 integrin inhibitory action. 2. The sulfonamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sub': 1', '2', '1', '2, 'Rand Reach independently represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkenyl group, a lower alkoxy group, a lower alkoxy lower alkyl group, a hydroxy group, or a hydroxy lower alkyl group, where Rand Rmay be bonded together to form a benzene ring which may have a substituent, an alicyclic hydrocarbon which has 4 to 7 carbon atoms and which may have a substituent, a heteroaryl ring which may have a substituent, or a hetero ring which may have a substituent, and'}{'sub': '5', 'Rrepresents a lower alkyl group which may have a substituent, a lower alkenyl group which may have a substituent, a lower alkylamino group, a phenyl group which may have a substituent, a heteroaryl group which may have a substituent, or a heterocyclic group which may have a substituent.'}3. The sulfonamide derivative or the pharmaceutically acceptable salt thereof according to the claim 1 , wherein represents a double bond.4. The sulfonamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sub': 1', '2, 'Rand Rare bonded together to form a benzene ring which may have a substituent, an alicyclic hydrocarbon which has 4 to 7 carbon atoms and which may have a substituent, a heteroaryl ring which may have a substituent, or a hetero ring which may have a substituent, and'}the substituent is selected from a lower alkyl group, a lower alkoxy group, a hydroxy lower alkyl group, an amino group, a lower alkylamino group, and a lower alkylamino lower alkyl group.5. The sulfonamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sub': 1', '2, 'Rand Reach independently represent a hydrogen atom, a lower alkyl group, or a hydroxy lower alkyl group,'}{'sub': 1', '2, 'Rand Rmay be bonded together to form an ...

SUBSTITUTED XANTHINE DERIVATIVES

This invention relates to novel deuterated compounds that are substituted xanthine derivatives and pharmaceutically acceptable salts thereof. In particular, this invention relates to novel substituted xanthine derivatives that are deuterated derivatives of a pentoxifylline metabolite. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed deuterated compounds and compositions in methods of treating diseases and conditions for which pentoxifylline and related compounds are beneficial. The compounds of the invention are represented by the following structural formula: 122-. (canceled)24. The compound of claim 23 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.25. The compound of claim 23 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6000.26. The compound of claim 23 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6600.27. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.28. A method of treating a disease or condition in a patient in need thereof claim 24 , comprising administering to the patient an effective amount of a compound of claim 24 , wherein the disease is selected from diabetic nephropathy and hypertensive nephropathy.29. A method of treating chronic kidney disease in a patient in need thereof claim 24 , comprising administering to the patient an effective amount of a compound of .30. The method of wherein the chronic kidney disease is glomerulonephritis claim 29 , focal segmental glomerulosclerosis claim 29 , nephrotic syndrome claim 29 , reflux uropathy claim 29 , or polycystic kidney disease.31. A method of treating chronic disease of the liver in a patient in need thereof claim 24 , comprising administering to the patient an effective amount of a compound of .32. The method of wherein the chronic disease of the ...

AMORPHOUS FORM OF LINAGLIPTIN AND PROCESS FOR PREPARATION THEREOF

The present invention relates to an amorphous form of linagliptin and processes for the preparation thereof. The invention also relates to a pharmaceutical composition comprising therapeutically effective amount of an amorphous form of linagliptin and use of said composition for treatment of diabetes especially type-I or type-II, prediabetes or reduction of glucose tolerance. 2. The amorphous form of linagliptin according to claim 1 , having a water content less than 0.5% wt/wt.3. An improved process for the preparation of an amorphous form of linagliptin according to claim 1 , the process comprising:(a) providing a solution of linagliptin in a suitable solvent or mixture of solvents;(b) obtaining the amorphous form of linagliptin by removal of solvent.4. The process according to wherein suitable solvent comprises water; alcohols such as methanol claim 3 , ethanol claim 3 , isopropanol and the like; ketones such as acetone claim 3 , butanone and the like; esters such as ethyl acetate claim 3 , butyl acetate and the like; halogenated hydrocarbons like methylene dichloride claim 3 , ethylene dichloride claim 3 , chlorobenzene claim 3 , and the like claim 3 , nitriles like acetonitrile; polar aprotic solvents like dimethylformamide claim 3 , dimethylacetamide claim 3 , N-methyl pyrrolidone claim 3 , dimethyl-sulfoxide claim 3 , tetrahydrofuran or mixtures thereof.5. The process according to wherein removal of solvent comprises using a rotational distillation device like a Buchi Rotavapor claim 3 , spray drying claim 3 , agitated thin film drying (“ATFD”) claim 3 , freeze drying (lyophilization) claim 3 , and the like.6. An improved process for the preparation of an amorphous form of linagliptin according to claim 1 , the process comprising:(a) suspending linagliptin in a suitable organic solvent and removing the solvent to obtain residue;(b) adding a suitable anti-solvent to the residue; and(c) obtaining the amorphous form of linagliptin.7. The process according to ...

8-[3-AMINO-PIPERIDIN-1-YL]-XANTHINES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

The present invention relates to substituted xanthines of general formula 2. 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine.3. 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine.5. The process according to claim 4 , wherein the tert.-butyloxycarbonyl group is cleaved by treatment with an acid such as trifluoroacetic acid or hydrochloric acid or by treatment with bromotrimethylsilane or iodotrimethylsilane claim 4 , optionally using a solvent such as methylene chloride claim 4 , ethyl acetate claim 4 , dioxane claim 4 , methanol claim 4 , isopropanol or diethyl ether at temperatures between 0 and 80° C. This application is a continuation of application Ser. No. 12/143,128, filed Jun. 20, 2008, which is a continuation of application Ser. No. 10/639,036, filed, Aug. 12, 2003. This application claims the benefit of U.S. provisional application Ser. Nos. 60/409,312, filed Sep. 9, 2002 and 60/461,752, filed Apr. 10, 2003, and German application Nos. DE 102 38 243.3, filed Aug. 21, 2002 and DE 103 12 353.9, filed Mar. 20, 2003.The present invention relates to compounds having valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).The present invention relates to new substituted xanthines of general formulathe tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV), the preparation thereof, the use thereof for the prevention or treatment of diseases or conditions associated with an increased DPP-IV activity or capable of being prevented or alleviated by reducing the DPP-IV ...

DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS

Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme. 2: A method according to claim 1 , wherein Ris methyl.3: A method according to claim 1 , wherein Ris methyl.4: A method according to claim 1 , wherein R′ is t-butyl.5: A method according to claim 1 , wherein A is an aryl group claim 1 , a (C-C) cycloalkyl group claim 1 , or a heteroaryl group.6: A method according to claim 1 , wherein in A at least one ring atom is a heteroatom.7: A method according to claim 1 , wherein in A at least one ring atom is a heteroatom selected from N claim 1 , S claim 1 , and O.8: A method according to claim 1 , wherein Rand Rtogether with the nitrogen atom to which they are linked form a piperidine ring optionally substituted by (C-C) alkyl optionally substituted by one or more halogen atoms claim 1 , an oxazine ring optionally substituted by (C-C) alkyl optionally substituted by one or more halogen atoms claim 1 , or an imidazole ring optionally substituted by (C-C) alkyl optionally substituted by one or more halogen atoms.9: A method according to claim 1 , wherein Rand Rtogether with the nitrogen atom to which they are linked form a piperidyl ring.10: A method according to claim 1 , wherein A is a phenyl optionally substituted with one or more Rgroups.11: A method according to claim 1 , wherein A is a heteroaryl ring optionally substituted with one or more Rgroups.12: A method according to claim 11 , wherein A is a heteroaryl ring selected from the group consisting of pyrrole claim 11 , pyrazole claim 11 , furan claim 11 , thiophene claim 11 , imidazole claim 11 , oxazole claim 11 , isoxazole claim 11 , thiazole claim 11 , pyridine claim 11 , pyrimidine claim 11 , pyrazine claim 11 , pyridazine claim 11 , and pyran.13: A method according to claim 1 , wherein Ris a halogen atom.14: A method according to claim 13 , wherein Ris chlorine.16: A method according to claim 15 , wherein Z is (CH)with m equal to 0.1718-. ( ...

8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions

The present invention relates to substituted xanthines of general formula wherein R 1 to R 3 are as defined herein, the tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

POLYMORPHS

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament. 1. Anhydrous polymorph A of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine , characterised in that it melts at 206±3° C.2. Polymorph A according to claim 1 , characterised in that in the X-ray powder diagram it has inter alia characteristic reflexes at the following d values: 11.49 Å claim 1 , 7.60 Å claim 1 , 7.15 Å claim 1 , 3.86 Å claim 1 , 3.54 Å and 3.47.3. Anhydrous polymorph B of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine claim 1 , characterised in that at a temperature of 10-40° C. it transforms reversibly into the polymorph A of .4. Polymorph B according to claim 3 , characterised in that in the X-ray powder diagram it has inter alia characteristic reflexes at the following d values: 11.25 Å claim 3 , 9.32 Å claim 3 , 7.46 Å claim 3 , 6.98 Å and 3.77 Å.5. Polymorph C of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine claim 3 , characterised in that it loses water at a temperature of 30-100° C. and in the DSC diagram it exhibits further thermal effects at approx. 150° C. and 175° C.6. Polymorph C according to claim 5 , characterised in that in the X-ray powder diagram it has inter alia characteristic reflexes at the following d values: 12.90 Å claim 5 , 11.10 Å claim 5 , 6.44 Å claim 5 , 3.93 Å and 3.74 Å.7. Anhydrous polymorph D of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine claim 5 , characterised in that it melts at 150±3° C.8. Anhydrous polymorph E of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine claim 5 , characterised in that it melts at 175±3° C.9. ...

NOVEL COMPOUNDS

The present invention relates to therapeutically active xanthine derivative compounds of Formula (I): 2. The method according to claim 1 , wherein said method treats the inflammatory disease or condition of nervous tissue claim 1 , and wherein the disease or condition is multiple sclerosis.3. The method according to claim 1 , wherein said method treats inflammatory sequelae of a viral or bacterial infection.4. The method according to claim 1 , wherein Ris hydrogen claim 1 , Calkyl claim 1 , CHCN or (CH)CF; and Ris Cunsubstituted alkyl claim 1 , (CH)CN claim 1 , Calkyl substituted with one or more fluorine substitutions claim 1 , unbranched Calkenyl claim 1 , or Calkyl substituted with cycloalkyl.5. The method according to claim 1 , wherein Ris hydrogen or methyl.6. The method according to claim 1 , wherein Ris Cunsubstituted n-alkyl claim 1 , (CH)CN claim 1 , Calkyl with one or more fluorine substitutions or Calkenyl.7. The method according to claim 1 , wherein Ris Cunsubstituted n-alkyl.8. The method according to claim 1 , wherein Ris chlorine or bromine.9. The method according to claim 1 , wherein Ris chlorine.10. The method according to claim 1 , wherein the compound of Formula (I) is selected from:(8-chloro-2,6-dioxo-1,2,6,7-tetrahydro-3H-purin-3-yl)acetonitrile;3-butyl-8-chloro-3,7-dihydro-1H-purine-2,6-dione;8-chloro-1-methyl-3-pentyl-3,7-dihydro-1H-purine-2,6-dione;8-chloro-3-(4,4,4-trifluorobutyl)-3,7-dihydro-1H-purine-2,6-dione;8-bromo-1-methyl-3-pentyl-3,7-dihydro-1H-purine-2,6-dione;8-chloro-3-(3,3,3-trifluoropropyl)-3,7-dihydro-1H-purine-2,6-dione;8-chloro-1-propyl-3-(2,2,2-trifluoroethyl)-3,7-dihydro-1H-purine-2,6-dione;3-butyl-8-chloro-1-methyl-3,7-dihydro-1H-purine-2,6-dione;(3-butyl-8-chloro-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetonitrile;8-chloro-3-(2-cyclopropylethyl)-3,7-dihydro-1H-purine-2,6-dione;8-chloro-1,3-bis(4,4,4-trifluorobutyl)-3,7-dihydro-1H-purine-2,6-dione;4-(8-chloro-1-methyl-2,6-dioxo-1,2,6,7-tetrahydro-3H-purin-3-yl) ...

8-[3-AMINO-PIPERIDIN-1-YL]-XANTHINES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

The present invention relates to substituted xanthines of general formula 1. 1-[(Quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine , or an enantiomer , a mixture of enantiomers or a salt thereof.2. 3-Methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine.3. A physiologically acceptable salt of a compound according to with an inorganic or organic acid or base.4. A pharmaceutical composition comprising a compound according to or a physiologically acceptable salt thereof claim 1 , optionally together with one or more inert carriers and/or diluents. The present invention relates to compounds having valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).The present invention relates to new substituted xanthines of general formulathe tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV), the preparation thereof, the use thereof for the prevention or treatment of diseases or conditions associated with an increased DPP-IV activity or capable of being prevented or alleviated by reducing the DPP-IV activity, particularly type I or type II diabetes mellitus, the pharmaceutical compositions containing a compound of general formula (I) or a physiologically acceptable salt thereof as well as processes for the preparation thereof.In the above formula IRdenotes a methyl group, a methyl group which is substituted by a dimethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, tert.-butylcarbonyl or a cyclohexylcarbonyl-group, a methyl group which is substituted by a naphthyl, methylnaphthyl, methoxynaphthyl, nitronaphthyl or dimethylaminonaphthyl group, ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CHRONIC DISEASES AND INFLAMMATORY DISORDERS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of chronic diseases and inflammatory disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of intermittent claudication, obstructed arteries in the limbs, vascular dementia, Peyronie's disease, neuropathic injuries, sickle cell disease, nausea and headaches in the mountains (altitude sickness), acute alcoholic and non-alcoholic steatohepatitis, alcoholic liver disease, fibrotic lesions induced by radiation therapy for cancer, cytokine release syndrome, endometriosis, venous disease, inflammation, cancer, stroke, thrombosis, sepsis, gangrene, infection, type 1 diabetes, type 2 diabetes, pancreatic beta cell degeneration, beta cell dysfunction, respiratory diseases, rheumatoid arthritis, arthritis, osteoarthritis and vascular disease. 2. A Pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 2 , which is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration claim 2 , delayed release or sustained release claim 2 , transmucosal claim 2 , syrup claim 2 , topical claim 2 , parenteral administration claim 2 , injection claim 2 , subdermal claim 2 , oral solution claim 2 , rectal administration claim 2 , buccal administration or transdermal administration.4. A method of treating chronic diseases and inflammatory disorders as the underlying etiology claim 3 , the method comprising administering to a patient in need thereof an effective amount of .5. The method of claim 4 , wherein the chronic ...

POLYMORPHS

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament. 1. A method of preparing polymorph D of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine , characterized in that it melts at 150±3° C. , wherein polymorph D is obtained by heating polymorph C of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine to a temperature of 30-100° C. or by drying at this temperature , wherein Polymorph C is characterized in that it loses water at a temperature of 30-100° C. and exhibits further thermal effects at a temperature of about 150° C. and about 175° C. in a differential scanning calorimetry (DSC) analysis.2. The method according to wherein polymorph C is obtained by a method comprising:(a) refluxing a solution of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in methanol to provide a hot methanolic solution,(b) cooling the hot methanolic solution to a temperature of 40-60° C. to provide a cooled methanolic solution,(c) adding tert-butylmethylether to the cooled methanolic solution to form a suspension,(d) cooling the suspension first to a temperature of 15-25° C. and then to a temperature of 0-5° C. to provide crystals,(e) suction filtering the crystals, and(f) drying the crystals obtained in step (e) in vacuo at a temperature of 70° C. to provide Polymorph C.3. The method according to claim 2 , wherein the X-ray powder diagram of Polymorph C has characteristic reflections at the following d values: 12.90 Å claim 2 , 11.10 Å claim 2 , 6.44 Å claim 2 , 3.93 Å and 3.74 Å.4. The method according to claim 2 , wherein the hot methanolic solution obtained in step (a) is filtered before cooling in step (b). This Application claims priority of EP 06 009 202, which is hereby incorporated by reference in ...

Trka kinase inhibitors, compositions and methods thereof

The present invention is directed to bicyclic heteroaryl benzamide compounds of formulas (I): which are tropomyos-in-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

CAFFEINATED COMPOUNDS AND COMPOSITIONS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES

Compounds and their pharmaceutically acceptable salts for treatment of β-amyloid diseases, such as observed in Alzheimer's disease and synucleinopathies, such as Parkinson's disease. 3. The compound of where Ris substituted with a benzyl group claim 1 , Ror Rare independently substituted with either a methyl or benzyl group and Ris substituted with a hydrogen and wherein the benzyl groups are each substituted with two hydroxyl groups.4. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.5. A method of treating the formation claim 1 , deposition claim 1 , accumulation claim 1 , or persistence of amyloid or α-synuclein fibrils claim 1 , comprising treating the fibrils with an effective amount of the compound of .6. A method of treating an amyloid disease or a synucleinopathy in a mammal suffering therefrom claim 1 , comprising administration of a therapeutically effective amount of the compound of .7. The method of where the amyloid disease is selected from the group of diseases consisting of Alzheimer's disease claim 5 , type II diabetes claim 5 , systemic AA amyloidosis claim 5 , Down's syndrome claim 5 , hereditary cerebral hemorrhage with amyloidosis of the Dutch type claim 5 , and cerebral β-amyloid angiopathy.8. The method of where the amyloid disease is Alzheimer's disease.9. The method of where the synucleinopathy is selected from the group consisting of Parkinson's disease claim 5 , familial Parkinson's disease claim 5 , Lewy body disease claim 5 , the Lewy body variant of Alzheimer's disease claim 5 , dementia with Lewy bodies claim 5 , multiple system atrophy claim 5 , and the Parkinsonism-dementia complex of Guam.10. The method of where the synucleinopathy is Parkinson's disease.11. The method of claim 5 , where the compound administered is in an amount between 0.1 mg/Kg/day and 1000 mg/Kg/day.12. The method of claim 5 , where the compound is administered in an amount between 1 mg/Kg/day and 100 mg/Kg/day.13 ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATORY DISORDERS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for treating or preventing inflammatory disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of intermittent claudication resulting from obstructed arteries in the limbs, and vascular dementia, improves blood flow through peripheral blood vessels and therefore helps with blood circulation in the arms and legs (e.g. intermittent claudication), and the brain (hence its use in vascular dementia), venous disease, Peyronie's disease, neuropathic injuries, strokes, sickle cell disease, nausea and headaches in the mountains (altitude sickness), non-alcoholic steatohepatitis and alcoholic liver disease, fibrotic lesions induced by radiation therapy for breast cancer, cytokine release syndrome, cancer, type 1 diabetes and type 2 diabetes, asthma, bronchodilation, kidney diseases, renal protection, vascular ischemia, neuroprotection, vasodilation, Alzheimer's disease, dementia, stroke, and treatment of endometriosis. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 2 , wherein said pharmaceutical composition is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration claim 2 , delayed release or sustained release claim 2 , transmucosal claim 2 , syrup claim 2 , topical claim 2 , parenteral administration claim 2 , injection claim 2 , subdermal claim 2 , oral solution claim 2 , rectal administration claim 2 , buccal administration or transdermal administration.4. Compounds and compositions of claim 3 , ...

ETHYNYL DERIVATIVES

It has been surprisingly been found that the compounds of general formula I are positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGluR4), useful for the treatment of Parkinson's disease, anxiety, emesis, obsessive compulsive disorder, autism, neuroprotection, cancer, depression and diabetes type 2. 3. The compound of formula IA according to claim 2 , wherein the compound is selected from the group consisting of3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1,8-dimethyl-quinazoline-2,4-dione8-Chloro-3-[2-chloro-4-(2-phenylethynyl)phenyl]-1-methyl-quinazoline-2,4-dione7-Chloro-3-[2-chloro-4-(2-phenylethynyl)phenyl]-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1,7-dimethyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1H-pyrido[2,3-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrido[2,3-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-8-ethyl-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrido[3,2-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrido[4,3-d]pyrimidine-2,4-dione1-[2-Chloro-4-(2-phenylethynyl)phenyl]-3,7-dimethyl-purine-2,6-dione2-(2-Chloro-4-(phenylethynyl)phenyl)-5,6-dihydro-1H-pyrrolo[3,2,1-ij]quinazoline-1,3(2H)-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-isopropyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-ethyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pteridine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1H-pyrimido[4,5-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrimido[4,5-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-6-fluoro-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-7,8-difluoro-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1,7-dimethyl-thieno[3,2-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2- ...

NOVEL EFFECTIVE ANTIVIRAL COMPOUNDS AND METHODS USING SAME

The present invention includes compounds that are useful in preventing or treating viral infections caused by an enveloped RNA virus, such as viral infections caused by a Filovirus, arenavirus, rhabdovirus, paramyxovirus, orthomyxovirus and/or retrovirus. The present invention further includes compositions comprising such compounds, and methods of treating a viral infection in a subject using such compounds. 1. A method of treating or preventing a viral infection in a subject in need thereof , the method comprising administering to subject an effective amount of at least one inhibitor of a channel selected from the group consisting of calcium-release activated calcium (CRAC) channel and transient receptor potential mucolipin I (TRPML1) channel , whereby the viral infection is treated or prevented in the subject.2. The method of claim 1 , wherein administration of the inhibitor blocks claim 1 , inhibits or interferes with viral spread or viral trafficking within the subject or to another subject.3. The method of claim 1 , wherein administration of the inhibitor blocks claim 1 , inhibits or interferes with viral budding within the subject.4. The method of claim 1 , wherein administration of the inhibitor blocks claim 1 , inhibits or interferes with virus dissemination within the subject or to another subject.5. The method of claim 1 , wherein administration of the inhibitor blocks claim 1 , inhibits or interferes with viral disease progression in the subject or viral disease transmission within the subject or to another subject.6. The method of claim 1 , wherein the virus is selected from the group consisting of a filovirus claim 1 , arenavirus claim 1 , rhabdovirus claim 1 , paramyxovirus claim 1 , retrovirus claim 1 , orthomyxovirus claim 1 , and any combinations thereof.7. The method of claim 6 , wherein the virus is selected from the group consisting of Influenza A claim 6 , Influenza B claim 6 , Influenza C claim 6 , Junin claim 6 , Ebola claim 6 , Marburg claim ...

POLYMORPHS

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament. 2. The method according to claim 1 , wherein anhydrous polymorph A has an X-ray powder diagram as shown in .3. The method of claim 1 , wherein anhydrous polymorph A is characterized in that the reflection at 11.59 Å in the X-ray powder diagram has a relative intensity of 100% and the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values: 11.3 Å claim 1 , 9.36 Å claim 1 , 7.48 Å claim 1 , and 7.0 Å.5. The method according to wherein anhydrous polymorph B has an X-ray powder diagram as shown in .6. The method of claim 1 , wherein anhydrous polymorph B is characterized in that the reflection at 11.3 Å in the X-ray powder diagram has a relative intensity of 100% and the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values: 11.59 Å claim 1 , 7.60 Å claim 1 , and 7.15 Å.8. A method of preparing a medicament claim 1 , the method comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'i) preparing the anhydrous polymorph A by the method of , and'}ii) combining the anhydrous polymorph A with one or more inert carriers to provide a medicament containing 0.1% to 0.5%, or 0.5% to 1.5%, or 1% to 3% of the anhydrous polymorph A based on the total weight of the polymorph A and the one or more inert carriers.9. A method of preparing anhydrous polymorph A or B claim 1 , or a mixture thereof claim 1 , of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine claim 1 , the method comprising crystallizing polymorph A or B claim 1 , or a mixture thereof claim 1 , from a solution of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in ethanol claim 1 ,wherein anhydrous polymorph A is characterised in ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF RESPIRATORY DISORDERS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of respiratory disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of viscid or excessive mucus, cough, inflammation, redness in sore throat, infection in the throat, sore throat, abnormal mucus secretion, impaired mucus transport, allergic rhinitis, asthma, COPD, respiratory muscular disorders and pain in acute sore throat. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 2 , wherein said pharmaceutical composition is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration claim 2 , delayed release or sustained release claim 2 , transmucosal claim 2 , syrup claim 2 , topical claim 2 , parenteral administration claim 2 , injection claim 2 , subdermal claim 2 , oral solution claim 2 , rectal administration claim 2 , buccal administration or transdermal administration.4. A method of treating respiratory disorders related diseases as the underlying etiology claim 3 , wherein the method comprises administering to a patient in need thereof an effective amount of .5. The method of claim 4 , wherein the respiratory disorders as the underlying etiology is selected from viscid or excessive mucus claim 4 , cough claim 4 , inflammation claim 4 , redness in sore throat claim 4 , infection in the throat claim 4 , sore throat claim 4 , abnormal mucus secretion claim 4 , impaired mucus transport claim 4 , allergic rhinitis claim 4 , asthma claim 4 , COPD claim 4 , respiratory muscular ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF PERIODONTITIS AND RHEUMATOID ARTHRITIS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of periodontitis and rheumatoid arthritis may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 2 , wherein said pharmaceutical composition is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration claim 2 , delayed release or sustained release claim 2 , transmucosal claim 2 , syrup claim 2 , topical claim 2 , parenteral administration claim 2 , injection claim 2 , subdermal claim 2 , oral solution claim 2 , rectal administration claim 2 , buccal administration or transdermal administration.4. A method of treating periodontitis and rheumatoid arthritis as the underlying etiology claim 3 , wherein the method comprises administering to a patient in need thereof an effective amount of .5. The pharmaceutical composition of claim 2 , further comprising a molecular conjugate of leflunomide and carboxylic acid compounds selected from a group consisting of R-Lipoic acid claim 2 , eicosapentaenoic acid claim 2 , docosahexaenoic acid claim 2 , fumaric acid claim 2 , arginine claim 2 , salsalate and nicotinic acid.6. The molecular conjugate of claim 5 , wherein the carboxylic acid compound is R-Lipoic acid.7. The molecular conjugate of claim 5 , wherein the carboxylic acid compound is eicosapentaenoic acid.8. The molecular conjugate of claim 5 , wherein the carboxylic acid compound is docosahexaenoic acid.9. The molecular conjugate of claim 5 , wherein the carboxylic acid compound is fumaric ...

Hsp90 inhibitors

The disclosure relates to Compounds of Formula (1): and pharmaceutically acceptable salts thereof wherein Z 1 , Z 2 , Z 3 , Xa, Xb, Xc, Y, X 2 , and X 4 are as defined herein, compositions comprising an effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof, and methods to treat or prevent a condition, such as cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof.

PROCESS FOR THE PREPARATION OF A XANTHINE-BASED COMPOUND

This invention relates to a method for preparation of a xanthine-based compound, as well as to intermediates useful in such preparation. 4. The method according to claim 1 , wherein the suitable base is NaCO claim 1 , KCO claim 1 , NaHCOor KHCO.5. The method according to claim 1 , wherein the suitable solvent comprises NMP claim 1 , DMSO claim 1 , DMAc or DMF.6. The method according to claim 1 , wherein X is Cl.7. The method according to claim 1 , wherein X is Cl claim 1 , the suitable base is NaHCOand the suitable solvent is NMP.8. The method according to claim 1 , wherein X is I.9. The method according to claim 1 , wherein X is I claim 1 , the suitable base is NaHCOand the suitable solvent is DMSO.10. The method according to claim 1 , wherein the reaction is conducted at elevated reaction temperature of from 20° C. to 120° C. claim 1 , or from 40° C. to 110° C. This invention relates to a method for preparation of a xanthine-based pharmaceutically active ingredient, namely Linagliptin, as well as to intermediates useful in such preparation.1-[(4-Methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, whose international nonproprietary name is Linagliptin, has the following structure as shown below:Up to now, several synthetic routes to synthesize the molecule have been described by several references.For example, a process for the preparation of Linagliptin is disclosed in the references WO 2004/018468 and WO 2006/048427.The reference WO 2014/059938 describes a further process for preparation of Linagliptin involving a phase transfer catalyst and using protected (R)-piperidine-3-amine derivatives. The process of WO 2014/059938 requires an amine protecting group, such as tert-butyloxy carbonyl (Boc) protection and de-protection of the intermediates used in the late stage of the synthesis process.The reference WO 2013/098775 describes a further process for preparation of Linagliptin: (R)-piperidine-3-amine (or its ...

Substituted xanthines and methods of use thereof

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

8-[3-AMINO-PIPERIDIN-1-YL]-XANTHINES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

The present invention relates to substituted xanthines of general formula 2. The compound of claim 1 , wherein{'sup': '1', 'Rdenotes a [2-(methylcarbonylamino)-phenyl]-carbonylmethyl group,'}a [2-(ethylcarbonylamino)-phenyl]-carbonylmethyl group ora [2-(isopropylcarbonylamino)-phenyl]-carbonylmethyl group,or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein{'sup': '1', 'Rdenotes a [2-(aminocarbonylmethoxy)-phenyl]-carbonylmethyl group,'}[2-(methylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group,a [2-(ethylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group ora [2-(isopropylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group,or a pharmaceutically acceptable salt thereof.4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , selected from the group consisting of:(14) 1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(15) 1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(16) 1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(17) 1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, and(18) 1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine.5. A physiologically acceptable salt of a compound according to claim 1 , with inorganic or organic acids or bases.6. A pharmaceutical composition comprising a pharmaceutically acceptable amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , optionally together with one or more inert carriers and/or diluents. The present invention relates to compounds having valuable pharmacological properties, particularly an inhibiting effect on the activity of ...

ETHYNYL DERIVATIVES

It has been surprisingly been found that the compounds of general formula I are positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGluR4), useful for the treatment of Parkinson's disease, anxiety, emesis, obsessive compulsive disorder, autism, neuroprotection, cancer, depression and diabetes type 2. 3. The compound of formula IA according to claim 2 , wherein the compound is selected from the group consisting of3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1,8-dimethyl-quinazoline-2,4-dione8-Chloro-3-[2-chloro-4-(2-phenylethynyl)phenyl]-1-methyl-quinazoline-2,4-dione7-Chloro-3-[2-chloro-4-(2-phenylethynyl)phenyl]-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1,7-dimethyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1H-pyrido[2,3-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrido[2,3-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-8-ethyl-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrido[3,2-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrido[4,3-d]pyrimidine-2,4-dione1-[2-Chloro-4-(2-phenylethynyl)phenyl]-3,7-dimethyl-purine-2,6-dione2-(2-Chloro-4-(phenylethynyl)phenyl)-5,6-dihydro-1H-pyrrolo[3,2,1-ij]quinazoline-1,3(2H)-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-isopropyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-ethyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pteridine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1H-pyrimido[4,5-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1-methyl-pyrimido[4,5-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-6-fluoro-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-7, 8-difluoro-1-methyl-quinazoline-2,4-dione3-[2-Chloro-4-(2-phenylethynyl)phenyl]-1,7-dimethyl-thieno[3,2-d]pyrimidine-2,4-dione3-[2-Chloro-4-(2- ...

COMPOUNDS AND COMPOSITIONS FOR TREATING CHEMICAL WARFARE AGENT-INDUCED INJURIES

Compounds and compositions for treating injuries caused by exposure to chemical warfare agents are described herein. This application is a continuation of U.S. application Ser. No. 15/922,402, filed Mar. 15, 2018, which is a continuation of U.S. application Ser. No. 13/661,812, filed Oct. 26, 2012, which is a continuation of U.S. application Ser. No. 12/466,195, filed May 14, 2009, which claims priority to U.S. Ser. No. 61/127,722, filed May 14, 2008, and U.S. Ser. No. 61/082,809, filed Jul. 22, 2008, each of which is incorporated herein by reference in its entirety.The invention relates to compounds and compositions useful for treating injuries caused by chemical warfare and similar agents.A variety of ion channel proteins exist to mediate ion flux across cellular membranes. The proper expression and function of ion channel proteins is essential for the maintenance of cell function and intracellular communication. Numerous diseases and disorders are the result of misregulation of membrane potential or aberrant calcium handling. Given the central importance of ion channels in modulating membrane potential and ion flux in cells, identification of agents that can promote or inhibit particular ion channels are of great interest, both as research tools and as therapeutic agents.The present invention provides compounds and compositions for treating or preventing injuries resulting from chemical warfare agents by modulating the activity of the TRPA1 channel.In one aspect, the invention features methods for treating injuries caused by exposure to a chemical warfare agent, or a similar agent, by administering a compound of formula (I) or a salt thereof,Wherein each of Rand Ris, independently, H, C-Calkyl, C-Calkenyl, or C-Calkynyl, each of which is optionally substituted with 1-4 R; L is NRSO, SONR, C(O)NR, NRC(O), OC(O)NR, NRC(O)O, NRC(O)NR, S, S(O), S(O), NR, CH, O, C(O)NS(O), S(O)NC(O), heteroaryl, or cyclyl; Ris C-Ccyclyl, heterocyclyl, aryl, or heteroaryl, each of ...

INTERMEDIATES AND PROCESSES FOR THE PREPARATION OF LINAGLIPTIN AND ITS SALTS

Disclosed are new intermediates for the synthesis of Linagliptin and of its salts and a process for its preparation involving said intermediates. 2. The compounds according to wherein R and Rare selected from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , sec-butyl claim 1 , tert-butyl claim 1 , phenyl claim 1 , benzyl claim 1 ,p-tolyl, p-methoxyphenyl, m-methoxyphenyl, p-nitrophenyl, p-chlorophenyl,{'sub': '1', '3,4-dimethoxyphenyl, 2-thiophenyl, 2-furanyl, cyclopentyl, cyclohexyl, —CH═CH-Ph, R and Rare linked together to form a cyclohexane or a 3-methyl or 4-methyl substituted cyclohexane.'}3. The compounds according to wherein R is hydrogen and Ris phenyl.5. The process according to wherein in step (a) the bases are selected from alkali and alkaline-earth metal hydroxides claim 4 , carbonates claim 4 , bicarbonates and phosphates claim 4 , or mixtures thereof; solvents are aprotic apolar or polar claim 4 , aromatic claim 4 , aliphatic claim 4 , ether claim 4 , ester claim 4 , keto solvents or mixtures thereof having a water content ranging from 0% to 6% (v/v); the optional phase transfer agent is selected from tetrasubstituted ammonium or phosphonium salts and the molar ratio of compound of formula (II) to compound of formula (VI) ranges from 1/1 to 1/1 claim 4 ,5; optional isolation in step (b) is effected by precipitation or crystallization in the presence of a straight or branched C1-C4 alcohol or of an ester or ether or mixtures thereof in the presence of aprotic apolar or polar claim 4 , aromatic claim 4 , aliphatic solvents or mixtures thereof and the deprotection is effected under mildly acid or basic conditions.6. The process according to wherein in step (a) the bases are selected from sodium carbonate claim 5 , potassium carbonate claim 5 , cesium carbonate claim 5 , sodium phosphate claim 5 , potassium phosphate; solvents are selected from acetonitrile claim 5 , ...

SALT FORMS OF ORGANIC COMPOUND

The present invention relates to novel salt forms of a certain DPP-4 inhibitor and their use in pharmaceutical compositions useful in the treatment of type 2 diabetes, as well as their production. 1. (canceled)2. An acid addition salt of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine with an acid selected from nitric acid , acetic acid , 2 ,2-dichloroacetic acid , adipic acid , D-ascorbic acid , L-ascorbic acid , D-aspartic acid , L-aspartic acid , benzenesulfonic acid , benzoic acid , 4-acetamido-benzoic acid , (+)-camphoric acid , (−)-camphoric acid , (+)-camphor-10-sulfonic , (−)-camphor-10-sulfonic , capric acid (decanoic acid) , caproic acid (hexanoic acid) , caprylic acid (octanoic acid) , carbonic acid , cinnamic acid , cyclamic acid , dodecylsulfuric acid , ethane-1 ,2-disulfonic acid , ethanesulfonic acid , 2-hydroxy-ethanesulfonic acid , formic acid , galactaric acid , gentisic acid , D-glucoheptonic acid , L-glucoheptonic acid , D-gluconic acid , L-gluconic acid; D-glucuronic acid , L-glucuronic acid , glutamic acid , glutaric acid , 2-oxo-glutaric acid , glycerophosphoric acid , glycolic acid , hippuric acid , isobutyric acid , D-lactic acid , L-lactic acid , lactobionic acid , lauric acid , maleic acid , D-malic acid , L-malic acid , malonic acid , D-mandelic acid , L-mandelic acid naphthalene-1 ,5-disulfonic acid , naphthalene-2-sulfonic acid , 1-hydroxy-2-naphthoic acid , nicotinic acid , oleic acid , orotic acid , oxalic acid , palmitic acid , pamoic acid (embonic acid) , propionic acid , D-pyroglutamic acid , L-pyroglutamic acid , salicyclic acid , 4-aminosalicyclic acid , sebacic acid , stearic acid , thiocyanic acid , p-toluenesulfonic acid and undecylenic acid.3. The salt according to claim 2 , which is selected from the group consisting of a besylate salt claim 2 , a benzoate salt claim 2 , an esylate salt claim 2 , a fumarate salt claim 2 , a mesylate salt claim 2 , a salicylate salt claim ...

SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5. 2. The method of claim 1 , wherein the TRPC5 mediated disorder is selected from the group consisting of: a neuropsychiatric disorder claim 1 , a neurodegenerative disorder claim 1 , nephropathy claim 1 , and seizure disorder.3. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Calkyl.4. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Calkyl and Ris independently C-Caryl or heteroaryl.5. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Caryl claim 1 , C-Caryloxy or heteroaryloxy.6. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Caryloxy.7. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Calkoxy.8. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Calkyl.9. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris or C-Cakylamino.10. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —S(O)— or —S(O)—.11. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Calkyl claim 1 , C-Chydroxyalkyl claim 1 , or C-Calkoxy.12. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydroxypropyl.13. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Calkyl.14. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris independently C-Caryl claim 1 , heteroaryl claim 1 , C-Ccycloalkyl claim 1 , or heterocycloalkyl.15. The method of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris phenyl claim 1 , pyridyl claim 1 , thiazolyl claim 1 , pyrimidinyl ...

POLYMORPHS

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament. 1. A method of preparing polymorph D of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine , characterized in that it melts at 150±3° C. , wherein polymorph D is obtained by heating polymorph C of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine to a temperature of 30-100° C. or by drying at this temperature , wherein Polymorph C is characterized in that it loses water at a temperature of 30-100° C. and exhibits further thermal effects at a temperature of about 150° C. and about 175° C. in a differential scanning calorimetry (DSC) analysis.2. The method according to wherein polymorph C is obtained by a method comprising:(a) refluxing a solution of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in methanol to provide a hot methanolic solution,(b) cooling the hot methanolic solution to a temperature of 40-60° C. to provide a cooled methanolic solution,(c) adding tert-butylmethylether to the cooled methanolic solution to form a suspension,(d) cooling the suspension first to a temperature of 15-25° C. and then to a temperature of 0-5° C. to provide crystals,(e) suction filtering the crystals, and(f) drying the crystals obtained in step (e) in vacuo at a temperature of 70° C. to provide Polymorph C.3. The method according to claim 2 , wherein the X-ray powder diagram of Polymorph C has characteristic reflections at the following d values: 12.90 Å claim 2 , 11.10 Å claim 2 , 6.44 Å claim 2 , 3.93 Å and 3.74 Å.4. The method according to claim 2 , wherein the hot methanolic solution obtained in step (a) is filtered before cooling in step (b). This Application claims priority of EP 06 009 202, which is hereby incorporated by reference in ...

Substituted xanthines and methods of use thereof

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

METHOD FOR PREPARING AN IMPORTANT INTERMEDIATE OF LINAGLIPTIN

The present invention discloses an improved process for preparing an important intermediate of linagliptin. In particular, disclosed are a process for preparing a compound V which is an important intermediate of linagliptin and has the structure V, and an industrial process of preparing linagliptin having excellent chemical and optical purities, which is an inhibitor of dipeptidyl peptidase-4 (DPP-IV), from the compound V. The process employs a phase-transfer catalyst, is high in yield, easy and simple to handle, environmentally friendly, suitable for industrial mass production, and can be implemented by a “one-pot process”. 2. The process according to claim 1 , wherein claim 1 ,{'sub': 1', '2', '3', '1', '2', '3, 'X, Xand Xare each independently selected from the group consisting of a halogen, such as fluorine, chlorine or bromine; and a sulfonate group, such as methylsulfonyloxy, phenylsulfonyloxy, p-toluenesulfonyloxy, p-chlorophenylsulfonyloxy, benzylsulfonate, 2-(4-nitrophenylethyl)sulfonate or trifluoromethylsulfonyloxy, Xis preferably bromine, Xis preferably chlorine, Xis preferably bromine or chlorine;'}{'sub': 5', '6, 'Rand Rare each independently H, C1-C16 alkoxycarbonyl, C6-C18 aryl C1-C16 alkoxycarbonyl, benzyl, p-methoxybenzyl, p-methylbenzyl, p-chlorobenzyl, p-bromobenzyl, p-nitrobenzyl, diphenylmethyl, 2,4-dimethoxybenzyl, 2-hydroxybenzyl, bis(4-methoxyphenyl)methyl, triphenylmethyl, (4-methoxyphenyl)diphenylmethyl, 9-phenylfluorenyl, formyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, phenylacetyl, phenylpropionyl, benzoyl, p-phenylbenzoyl, phthaloyl, 4-nitrophthaloyl, dithiosuccinoyl, tetrachlorophthaloyl, p-toluenesulfonyl, benzenesulfonyl, methanesulfonyl, 2,4,6-trimethoxybenzenesulfonyl, pentamethylbenzenesulfonyl, 4-methoxybenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2,6-dimethoxy-4-methyl-benzenesulfonyl, 2-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl, 2,4-dinitrobenzenesulfonyl, pyridine-2-sulfonyl, 2-(trisilyl)ethylsulfonyl, 9- ...

POLYMORPHS

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament. 113-. (canceled)14. A method of preparing an anhydrous polymorph A of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine , the method comprising:(a) dissolving 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in absolute ethanol to provide a solution;(b) refluxing the solution to provide a hot solution and, optionally filtering the hot solution to provide a hot filtrate,(c) cooling the hot solution or the hot filtrate until crystallisation sets in,(d) diluting the cooled solution or the cooled filtrate with a solvent to provide a solvent mixture,(e) suction filtering the solvent mixture, and said anhydrous polymorph A melts at 206±3° C., and', 'said anhydrous polymorph A exhibits an X-ray powder diagram having characteristic reflections at the following d values: 11.59 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Åand 3.47 Å., '(f) drying the solids collected by filtration at 45° C. in vacuo to provide said anhydrous polymorph A; wherein'}15. The method of claim 14 , wherein the solvent used for diluting the hot solution or hot filtrate in Step (d) is tert.-butylmethylether.16. The method according to claim 14 , wherein anhydrous polymorph A has an X-ray powder diagram as shown in .17. The method of claim 14 , further characterized in that the reflection at 11.59 Å in the X-ray powder diagram has a relative intensity of 100% and further characterized in that the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values: 11.25 Å claim 14 , 9.32 Å claim 14 , 7.46 Å claim 14 , and 6.98 Å.20. The method of claim 19 , wherein the solvent used for diluting the hot solution or hot filtration in Step (d) is tert.-butylmethylether.21. The method according to ...

COMPOUNDS AND COMPOSITIONS FOR TREATING CHEMICAL WARFARE AGENT-INDUCED INJURIES

Compounds and compositions for treating injuries caused by exposure to chemical warfare agents are described herein. 3. The method of claim 1 , wherein the compound is administered orally claim 1 , via intramuscular injection claim 1 , or topically.4. The method of claim 1 , wherein the chemical warfare agent is tear gas.5. The method of claim 1 , wherein the chemical warfare agent is chlorine.6. The method of claim 1 , wherein the chemical warfare agent is mustard gas.7. The method of claim 1 , wherein the subject is a human.8. The method of claim 2 , wherein the compound is administered orally claim 2 , via intramuscular injection claim 2 , or topically.9. The method of claim 2 , wherein the chemical warfare agent is tear gas.10. The method of claim 2 , wherein the chemical warfare agent is chlorine.11. The method of claim 2 , wherein the chemical warfare agent is mustard gas.12. The method of claim 2 , wherein the subject is a human. This application is a continuation of U.S. application Ser. No. 13/661,812, filed Oct. 26, 2012, which is a continuation of U.S. application Ser. No. 12/466,195, filed May 14, 2009, which claims priority to U.S. Ser. No. 61/127,722, filed May 14, 2008, and U.S. Ser. No. 61/082,809, filed Jul. 22, 2008, each of which is incorporated herein by reference in its entirety.The invention relates to compounds and compositions useful for treating injuries caused by chemical warfare and similar agents.A variety of ion channel proteins exist to mediate ion flux across cellular membranes. The proper expression and function of ion channel proteins is essential for the maintenance of cell function and intracellular communication. Numerous diseases and disorders are the result of misregulation of membrane potential or aberrant calcium handling. Given the central importance of ion channels in modulating membrane potential and ion flux in cells, identification of agents that can promote or inhibit particular ion channels are of great interest, both ...

8-[3-AMINO-PIPERIDIN-1-YL]-XANTHINES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

The present invention relates to substituted xanthines of general formula 2. The method according to claim 1 , wherein the amino group of the 3-aminopiperidine claim 1 , an enantiomer thereof or a salt thereof claim 1 , is protected during the reaction by a protecting group which is cleaved after the reaction.3. The method according to claim 2 , wherein the protecting group is tert-butoxycarbonyl.4. The method of claim 1 , wherein Zis chlorine claim 1 , bromine claim 1 , methanesulphonyl or methanesulphonyloxy.6. The compound of claim 4 , wherein Zis chlorine claim 4 , bromine claim 4 , methanesulphonyl or methanesulphonyloxy. The present invention relates to compounds having valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).The present invention relates to new substituted xanthines of general formulathe tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV), the preparation thereof, the use thereof for the prevention or treatment of diseases or conditions associated with an increased DPP-IV activity or capable of being prevented or alleviated by reducing the DPP-IV activity, particularly type I or type II diabetes mellitus, the pharmaceutical compositions containing a compound of general formula (I) or a physiologically acceptable salt thereof as well as processes for the preparation thereof.In the above formula IRdenotes a methyl group, a methyl group which is substituted by a dimethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, tert.-butylcarbonyl or a cyclohexylcarbonyl-group, a methyl group which is substituted by a naphthyl, methylnaphthyl, methoxynaphthyl, nitronaphthyl or ...

An improved process for preparing Linagliptin and its key Intermediates

The present invention relates to a process for the preparation of Linagliptin or a pharmaceutically acceptable slat thereof. Further aspects of the present invention relates to process for the preparation of Linagliptin key intermediate, having purity more than 98.0%. 124-. (canceled)26. The process according to claim 25 , wherein the suitable solvent is selected from the group comprising one or more dimethyl acetamide claim 25 , dimethyl formamide and dimethyl sulfoxide or mixture thereof.27. The process according to claim 26 , wherein the suitable solvent used in step (b) and (c) is combination of dimethyl acetamide claim 26 , dimethyl formamide claim 26 , dimethyl sulfoxide and water.28. The process according to claim 25 , wherein suitable base used in step a) and c) comprising one or more of inorganic bases or organic bases or mixture thereof.29. The process according to claim 25 , wherein the substantially pure 8-bromo xanthine has the purity more than 99% by HPLC.30. The process according to claim 25 , wherein the substantially pure Boc-Linagliptin has the purity more than 98% by HPLC.33. The according to claim 32 , wherein the organic base is selected from the group of triethyl amine (Et3N) claim 32 , trimethyl amine (Me3N) claim 32 , pyridine claim 32 , tributylamine and diisopropyl ethyl amine (DIPEA).34. The process according to claim 32 , wherein suitable solvent is selected from dimethyl formamide claim 32 , dimethylacetamide claim 32 , dimethyl sulfoxide and water or mixtures thereof.35. The process according to claim 32 , wherein the substantially pure Boc-Linagliptin has the purity more than 95% by HPLC.36. The process according to claim 32 , wherein the 3-(R)-Bocaminopiperidine or its salt is 1 to 1.5 molar equivalents for the equivalent of 8-bromo xanthine of Formula II or its salt.37. The process according to claim 32 , wherein the base is 1 to 4 molar equivalents per the equivalent of the compound of Formula II or its salt.38. The process ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF MUCOSITIS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of mucositis may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of mucus diseases related to painful inflammation and ulceration of the digestive tract lining and in the mouth. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 2 , wherein said pharmaceutical composition is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration claim 2 , delayed release or sustained release claim 2 , transmucosal claim 2 , syrup claim 2 , topical claim 2 , parenteral administration claim 2 , injection claim 2 , subdermal claim 2 , oral solution claim 2 , rectal administration claim 2 , buccal administration or transdermal administration.4. A method of treating mucositis as the underlying etiology claim 3 , the method comprising administering to a patient in need thereof an effective amount of .5. The method of claim 4 , wherein the mucositis as the underlying etiology is selected from mucus diseases related to painful inflammation and ulceration of the digestive tract lining and in the mouth.6. The pharmaceutical composition of claim 2 , further comprising a molecular conjugate of 2-(2 claim 2 ,6-dichlorophenyl)guanidine and carboxylic acid compounds selected from a group consisting of R-Lipoic acid claim 2 , acetyl cysteine claim 2 , caprylic acid claim 2 , and salsalate.7. The molecular conjugate of claim 6 , wherein the carboxylic acid compound is R-Lipoic acid.8. The molecular conjugate of claim 6 , ...

XANTHINE DERIVATIVE INHIBITORS OF BET PROTEINS

This invention relates to xanthine derivative compounds that are inhibitors of BET bromodomains proteins, the method of preparation thereof and applications thereof. 3. The inhibitor according to claim 1 , wherein:X represents an oxygen atom;{'sub': 'o', 'claim-text': {'sub': o', 'p', 'p', '1', '4, 'wherein Rrepresents —C(O)ORwherein Rrepresents a C-Calkyl;'}, 'Y represents an oxygen atom, an amino group, NHR, or a linker-ligand for the E3 ubiquitin ligase;'}{'sub': '1', 'Rrepresents a hydrogen atom or a lone pair;'}{'sub': 3', '1', '6', '1', '4', '5', '12', '1', '6, 'claim-text': a halogen atom, or', {'sub': 1', '4, 'a C-Calkyl;'}], 'Rrepresents a C-Calkyl, preferably a C-Calkyl, a linker-ligand for the E3 ubiquitin ligase, or a (C-C)aryl-(C-C)alkyl, optionally substituted by{'sub': 7', '1', '6', '1', '4, 'Rrepresents a C-Calkyl, preferably a C-Calkyl and even more preferably a methyl or ethyl group;'}{'sub': 8', 'q', '2', 'q', '2', 'q, 'Rrepresents a hydrogen atom, —SH, —SR—, —CH—O—Ror —CH—S—R;'}{'sub': 'q', 'claim-text': [{'sub': 1', '6', '1', '4, 'C-Calkyl, preferably a C-Calkyl,'}, 'amino groups,', 'halogen atoms,', {'sub': 1', '4, '(C-C)alkanoic acid,'}, {'sub': 2', '1', '4, '—S(O)—(C-C)alkyl,'}, {'sub': '2', '—S(O)-piperidine,'}, {'sub': '2', '—S(O)—(N,N)dimethylamine,'}, {'sub': '2', '—S(O)-morpholine,'}, 'nitro groups,', {'sub': 1', '4, '—C(═O)—O—(C-C)alkyl,'}, {'sub': 2', '1', '4, '—S(O)—N(H)—(C-C)alkyl,'}, {'sub': 1', '4, 'oxo-pyrazole optionally substituted by one or more (C-C)alkanoic acid,'}, 'ketone groups,', {'sub': 1', '4', '1', '4, 'pyrazole optionally substituted by one or more (C-C)alkanoic acid or (C-C)alkyl,'}, {'sub': 1', '4, 'pyrrolidine optionally substituted by one or more (C-C)alkanoic acid,'}, 'phenyl,', 'benzyl,', 'oxy-phenyl,', 'oxy-benzyl,', {'sub': 1', '4, 'thiazolidin optionally substituted by one or more (C-C)alkanoic acid,'}, '—C(═O)—N(H)-benzyl,', '—N(H)-quinazolinone,', '—OH,', {'sub': 1', '4, 'thiophenyl optionally substituted ...

Substituted Xanthines and Methods of Use Thereof

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

CRYSTAL FORM OF 4H-PYRAZOLO[1,5-alpha]BENZOIMIDAZOLE COMPOUND, PREPARATION METHOD THEREOF AND INTERMEDIATE THEREOF

The invention discloses a crystal form A of a compound (I) and a preparation method thereof, and further discloses an application of the crystal form A as a PDE2 or TNF-α inhibitor. 3. A crystal form A of compound (I) according claim 1 , wherein the XRPD pattern of the crystal form A is as shown in .4. A crystal form A of compound (I) according claim 1 , wherein the DSC diagram of the crystal form A is as shown in .5. A crystal form A of compound (I) according claim 1 , wherein the TGA diagram of the crystal form A is as shown in .6. A preparation method of the crystal form A according to claim 1 , comprising dissolving any form of the compound (I) in ester solvent claim 1 , alcoholic solvent claim 1 , acetonitrile claim 1 , acetone or a mixed solvent of the alcoholic solvent with water while heating claim 1 , and then cooling crystallization.7. A preparation method of the crystal form A according to claim 6 , further comprising a step of concentrating the solvent to 1/30-½ of its original volume claim 6 , after the step of dissolving while heating claim 6 , preferably 1/20-⅕.8. A preparation method of the crystal form A according to claim 6 , wherein the weight ratio of the compound (I) to the solvent is selected from 10:1 to 1:1 claim 6 , preferably selected from 6:1 to 3:1 claim 6 , and more preferably selected from 5:1 to 4:1.9. A preparation method of the crystal form A according to claim 6 , wherein the heating temperature is selected from 40° C. to refluxing temperature claim 6 , and preferably selected from 50° C. to 60° C.10. The preparation method of the crystal form A according to claim 6 , wherein the cooling crystallization temperature is selected from 0° C. to 30° C. claim 6 , and preferably selected from 20° C. to 30° C.11. The preparation method of the crystal form A according to claim 6 , wherein the ester solvent is selected from the group consisting of ethyl acetate claim 6 , isopropyl acetate and propyl acetate claim 6 , and preferably selected ...

PREVENTION OR TREATMENT OF URIC ACID OR GOUT DISEASE

The present invention relates to the use of a compound of formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a pharmaceutical composition containing the same in reducing uric acid level, preventing or reducing inflammations, and preventing or treating uratic or gouty diseases. In particular, the present invention relates to the use of a compound of formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof, or a pharmaceutical composition containing the same in the manufacture of a medicament for the treatment or prevention of hyperuricemia, gout, gouty inflammations, pain and uric acid nephropathy. 114.-. (canceled)16. The compound according to claim 15 , or a pharmaceutically acceptable salt thereof or a solvate thereof claim 15 , wherein{'sub': '1', 'Rrepresents hydrogen or methyl,'}{'sub': '2', 'Rrepresents ethyl, cyclopropylethyl, cyclopropylmethyl, propyl, 2-methylpropyl, butyl, 3-methylbutyl or pentyl, and'}{'sub': '3', 'Rrepresents fluorine or chlorine.'}17. The compound according to claim 15 , or a pharmaceutically acceptable salt thereof or a solvate thereof claim 15 , wherein the compound is selected from the group consisting of:8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione,8-chloro-3-butyl-3,7-dihydro-1H-purine-2,6-dione,8-chloro-1-methyl-3-butyl-3,7-dihydro-1H-purine-2,6-dione,8-chloro-1-methyl-3-pentyl-3,7-dihydro-1H-purine-2,6-dione,8-chloro-3-(3-methylbutyl) -3,7-dihydro-1H-purine-2,6-dione,8-chloro-3-(2-cyclopropylethyl)-3,7-dihydro-1H-purine-2,6-dione,8-chloro-3-(2-methylpropyl)-3,7-dihydro-1H-purine-2,6-dione,8-chloro-3-(cyclopropylmethyl)-3,7-dihydro-1H-purine-2,6-dione,8-chloro-1-methyl-3-(3-methylbutyl)-3,7-dihydro-1H-purine-2,6-dione, and8-chloro-1-methyl-3-(2-cyclopropylethyl)-3,7-dihydro-1H-purine-2,6-dione.18. The compound according to claim 15 , or a pharmacologically acceptable salt or a solvate thereof claim 15 , which is a hydrate.19. The compound according to claim 16 , or a ...

DUAL SELECTIVE PI3 DELTA AND GAMMA KINASE INHIBITORS

The present invention relates to dual delta (δ) and gamma (γ) PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of Pi3K kinase mediated diseases or disorders with them. 1. A compound selected from 2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one and pharmaceutically acceptable salts thereof.2. A compound selected from (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one and pharmaceutically acceptable salts thereof.3. The compound according to claim 2 , wherein the compound is substantially free of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one claim 2 , and pharmaceutical acceptable salts thereof.4. The compound of claim 2 , wherein the compound has an enantiomeric excess greater than about 95%.5. (S)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one.6. The compound of claim 5 , wherein the compound is substantially free of (R)-2-(1-(9H-purin-6-ylamino)propyl)-3-(3-fluorophenyl)-4H-chromen-4-one.7. The compound of claim 5 , wherein the compound has an enantiomeric excess greater than about 95%.8. A pharmaceutical composition comprising a compound of and at least one pharmaceutically acceptable carrier.9. A method of inhibiting a catalytic activity of a P13 δ kinase present in a cell claim 2 , comprising contacting the cell with an effective amount of a compound of .10. A method of inhibiting a catalytic activity of a P13 γ kinase present in a cell claim 2 , comprising contacting the cell with an effective amount of a compound of .11. A method of inhibiting a catalytic activity of a PI3 δ kinase and PI3 γ kinase present in a cell claim 2 , comprising contacting the cell with an effective amount of a compound of .12. The method of claim 9 , wherein the inhibition takes place in a subject suffering from a disease claim 9 , disorder or condition selected from cancer claim 9 , a ...

SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5. 2. The method of claim 1 , wherein the TRPC5 mediated disorder is selected from the group consisting of: a neuropsychiatric disorder claim 1 , a neurodegenerative disorder claim 1 , nephropathy claim 1 , and seizure disorder.322-. (canceled)2426-. (canceled)2832-. (canceled) This application is a Continuation of, and claims priority to, U.S. patent application Ser. No. 15/968,941, filed May 2, 2018 (allowed), which is a Continuation of, and claims priority to, U.S. patent application Ser. No. 15/622,838, filed Jun. 14, 2017 (U.S. Pat. No. 9,969,736); which is a Continuation of, and claims priority to, U.S. patent application Ser. No. 15/137,327, filed Apr. 25, 2016 (abandoned); which is a Continuation of, and claims priority to, U.S. patent application Ser. No. 14/210,781, filed Mar. 14, 2014, (U.S. Pat. No. 9,359,359); which claims priority to U.S. Provisional Application No. 61/789,724, filed Mar. 15, 2013 (expired), the contents of which are incorporated herein by reference in its entirety.A variety of ion channel proteins exist to mediate ion flux across cellular membranes. The proper expression and function of ion channel proteins is essential for the maintenance of cell function, intracellular communication, and the like. Numerous diseases are the result of misregulation of membrane potential or aberrant calcium handling. Given the central importance of ion channels in modulating membrane potential and ion flux in cells, identification of agents that can promote or inhibit particular ion channels are of great interest as research tools and as possible therapeutic agents.The present invention provides methods of treating a TRPC5 mediated disorder in a subject, comprising administering to the subject a compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein constituent members are provided herein.The present invention ...

Novel compounds

The present invention relates to a tris salt of 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione of Formula (A): corresponding manufacture processes, pharmaceutical formulations containing and uses of the aforementioned compound in therapy, particularly in treatment of diseases where under-activation of the HM74A receptor contributes to the disease or where activation of the receptor will be beneficial.

CRYSTALLINE LINAGLIPTIN INTERMEDIATE AND PROCESS FOR PREPARATION OF LINAGLIPTIN

The present invention provides novel crystalline forms B1 & B2 of linagliptin intermediate of structural formula V and methods for production of novel crystalline form of linagliptin intermediate represented by the following structural formula V. 2. The crystalline form B1 of Linagliptin intermediate of formula V claim 1 , of having prominent peaks at 3.14±0.2 claim 1 , 6.31±0.2 claim 1 , 8.34±0.2 claim 1 , 10.93±0.2 claim 1 , 13.75±0.2 & 14.46±0.2 degrees 2θ.3. The crystalline form B1 of Linagliptin intermediate of formula V claim 1 , of having DSC endotherms at 53.87 & 162.97° C.4. The process for preparation of crystalline form B1 of Linagliptin intermediate of formula V claim 1 , of comprising following steps of:a. Heating crude linagliptin intermediate of formula V in a solvent.b. Adding a suitable anti-solvent to the reaction mass of above step at elevated temperature.c. Heating the reaction mass to an elevated temperature.d. Reaction mass was cooled and isolated the crystalline form of Linagliptin intermediate of formula V.5. The process for preparation of claim 4 , wherein solvent is acetonitrile.6. The process for preparation of claim 4 , wherein anti-solvent is water.8. The crystalline form B2 of Linagliptin intermediate of formula V claim 7 , of having prominent peaks at 3.43±0.2 claim 7 , 8.10±0.2 claim 7 , 9.96±0.2 & 17.02±0.2 degrees 2θ.9. The crystalline form B2 of Linagliptin intermediate of formula V claim 7 , of having DSC endotherms at 168.69° C.10. The process for preparation of crystalline form B2 of Linagliptin intermediate of formula V claim 7 , of comprising following steps of:a. Treating crude linagliptin intermediate of formula V with preheated solvent.b. Adding an anti-solvent to the reaction mass of above step.c. Heating the reaction mass to an elevated temperature.d. Reaction mass was cooled and isolated the crystalline form of Linagliptin intermediate of formula V. This application is a continuation of International Application No. PCT/ ...

XANTHINE DERIVATIVES AND USES THEREOF AS INHIBITORS OF BROMODOMAINS OF BET PROTEINS

The present invention relates to a compound having the following formula (I): (I) wherein: —R is a (C-C)alkyl group; —R″ is preferably H; —Ar is a (C-C)arylene radical; —Xis —C(═O)— or —SO—; and —R′ is chosen from the group consisting of possibly substituted (C-C)alkyl, heteroaryl, (C-C)aryl, and (hetero)cycloalkyl groups, or a pharmaceutically acceptable salt and/or tautomeric form thereof, or its racemates, diastereomers or enantiomers 4. The compound of claim 1 , wherein Ar is a phenylene (—CH—) radical.5. The compound of claim 1 , wherein R″ is H.6. The compound of claim 1 , wherein R is methyl or ethyl claim 1 , preferably ethyl.9. The compound of claim 1 , for use as a medicament.10. A pharmaceutical composition claim 1 , comprising a compound according to claim 1 , and also at least one pharmaceutically acceptable excipient.11. The compound of claim 1 , for use in the treatment of cancer claim 1 , inflammatory disease claim 1 , sepsis claim 1 , autoimmune disease claim 1 , neurodegenerative disease claim 1 , cardiovascular disorder claim 1 , renal disorder claim 1 , viral infection claim 1 , or obesity. The present invention concerns xanthine derivatives, their preparation process as well as their uses as inhibitors of bromodomains of BET proteins.Bromodomains (BRD) are protein domains called protein interaction modules that preferentially bind ε-N-acetylated lysine residues through structurally well-defined pockets BRDs are found in 8 protein families which include a total of 46 nuclear or cytoplasmic proteins in human with diverse structures and functions, including chromatin-modifying enzymes, helicases, chromatin remodelers, transcriptional co-activators and mediators, and the bromodomain and extra-terminal domain (BET) family of proteins BET proteins (BRD2, BRD3, BRD4, and the testis-specific BRDT) have a conserved modular architecture including two N-terminal tandem BRDs (BD1 and BD2) The BETs play a central role in chromatin biology by acting as tissue ...

Inhibiting the transient receptor potential a1 ion channel

The present invention relates to pharmaceutical compounds of the Formula (I), or a pharmaceutically acceptable salt or composition thereof, and methods of their use for the treatment of pain, respiratory conditions, as well as inhibiting the Transient Receptor Potential A1 ion channel (TRPA1).

Xanthine derivative, production and use thereof as a medicament

The invention relates to substituted xanthines of general formula (I) wherein R1 - R4 are defined as cited in claim 1, the tautomers, stereoisomers, mixtures, prodrugs and salts thereof which exhibit valuable pharmacological properties, particularly an inhibitory effect on the activity of the dipeptidylpeptidase-IV enzyme.

8-[3-amino-piperidin-1-yl]-xanthine, the production thereof and the use in the form of a dpp inhibitor

The invention relates to substituted xanthines of general formula (I), wherein R is such as defined in claim 1, and to the tautomers, stereoisomers, mixtures and the salts thereof, said products exhibiting precious pharmacological properties, in particular an inhibiting effect on a dipeptidylpeptidasa-IV (DPP-IV) enzyme activity.

Hydrochlorides and hydrates of 1-[(3-cyanopyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-aminopiperidin-1-yl)xanthine, their preparation and their use as medicaments

The invention relates to salts of 1-[(3-cyanopyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-aminopiperidin-1-yl]xanthine with hydrochloric acid, and also to their enantiomers, mixtures thereof and hydrates thereof.

8-[3-amino-piperidin-1-yl]-xanthine, the production thereof and the use in the form of a ddp-iv inhibitor

Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor

Compounds having a structure according to formula (I), (II), or (III) where R 1 , R 2 , R 3 , R 5 X 1 , X 2 , and X 3 are as defined herein, are agonists for the Toll-like receptor 7 (TLR7) and can be used as adjuvants for stimulating the immune system. Some such compounds can be used in conjugates for targeted delivery to the organ or tissue of intended action.

Toll-like receptor 7 (tlr7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor

Compounds having a structure according to formula (I), (II), or (III) where R1, R2, R3, R5 X1, X2, and X3 are as defined herein, are agonists for the Toll-like receptor 7 (TLR7) and can be used as adjuvants for stimulating the immune system. Some such compounds can be used in conjugates for targeted delivery to the organ or tissue of intended action.

1-Arylpyrimidine derivatives and their pharmaceutical use

크산틴 유도체 및 이의 제조방법

본 발명은 약리학적 특성, 특히 디펩티딜펩티다제-IV 효소의 활성에 대해 억제 효과를 나타내는 화학식 I의 치환된 크산틴, 이의 호변이성체, 입체이성체, 혼합물, 프로드럭 및 염(여기서, R 1 내지 R 4 는 청구의 범위 제1항에서 정의한 바와 같다)에 관한 것이다. 크산틴 유도체, 호변이성체, 입체이성체, DPP-IV, I형 당뇨병, II형 당뇨병

Hsp90 inhibitors

The disclosure relates to Compounds of Formula (1) and pharmaceutically acceptable salts thereof wherein (a) each of Z 1 , Z 2 and Z 3 is independently CH or N; (b) Y is S; (c) Xa and Xb are O; (d) Xc is -CH 2 -; (e) X 2 is -NR 1 R 2 , wherein R 1 and R 2 are each independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, or alkylheteroarylalkyl; (f) X 4 is hydrogen or halogen; and (g) R is R 10 -NH-R 11 wherein R 10 is ethylene or propylene, and R 11 is a branched alkyl. Compositions comprising an effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof, and methods to treat or prevent a condition, such as cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof.

ACC INHIBITORS AND THEIR APPLICATION

Согласно настоящему изобретению предложены соединения, подходящие для применения в качестве ингибиторов ацетил-КоА-карбоксилазы (АКК), их композиции и способы применения таких соединений. The present invention provides compounds suitable for use as acetyl CoA carboxylase (ACC) inhibitors, their compositions and methods for using such compounds.

8-[3-氨基-哌啶-1-基]-黄嘌呤化合物，其制备方法及作为药物制剂的用途

本发明是关于以下通式的经取代的黄嘌呤，其中R 1 至R 3 均如权利要求中定义，其互变异构体、立体异构体、混合物、前体药物及其盐，其具有有价值的药理学性质，特别是对于酶二肽基肽酶-IV的活性的抑制作用。

利格列汀新晶型及其制备方法

本发明涉及利格列汀的一种新晶型，也涉及制备该新晶型的方法。本发明的利格列汀新晶型通过常规手段制备，具有良好的结晶纯度及物理化学稳定性，生产操作简单，易于商业化。

具有hm74a受体活性的药物

本发明提供了具有式(II)的为黄嘌呤衍生物的治疗活性化合物，制备所述衍生物的方法，含有所述活性化合物的药物制剂以及所述化合物在治疗、特别是在治疗由HM74A受体激活不足所引起的疾病或者受益于激活该受体的疾病中的用途，其中R 1 选自：氢以及可任选被一个或多个选自CN和CF 3 中的基团取代的C 1-4 烷基，R 2 选自：未被取代的C 2-10 烷基、被一个或多个选自氟和CN中的基团取代的C 1-10 烷基、C 5 链烯基、直链C 4 链烯基、以及被环烷基取代的C 1-4 烷基，和R 3 选自卤素和CN。

多晶型

本发明涉及1‑[(4‑甲基‑喹唑啉‑2‑基)甲基]‑3‑甲基‑7‑(2‑丁炔‑1‑基)‑8‑(3‑(R)‑氨基‑哌啶‑1‑基)‑黄嘌呤的多晶型晶体变体、其制备方法及其在制备药物中的用途。

Medicaments with HM74A receptor activity

本发明提供了具有式(II)的为黄嘌呤衍生物的治疗活性化合物，制备所述衍生物的方法，含有所述活性化合物的药物制剂以及所述化合物在治疗、特别是在治疗由HM74A受体激活不足所引起的疾病或者受益于激活该受体的疾病中的用途，其中R 1 选自：氢以及可任选被一个或多个选自CN和CF 3 中的基团取代的C 1-4 烷基，R 2 选自：未被取代的C 2-10 烷基、被一个或多个选自氟和CN中的基团取代的C 1-10 烷基、C 5 链烯基、直链C 4 链烯基、以及被环烷基取代的C 1-4 烷基，和R 3 选自卤素和CN。

Xanthine derivatives as selective hm74a agonists

本发明涉及为黄嘌呤衍生物的式(I)化合物，制备所述衍生物的方法，含有所述化合物的药物制剂以及所述化合物在治疗、例如在治疗由HM74A受体激活不足所引起的疾病或者受益于激活HM74A受体的疾病中的用途。

TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS HAVING A TRICYCLIC GROUP, CONJUGATES THEREOF, AND METHODS AND USES THEREOF

Certain chemical entities, compositions and methods

The small molecule for CEREBLON to enhancement effect T cell function

公开用以增强效应T细胞功能的针对cereblon的小分子。也公开制备这些分子的方法和使用它们治疗各种疾病状态的方法。

PESTICIDALLY ACTIVE HETEROCYCLIC DERIVATIVES WITH SULFUR-CONTAINING SUBSTITUTES

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2020 113 417 A (51) МПК C07D 473/04 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2020113417, 14.09.2018 (71) Заявитель(и): ЗИНГЕНТА ПАРТИСИПЕЙШНС АГ (CH) Приоритет(ы): (30) Конвенционный приоритет: 18.09.2017 IN 201711033014 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 20.04.2020 (86) Заявка PCT: (87) Публикация заявки PCT: WO 2019/053182 (21.03.2019) A Адрес для переписки: 105082, Москва, Спартаковский пер., д. 2, стр. 1, секция 1, этаж 3, "ЕВРОМАРКПАТ", Веселицкий Максим Борисович R U (57) Формула изобретения 1. Соединение формулы I A 2 0 2 0 1 1 3 4 1 7 (54) ПЕСТИЦИДНО АКТИВНЫЕ ГЕТЕРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ С СЕРОСОДЕРЖАЩИМИ ЗАМЕСТИТЕЛЯМИ 2 0 2 0 1 1 3 4 1 7 EP 2018/074867 (14.09.2018) R U (43) Дата публикации заявки: 20.10.2021 Бюл. № 29 (72) Автор(ы): РЕНДЛЕР Зебастиан (CH), ЭДМУНДС Эндрю (CH), МЮЛЕБАХ Мишель (CH), ЭМЕРИ Даниэль (CH), РАВАЛ Гириш (IN), СЕН Индира (IN), СИКЕРВАР Викас (IN) где А представляет собой СН или N; X представляет собой S, SO или SO2; R1 представляет собой С1-С4алкил, С1-С4галогеналкил или С3-С6циклоалкилС1-С4алкил; R7 и R8 независимо друг от друга представляют собой галоген, циано, C1-С6алкил, C1-С6галогеналкил, С3-С6циклоалкил, С1-С4алкокси, С1-С4алкоксиС1-С4алкил, С1-С4 алкилсульфанил, С1-С4алкилсульфанил-С1-С4алкил, С1-С4алкилсульфинил-С1-С4алкил, С1-С4алкилсульфонил-С1-С4алкил или С1-С4алкоксикарбонил; Стр.: 1 Q представляет собой радикал, выбранный из группы, состоящей из формул Q1, Q2, Q3 и Q4, A где А, X, R1, R2, G2, R7 и R8 определены под формулой I в п. 1. 3. Соединение формулы I-Q1 по п. 2, где R2 представляет собой C1-С4галогеналкилсульфанил, С1-С4галогеналкилсульфинил, C1-С4галогеналкилсульфонил; предпочтительно С1-С4галогеналкил. 4. Соединение формулы I по п. 1, представленное соединениями формулы I-Q2 R U 2 0 2 0 1 1 3 4 1 7 2 0 2 0 1 1 3 4 1 7 A R U где стрелка обозначает точку присоединения к кольцу, ...

Substituted aryl sulfone derivatives as calcium channel blockers

A series of substituted aryl sulfone derivatives represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, calcium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, diabetic neuropathy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, sleep disorder, bipolar disorder and stroke, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.

Polymorph

【課題】I型及びII型糖尿病、前糖尿病又は減少した糖耐性、さらに関節リウマチ、肥満、又はカルシトニン誘導骨粗鬆症を有する患者、並びに同種移植が行われた患者を治療するのに好適な医薬組成物を提供すること。【解決手段】1-[(4-メチル-キナゾリン-2-イル)メチル]-3-メチル-7-(2-ブチン-1-イル)-8-(3-(R)-アミノ-ピペリジン-1-イル)-キサンチンの多形体結晶修飾、それらの製造及び薬剤の調製のためのそれらの使用方法を提供する。【選択図】なし

Dual selective PI3 delta and gamma kinase inhibitors

本发明涉及双重delta(δ)及gamma(γ)PI3K蛋白激酶调节剂、其制备方法、含有其的药物组合物及用其治疗、预防和/或改善Pi3K激酶介导的疾病或病症的方法。

Novel compounds

본 발명은 크산틴 유도체인 치료 활성 화합물, 상기 유도체의 제조 방법, 상기 활성 화합물을 함유하는 제약 제제, 및 치료에서, 특히 HM74A 수용체의 불충분-활성화가 기여하거나 또는 상기 수용체의 활성화가 유익하게 되는 질환의 치료에서의 화학식 II를 갖는 화합물의 용도에 관한 것이다. The present invention relates to a therapeutically active compound which is a xanthine derivative, a method of preparing the derivative, a pharmaceutical formulation containing the active compound, and a treatment, in particular, a disease in which insufficient-activation of the HM74A receptor contributes or the activation of the receptor is beneficial. The use of a compound having formula II in the treatment of <화학식 II> <Formula II> 상기 식에서, Where R 1 은 수소 및, CN 및 CF 3 으로부터 선택된 하나 이상의 기로 임의로 치환될 수 있는 C 1 -4 알킬로부터 선택되고; R 1 is selected from C 1 -4 alkyl optionally substituted by at least one group selected from a hydrogen and a, CN, and CF 3; R 2 는 C 2 -10 비치환된 알킬, 불소 및 CN으로부터 선택된 하나 이상의 기로 치환된 C 1 -10 알킬, C 5 알케닐, 비분지된 C 4 알케닐, 및 시클로알킬로 치환된 C 1 -4 알킬로부터 선택되고; R 2 is a substituted C 2 to C -10 unsubstituted alkyl, a C 1 -10 substituted with one or more groups selected from fluorine and CN alkyl, C 5 alkenyl ring, an unbranched C 4 alkenyl, and cycloalkyl 1- 4 is selected from alkyl; R 3 은 할로겐 및 CN으로부터 선택된다. R 3 is selected from halogen and CN. 크산틴 유도체, HM74A 수용체, 심혈관 질환, 지질 대사 장애  Xanthine derivative, HM74A receptor, cardiovascular disease, lipid metabolism disorder

Substituted with sulfamides xantine derivatives for application as phosphoenolpyruvatcarboxykinase (pepck) inhibitors

Настоящее изобретение относится к замещенным сульфамидами производным ксантина формулы I или к их фармацевтически приемлемым солям, где R 1 , R 2 и R 3 являются такими, как приведено в описании изобретения. Соединения формулы (I) и их фармацевтически приемлемые соли проявляют активность в качестве модуляторов глюконеогенеза и могут использоваться для получения фармацевтических композиций, которые могут быть полезны для лечения диабета типа 2. 2 н. и 33 з.п. ф-лы, 1 табл. ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (11) 2 340 613 (13) C2 (51) ÌÏÊ C07D 473/04 (2006.01) A61K 31/52 (2006.01) A61P 3/10 (2006.01) C07D 473/06 (2006.01) ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÎÏÈÑÀÍÈÅ ÈÇÎÁÐÅÒÅÍÈß Ê ÏÀÒÅÍÒÓ (21), (22) Çà âêà: 2005128833/04, 12.02.2004 (24) Äàòà íà÷àëà îòñ÷åòà ñðîêà äåéñòâè ïàòåíòà: 12.02.2004 (30) Êîíâåíöèîííûé ïðèîðèòåò: 19.02.2003 US 60/448,562 (73) Ïàòåíòîîáëàäàòåëü(è): Ô.ÕÎÔÔÌÀÍÍ-Ëß ÐÎØ Àà (CH) (43) Äàòà ïóáëèêàöèè çà âêè: 27.07.2006 R U (72) Àâòîð(û): ÔÎÓËÈ Ëóèñà Õåëåí (US), ÕÜÞÁÈ Íèêîëàñ Äæîí Ñèëâåñòåð (US), ÏÈÒÐÀÍÈÊÎ-ÊÎÓË Øåððè Ëèíí (US), ÞÍÜ Âý (US), ÄÀÍÒÅÍ Ïèò Óèëëü ì (US) (45) Îïóáëèêîâàíî: 10.12.2008 Áþë. ¹ 34 2 3 4 0 6 1 3 (56) Ñïèñîê äîêóìåíòîâ, öèòèðîâàííûõ â îò÷åòå î ïîèñêå: RU 95109100 A1, 10.03.1995. WO 01/77110 A1, 18.10.2001. EP 0956855 A1, 24.04.1998. (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 19.09.2005 2 3 4 0 6 1 3 R U (87) Ïóáëèêàöè PCT: WO 2004/074288 (02.09.2004) C 2 C 2 (86) Çà âêà PCT: EP 2004/001289 (12.02.2004) Àäðåñ äë ïåðåïèñêè: 101000, Ìîñêâà, Ì.Çëàòîóñòèíñêèé ïåð., 10, êâ.15, "ÅÂÐÎÌÀÐÊÏÀÒ", ïàò.ïîâ. È.À.Âåñåëèöêîé, ðåã. ¹ 11 (54) ÇÀÌÅÙÅÍÍÛÅ ÑÓËÜÔÀÌÈÄÀÌÈ ÏÐÎÈÇÂÎÄÍÛÅ ÊÑÀÍÒÈÍÀ ÄËß ÏÐÈÌÅÍÅÍÈß Â ÊÀ×ÅÑÒÂÅ ÈÍÃÈÁÈÒÎÐΠÔÎÑÔÎÅÍÎËÏÈÐÓÂÀÒÊÀÐÁÎÊÑÈÊÈÍÀÇÛ (ÐÅÐÑÊ) (57) Ðåôåðàò: Íàñòî ùåå èçîáðåòåíèå îòíîñèòñ ê çàìåùåííûì ñóëüôàìèäàìè ïðîèçâîäíûì êñàíòèíà ôîðìóëû I èëè ê èõ ôàðìàöåâòè÷åñêè ïðèåìëåìûì ñîë ì, ãäå R 1, R 2 è R 3 âë þòñ òàêèìè, êàê ïðèâåäåíî â îïèñàíèè èçîáðåòåíè . Ñîåäèíåíè ôîðìóëû (I) è ...

DERIVATIVE XANTHINE

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2017 145 919 A (51) МПК C07D 473/06 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2017145919, 26.05.2016 (71) Заявитель(и): ЦЗЯНСУ ТАСЛИ ДИИ ФАРМАСЬЮТИКАЛ КО., ЛТД. (CN) Приоритет(ы): (30) Конвенционный приоритет: 29.05.2015 CN 201510290336.0 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 29.12.2017 R U (43) Дата публикации заявки: 02.07.2019 Бюл. № 19 (72) Автор(ы): ГАО Юйчже (CN), ВАН Гочэн (CN) (86) Заявка PCT: (87) Публикация заявки PCT: WO 2016/192559 (08.12.2016) A Адрес для переписки: 123242, Москва, пл. Кудринская, д. 1, а/я 35, "Михайлюк, Сороколат и партнеры патентные поверенные" (57) Формула изобретения 1. Производное ксантина, представленное формулой I, и его сольваты или их фармацевтически приемлемые соли, A формула I, где R U 2 0 1 7 1 4 5 9 1 9 (54) ПРОИЗВОДНОЕ КСАНТИНА 2 0 1 7 1 4 5 9 1 9 CN 2016/083406 (26.05.2016) R выбран из ; Стр.: 1 R1 выбран из циано или метоксикарбонила; R2 выбран из водорода, атомов галогена, линейной или разветвленной C1-6алкильной группы, которая является замещенной или незамещенной 1-5 атомами галогена, линейной или разветвленной C1-6алкоксигруппы, которая является замещенной или незамещенной 1-5 атомами галогена; каждый из X и Y независимо выбран из C или N; n равняется 0, 1, 2, 3 или 4. 2. Производные ксантина и их сольваты или их фармацевтически приемлемые соли по п. 1, где R2 выбран из водорода, атомов галогена, метила, этила, изопропила, метоки, этокси, трифторметила или трифторметокси; n равняется 0, 1 или 2. 3. Производные ксантина и их сольваты или их фармацевтически приемлемые соли по п. 2, где R2 выбран из водорода, атома хлора, атома фтора, атома брома, метила или метокси. 4. Производные ксантина и их сольваты или их фармацевтически приемлемые соли 2 0 1 7 1 4 5 9 1 9 A I-1, или I-2, или A 2 0 1 7 1 4 5 9 1 9 R U по п. 3, где R2 выбран из водорода или атома фтора. 5. Производные ксантина и их ...

Oxipurinol class compound and its application

羟基嘌呤类化合物式(I)、其互变异构体或其药学上可接受的盐、及其作为PDE2或TNF‑α抑制剂的应用。

ACC inhibitors and uses thereof

Certain chemical entities, compositions and methods

PI3 키나제 활성을 조절하는 화학 물질, 및 PI3 키나제 활성과 관련된 질환 및 상태의 치료를 위한 화학 물질, 제약 조성물 및 방법이 본원에 기재된다.

Crystalline form of linagliptin and preparation method thereof

본 발명은 리나글립틴 결정형 및 이의 제조방법에 관한 것으로서, 본 발명에 따른 리나글립틴 결정형은 열안정성이 우수하고 단일 결정형으로 재현성 있게 제조할 수 있을 뿐만 아니라 이로 인하여 일정한 품질로 대량 생산이 가능하므로 당뇨병 치료용 약학 조성물로 유용하게 사용할 수 있다. The present invention relates to a linagliptin crystalline form and a method for producing the same, and the linagliptin crystalline form according to the present invention has excellent thermal stability and can be reproducibly prepared as a single crystalline form, and thus can be mass-produced with a constant quality. It can be usefully used as a pharmaceutical composition for the treatment of diabetes.

Processes for preparing isoquinolinones and solid forms of isoquinolinones

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI 3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

Certain chemical entities, compositions and methods

Chemical entities that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with P13 kinase activity are described herein.

Formulations of (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

Solid forms of (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1 (2H)-one and methods of use thereof

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

Processes for preparing isoquinolinones and solid forms of isoquinolinones

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

Processes for preparing isoquinolinones and solid forms of isoquinolinones

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

Solid forms of (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one and methods of use thereof

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including Pl3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.

Processes for preparing isoquinolinones and solid forms of isoquinolinones

Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.