НОВЫЕ АНАЛОГИ ВИТАМИНА D

Изобретение относится к новому соединению формулы I где X означает водород или гидрокси; R1 и R2, которые могут быть одинаковыми или разными, означают водород, (C1-C4)алкил; R3 означает водород, метил, фтор или хлор, и к его способным гидролизоваться in vivo сложным эфирам с фармацевтически приемлемыми кислотами. Изобретение также относится к фармацевтической композиции, обладающей активностью ингибирования пролиферации и промотирования дифференциации клеток, содержащей эффективное количество соединения формулы (I) вместе с фармацевтически приемлемыми носителями и/или разбавителями; и к применению соединения формулы (I) для приготовления медикамента для лечения или профилактики болезни, характеризующейся аномальной дифференциацией клеток и/или пролиферацией клеток. 2 н. и 11 з.п. ф-лы, 3 табл.

АНАЛОГИ ВИТАМИНА D, СПОСОБ ИХ ПОЛУЧЕНИЯ, СПОСОБЫ ПОЛУЧЕНИЯ СОЕДИНЕНИЙ

Изобретение относится к аналогам витамина D формулы I, в которой Q представляет собой С1-С8 гидрокарбиленовый бирадикал; R представляет собой С1-С6 гидрокарбид; выражение гидрокарбид (гидрокарбилен) обозначает радикал (бирадикал), полученный после удаления 1 (2) атома(ов) водорода из неразветвленного, разветвленного или циклического, насыщенного или ненасыщенного углеводорода, или в которой две группы R, взятые вместе с атомом углерода, несущим гидроксильную группу, могут образовывать С3-С8 карбоциклическое кольцо. Описывается также способ их получения, а также способы получения используемых промежуточных продуктов. Соединения обладают иммуномодулирующим и антивоспалительным действием, а также проявляют высокую активность в индуцировании дифференциации и ингибировании нежелательной пролиферации клеток, включая клетки кожи и раковые клетки. 4 с. и 5 з.п.ф-лы, 3 табл.

СПОСОБЫ ПОЛУЧЕНИЯ СЛОЖНЫХ ЭФИРОВ СТАНОЛОВ/СТЕРИНОВ

Изобретение относится к улучшенному способу прямой этерификации станолов/стеринов взаимодействием станола/стерины и кислоты, взятых в стехиометрическом соотношении, в присутствии достаточного количества катализатора, который может быть кислотным или основным, и в присутствии достаточного количества обесцвечивающего агента, предпочтительно активированного угля. Способ пригоден для крупномасштабного производства эфиров с высоким выходом и позволяет отказаться от использования органических растворителей или минеральных кислот. 3 с. и 17 з.п. ф-лы.

НОВЫЕ АКТИВАТОРЫ РЕЦЕПТОРОВ ВИТАМИНА D И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

Настоящее изобретение относится к новым соединениям формулы (I) или их фармацевтически приемлемым солям, используемым для лечения или предупреждения расстройств, опосредуемых рецепторами витамина D, а также к фармацевтической композиции, содержащей данные соединения.В формуле (I) атом углерода, к которому присоединен X, имеет S или R конфигурацию, X представляет собой -CHOC(O)R, Yи Yкаждый представляет собой водород, Yи Yвместе образуют метиленовую группу, Zпредставляет собой фтор, гидроксильную группу или гидроксиметил, Zпредставляет собой фтор или гидроксильную группу, Rпредставляет собой Cалкил, Cалкиламино, CалкилкарбонилоксиCалкил или гидроксиCалкил. 3 н. и 2 з.п. ф-лы, 4 ил., 6 табл., 19 пр.

НОВЫЙ СПОСОБ ПОЛУЧЕНИЯ ПРОМЕЖУТОЧНЫХ СОЕДИНЕНИЙ, ПРИМЕНЯЕМЫХ ДЛЯ СИНТЕЗА АНАЛОГОВ ВИТАМИНА D

FIELD: chemistry. SUBSTANCE: present invention relates to novel methods for synthesis of intermediate compounds which are used in synthesis of calcipotriol. EFFECT: present invention relates to use of intermediate compounds, obtained using said methods for synthesis of calcipotriol or monohydrate of calcipotriol. 15 cl, 10 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 378 252 (13) C2 (51) МПК C07C 401/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21), (22) Заявка: 2006138613/04, 23.03.2005 (24) Дата начала отсчета срока действия патента: 23.03.2005 (73) Патентообладатель(и): ЛЕО ФАРМА А/С (DK) (43) Дата публикации заявки: 10.05.2008 2 3 7 8 2 5 2 (45) Опубликовано: 10.01.2010 Бюл. № 1 (56) Список документов, цитированных в отчете о поиске: CALVERLEY M.J. et al // Tetrahedron, v 43, #20, (1987), p.4609-4619 ANDREAS STEINMEYER et al // Steroids, 66 (2001) p.257266. WO 87/00834 A1, 12.02.1987. US 5244104 A, 21.09.1993. 2 3 7 8 2 5 2 R U (86) Заявка PCT: DK 2005/000203 (23.03.2005) C 2 C 2 (85) Дата перевода заявки PCT на национальную фазу: 02.11.2006 (87) Публикация PCT: WO 2005/095336 (13.10.2005) Адрес для переписки: 129090, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Е.Е.Назиной (54) НОВЫЙ СПОСОБ ПОЛУЧЕНИЯ ПРОМЕЖУТОЧНЫХ СОЕДИНЕНИЙ, ПРИМЕНЯЕМЫХ ДЛЯ СИНТЕЗА АНАЛОГОВ ВИТАМИНА D (57) Реферат: Настоящее изобретение относится к новым способам получения промежуточных соединений, которые являются применимыми в синтезе кальципотриола. Кроме того, настоящее изобретение относится к применению промежуточных соединений, полученных указанными способами для получения кальципотриола или моногидрата кальципотриола. 5 н. и 10 з.п.ф-лы. Ñòð.: 1 ru R U (30) Конвенционный приоритет: 02.04.2004 US 60/558,546 (72) Автор(ы): ХАНСЕН Эрик Торнгард (DK), САБРО Томас Петер (DK), КЕЛВЕРЛИ Мартин Джон (DK), ПЕДЕРСЕН Хенрик (DK), ДЮССЕН Хайнц-Йозеф Вильгельм (DK) RUSSIAN ...

АНАЛОГИ ВИТАМИНА D, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ИНГИБИРОВАНИЯ, СПОСОБ ПОЛУЧЕНИЯ ФАРМАЦЕВТИЧЕСКОГО ПРЕПАРАТА

Изобретение относится к новым аналогам витамина D формулы I, где Х - Н или ОН, R1 и R2 - СН3 или С2Н5 или вместе с атомом углерода, несущим группу X, могут образовывать С3-С5 карбоцикл, Q - одинарная связь или С1-С8-гидрокарбилен, в которой одна из групп-CH2-, нe связанная с СО-группой, необязательно замещена ОН группой или заменена на атом кислорода, Y - одинарная связь или C1-C8-гидрокарбилен, или к их другим производным. Эти соединения обладают антивоспалительными и иммуномодулирующими эффектами, а также высокой активностью при индуцировании дифференциации и ингибировании нежелательной пролиферации некоторых клеток. 5 с. и 5 з.п. ф-лы, 5 табл.

АНАЛОГИ ВИТАМИНА D, СОЕДИНЕНИЯ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описываются новые аналоги витамина D общей формулы I, где значения R1, R2, R3, R4, R5, R'2, R'3, R'4, R'5, X, У, У' указаны в п.1 формулы, которые проявляют селективную активность в отношении клеточных функций. Описывается способ их получения и фармацевтическая композиция на основе соединений формулы I. 10 с. и 14 з.п. ф-лы, 5 ил., 3 табл.

АНАЛОГИ ВИТАМИНА Д, СПОСОБ ИХ ПОЛУЧЕНИЯ, ПРОМЕЖУТОЧНОЕ СОЕДИНЕНИЕ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ПОДАВЛЕНИЯ БОЛЕЗНЕННЫХ СОСТОЯНИЙ

Изобретение относится к соединениям формулы (1), где Х -гидрокси; R1 и R2 могут быть одинаковы или различны, представляют метил, этил или трифторметил, Q представляет простую связь или Q = (CH2)n, где n = 0,1-4, a m - 0 или 1. Соединения обладают противовоспалительной и иммуномодуляторной активностью, а также высокой способностью вызывать дифференциацию и ингибирование нежелательной пролиферации некоторых клеток. Описывается их способ получения, промежуточное соединение для получения соединения формулы I, а также фармацевтическая композиция, проявляющая антипролиферативную активность и способ подавления болезненных состояний, характеризующихся патологической клеточной дифференциацией или пролиферацией, таких как рак и псориаз, с использованием соединения формулы I. 5 с. и 6 з.п. ф-лы, 2 табл.

АНАЛОГИ ВИТАМИНА D, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Аналоги витамина D общей формулы I, где Y - сера, R - С1-С3-алкил, или R-С-R может образовывать бензильный радикал, Q - С2-С4-алкилен, причем одна или более гидроксигрупп защищены в виде групп, которые могут быть преобразованы в гидроксигруппы in vivo, проявляют противовоспалительные и иммуномодулирующие эффекты, также как и сильную активность при индуцировании дифференциации и ингибировании нежелательной пролиферации определенных клеток. 4 с. и 5 з.п. ф-лы, 2 табл.

АНАЛОГИ ВИТАМИНА D3, СПОСОБЫ ИЗ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ

Изобретение относится к неизвестному до сих пор классу соединений, которые обладают противовоспалительными и иммуномодулирующими действиями, к фармацевтическим препаратам, содержащим эти соединения, к способу лечения и к способу получения вышеуказанных соединений. Соединения формулы (I), где U -группа-(СН2)n -У-(СН2)m -, n = 0,1 или 2, m = 1 или 2, У - кислород или сера, при этом 22- или 23-метилен может быть заменен кислородом, или 22- или 23-метилен может быть заменен группой -СН = СН-; R1-метил или этил, а атом углерода, непосредственно связанный с С-25 атомом, может быть замещен одним или несколькими атомами фтора; имеющиеся гидроксигруппы могут быть защищены с помощью групп, способных отщепляться in vivo. Способ получения соединений формулы (I), где гидроксигруппа модифицирована путем взаимодействия с трет-бутилбромацетатом в присутствии основания и катализатора в растворителе с последующим взаимодействием полученного сложного эфира с метил- или этилмагнийгалогенидом с получением соединения ...

ГИДРАТ КАЛЬПОТРИОЛА И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Данное изобретение касается кадьципотриола-гидрата новой кристаллической формы кальципотриола, с техническими свойствами высокого качества и превосходной стабильностью.

АНАЛОГИ ВИТАМИНА D

... 1. Аналоги витамина D формулы I где Х представляет собой водород или гидрокси группу; R1 и R2 представляют собой метил или этил, или, вместе с атомом углерода, несущим группу X, могут образовывать С3-C5-карбоцикл; Q представляет собой или одинарную связь, или С1-С8-гидрокарбилен, в котором одна из метиленовых групп, не связанных непосредственно с карбонильной группой, может быть необязательно замещена атомом кислорода (или метил на гидрокси группу); Y представляет собой или одинарную связь, или C1-С8-гидрокарбилен; и производные формулы I, где одна или более гидрокси-группы замаскированы в виде групп, которые могут превращаться в гидрокси-группы in vivo. 2. Соединение формулы I по п. 1, отличающееся тем, что Х представляет собой гидроксогруппу, a Y - одинарную связь. 3. Соединение по любому из пп. 1-2, отличающееся тем, что оно является диастереомером в чистом виде, или смесью таких диастереоизомеров. 4. Соединение по п. 2, отличающееся тем, что оно представляет собой 24-оксо-1(S), 3(R) ...

АНАЛОГИ ВИТАМИНА D

... 1. Соединение формулы 1 в которой X представляет водород или гидрокси; R1 и R2 представляют метил или этил; Q представляет метилен, этилен, три- или тетраметилен и может быть необязательно замещен оксигруппой, -OR3, где R3 представляет водород, метил или этил; Y представляет либо одинарную связь, либо С1-С2-гидрокарбилен, причем гидрокарбилен означает бирадикал, полученный после удаления 2 атомов углерода у неразветвленного, разветвленного или циклического насыщенного или ненасыщенного углеводорода; и один или несколько углеродов в R1, R2 и/или Y могут быть необязательно замещены одним или несколькими атомами фтора или гидроксильной группой. 2. Соединение формулы 1 по п.1, в которой Х представляет гидрокси и Y представляет одинарную связь. 3. Соединение формулы 1 по пп.1 и 2, в которой R1 и R2 одинаковые и представляют метил или этил или разные и представляют водород и циклопропил. 4. Соединение по п.1 или 2, отличающееся тем, что представлено в чистой форме диастереоизомера или смеси таких ...

АНАЛОГИ ВИТАМИНА D

Соединения формулы применимы в качестве средств для лечения гиперпролиферативных кожных болезней, например псориаза, новообразований, например рака молочной железы, лечения опухолевых заболеваний, например лейкоза, и заболеваний жировых желез, например угрей и себорейного дерматита. Соединения получают удалением силильных защитных групп в соответствующих соединениях с силилзащищенными гидроксигруппами.

АНАЛОГИ ВИТАМИНА D

Изобретение относится к соединениям 1,25-диокси-16-ен-24-оксо-холекальциферола и 1,24,25-триокси-16-ен-холекальциферола, который стимулирует дифференциацию клеток HL-60, что придает им ценность как средства для лечения связанных с опухолями заболеваний, таких как лейкемия, а также снижает пролиферацию человеческих кератиноцитов, что придает им ценность как средств для лечения гиперпролиферативных заболеваний кожи, таких как псориаз. Соединения получаются путем перфузии 1,25-диокси-16-ен-холекальциферола в почки крыс, экстракции перфузата и извлечения 1,25-диокси-16-ен-24-оксохолекальциферола и 1,24,25-триокси-16-ен-холекальциферола.

ПРОИЗВОДНЫЕ 22-ТИАВИТАМИНА D3

... 1. Соединение общей формулы I где R1 представляет собой С1-10-алкил, который может быть замещен одной или более гидроксильными группами, R2 представляет собой атом водорода или гидроксильную группу, и R3 представляет собой атом водорода или гидроксильную группу. 2. Соединение по п.1, в котором R3 представляет собой гидроксильную группу. 3. Соединение по п.2, в котором R1 представляет собой С1-10-алкил, замещенный одной или более гидроксильными группами. 4. Соединение по п.1 общей формулы II: где R1, представляет собой С1-10-алкил, который может быть замещен одной или более гидроксильными группами, а R2 представляет собой атом водорода или гидроксильную группу. 5. Соединение по п.4, в котором R1 представляет собой С1-10-алкил, замещенный одной или более гидроксильными группами. 6. Соединение по п. 5, в котором R1 представляет собой группу общей формулы III где R4 и R5, которые могут быть одинаковыми или различными, каждый представляет собой атом водорода или гидроксильную группу, при условии ...

НОВЫЕ ПРОИЗВОДНЫЕ ВИТАМИНА D С КАРБО- ИЛИ ГЕТЕРОЦИКЛИЧЕСКИМИ ЗАМЕСТИТЕЛЯМИ НА C-25, СПОСОБ ИХ ПОЛУЧЕНИЯ, ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ И ПРИМЕНЕНИЕ ДЛЯ ПРИГОТОВЛЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВ

... 1. Производные витамина D общей формулы I где Y1 обозначает атом водорода, гидроксигруппу, алканоилоксигруппу с 1-12 С-атомами или ароилоксигруппу, Y2 обозначает атом водорода или алканоилоксигруппу с 1-12 С-атомами или ароилгруппу, R1 и R2 обозначают атом водорода или вместе обозначают экзоциклическую метиленовую группу, R3 и R4 независимо друг от друга обозначают атом водорода, атом хлора или фтора, алкильную группу с 1-4 атомами углерода, вместе обозначают метиленовую группу или вместе с четвертичным углеродным атомом 20 обозначают 3-7-членное, насыщенное или ненасыщенное карбоциклическое кольцо, Q обозначает углеродную единицу с прямой или разветвленной цепью, содержащую до 10 атомов углерода, которая может иметь в любых положениях гидроксильные группы (α- или β-), которые, в свою очередь, могут быть этерифицированными (превращенными в группы простых или сложных эфиров), кетогруппы, аминогруппы или атомы галогена, R5 и R6 одновременно обозначают атом водорода, атом хлора или фтора, ...

НОВЫЕ АНАЛОГИ ВИТАМИНА D, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ, СПОСОБ ЛЕЧЕНИЯ И ПРОФИЛАКТИКИ ПАТОЛОГИЧЕСКИХ СОСТОЯНИЙ

Изобретение относится к соединениям формулы, приведенной в описании. Соединения обладают противовоспалительным и иммуномодулирующим действием, а также высокой активностью в индуцировании, дифференциации и торможении нежелательной пролиферации некоторых клеток.

ПРОИЗВОДНЫЕ ВИТАМИНА D3

... 1. Соединение формулы I где Q обозначает метилен, этилен, три-, тетра- или пентаметилен, -СН= СН-, -СН= СН-СН= СН-, -CH= CH-C≡C-, -СН=СН-СН2-, -С≡С-, -С=С-СН2-, -CH(R)-(CH2)2-, -CH(R)-CH=CH- или -CH(R)-C≡C-, где R - C1-С3 алкил; Y обозначает одинарную связь, карбонильную группу или бирадикал метилен, этилен, -СН (ОН)-, -O-(С6H4)-(орто, мета, пара) или -S-(С6H4)-(орто, мета, пара); R1 и R2, которые могут быть одинаковыми или различными, обозначают водород или радикал C1-C6 гидрокарбил; или R1 и R2, вместе с атомом углерода (помеченным звездочкой в формуле I), несущим группу Z, могут образовывать С3-С6 карбоциклическое кольцо; Z обозначает водород или гидрокси; при условии, что, когда одновременно, Q обозначает этилен, Y означает метилен, карбонил или -СН (ОН)-, R1 и R2 обозначают метил, и Z обозначает гидрокси, то конфигурация при С-20 не может быть . 2. Диастереоизомер соединения по п.1 в чистом виде, или смесь диастереоизомеров соединения по п.1. 3. Соединение по п.1, представляющее собой ...

НОВЫЕ АНАЛОГИ ВИТАМИНА Д, СПОСОБ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ЛЕЧЕНИЯ

Изобретение относится к соединению формулы (I), где R обозначает насыщенную или ненасыщенную алкильную группу с прямой или разветвленной цепью, содержащую от 4 до 12 атомов углерода, которая необязательно замещена гидроксильной группой и возможно содержит кольцевые структуры и в которой по крайней мере один атом углерода, не содержащий гидроксильной группы, замещен одним или большим количеством атомов галогена или азидо-групп, и предшественнику лекарственного средства соединения I, в котором одна или несколько гидроксильных групп маскированы в виде групп, способных вновь восстанавливать гидроксильные группы в условиях in vivo, в чистом виде или в виде смеси. Соединения оказывают антивоспалительное и иммуномодулирующее воздействие, а также проявляют сильную активность, стимулируя дифференциацию и ингибируя нежелательное разрастание некоторых клеток.

НОВЫЙ СПОСОБ ПОЛУЧЕНИЯ ПРОМЕЖУТОЧНЫХ СОЕДИНЕНИЙ, ПРИМЕНЯЕМЫХ ДЛЯ СИНТЕЗА АНАЛОГОВ ВИТАМИНА D

... 1. Способ получения соединения общей структуры Va, Vb, VIIIa, VIIIb, XIVa, XIVb, XVIa, XVIb или XX соответственно где R1 и R2 являются одинаковыми или различными и представляют собой водород или защитную гидроксигруппу, и где R5 представляет собой водород или защитную гидроксигруппу; причем способ включает в себя взаимодействие соединения общей структуры IIIa, IIIb, VIa, VIb, XIIIa, XIIIb, XVa, XVb или IXX соответственно где R1, R2 и R5 такие, как указано выше, с фосфонатом общей структуры VII где R3 и R4 являются одинаковыми или различными и представляют собой алкил, галогеналкил, гидроксиалкил, алкенил, алкинил, аралкил, аралкенил, аралкинил или арил, каждый из которых является необязательно замещенным одним или более заместителями, выбранными из группы, состоящей из алкила, аралкила, циклоалкила, циклоалкенила, галогеналкила, гидроксиалкила, алкенила, алкинила, аралкила, аралкенила, аралкинила, арила, оксо, алкоксикарбонила, алкилкарбонилокси, галогена, алкокси, карбокси, сульфо или ...

НОВЫЕ АКТИВАТОРЫ РЕЦЕПТОРОВ ВИТАМИНА D И СПОСОБЫ ИХ ПОЛУЧЕНИЯ

... 1. Соединение формулы (I): ! ! или его фармацевтически приемлемая соль или пролекарство, где ! атом углерода, к которому присоединен Х, имеет S или R конфигурацию; ! X представляет собой -CH2OR1, -CH2OC(O)R2, -CR3R4-(CH2)m-CR5R6-CR7(CH3)2 или OR8; ! Y1 и Y2 каждый представляет собой водород или они вместе образуют метиленовую группу; ! Y3 и Y4 каждый представляет собой водород или они вместе образуют метиленовую группу; ! Z1 представляет собой фтор, гидроксильную группу или гидроксиметил; ! Z2 представляет собой фтор или гидроксильную группу; ! R1 представляет собой водород, алкил или арил; ! R2 представляет собой алкил, алкиламино, алкилкарбонилоксиалкил или гидроксиалкил; ! R3 и R4 независимо представляют собой водород или алкоксигруппу, при условии, что одновременно они оба не являются алкоксигруппой; ! R5 и R6 независимо представляют собой водород или алкил; ! R7 представляет собой водород, алкоксигруппу или гидроксильную группу; ! R8 представляет собой -CH2CH2C(CH3)2OH; и ! m равно ...

АНАЛОГИ ВИТАМИНА D

... 1. Аналоги витамина D, представляющие собой соединения, выбранные отдельно или в смеси, из группы, состоящей из: (4Е,6Е)-7-{3-[2-(3,4-Бис-гидроксиметилфенил)этил]фенил}-3-этил-нона-4,6-диен-3-ол, (Е)-6-[3-(3, 4-Бис-гидроксиметилбензилокси)фенил]-1,1,1-трифтор-2-трифторметилокт-5-ен-3-ин-2-ол, (3Е,5Е)-6-[3-(3,4-Бис-гидроксиметилбензилокси)фенил]-1,1,1-трифтор-2-трифторметилокта-3,5-диен-2-ол, (Е)-6-{3-[2-(3,4-Бис-гидроксиметилфенил)этил]фенил}-1,1,1-трифтор-2-трифторметилокт-5-ен-3-ин-2-ол, (3Е,5Е)-6-{3-[2-(3,4-Бис-гидроксиметилфенил)этил]фенил}-1,1, 1-трифтор-2-трифторметилокта-3,5-диен-2-ол, а также их геометрических изомеров и указанных выше соединений, в которых одна или несколько гидроксильных групп имеют защитную группу типа -(С=О)-R, где R обозначает линейный или разветвленный алкильный радикал, содержащий от 1 до 6 атомов углерода, или арильный радикал, содержащий от 6 до 10 атомов углерода, или аралкильный радикал, содержащий от 7 до 11 атомов углерода; при этом арильный радикал ...

СЛОЖНЫЕ ЭФИРЫ АНАЛОГОВ 3-ДЕЗОКСИВИТАМИНА D3

... 1. Соединение формулы или его соль, где пунктирная линия необязательно означает двойную связь, L означает соединительный фрагмент, выбранный из группы, включающей -СН2-СН2-СН2-, -СН2-СН=СН-, -СН2-С≡С-, -СН2-СН2-С(=О)- и -СН=СН-СН=СН-, каждый R2 и R3 независимо означает алкил или галогеналкил или R2 и R3 вместе с атомом углерода, к которому они присоединены, образуют циклоалкил, а каждый R1 и R4 независимо означает водород, алкил, ацильную группу или другую гидроксизащитную группу, при условии, что по меньшей мере один из R1 и R4 означает ацильную группу. 2. Соединение по п.1 формулы где R1, R2, R3, R4 и L имеют значения, указанные в п.1. 3. Соединение по п.1 формулы где L выбирают из группы, включающей -CH2-CH2-CH2-, -CH2 -CH=CH-, -СН2-С≡С- и -СН=СН-СН=СН-. 4. Соединение по п.1, где L выбирают из группы, включающей -СН2-СН=СН- и -CH2-C≡C-. 5. Соединение по п.1, где R1 означает ацильную группу. 6. Соединение по п.1, где R4 означает ацильную группу. 7. Соединение по п.1, где каждый R2 и R3 ...

ФТОРИРОВАННОЕ ПРОИЗВОДНОЕ ВИТАМИНА D3

Изобретение относится к 1альфа-фтор-25-гидрокси-16-ен-23-инхолекальциферолу формулы, приведенной в описании, и который используется в качестве агента для лечения заболеваний сальной железы, таких, как угревая сыпь или себорейный дерматит. Он может быть получен удалением силильных защитных групп из соответствующего соединения с защищающими гидроксилсилильными группами.

1,3-Динитроглицериновые эфиры простагландина Е @ или 9-оксима простагландина Е @ , обладающие вазодилататорной и антиагрегационной активностями

Использование: в качестве сосудорасширяющего средства, обладающего также антиэгрегационным действием на тромбоциты . Сущность: продукт 1,3-динитроглице- риновые эфиры простагландина Ei или 9-оксима поостагландина EI общей формулы О и Г-ОМО, oj-н ON07 ОН ОН где А - 0 или NOH; выход 57.4 и 11,3%. Реагент 1: простагландин Ei или оксим простагландина Ei. Реагент2: 1,3-динитрат глицерина . Условия реакции в среде абсолютного ацетона в присутствии п-толу- олсульфохлорида и триэтиламина 2 табл. Ё ...

Натриевая соль 9-окси -19,20,-биС-НОРпРОСТАНОВОй КиСлОТы, пРОяВ-ляющАя гипОлипЕМичЕСКую и пРОТиВО-язВЕННую АКТиВНОСТь

Способ получения простагландинов или их солей

Способ получения /4,5,6R,8R/метилового эфира 9-оксо-11 @ ,15 @ -дигидрокси-16-фенокси-17,18,19,20 тетранорпроста-4,5,13 /Е/-триеновой кислоты

Изобретение относится к нроиз- .водному нростагландинов, в частности к получению специфического стереоизо- мера метилового эфира 9-оксо-11а, 1 5с(,-дигидрокси-16-фенокси-17,18,19- 20-тетранорпроста-4,5,13 (Е)-триеновой кислоты (эк)-ингибитора кислотной секреции желудка, который может быть использован в медицине. Цель изобре- .тения - создание более активного сте- реоизомера простагландинового ряда. Синтез ЭУ. ведут этерификацией (4,5, 6R,8R)-9-OKco-l Ы, 15об-дигидрокси-16- фенокси-17,18,19,20-тетранорпроста- 4,5,13(Е)-триеновой кислоты диазоме- таном. Специфический стереоизомер ЭК ингибирует кислотную желудочнук секрецию при дозе, в 32 раза меньшей, чем известное идентичное соединение но в виде смеси 4 стереоизомеров. а IQ О) сн ...

Способ получения производных простаноиновой кислоты

... 1. способ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ ПРОСТАНОИНОВОЙ КИСЛОТЫ общей формулы (i) в соон ...к .,он I -группа Cv. ««-С , ОНи отличающийся тем, что соединения формулы (II) .. RO О где К - бензил; S D - радикал OR ел подвергают гидрогенолизу на палладии на угле в среде органического растворителя при комнатной температуре. 2. Способ по п. 1, о т л и ч а ющ и и с я тем, что в качестве органического растворителя используют смесь уксусной кислоты и этанола.

Способ получения простагландиновых эфиров

Способ получения производных простагландина

Способ получения диалкилфосфонатов

Способ получения -кетофосфонатов

Способ получения простагландинов

СПОСОБ ПОЛУЧЕНИЯ ПРОСТ АГЛАНДИНОВ общей формулы . где А - рксогруппа или группа формулы хОН н te - о или I; (ТТП - твтрагидропиранил , отличаюшийся тем, что соединение обшей форму лы |где NV и И имеют указанные значешш, подвергают взаимодействию с 4 -оксидифенилом Влп|жрутствииаиаикл6гексилкарбо диимида с последующим шлделением це- f .левого продукта.-iVi-i ...

Способ получения производных ( @ )-16-фенокси-9-кетопростатриеновой кислоты или их солей

Способ получения производных (del-1б-фенокси-9-кетопростатриеновой кислоты формулы 1: r NcH c CHX-4/« N V OCeHs ОН он где R - водород или С -С -алкил, или их солей, отличающийся |тем, что соединение общей формулы lit « С СН V.j«sK,x (сЯз),8Ю ОЙ(СНз), (CH3)jC c(ai3)j где R- е -Сц -алкил, подвергают.кислому гидролизу при 035 С и при необходимости полученное соединение общей формулы I, где fe - С.ц-С2|.-алкил, подвергают гидролизу в присутствии панкреатической липазы при комнатной температуре для получения соединения общей -формулы 1, где R - водород, или при необходююсти соединение общей формулы I, где R зодород , обрабатывают диазогшкгшом для получения соединения общей форму .лы I, где R - С.,-С -алкил, или основанием при 0-100 С для получения солей, кототрые при необходимости обрабатывают кислотой для получения со-, СО единения общей формулы I,,где R - водород , после чего целевые продукты выделяют.

Способ получения простагландиновых эфиров

Способ получения производных 11-дезоксипростагландина

Verfahren zur Herstellung von Zwischenverbindungen für Vitamin-D-Derivate sowie Verbindungen

A CRYSTALLINE PROSTAGLANDIN SALT

3-OXACARBINOLANALOGE VON PROSTAGLANDIN E TIEF 1 , VERFAHREN ZU DEREN HERSTELLUNG UND ARZNEIMITTEL, WELCHE DIESE ENTHALTEN

NEUARTIGE PROSTAGLANDINVERBINDUNGEN UND VERFAHREN ZU DEREN HERSTELLUNG

(13S)-SUBSTITUIERTE SULFINYLPROSTAGLANDINDERIVATE UND VERFAHREN ZUR HERSTELLUNG DERSELBEN

NEUE 11-DEOXY-PROSTAGLANDINE E, F TIEF ALPHA UND F TIEF BETA

PROSTAGLANDIN-ANALOGA UND VERFAHREN ZU DEREN HERSTELLUNG

NEUE CYCLOPENTANDERIVATE, VERFAHREN ZU IHRER HERSTELLUNG UND PHARMAZEUTISCHE ZUSAMMENSETZUNGEN

PROCESS FOR THE PREPARATION OF CYCLOHEXENE DERIVATIVES, AND A STARTING PRODUCT AND INTERMEDIARY PRODUCTS IN THIS PROCESS

VERFAHREN ZUR HERSTELLUNG VON 24(S)-HYDROXYVITAMIN D2

1-Alpha-hydroxy-vitamin=D prepn. - by allylic oxidn. of 5,6-trans-vitamin=D followed by irradiation

... 1-Alpha-hydroxylated vitamin D cpds. (I) are prepd. by allylic oxidn. of 5,6-trans-vitamin D, followed by exposing the oxidation prods. to actinic radiation in the presence of a photosensitising agent. (I) are used for treatment of calcium metabolism disorders. The process gives (I) in yields of 20-30%, which is higher than prior processes.

Verfahren zur Herstellung von Dihydrotachysterinen

VERFAHREN ZUR PHOTOCHEMISCHEN UMWANDLUNG VON TACHYSTEROL-DERIVATEN IN PRAEVITAMIN D-DERIVATE UND VON TRANSVITAMIN D-DERIVATEN IN CISVITAMIN D-DERIVATE.

Vitamin D3 Analoge

ZWISCHENPRODUKTE ZUR HERSTELLUNG VON 18-OXA-, 19-OXA-, 20-OXA- UND 19-OXAOMEGA-HOMO-PROSTAGLANDINEN SOWIE VERFAHREN ZU DEREN HERSTELLUNG

VERFAHREN ZUR HERSTELLUNG VON ALDEHYDEN

17-ALPHA-SUBSTITUIERTE-11-BETA-SUBSTITUIERTE-4-ARYL UND 21-SUBSTITUIERTE 19-NORPREGNADIENEDIONE MIT ANTIGESTAGENER AKTIVITÄT

N-HYDROXYPROPYLAMIDE DER ALL-E- UND 13-Z-RETINSAEURE

PROCESS FOR THE TREATMENT OF METHANOLIC-AQUEOUS RESIDUES AS A RESULT OF THE SYNTHESES WITH TRIPHENYL-PHOSPHONIUM SALTS

7-FLUORPROSTAGLANDINE UND DEREN HERSTELLUNGSVERFAHREN.

2-METHYLEN-18,19-DINOR-1ALFA-HYDROXY-HOMOPREGNACALCIFEROL UND DESSEN VERWENDUNGEN

Verfahren zur Herstellung von Carotinoidverbindungen

CYCLOALIPHATIC UNSATURATED ALCOHOLS

... 1,240,310. Cycloolefinic unsaturated alcohols. R. FIRMENICH, G. FlRMENICH, R. E. FIRMENICH and F. H. FIRMENICH, [trading as FIRMENICH & CIE.]. 7 Nov., 1968 [9 Nov., 1967; 1 Nov., 1968], No. 3392/71. Divided out of 1,240,309. Heading C2C. The invention comprises compounds of the general formulµ in which the dotted lines represent a double bond in either the 1- or 2-position in the ring. They may be prepared by reacting - or (#-cyclocitral with an organometallic compound of formula ME-CH=CH-CH 3 or ME-C=C-CH 3 , in which ME is a metal function, e.g. Li- or BrMg-, and hydrolysing the product.

TERTIARY ALCOHOLS

... 1393720 Tertiary alcohols FIRMENICH SA 5 Feb 1973 [3 Feb 1972] 30087/74 Divided out of 1393719 Heading C2C The invention comprises a process for preparing compounds of the formula wherein the ring contains one endocyclic double bond in positions 1, 2, 3 or 4, or an exocyclic double bond in position 2, or two conjugated double bonds in positions 1 and 3, 2 (exocyclic) and 3, or 2 (endocyclic) and 4, or two non- conjugated double bonds in positions 1 and 4, by reacting together compounds of the formulµ and CH 2 =CH-CH 2 ME where X is a leaving group and ME is a metallic function. The invention further comprises compounds of Formula I other than the compound having two conjugated double bonds in positions 2 (endocyclic) and 4.

PROSTAGLANDINS AND THE PREPARATION THEREOF

... 1403501 Silylated prostadienoates UPJOHN CO 30 March 1973 [27 April 1972] 15426/73 Heading C3 [Also in Division C2] Methyl 9-oxo-11a,15-bis-(trimethylsilyloxy)- cis-4, trans-13-prostadienoate is prepared by oxidizing methyl 9-hydroxy-11,15-bis-(trimethylsilyloxy)-cia-4, trans-13-prostadienoate resulting from the silylation of methyl 9,11- 15-trihydroxy-cis-4, trans-13-prostadienoate. Trimethylsilyl 9,11,15 tris-(trimethylsilyloxy)-cis-4, trans-13-prostadienoate is obtained by silylating 4,5-cis-didehydro-PGF 1 .

PROSTAGLANDINS AND THE PREPARATION THEREOF

... 1396206 Prostaglandins UPJOHN CO 30 March 1973 [27 April 1972] 15424/73 Headings C2C and C2P [Also in Division C3] The invention comprises optically active prostaglandins of the formula or racemates thereof, wherein (a) X is trans- CH=CH- or -CH 2 CH 2 -, and Y is -CH 2 - CH 2 -, or (b) X is trans-CH=CH- and Y is cis-CH=CH-; C n H 2n is C 1-9 alkylene with 1 to 6 carbon atoms in the chain between -CFR 2 - and terminal methyl; g is 2 to 5, M is R 1 is H, C 1-12 alkyl, C 3-10 cycloalkyl, C 7-12 aralkyl, phenyl optionally substituted 1 to 3 times by chlorine atoms or C 1-4 alkyl radicals, R 2 is H, methyl, ethyl or F, and D is one of the four carbocylic radicals the alkanoates thereof wherein the alkanoic acid from which the alkanoate is derived contains 2 to 12 C atoms, and pharmacologically acceptable salts thereof when R 1 is H and their preparation. The PGF 2 analogues are prepared by hydrolysing tetrahydropyranyl ethers of the Formula LI wherein THP is 2-tetrahydropyranyl and M1 Подробнее

CYCLOPENTANE DERIVATIVES

... 1448268 Prostaglandin intermediates MAY & BAKER Ltd 11 Nov 1974 [13 Nov 1973] 52695/73 Heading C3S [Also in Division C2] Trimethylsilyl esters of acids of the Formula III wherein R1 is propoxymethyl, 2-ethoxyethyl and 3-methoxypropyl and the symbols R6 together form an ethylene linkage, are prepared by reacting the free acids with hexamethyldisilazone and trimethylchlorosilane.

2-HYDROXYMETHYLCYCLOPENTANE DERIVATIVES

... 1384910 Hydroxymethylcyclopentane derivatives SANKYO CO Ltd 29 Nov 1972 [29 Nov 1971] 55178/72 Heading C2C The invention comprises hydroxymethylcyclopentane derivatives of the Formula I wherein A is a straight or branched C 1-8 alkylene group; Z is CN, CONH 2 , COOH or C 2-7 alkoxycarbonyl; and R is substituted or unsubstituted tetrahydropyranyl or tetrahydrothiapyranyl, or alkoxyalkyl; their preparation by reducing a compound of the formula IX or X wherein Y is CN, CONH 2 or C 2-7 alkoxycarbonyl ; and R 1 is C 1-4 alkyl; and their oxidation to the corresponding cyclopentanecarbaldehydes. Methyl 2 - (6 - ethoxycarbonylhexyl) - 3,5- bis - (2 - tetrahydropyranyloxy)- 1# - cyclopentane carboxylate is prepared by etherifying the corresponding 3,5-dihydroxy compound, resulting from the hydrolysis of the appropriate 3,5- diacetoxy compound, which is obtained by reacting pertrifluoroacetic acid with methyl 5- acetoxy - 3 - acetyl - 2 - (6 - ethoxycarbonylhexyl) - 1# - cyclopentanecarboxylate, ...

PROSTAGLANDIN COMPOUNDS

... 1405340 Cyclodextrin clathrate complexes ONO PHARMACEUTICAL CO Ltd 23 Aug 1973 [24 Aug 1972] 40044/73 Heading C3U [Also in Division C2] Cyclodextrin clathrates of the novel prostaglandins of the formula wherein A is = O or and B is or, when A is = O, additionally the group -CH=CH-, X is -CH 2 CH 2 or cis-CH=CH-, Y is -CH 2 CH 2 - or trans-CH=CH- and n is 4 to 10, are obtained by heating together solutions of the cyclodextrin in water or organic solvents which are miscible with water and solutions of the prostaglandin in water-miscible organic solvents. Reference has been directed by the Comptroller to Specifications 1,282,661, 1,198,071, 1,097,533, 1,097,157, 1,040,544 and 851,827.

PHARMACEUTICALLY USEFUL PROSTAGLANDIN DERIVATIVES

... 1410853 Prostaglandins SANKYO CO Ltd 24 Aug 1973 [1 Sept 1972] 40175/73 Heading C2C Novel compounds of Formula I in which A=C 4-8 alkylene, R1= C 4-10 alkyl, R2=H or C 1-6 alkyl and R3=H or C 1-6 alkoxycarbonyl, and pharmaceutically acceptable acid addition salts thereof, are prepared by reducing a compound of Formula II, II or IV with a metal hydride complex reducing agent and, if appropriate, salifying the product obtained. Compounds I in which both R2 and R3 are H can also be prepared by hydrolysis of a compound I in which R2=alkyl and/or R3= alkoxycarbonyl. The corresponding groups can also be removed from compounds II, III and IV, to give compounds in which R2 and R3 are H. Starting materials of Formulae II and IV and intermediates therefor are prepared by the following reaction schemes Pharmaceutical compositions having oxytocic activity, for parenteral administration, comprise a compound I, or a pharmaceutically ...

PROSTAGLANDIN DERIVATIVES

... 1445629 Prostaglandins AMERICAN HOME PRODUCTS CORP 18 Oct 1973 [27 Oct 1972 26 July 1973] 3863/76 Divided out of 1445628 Heading C2C Novel compounds I are prepared by oxidation of compounds Ia with dichlorodicyanoquinone. Compounds Ia are prepared by reducing 15-PGA 2 or 15-epi PGA 2 with sodium boro. hydride.

CALCIFEROL DERIVATIVE

... 1437661 Calciferol derivatives WISCONSIN ALUMNI RESEARCH FOUNDATION 12 Feb 1974 [16 Feb 1973] 06378/74 Heading C2V The invention comprises 22-dehydro-25-hydroxycholecalciferol of formula which has antirachitic activity. The preparation of the material is described.

PROSTENOIC ACID DERIVATIVES AND METHOD FOR PREPARING SAME

... 1471070 Prostaglandins AMERICAN CYANAMID CO 29 April 1974 [11 May 1973] 18749/74 Heading C2C [Also in Division C3] The invention comprises prostaglandins of the Formula A wherein R 1 is C 1-4 alkoxy, #-hydroxy-C 1-4 alkoxy or #-tetrahydropyran-21-yloxy-C 1-4 alkoxy ; R 2 is H, C 1-4 alkyl or triphenylmethyl; R 3 is straight chain C 2-10 alkyl optionally substituted with 1 or 2 C 1-4 alkyl radicals, straight chain C 3-10 alkenylmethyl, optionally substituted by 1 or 2 C 1-4 alkyl radicals, C 4-9 cycloalkyl, C 5-10 alkylcycloalkyl, C 6-12 cycloalkyl-alkyl, in which the cycloalkyl is optionally substituted by a C 1-4 alkyl radical, C 5-9 cycloalkenyl, C 6-10 alkyl-cycloalkenyl, C 6-12 cycloalkenyl-alkyl in which the cycloalkenyl is optionally substituted by a C 1-4 alkyl radical, adamantyl or adamantyl-C 1-4 alkyl; R 4 is OH, C 1-12 alkoxy, C 1-12 alkoxy or 2-tetrahydropyranyloxy; R 3 is H or C 1-3 alkyl; V is >C=O, and Z is -(CH 2 ) n -, -(CH 2 ) n -C(R 5 ) 2 .CH 2 -, -(CH 2 ) n ...

VITAMIN D3

REDUCTION PROCESS FOR THE PREPARATION OF PROSTAGLANDINS AND INTERMEDIATES THEREFOR

... 1430191 Prostaglandin intermediates IMPERIAL CHEMICAL INDUSTRIES Ltd 20 Dec 1973 [15 Jan 1973] 2031/73 Heading C2C [Also in Division C3S] Prostaglandin intermediates of the formula wherein R1 is a branched or unbranched alkyl or alkenyl radical of 4 to 10 carbon atoms; a radical of the formula wherein A1 is an alkylene radical of 1 to 9 carbon atoms and R5 is an alkyl radical of 1 to 9 carbon atoms or a cycloalkyl radical of 5 to 7 carbon atoms, provided that A1 and R5 together contain not more than 10 carbon atoms; a radical of the formula wherein A2 is a direct bond or an alkylene radical of 1 to 3 carbon atoms, and R6 is an aryl radical which is unsubstituted or which is substituted by halogen atoms, nitro radicals, alkyl, halogenoalkyl, or alkoxy radicals each of 1 to 3 carbon atoms or dialkylamino radicals wherein each alkyl is of 1 to 3 carbon atoms; a radical of the formula wherein A3 is an alkylene radical of ...

LACTOLS AND LACTONES

... 1425962 Hexahydrocyclopenta[b]furans CARLO ERBA SpA 23 March 1973 [13 April 1972 28 April 1972] 27313/75 Divided.out of 1425961 Heading C2C The invention comprises hexahydrocyclopenta[b]furans of the Formula XV wherein P is H and OH or P is an oxo group; Y1 is OH, or an esterified or etherified hydroxy group; A is trans CH=CCl or -C#C-, one of R11 4 and R11 5 is H and the other is OH or etherified hydroxy, or R11 4 and R11 5 together form an oxo group; R6 is H or C 1-4 alkyl; and n is 3 or 4, the lactol or lactone ring being in the transconfiguration with respect to the aliphatic side chain and the bonds linking the lactol or lactone ring to ring A being in the cis-configuration to each other, and their preparation. The compounds are obtained by halogenating compounds of the Formula VIII to give compounds of Formula XV above in which A is CH=CCl, P is oxo and R11 4 and R11 5 together form an oxo group, and then optionally ...

1A-HYDROXYVITAMIN D2 ANALOGS AND PROCESS FOR PREPARING SAME

PHARMACEUTICAL PREPARATIONS CONTAINING VITAMIN A DERIVATIVES

SECO-STEROL COMPOUNDS EFFECTIVE IN INDUCING THE DIFFERENTIATION OF MALIGNANT CELLS

Vitamin D homologs

This invention provides novel vitamin D-related compounds characterized by extended unsaturated side chain structures. Such compounds exhibit increased activity in arresting the proliferation and promoting the differentiation of malignant cells with only minimal calcemic activity and thus represents new therapeutic agents applicable and uniquely useful in differentiation therapy of malignant diseases. The activity characteristics of these compounds provide the basis of a method for the treatment of neoplastic diseases, specifically leukemoid diseases.

1,23-DIHYDROXYVITAMIN D COMPOUNDS

Processes for preparing calcitroic acid and esters thereof

A method for chemically synthesizing calcitrioic acid and esters thereof. Calcitroic acid displays antirachitic (vitamin D-like) activity.

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

Chemical compounds

Compounds of the general formula I wherein R represents a hydrogen atom or a hydroxyl protecting group, Y represents a hydrogen atom or an optionally protected hydroxyl group, X represents the residue of a dienophile and either R1 represents a halogen atom a hydrocarbylsulphonyloxy group or a group of the formula -Z-R3 (in which Z represents -O-, -S-, -SO-, -NR4- or -CR4R5- and R3, R4 and R5, which may be the same or different, each represent a hydrogen atom or a straight or branched aliphatic group having 1-12 carbon atoms and which may optionally carry one or more substituents) and R2 represents a hydrogen atom or R1 and R2 together represent an oxo group or an optionally substituted alkylidene group, except that R1 and R2 together with the group -CH(CH3)CH- to which they are attached do not represent a group having the branched 17 beta -hydrocarbyl side chain skeleton of vitamin D2 or vitamin D3 or use in the preparation of novel vitamin D analogues.

26,26,26,27,27,27-HEXAFLUORO-CHOLESTEROL DERIVATIVES

Compounds are described of formula (I> in which n is 1 or 2; m is 2-5 and x is -CH=CH- or -CH2-CH2-; or m is 1-4 and x is -CH=C=CH-; R<1> is phenyl, substituted phenyl or naphthyl; Y substituted or unsubstituted 3-phenoxy-2-hydroxypropyl. These compounds inhibit gastric acid secretion and provide gastrointestinal cytoprotection, and may be formulated for use in the treatment of ulcers.

CYCLOPENTYL ETHERS AND THEIR PREPARATION AND PHARMACEUTICAL FORMULATION

23,25-DIHYDROXYVITAMIN D3 PRECURSORS

Prostaglandins

PCT No. PCT/GB82/00348 Sec. 371 Date Aug. 23, 1983 Sec. 102(e) Date Aug. 23, 1983 PCT Filed Dec. 10, 1982 PCT Pub. No. WO83/02273 PCT Pub. Date Jul. 7, 1983.Novel compounds have a formula (I) (I) wherein represents a bicyclo ?2,2,1! hept-2Z-ene, bicyclo ?2,2,1! heptane, 7-oxa-bicyclo ?2,2,1! hept-2Z-ene, 7-oxa-bicyclo ?2,2,1! heptane, bicyclo ?2,2,2! oct-2Z-ene or bicyclo ?2,2,2! octane substituted at the 5-position by the group R1 and at the 6-position by the group ANR2R, a 6,6-dimethyl-bicyclo ?3,1,1! heptane substituted at the 2-position by the group R1 and at the 3-position by the group ANR2R or at the 2-position by the group ANR2R and at the 3-position by the group R1, a cyclohex-1-ene or cyclohexane substituted at the 4-position by the group R1 and at the 5-position by the group ANR2R or a 1-hydroxycyclopentane substituted at the 2-position by the group R1 and at the 2-position by the group ANR2R, R1 is a 6-carboxyhex-2-enyl group or a modification thereof as defined herein; A is ...

Steroid intermediates in the synthesis of-hydroxyvitamin D2

This invention relates to hydroxylated derivatives of vitamin D2, to processes for preparing such compounds, to intermediates utilized in such processes and to certain isotopically labelled vitamin D2 compounds. The vitamin D2 derivatives would find application in the treatment of or prophylaxsis for various disease states characterized by calcium and phosphorous imbalances and as a substitute for vitamin D3 and its metabolites in their various applications.

15-SUBSTITUTED PROSTANOIC ACIDS AND ESTERS

... 1421946 Prostaglandins AMERICAN CYANAMID CO 29 June 1973 [24 July 1972] 31235/73 Heading C2C] The invention comprises prostaglandins of the Formula A wherein m is 3 to 9, R 1 is C 2-7 alkyl, R 2 is H or C 1-12 alkyl, X is halogen, SH, -N 3 , NH 2 , -SCN, C 1-4 alkanoylthio, or C 1-4 alkylsulphonyloxy, with the proviso that when X is C 1-4 alkylsulphonyloxy then R 2 is C 1-12 alkyl, and pharmaceutically acceptable salts thereof when R 2 is H and their preparation. The compounds are prepared by reacting compounds of the Formula IV wherein R1 2 is C 1-12 alkyl with C 1-4 alkylsulphonyl halides, reacting the resulting compounds of Formula A above in which R 2 is C 1-12 alkyl and X is C 1-4 alkylsulphonyloxy with metal halides sodium azide, potassium thiocyanate or potassium thiolalkanoates to give compounds of the above A in which R 2 is C 1-12 alkyl and X is halogen, C 1-4 alkanoylthio, -N 3 or -SCN, and if desired catalytically hydrogenating the compounds in which X is -N 3 to obtain ...

PHARMACEUTICALLY USEFUL PROSTAGLANDIN DERIVATIVES

... 1410854 Prostaglandins SANKYO CO Ltd 24 Aug 1973 [1 Sept 1972] 40176/73 Heading C2C Novel compounds of Formula I in which A=C 4-8 alkylene, R1 = C 4-10 alkyl, R2=H or C 1-6 alkyl and R3=H or C 1-6 alkoxycarbonyl, and pharmaceutically acceptable salts thereof, are prepared by reducing a compound of Formula II in which Z=a protected carbonyl group, with a metal hydride complex reducing agent, to give a compound of Formula III removing the protecting group from the compound of Formula III and, if appropriate, salifying the product obtained. Compounds I in which R2 and R3 are both H can also be prepared by hydrolysis of a compound I in which R2= alkyl and/or R3=alkoxycarbonyl. The corresponding groups can also be removed from compounds III, to give compounds in which R2=R3=H. Starting materials of Formula II and intermediates therefor are prepared as shown in the following reaction scheme Pharmaceutical compositions ...

PROSTANOIC ACID DERIVATIVES

... 1431414 Prostanoic acid derivatives SANKYO CO Ltd 11 April 1974 [19 April 1973] 16159/74 Heading C2C Novel compounds I in which A is C 1-5 alkylene, R1 is C 4-10 alkyl and R2 is H or C 1-6 alkyl, and pharmaceutically acceptable salts thereof, are prepared by oxidizing a compound II in which R3 and R4 are the same or different hydroxyl-protecting groups to give a compound III removing the hydroxyl-protecting groups from compound III, and, if desired, salifying the product obtained. Compounds II and intermediates therefor are prepared as shown in the following reaction scheme in which R6, R7 and R8 are hydroxyl-protecting groups. Pharmaceutical compositions having oxytocic and gastric acid secretion inhibitory activity, for oral or parenteral administration, comprise one of the above novel compounds together with a pharmaceutical diluent or carrier.

CHOLECALCIFEROL DERIVATIVES

SULPHONE INTERMEDIATES FOR THE SYNTHESIS OF VITAMIN A

... 1353858 Sulphones for vitamin A synthesis RHONE-POULENC SA 19 Jan 1972 [20 Jan 1971] 2582/72 Headings C2C and C2V Novel compounds (I) where R is aryl and Y is H or Q being H or a hydrocarbon radical, are made by reacting vinyl-#-ionol either with RSO 2 M (M is an alkali metal) or first with a phosphorus trihalide and then reacting the corresponding halide, e.g. bromide, so obtained with RSO 2 M; the compounds (I) obtained (i.e. Y is H) react with XCH 2 C(Me) : CHCO 2 Q (X is Cl, Br or I) in the presence of base to give (I) wherein Y is -CH 2 C(Me) : CHCO 2 Q and these can be converted into vitamin A acid or esters thereof.

ISOXAZOLYL DERIVATIVES USEFUL AS ODORIFEROUS AND FLAVOURING AGENTS

... 1391735 Perfumes FIRMENICH SA 30 March 1973 [30 March 1972] 15561/73 Heading A5B [Also in Divisions A2 and C2] Compounds of the formula: wherein the carbocyclic ring contains one endocyclic double bond in position 1, 2, 3 or 4, or an exocyclic double bond in position 2, or two conjugated double bonds in positions 1 and 3, the double bonds being represented by the dotted lines, and R1, R2, R3, R4 and R5 are H or alkyl of 1 to 6 carbon atoms may be used in perfume compositions.

CONTINUOUS PHOTOLYTIC PROCESS FOR THE PREPARATION OF VITAMIN D RELATED SUBSTANCES

The present application provides a novel method for generation of a vitamin D2 compound using a continuous flow photoisomerization reactor. A compound represented by formula I: [structure] as further defined herein, is mixed with a solvent and a sensitizer, and is then passed through the continuous flow photoisomerization reactor. If X3 and X4 of formula II is tert-butyldimethylsilyl, then formula II is mixed with a deprotection reagent to obtain the vitamin D2 analog. 2. The method of wherein the sensitizer comprises 9-acetylanthracene.3. The method of wherein the deprotection reagent comprises tetrabutylammonium fluoride.4. The method of wherein the deprotection reagent comprises hydrochloric acid.5. The method of wherein the solvent in step a) is selected from the group consisting of heptane claim 1 , methanol claim 1 , toluene claim 1 , 1 claim 1 ,2-dichloroethane claim 1 , t-butyl methyl ether claim 1 , ethyl acetate claim 1 , and mixtures thereof.6. The method of wherein the solvent is deoxygenated.7. The method of wherein the solvent is deoxygenated by He sparging.8. The method of wherein the concentration of the compound of formula I in the solvent is about 5 mg/mL to about 50 mg/mL.9. The method of wherein the concentration of the compound of formula I in the solvent is at least about 50 mg/mL.10. The method of wherein the second mixture of step c) flows through the continuous flow photoisomerization reactor at a rate of about 2 mL/min to about 22 mL/min.11. The method of wherein the second mixture of step c) flows through the continuous flow photoisomerization reactor at a rate of at least about 22 mL/min.12. The method of wherein the second mixture of step c) flows through the continuous flow photoisomerization reactor at a temperature of between about 10° C. and about 30° C.13. The method of wherein the ratio of the sensitizer to the first mixture in step b) is about 0.4 wt % to about 16 wt %.14. The method of wherein the solvent in step a) comprises ...

2-Methylene-20(21)-Dehydro-19,24,25,26,27-Pentanor-Vitamin D Analogs

This invention discloses 2-methylene-20(21)-dehydro-19,24,25,26,27-pentanor-vitamin D analogs, and specifically 2-methylene-20(21)-dehydro-19,24,25,26,27-pentanor-1α-hydroxyvitamin D, and pharmaceutical uses therefor. This compound exhibits relatively high transcription activity as well as pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also shows lower activity in vivo on bone calcium mobilization and lower in vivo intestinal calcium transport activity as compared to the native hormone 1α,25-dihydroxyvitamin D, and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as secondary hyperparathyroidism and renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity. 2. The compound of wherein Xis hydrogen.3. The compound of wherein Xis hydrogen.4. The compound of wherein Xand Xare both t-butyldimethylsilyl.5. A pharmaceutical composition containing an effective amount of at least one compound as claimed in together with a pharmaceutically acceptable excipient.6. The pharmaceutical composition of wherein said effective amount comprises from about 0.01 μg to about 1000 μg per gram of composition.7. The pharmaceutical composition of wherein said effective amount comprises from about 0.1 μg to about 500 μg per gram of composition.9. A pharmaceutical composition containing an effective amount of 2-methylene-20(21)-dehydro-19 claim 5 ,24 claim 5 ,25 claim 5 ,26 claim 5 ,27-pentanor-1α-hydroxyvitamin Dtogether with a pharmaceutically acceptable excipient.10. The pharmaceutical composition of wherein said effective amount comprises from about 0.01 μg to about 1000 μg per gram of composition.11. The ...

Crystallization of (20R) and (20S) Analogs of 2-Methylene-19-Nor-24-Dimethyl-1alpha,25-Dihydroxyvitamin D3

Disclosed are methods of purifying (20R) and (20S) analogs of 2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin Dto obtain the (20R) and (20S) analogs in crystalline form. The method includes the steps of preparing a solvent of either diethyl ether or a mixture of 2-propanol and hexane, dissolving a product containing the (20R) and (20S) analog to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals. 2. (20S)-2-methylene-19-nor-22-dimethyl-1α ,25-dihydroxyvitamin Din crystalline form.3. A crystalline form of (20S)-2-methylene-19-nor-22-dimethyl-1α ,25-dihydroxyvitamin Dhaving molecular packing arrangement defined by space group P2 and unit cell dimensions a=7.57 Å b=14.79 Å c=14.48 Å α=90° , β=102.2° and γ=90°.4. A three dimensional structure for (20S)-2-methylene-19-nor-22-dimethyl-1α claim 3 ,25-dihydroxyvitamin Das defined by the molecular packing arrangement set forth in .5. A method of purifying (20S)-2-methylene-19-nor-22-dimethyl-1α claim 3 ,25-dihydroxyvitamin D claim 3 , comprising the steps of:(a) preparing a solvent comprising diethyl ether;{'sub': '3', '(b) dissolving a product containing (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin Dto be purified in said solvent;'}{'sub': '3', '(c) cooling said solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin Dcrystals; and'}{'sub': '3', '(d) separating the (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin Dcrystals from the solvent.'}6. The method of including the further step of allowing said solvent and dissolved product to cool to ambient temperature prior to cooling below ambient temperature.7. The method of wherein said solvent comprises 100% diethyl ether claim 5 , by volume.8. The method of wherein the step of separating ...

Crystallization of (20R)-2-Methylene-19-Nor-24-Difluoro-1alpha,25-Dihydroxyvitamin D3

Disclosed are methods of purifying the compound (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin Dto obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals. 2. A crystalline form of (20R)-2-methylene-19-nor-24-difluoro-1α ,25-dihydroxyvitamin Dhaving molecular packing arrangement defined by space group C2 and unit cell dimensions a=23.84 Å b=6.27 Å c=20.71 Å α=90° , β=126.52° and γ=90°.3. A three dimensional structure for (20R-2-methylene-19-nor-24-difluoro-1α claim 2 ,25-dihydroxyvitamin Das defined by the molecular packing arrangement set forth in .4. A method of purifying (20R)-2-methylene-19-nor-24-difluoro-1α claim 2 ,25-dihydroxyvitamin D claim 2 , comprising the steps of:(a) preparing a solvent comprising hexane;{'sub': '3', '(b) adding a product containing (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin Dto be purified to said hexane to form a suspension of the product in the hexane;'}(c) adding 2-propanol dropwise to the suspension to form a mixture of the product in the hexane and 2-propanol;{'sub': '3', '(d) heating the mixture to dissolve the product containing (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin Dto be purified in said mixture;'}{'sub': '3', '(e) cooling said mixture and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin Dcrystals; and'}{'sub': '3', '(f) separating the (20R)-2-methylene-19-nor-24-difluoro-1α,25-dihydroxyvitamin Dcrystals from the solvent.'}5. The method of including the further step of allowing said mixture and dissolved product to cool to ambient temperature prior to cooling below ambient temperature.6. ...

Crystallization of (20R) 19-Nor-24-Difluoro-1alpha,25-Dihydroxyvitamin D3

Disclosed are methods of purifying the compound (20R)-19-nor-24-difluoro-1α,25-dihydroxyvitamin D 3 to obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals.

Crystallization of (20R,22R)-2-Methylene-19-Nor-22-Methyl-1alpha,25-Dihydroxyvitamin D3 and Related Precursors

Disclosed are methods of purifying the compound (20R,22R)-2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin Dto obtain the compound in crystalline form. The methods typically include the steps of dissolving a product containing the compound in a solvent comprising hexane and 2-propanol, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of crystals, and recovering the crystals. Certain diol precursors formed during the synthesis of the compound and its diasteromers also may be obtained in crystalline form using ethyl acetate as a solvent. 2. A crystalline form of (20R ,22R)-2-methylene-19-nor-22-methyl-1α ,25-dihydroxyvitamin Dhaving molecular packing arrangement defined by space group C2 and unit cell dimensions a=27.03 Å b=6.47 Å c=17.41 Å α=90° , β=103.35° and γ=90°.3. A three dimensional structure for (20R claim 2 ,22R)-2-methylene-19-nor-22-methyl-1α claim 2 ,25-dihydroxyvitamin Das defined by the molecular packing arrangement set forth in .4. A method of purifying (20R claim 2 ,22R)-2-methylene-19-nor-22-methyl-1α claim 2 ,25-dihydroxyvitamin D claim 2 , comprising the steps of:(a) preparing a solvent comprising hexane;{'sub': '3', '(b) adding a product containing (20R,22R)-2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin Dto be purified to said hexane to form a suspension of the product in the hexane;'}(c) adding 2-propanol dropwise to the suspension to form a mixture of the product in the hexane and 2-propanol;{'sub': '3', '(d) heating the mixture to dissolve the product containing (20R,22R)-2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin Dto be purified in said mixture;'}{'sub': '3', '(e) cooling said mixture and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of (20R,22R)-2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin Dcrystals; and'}{'sub': '3', '(f) separating the (20R,22R)-2-methylene-19-nor-22-methyl-1α,25- ...

A-Ring Modified 19-Nor-Vitamin D Analogs and Their Uses

Disclosed are 19-nor-vitamin D compounds, and specifically seco-A-2,19-dinor-1,25-dihydroxyvitamin Das well as pharmaceutical uses therefor. These compounds exhibit relatively high activity in vivo, specifically in intestinal tissues, but relatively low VDR binding activity, cell differentiation activity and gene transcription activity. There is thus potential for these compounds to have strong cell selectivity for use as therapeutic agents against some cancers, such as colon cancer or polyps, as well as hyperplastic intestinal disorders, such as Crohn's disease, ulcerative colitis and celiac disease. These compounds also have relatively high intestinal calcium transport activity evidencing potential in the treatment of bone diseases. 2. The compound of wherein X is hydrogen.4. The compound of wherein X is hydrogen.5. A pharmaceutical composition containing an effective amount of at least one compound as claimed in together with a pharmaceutically acceptable excipient.6. The pharmaceutical composition of wherein said effective amount composes from about 0.01 μg to about 1000 μg per gram of composition.7. The pharmaceutical composition of wherein said effective amount comprises from about 0.1 μg to about 500 μg per gram of composition.9. A pharmaceutical composition containing an effective amount of seco-A-2 claim 5 ,19-dinor-1 claim 5 ,25-dihydroxyvitamin Dtogether with a pharmaceutically acceptable excipient.10. The pharmaceutical composition of wherein said effective amount comprises from about 0.01 μg to about 1000 μg per gram of composition.11. The pharmaceutical composition of wherein said effective amount comprises from about 0.1 μg to about 500 μg per gram of composition.13. The method of wherein the vitamin D analog is administered orally.14. The method of wherein the vitamin D analog is administered parenterally.15. The method of wherein the vitamin D analog is administered transdermally.16. The method of wherein the vitamin D analog is administered ...

2-METHYLENE-19,23,24-TRINOR-1ALPHA-HYDROXYVITAMIN D3

Compounds of Formula I are provided where Rand Rare independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions. 2. The compound of claim 1 , wherein Rand Rare both hydroxy protecting groups.3. The compound of claim 2 , wherein Rand Rare both t-butyldimethylsilyl groups.9. A pharmaceutical composition comprising an effective amount of the compound of and a pharmaceutically acceptable carrier.10. The pharmaceutical composition of claim 9 , wherein the effective amount comprises from about 0.01 μg to about 1 mg of the compound per gram of the composition.11. The pharmaceutical composition of claim 9 , wherein the effective amount comprises from about 0.1 μg to about 500 μg of the compound per gram of the composition.12. A method of preventing or treating a biological condition comprising administering an effective amount of the compound of or a pharmaceutical composition comprising an effective amount of the compound of to a subject claim 9 , wherein the biological condition is selected from psoriasis; leukemia; colon cancer; breast cancer; prostate cancer; multiple sclerosis; lupus; diabetes mellitus; host versus graft reaction; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis claim 9 , asthma claim 9 , or inflammatory bowel diseases; a skin condition selected from wrinkles claim 9 , lack of adequate skin firmness claim 9 , lack of adequate dermal hydration claim 9 , or insufficient sebum secretion; or renal osteodystrophy.13. The method of claim 12 , wherein the biological condition is psoriasis.14. The method of claim 12 , wherein the biological condition is renal osteodystrophy.15. The method of claim 12 , wherein the compound or the pharmaceutical composition is administered orally.16. The method of claim 12 , wherein the compound or the pharmaceutical composition is administered parentally.17. ...

Novel Vitamin D Receptor Modulators with Partial Agonist Activity

The present invention provides a compound which functions as a selective vitamin D receptor modulator and has action-selectivity or tissue-selectivity such that it does not induce hypercalcemia but causes other effects. There is provided a compound represented by formula (I), a solvate thereof or a prodrug thereof. 2. The compound claim 1 , solvate thereof or prodrug thereof according to claim 1 , wherein the compound represented by the formula (I) is selected from the group consisting of (25S)-25-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-23 claim 1 ,23 claim 1 ,24 claim 1 ,24-tetradehydro-19 claim 1 ,26 claim 1 ,27-trinorvitamin D claim 1 , (25R)-25-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-23 claim 1 ,23 claim 1 ,24 claim 1 ,24-tetradehydro-19 claim 1 ,26 claim 1 ,27-trinorvitamin D claim 1 , (25R)-26-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-23 claim 1 ,23 claim 1 ,24 claim 1 ,24-tetradehydro-19 claim 1 ,27-dinorvitamin D claim 1 , (25S)-26-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-23 claim 1 ,23 claim 1 ,24 claim 1 ,24-tetradehydro-19 claim 1 ,27-dinorvitamin D claim 1 , (25R)-25-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-20 claim 1 ,20 claim 1 ,22 claim 1 ,22 claim 1 ,23 claim 1 ,23 claim 1 ,24 claim 1 ,24-octadehydro-19 claim 1 ,21 claim 1 ,26 claim 1 ,27-tetranorvitamin D claim 1 , (25S)-25-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-20 claim 1 ,20 claim 1 ,22 claim 1 ,22 claim 1 ,23 claim 1 ,23 claim 1 ,24 claim 1 ,24-octadehydro-19 claim 1 ,21 claim 1 ,26 claim 1 ,27-tetranorvitamin D claim 1 , (25R)-25-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-23 claim 1 ,23 claim 1 ,24 claim 1 ,24-tetradehydro-19 claim 1 ,27-dinorvitamin Dand (25S)-25-(1-Adamantyl)-1α claim 1 ,25-dihydroxy-2-methylene-23 claim 1 ,23 claim 1 ,24 claim 1 ,24-tetradehydro-19 claim 1 ,27-dinorvitamin D.3. A composition comprising the compound claim 1 , solvate thereof or prodrug thereof according to .4. The composition according to ...

CRYSTALLINE FORM OF MAXACALCITOL

The present invention relates to maxacalcitol hydrate, a new crystalline form of maxacalcitol, with superior technical properties e.g. in the manufacture of crystal suspension formulations, and with superior stability properties. 1. A crystalline form of maxacalcitol , which is maxacalcitol hydrate.2. The crystalline form of claim 1 , characterized by a X-ray powder diffraction (XRD) pattern comprising distinctive peaks at 2 theta values of approximately 5.8 claim 1 , 6.3 claim 1 , 12.0 claim 1 , 13.1 claim 1 , 13.5 claim 1 , 13.9 claim 1 , 14.2 claim 1 , 14.5 claim 1 , 14.9 claim 1 , 15.3 claim 1 , 16.0 claim 1 , 16.2 claim 1 , 17.0 claim 1 , 17.9 claim 1 , 18.3 claim 1 , 19.3 claim 1 , 23.5 claim 1 , 24.0 claim 1 , 24.3 claim 1 , 25.4 and 26.2 degree±0.2 degrees 2 theta.3. The crystalline form of claim 1 , characterized by a weight loss of about 4.5% at 120° C. for 240 minutes as measured by thermogravimetric analysis (TGA).4. The crystalline form of claim 1 , characterized by a water content of about 4.2% by weight as measured by Karl-Fischer method.5. The crystalline form of claim 1 , characterized by a melting point of about 86° C. as measured by differential scanning calorimetry (DSC) spectrum.6. The crystalline form of claim 1 , which is more stable to storage than anhydrous form claim 1 , showing no degradation under an inert gas atmosphere at 25° C. for at least 32 days.7. A process for preparing a crystalline form of maxacalcitol hydrate comprising:(a) dissolving a crystalline or non-crystalline maxacalcitol in a polar organic solvent to form a first solution;(b) combining the first solution with water to form a second solution;(c) cooling the second solution to form a crystalline precipitate; and(d) isolating the crystalline precipitate from the second solution to obtain the crystalline form of maxacalcitol hydrate.8. The process of claim 7 , wherein the crystalline form of maxacalcitol hydrate is characterized by a powder X-ray diffraction (XRD) pattern ...

COMPOSITIONS RELATING TO VITAMIN D

Compounds include compounds of the Formula I, namely, (R)-(L)-Z wherein R, L, p and q are as defined herein. 819.-. (canceled) The subject application claims benefit under 35 USC § 119(e) of U.S. provisional Application No. 62/018,008, filed Jun. 27, 2014. The entire contents of the above-referenced patent application are hereby expressly incorporated herein by reference.This invention relates to compositions, methods and kits for determining the presence and/or amount of vitamin D analytes, including vitamin D isomers, and metabolites thereof in a sample suspected of containing the same.The term “vitamin D” refers to a group of fat-soluble secosteroids. In humans, vitamin D is unique because it can be ingested as cholecalciferol (vitamin D) or ergocalciferol (vitamin D) and because the body can also synthesize it (from cholesterol) when sun exposure is adequate. Because of this latter property, vitamin D is considered by some to be a non-essential dietary vitamin although most consider it an essential nutrient. Vitamin D has an important physiological role in the positive regulation of calcium ion homeostasis. Vitamin Dis the form of the vitamin synthesized by animals. It is also a common supplement added to milk products and certain food products as is vitamin D.Both dietary and intrinsically synthesized vitamin Dmust undergo metabolic activation to generate bioactive metabolites. In humans, the initial step of vitamin Dactivation occurs primarily in the liver and involves hydroxylation to form the intermediate metabolite 25-hydroxycholecalciferol. Calcidiol is the major form of Vitamin Din the circulatory system. Vitamin Dalso undergoes similar metabolic activation to 25-hydroxyvitamin D. Collectively these compounds are called 25-hydroxyvitamin D (abbreviated 25(OH)D) and they are the major metabolites that are measured in serum to determine vitamin D status; 25(OH)D and its epimers are both pre-hormones that need to be converted into 1,25(OH)D to exert ...

Release reagent for vitamin d compounds

A reagent composition for releasing vitamin D compounds bound to vitamin D-binding protein and an in vitro method for the detection of a vitamin D compound in which the vitamin D compound is released from vitamin D-binding protein by the use of this reagent composition as well as the reagent mixture obtained in this manner. Also disclosed is the use of the reagent compositions to release vitamin D compounds as well as a kit for detecting a vitamin D compound.

RELEASE REAGENT FOR VITAMIN D COMPOUNDS

A reagent composition for releasing vitamin D compounds bound to vitamin D-binding protein and an in vitro method for the detection of a vitamin D compound in which the vitamin D compound is released from vitamin D-binding protein by the use of this reagent composition as well as the reagent mixture obtained in this manner. Also disclosed is the use of the reagent compositions to release vitamin D compounds as well as a kit for detecting a vitamin D compound. 1. An in vitro method for releasing a vitamin D compound from vitamin D-binding protein comprising the step of:a) providing a sample to be investigated and [{'sub': '3', 'sup': '−', 'i) a reagent containing one or more hydrogen carbonate salt(s) and one or more carbonate ester(s), wherein the total concentration of hydrogen carbonate ions (HCO) released from the hydrogen carbonate salt(s) and/or the carbonate esters(s) is 0.1 M to 2.0 M,'}, 'ii) a reducing agent, and', 'iii) an alkalinising agent,', 'thereby releasing the vitamin D compound from vitamin D-binding protein., 'b) mixing the sample from step (a) with'}2. The method according to claim 1 , wherein the reagent according to step (i) is soluble in an aqueous solution under the appropriate conditions for releasing a vitamin D compound from vitamin D-binding protein.3. The method according to claim 1 , wherein the carbon ester(s) are a cylic or non-cyclic carbonate ester or a hydroxylated or halogenized derivative thereof claim 1 , respectively.4. The method according claim 1 , wherein the sample is a liquid sample.5. The method according to claim 1 , wherein the sample is blood claim 1 , serum or plasma.6. An in vitro method for measuring a vitamin D compound comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) releasing a vitamin D compound from vitamin D-binding protein according to the method of ; and'}b) measuring the vitamin D compound released in step (a).7. The method according to claim 6 , wherein the vitamin D compound ...

COMPOSITIONS AND METHODS FOR DETECTING VITAMIN D

Compounds include carbamate derivatives of vitamin D including vitamin Dand vitamin D. The compounds are useful in methods and kits for determining the presence and/or amount of vitamin D including vitamin D analogs and metabolites thereof in a sample suspected of containing the same. 2. The compound according to wherein Z is a branched alkyl group or a branched alkenyl group having 4 to 10 carbon atoms wherein a terminal carbon atom of the branched alkyl group or the branched alkenyl group comprises a hydroxyl.3. The compound according to wherein Ris a member of a signal producing system selected from the group consisting of fluorescent compounds claim 1 , chemiluminescent compounds claim 1 , sensitizers claim 1 , enzymes and radiolabels.5. The compound according to wherein Ris a member of a signal producing system selected from the group consisting of fluorescent compounds claim 4 , chemiluminescent compounds claim 4 , sensitizers claim 4 , enzymes and radiolabels.6. The compound according to wherein Ris a member of a signal producing system that comprises a particle.7. The compound according to wherein the particle is selected from the group consisting of fluorescent particles claim 6 , chemiluminescent particles claim 6 , sensitizer particles and magnetic particles.8. A method of determining in a sample the presence and/or amount of vitamin D claim 6 , the method comprising: (i) the sample,', {'claim-ref': {'@idref': 'CLM-00005', 'claim 5'}, '(ii) the compound according to , and'}, '(iii) a specific binding member for vitamin D;, '(a) providing in combination in a medium{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) subjecting the combination to conditions for binding of the compound of to the specific binding member to form a complex, and'}(c) measuring the amount of the complex, the amount of the complex being related to the presence and/or amount of vitamin D in the sample.10. The compound according to wherein L is a chemiluminescent particle.12. The ...

AMELIORATION OF INTESTINAL FIBROSIS AND TREATMENT OF CROHN'S DISEASE

Methods of treating patients with inflammatory bowel disease, intestinal fibrosis, or Crohn's disease involve administering a therapeutic amount of CARD-024 or related compound. 2. The method according to claim 1 , wherein the compound of Formula (I) comprises CARD-024.3. The method according to claim 1 , comprising administering a composition comprising a compound of Formula (I) and a pharmaceutically acceptable carrier.4. The method according to claim 3 , wherein the composition comprises a tablet.5. The method according to claim 1 , wherein the subject is diagnosed with Crohn's disease.7. The method according to claim 6 , wherein the compound has a single bond between carbon 22 and carbon 23.8. The method according to claim 7 , wherein carbon 24 is in the S configuration.9. The method according to claim 7 , wherein carbon 24 is in the R configuration.10. The method according to claim 6 , wherein the compound has a double bond in the E configuration between carbon 22 and carbon 23.11. The method according to claim 10 , wherein carbon 24 is in the S configuration.12. The method according to claim 10 , wherein carbon 24 is in the R configuration.13. The method according to claim 6 , wherein the subject is diagnosed with inflammatory bowel disease.14. The method according to claim 6 , wherein the subject is diagnosed with Crohn's disease.15. The method according to claim 6 , wherein the subject is a human subject.17. The method according to claim 16 , wherein the composition comprises CARD-024.18. The method according to claim 16 , wherein the asymmetric carbon 24 is in the R claim 16 ,S configuration.19. The method according to claim 16 , wherein the asymmetric carbon 24 is in the R configuration.20. The method according to claim 16 , wherein the asymmetric carbon 24 is in the S configuration.21. The method according to claim 16 , comprising administering 5 mcg to 500 mcg of the compound.22. The method according to claim 16 , comprising administering 1 to 4 doses ...

COMPOSITIONS RELATING TO VITAMIN D

This invention relates to compositions, methods and kits for determining the presence and/or amount of vitamin D analytes, including vitamin D isomers, and metabolites thereof in a sample suspected of containing the same. Compounds include compounds of the Formula I, namely, (R)-(L)-Z wherein R, L, p and q are as defined herein. These compounds are capable of binding specifically to corresponding antibodies. Compounds and antibodies in accordance with the principles described herein can have therapeutic activity. These compounds may be administered in therapeutically effective amount, which is an amount to provide treatment of a particular disease state associated with vitamin D. Administration of the examples of compounds in accordance with the principles described herein can be by means of any of the accepted modes of administration for agents that serve similar utilities. 9. The compound according to wherein s′ is 1.10. The compound according to wherein Ris H.11. The compound according to wherein r′ is 2.15. The compound according to wherein Z′ is a poly(amino acid) immunogenic carrier selected from the group consisting of bovine serum albumin claim 8 , bovine gamma globulin claim 8 , keyhole limpet hemocyanin claim 8 , and egg ovalbumin.16. The compound according to wherein Z′ is a poly(amino acid) label that is an enzyme or a non-poly(amino acid) label moiety selected from the group consisting of polynucleotides coding for a catalyst claim 8 , promoters claim 8 , dyes claim 8 , fluorescent molecules claim 8 , chemiluminescent molecules claim 8 , coenzymes claim 8 , enzyme substrates claim 8 , radioactive groups claim 8 , small organic molecules claim 8 , amplifiable polynucleotide sequences claim 8 , and particles.18. The compound according to wherein Z″ is OH.19. A pharmaceutical composition comprising an effective amount of the compound according to . The subject application claims benefit under 35 USC §119(e) of U.S. provisional Application No. 62/018,008, ...

LOW CALCEMIC, HIGHLY ANTIPROLIFERATIVE, ANALOGS OF CALCITRIOL

The disclosure provides compounds, compositions and methods using these compounds and compositions to stimulate the differentiation of cells and inhibit excessive cell proliferation of certain cells, including cancer cells and skin cells, which may be useful in the treatment of diseases characterized by abnormal cell proliferation and/or cell differentiation such as leukemia, myelofibrosis and psoriasis without the well known effect on calcium metabolism, which gives rise to hypercalcemia. 29-. (canceled)10. A pharmaceutical composition claim 1 , comprising an effective amount of one or more of the compounds of formula I of claim 1 , together with one or more pharmaceutically acceptable carriers claim 1 , optionally in topical claim 1 , oral or injectable form.11. The compound of formula I of or the pharmaceutical composition of for use in treating patients suffering from disorders characterized by abnormal cell-proliferation and/or cell-differentiation.12. The compound of formula I of or the pharmaceutical composition of for use in treating patients suffering from secondary hyperparathyroidism.14. The method of claim 13 , wherein the base is an alkali metal or organolithium compound; and the protecting group is a silyl protecting group.15. The method of claim 14 , wherein the alkali metal is sodium hydride or lithium hydride; the organolithium compound is n-butyl lithium claim 14 , sec-butyl lithium or tert-butyl lithium claim 14 , and the silyl protecting group is tert-butyldimethylsilane. This application is a continuation of U.S. application Ser. No. 12/596,252, filed on Jan. 28, 2010, now pending, which is a 35 USC §371 National Stage application of International Application No. PCT/US2008/060885 filed Apr. 18, 2008, now pending; which claims the benefit under 35 USC §119(e) to U.S. Application Ser. No. 60/923,998 filed Apr. 18, 2007, now abandoned. The disclosure of each of the prior applications is considered part of and is incorporated by reference in the ...

Enzymatic Production or Chemical Synthesis and Uses for 5,7-Dienes and UVB Conversion Products Thereof

Provided herein are steroidal compounds that are androsta-5,7-dienes or a pregna-5,7-dienes and ultraviolet B (UVB) conversion products thereof which includes pharmaceutical compositions of the steroidal compounds as shown in Tables 1 and 2. Also provided is a method for producing hydroxylated metabolites of cholecalciferol or ergocalciferol via the P450scc (CYP11A1) or CYP27B1 enzyme systems where the hydroxylase has an activity to hydroxylate position C20 of a secosteroid or its 5,7-dieneal precursor and the hydroxylated metabolites so produced. In addition, a method for inhibiting proliferation of either a normally or abnormally proliferating cell by contacting the cell with any of the compounds described herein. A related method is provided of treating a condition associated with the proliferating cell such as a cancer, a skin disorder, a defect in cell differentiation, cosmetic, prophylaxsis, or healthy cell maintenance. 1. A method for inhibiting proliferation of a cell , comprising:contacting the cell with one or more steroidal compounds identified in one or both of Tables 1A or 2A.2. The method of claim 1 , wherein the one or more steroidal compounds of Tables 1A or 2A are derivatized further to comprise an ether or an ester substituent or are one or more of an androsta-5 claim 1 ,7-diene or a pregna-5 claim 1 ,7-diene claim 1 , said compound converted in vivo to a corresponding ultraviolet B conversion compound after contacting the cell.3. The method of claim 1 , wherein the cell is a normally proliferating or abnormally proliferating adrenal cell claim 1 , gonadal cell claim 1 , keratinocyte or melanocyte claim 1 , pancreatic cell claim 1 , cell from the gastrointestinal tract claim 1 , prostate cell claim 1 , breast cell claim 1 , lung cell claim 1 , immune cell claim 1 , hematologic cell claim 1 , kidney cell claim 1 , brain cell claim 1 , cell of neural crest origin claim 1 , skin cell claim 1 , mesenchymal cell claim 1 , leukemia cell claim 1 , ...

(22E)-2-METHYLENE-22-DEHYDRO-1ALPHA,24,25-TRIHYDROXY-19-NOR-VITAMIN D3 ANALOGS

Disclosed are (22E)-2-methylene-22-dehydro-1,24,25-trihydroxy-19-nor-vitamin Dcompounds, their biological activities, and various pharmaceutical uses for these compounds. Particularly disclosed are (22E)-(24R)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin Dand (22E)-(24S)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D, their biological activities, and various pharmaceutical uses for these compounds. 2. The compound of claim 1 , wherein Xand Xare t-butyldimethylsilyl.3. The compound of claim 1 , wherein Xand Xare hydrogen.4. The compound of claim 1 , wherein Xand Xare triethylsilyl.5. The compound of claim 1 , wherein Xand Xare hydrogen.6. The compound of claim 1 , wherein X claim 1 , X claim 1 , X claim 1 , and Xare hydrogen.9. A pharmaceutical composition containing an effective amount of the compound of and a pharmaceutically acceptable excipient.10. A pharmaceutical composition containing an effective amount of the compound of and a pharmaceutically acceptable excipient.11. A pharmaceutical composition containing an effective amount of the compound of and a pharmaceutically acceptable excipient.12. A method of treating or preventing a bone disease or disorder in a patient in need thereof claim 1 , the method comprising administering to the patient an effective amount of the compound of .13. A method of treating or preventing a bone disease or disorder in a patient in need thereof claim 7 , the method comprising administering to the patient an effective amount of the compound of .14. A method of treating or preventing a bone disease or disorder in a patient in need thereof claim 8 , the method comprising administering to the patient an effective amount of the compound of .15. A method for increasing bone strength in a patient in need thereof claim 1 , the method comprising administering to the patient an effective amount of the compound of .16. A method for increasing bone strength in a patient in need thereof claim 7 , the method ...

23-YNE-VITAMIN D3 DERIVATIVE

To provide a novel vitamin Dderivative useful as a therapeutic agent for osteoporosis. 113-. (canceled) The present invention relates to a vitamin Dderivative or a medicinally acceptable solvate thereof which is useful as a drug, to a therapeutic agent using the same, to a pharmaceutical composition comprising the same, and to a production intermediate thereof. More specifically, the present invention relates to a 23-yne-vitamin Dderivative or a medicinally acceptable solvate thereof, to a pharmaceutical composition comprising the same, to a therapeutic agent comprising the same as an active ingredient for osteoporosis, malignant tumor psoriasis, hyperparathyroidism, inflammatory airway disease, rheumatoid arthritis, diabetes mellitus, hypertension, alopecia, acne, or dermatitis, and to a production intermediate thereof.Activated vitamin Dderivatives regulate bone remodeling, consisting of bone formation and bone resorption, and show bone a density-increasing effect. Thus, they are being used as a valuable therapeutic agent for osteoporosis. However, these active vitamin Dderivatives, 1α,25-dihydroxyvitamin Dfor example, do not necessarily show a satisfactory amount of increase in the bone mineral density. When the dose is increased in order to increase the bone mineral density, there occurs an increase in a serum calcium value rather than further increase in the bone mineral density, causing elevation of the serum calcium value by 1 mg/dL or more, a value considered as one of the criteria for clinical undesirability. Thus, there are occasional cases where a sufficient bone mineral density-increasing effect is not obtained (International Publication No. WO 01/62723). Therefore, there is an earnest desire for an activated vitamin Dderivative which exhibits a strong bone mineral density-increasing effect without increasing the serum calcium value. Heretofore, there have been synthesized a multitude of vitamin Dderivatives in an effort to obtain such a derivative, but ...

Improved photochemical synthesis of vitamin d3 using sensitizers

The present invention discloses an improved photochemical synthesis of vitamin D3 from 7-dehydrocholesterol alone or in combination with sterol precursors in presence of the photosensitizer of Formula I in high yield and with reduced levels of impurities.

RELEASE REAGENT FOR VITAMIN D COMPOUNDS

A reagent composition for releasing vitamin D compounds bound to vitamin D-binding protein and an in vitro method for the detection of a vitamin D compound in which the vitamin D compound is released from vitamin D-binding protein by the use of this reagent composition as well as the reagent mixture obtained in this manner. Also disclosed is the use of the reagent compositions to release vitamin D compounds as well as a kit for detecting a vitamin D compound. 1. An in vitro method for releasing a vitamin D compound from vitamin D-binding protein comprising the step of:a) providing a sample to be investigated and [{'sub': 3', '3', '3, 'sup': −', '−', '−, 'i) a reagent containing one hydrogen carbonate salt and a substance capable of releasing hydrogen carbonate ions (HCO) upon hydrolysis, wherein the total concentration of hydrogen carbonate ions (HCO) from the hydrogen carbonate salt and released from the substance capable of releasing hydrogen carbonate ions (HCO) is 0.1 M to 2.0 M,'}, 'ii) a reducing agent, and', 'iii) an alkalinising agent,', 'thereby releasing the vitamin D compound from vitamin D-binding protein., 'b) mixing the sample from step (a) with'}2. The method according to claim 1 , wherein the reagent according to step (i) is soluble in an aqueous solution under the appropriate conditions for releasing a vitamin D compound from vitamin D-binding protein.3. The method according to claim 1 , wherein the substance capable of releasing hydrogen carbonate ions (HCO) upon hydrolysis is a cylic or non-cyclic carbonate ester or a hydroxylated or halogenized derivative thereof claim 1 , respectively.4. The method according claim 1 , wherein the sample is a liquid sample.5. The method according to claim 1 , wherein the sample is blood claim 1 , serum or plasma.6. An in vitro method for measuring a vitamin D compound comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) releasing a vitamin D compound from vitamin D-binding protein ...

POLYENE COMPOUND, PREPARATION METHOD AND USE THEREOF

Disclosed are a polyene compound, preparation method and use thereof. Provided in the present invention is the preparation method of a polyene compound I, comprising the following steps: under an action of a base and in an organic solvent, conducting a Witting reaction on a compound II and a compound III to obtain the polyene compound I. By the preparation method in the present invention, a coupling reaction results in good product purity without producing an obvious by-product and involves no heavy metal, thus facilitating a control over product quality and costs, having a simple operation and mild reaction condition, enabling high reaction conversion, a high yield, few by-products, high resultant product purity, low production costs and simple post-processing, and being suitable for industrial production. 3. The preparation method of the polyene compound I according to claim 2 , wherein:in the preparation method of the polyene compound I, the organic solvent is an ether solvent;or,in the preparation method of the polyene compound I, the volume-to-mass ratio of the organic solvent to the compound II is 5 mL/g-50 mL/g;or,in the preparation method of the polyene compound I, the base is an organic base;or,in the preparation method of the polyene compound I, the molar ratio of the base to the compound II is 0.8-1.5;or,in the preparation method of the polyene compound I, the molar ratio of the compound III to the compound II is 0.8-1.5;or,in the preparation method of the polyene compound I, the temperature of the Wittig-Horner reaction is −80° C. to −50° C.;or,in the preparation method of the polyene compound I, the reaction time of the Wittig-Horner reaction is 0.5 h-5.0 h;or,the preparation method of the polyene compound I is carried out in the presence of an inert gas;or,the preparation method of the polyene compound I is carried out under anhydrous conditions;or,the preparation method of the polyene compound I comprises step 1 or step 2,step 1: adding a base into a ...

SYNTHETIC INTERMEDIATE OF MAXACALCITOL, PREPARATION METHOD THEREFOR AND USE THEREOF

The present invention provides a new method for synthesizing maxacalcitol and an intermediate thereof. According to the method, the maxacalcitol is creatively synthesized through the steps of: taking vitamin D2 as an initial raw material, obtaining a compound represented by formula II, oxidizing, chirally reducing, grafting with a side chain, introducing a hydroxyl group on the C-1 position, and photochemically overturning. 2. The compound according to claim 1 , wherein the hydroxyl protection group is selected from a silicon ether protection group.3. The compound according to claim 2 , wherein the hydroxyl protection group is selected from a t-butyldimethylsilyl claim 2 , a trimethylsilyl claim 2 , a triethylsilyl claim 2 , a t-butyldiphenylsilyl or a triisoprolylsilyl.5. The preparation method according to claim 4 , wherein the oxidizing agent is selected from oxygen; the catalyst is selected from a copper catalyst.6. The preparation method according to claim 4 , wherein the catalyst is 2 claim 4 ,2-bipyridine copper complex.9. The preparation method according to claim 8 , wherein the chiral auxiliary reagent is selected from (R)-2-methyl-CBS-oxazaborolidine claim 8 , (R)-2-ethyl-CBS-oxazaborolidine or (R)-2-isopropyl-CBS-oxazaborolidine.10. The preparation method according to claim 8 , wherein the borane is selected from BH claim 8 , borane-tetrahydrofuran complex claim 8 , borane-triethylamine complex claim 8 , borane-ethyl ether complex claim 8 , borane-methyl sulfide complex or borane-N claim 8 ,N-diethylaniline complex.11. The preparation method according to claim 8 , wherein a molar ratio of the compound III claim 8 , the chiral auxiliary reagent and the borane is 1:(0.1-1):(1-2); the reaction temperature is −60° C. to 0° C.12. The preparation method according to claim 11 , wherein the molar ratio of the compound III claim 11 , the chiral auxiliary reagent and the borane is 1:0.6:1; the reaction temperature is −20° C.19. A use of the compound III according ...

PROCESS FOR PRODUCING 7-DEHYDROCHOLESTEROL AND VITAMIN D3

According to the present invention, there can be provided A process for producing 7-dehydrocholesterol (hereinafter, “7DHC”), comprising culturing, in a medium, a 7DHC-producing microorganism in which the 7DHC reducing activity is reduced or lost as compared to a parent strain through deletion, substitution, or addition of at least one base in a gene which is present in the chromosomal DNA of the parent strain and encodes a protein having 7DHC reducing activity, and the microorganism produces 7DHC, allowing 7DHC to be produced and accumulated in the culture, and collecting the 7DHC from the culture; and a process for producing vitamin D3, comprising irradiating, with ultraviolet light, the 7DHC produced by the production process. 1. A process for producing 7-dehydrocholesterol (hereinafter , “7DHC”) , comprising:{'i': 'Labyrinthulea', 'culturing, in a medium, a 7DHC-producing microorganism in which the 7DHC reducing activity is reduced or lost as compared to a parent strain through deletion, substitution, or addition of at least one base in a gene which is present in the chromosomal DNA of the parent strain and encodes a protein having 7DHC reducing activity, and the microorganism produces 7DHC;'}allowing 7DHC to be produced and accumulated in the culture; andcollecting the 7DHC from the culture.2. The production process according to claim 1 , wherein the gene encoding a protein having 7DHC reducing activity is a gene having any of the following DNAs [1] to [6]:[1] a DNA encoding a protein having the amino acid sequence represented by SEQ ID NO: 2;[2] a DNA encoding a mutated protein consisting of the amino acid sequence of SEQ ID NO: 2 with deletion, substitution, or addition of 1 to 20 amino acids, and having 7DHC reducing activity;[3] a DNA encoding a homologous protein having at least 95% identity with the amino acid sequence represented by SEQ ID NO: 2, and having 7DHC reducing activity;[4] a DNA having the base sequence represented by SEQ ID NO: 1;[5] a DNA ...

Versatile and Functionalised Intermediates for the Synthesis of Vitamin D and Novel Vitamin D Derivatives

Novel intermediates for the complete synthesis of vitamin D are provided that allow a great versatility of functional groups in the final vitamin derivatives. Vitamin derivatives that are epimeric in position 3 and vitamin derivatives with a wide range of functionalities in position 18, including compounds with isotopic labelling are provided. 2. A compound of formula (I) claim 1 , according to claim 1 , where Ris hydrogen.7. A compound of formula (I) claim 1 , according to claim 1 , selected from the group consisting of:3-epi-25-tert-butyl ester-1α-hydroxyvitam in D33-epi-16-en-25-tert-butylester-1α-hydroxyvitamin D33,20-diepi-25- tert-butylester-1α-hydroxyvitamin D33,20-diepi-16-en-25- tert-butylester-1α-hydroxyvitamin D33-epi-25- tert-butylester-vitamin D33-epi-16-en-25-tert-butylester-vitamin D33,20-diepi-25- tert-butylester-vitamin D33,20-diepi-16-en-25- tert-butylester-vitamin D318-trideutero-3-epi-25-tert-butylester-1α-hydroxyvitamin D318-trideutero-3-epi-16-en-25-tert-butylester-1α-hydroxyvitamin D318-trideutero-3,20-diepi-25- tert-butylester-1α-hydroxyvitamin D318-trideutero 3,20-diepi-16-en-25-tert-butylester-1α-hydroxyvitamin D318-trideutero-25- tert-butylester-1α-hydroxyvitamin D318-trideutero-16-en-25-tert-butylester-1α-hydroxyvitamin D318-trideutero-20-epi-25-tert-butylester-1α-hydroxyvitamin D318-trideutero-20-epi-16-en-25- tert-butylester-1α-hydroxyvitamin D318-trideutero-3-epi-25-tert-butylester-vitamin D318-trideutero-3-epi-16-en-25-tert-butylester-vitamin D318-trideutero-3,20-diepi-25-tert-butylester-vitamin D318-trideutero-3,20-diepi-16-en-25-tert-butylester-vitamin D318-trideutero-25- tert-butylester-vitamin D318-trideutero-16-en-25-tert-butylester-vitamin D318-trideutero-20-epi-25-tert-butylester-vitamin D3 and18-trideutero-20-epi-16-en-25- tert-butylester-vitamin D3.17. A process for the preparation of compounds of formula (XVI) according to claim 16 , which comprises:a) protecting the hydroxyl group of oct-1-en-7-yn-3-ol,b) treating the ...

Unnatural Analogues of Calcitriol and Uses Thereof

Disclosed is a compound of Formula (I) 2. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein X is oxygen.3. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein X is sulfur.4. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein Ris ═CH.5. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein Ris cyclopropyl.6. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein Rand Rare each H.7. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein a is 0 and Ris selected from one or more of (i) optionally substituted Calkyl; and (ii) Calkyl or hydroxy Calkyl claim 1 , the optional substituents as defined above.8. The compound or a pharmaceutically acceptable salt thereof of claim 7 , wherein Ris isopentyl claim 7 , 3-hydroxy-3-methylbutyl claim 7 , 2 claim 7 ,3-dimethylbutyl claim 7 , 2 claim 7 ,3-dimethyl-3-hydroxybutyl claim 7 , 3-ethylpentyl claim 7 , 3-ethyl-3-hydroxypentyl claim 7 , 4-ethylhexyl claim 7 , or 4-ethyl-4-hydroxyhexyl.9. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein a is 1 to 5 and Ris selected from one or more of (i) optionally substituted aryl; and (ii) aryl substituted with a Calkyl or a Chydroxyalkyl claim 1 , the optional substituents as defined above.10. The compound or a pharmaceutically acceptable salt thereof of claim 9 , wherein Ris aryl substituted with isopropyl or 2-hydroxypropan-2-yl.11. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein a is 1.12. The compound or a pharmaceutically acceptable salt thereof of wherein the compound is selected from the group consisting of(1R, 3R)-5-((E)-2-((3αS, 7αS)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7α-methyldihydro-1H-inden-4(2H, 5H, 6H, 7H, 7αH)-ylidene)ethylidene)-2-methylenecyclohexane-1,3-diol (Vida-5);(4R,8R)-6-((E)-2-((1S,7S)-1-((R)-1-(3-ethyl-3-hydroxypentyloxy)ethyl)-7 ...

METHODS FOR IMPROVED PRODUCTION OF VITAMINS D2 AND D3

It is an object of the present invention to provide methods for producing vitamin D that gives improved yields and reduced side product contamination. In various aspects, these methods provide for production of vitamin-Dusing ergosterol as provitamin Dor a dihydroxy derivative thereof as a starting material, or production of vitamin-Dusing 7-dehydrocholesterol as provitamin Dor a dihydroxy derivative thereof as the starting material. The methods described herein comprise irradiating the starting material in a solution including an organic or inorganic base with light in the wavelength range 245-360 nanometers (nm) to obtain a product containing pre-vitamin-Dor pre-vitamin-D, and heating the product to convert the resulting pre-vitamin-Dor pre-vitamin-Dto vitamin Dor vitamin D. In various embodiments, these methods further comprise recovering vitamin Dor vitamin Dfrom this reaction as a purified product. 1. A method of production of vitamin-Dusing ergosterol or a dihydroxy derivative thereof as a starting material , or production of vitamin-Dusing 7-dehydrocholesterol or a dihydroxy derivative thereof as the starting material , comprising:{'sub': 2', '3, '(a) irradiating the starting material in a solution comprising an organic or inorganic base with ultraviolet light to obtain a product containing pre-vitamin-Dor pre-vitamin-D, and'}{'sub': 2', '3', '2', '3, '(b) heating the product to convert the pre-vitamin-Dor pre-vitamin-Dto vitamin Dor vitamin D.'}2. A method according to claim 1 , wherein the ultraviolet light comprises light of between about 245 and about 360 nanometers.3. A method according to or claim 1 , wherein the base is an organic base.4. A method according to one of - claim 1 , wherein the base is selected from the group consisting of an aliphatic amine or an aromatic amine.5. A method according to claim 4 , wherein the base is selected from the group consisting of methylamine claim 4 , ethylamine claim 4 , triethylamine claim 4 , isopropylamine claim ...

1-ALPHA,25-DIHYDROXY-24,24-DIFLUORO-19-NOR-VITAMIN D3 ANALOGS AND THEIR PHARMACEUTICAL USES

Disclosed are 1α,25-dihydroxy-24,24-difluoro-2-methylene-19-nor-vitamin D analogs and their pharmaceutical uses. These new vitamin D analogs are 19-nor-vitamin D analogs having two fluorine atom substitutions at the 24 position (C-24) in the side chain and optionally having a 2-methylene substituent. 2. The compound of wherein Xis hydrogen.3. The compound of wherein Xis hydrogen.4. The compound of wherein Xand Xare both t-butyldimethylsilyl.5. The compound of wherein Xis hydrogen.6. The compound of wherein Xis triethylsilyl.11. A pharmaceutical composition containing an effective amount of the compound of or a pharmaceutical salt thereof together with a pharmaceutically acceptable excipient.12. The pharmaceutical composition of wherein said effective amount comprises about 1.0 μg to about 1000.0 μg per gram of the composition.13. A method of treating or preventing a bone disease or disorder in a patient in need thereof claim 1 , the method comprising administering to the patient an effective amount of the compound of .14. The method of claim 13 , wherein the bone disease or disorder is a metabolic bone disease or disorder where an increase in bone mass is desirable.15. The method of claim 14 , wherein the metabolic bone disease is selected from a group consisting of osteoporosis claim 14 , osteopenia claim 14 , and osteomalacia.16. A method for increasing bone strength in a patient in need thereof claim 1 , the method comprising administering to the patient an effective amount of the compound of .17. A method of treating or preventing a skin disease claim 1 , disorder claim 1 , or condition in a patient in need thereof claim 1 , the method comprising administering to the patient an effective amount of the compound of .18. The method of claim 17 , wherein the skin disease claim 17 , disorder claim 17 , or condition is selected from a group consisting of psoriasis claim 17 , acne claim 17 , lack of adequate skin firmness claim 17 , lack of adequate dermal hydration ...

RELEASE REAGENT FOR VITAMIN D COMPOUNDS

A reagent composition for releasing vitamin D compounds bound to vitamin D-binding protein and an in vitro method for the detection of a vitamin D compound in which the vitamin D compound is released from vitamin D-binding protein by the use of this reagent composition as well as the reagent mixture obtained in this manner. Also disclosed is the use of the reagent compositions to release vitamin D compounds as well as a kit for detecting a vitamin D compound. 1. An in vitro method for releasing a vitamin D compound from vitamin D-binding protein comprising the step of:a) providing a sample to be investigated and [{'sub': 3', '3', '3, 'sup': −', '−', '−, 'i) a reagent containing one hydrogen carbonate salt and a substance that releases hydrogen carbonate ions (HCO) upon hydrolysis, wherein the total concentration of hydrogen carbonate ions (HCO) from the hydrogen carbonate salt and released from the substance capable of releasing hydrogen carbonate ions (HCO) is 0.1 M to 2.0 M,'}, 'ii) a reducing agent, and', 'iii) an alkalinising agent,', 'thereby releasing the vitamin D compound from vitamin D-binding protein., 'b) mixing the sample from step (a) with'}2. The method according to claim 1 , wherein the reagent according to step (i) is soluble in an aqueous solution under the appropriate conditions for releasing a vitamin D compound from vitamin D-binding protein.3. The method according to claim 1 , wherein the substance capable of releasing hydrogen carbonate ions (HCO) upon hydrolysis is a cylic or non-cyclic carbonate ester or a hydroxylated or halogenized derivative thereof claim 1 , respectively.4. The method according claim 1 , wherein the sample is a liquid sample.5. The method according to claim 1 , wherein the sample is blood claim 1 , serum or plasma.6. An in vitro method for measuring a vitamin D compound comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claims 1'}, 'a) releasing a vitamin D compound from vitamin D-binding protein according to ...

METHODS FOR IMPROVED PRODUCTION OF VITAMINS D2 AND D3

It is an object of the present invention to provide methods for producing vitamin D that gives improved yields and reduced side product contamination. In various aspects, these methods provide for production of vitamin-Dusing ergosterol as provitamin Dor a dihydroxy derivative thereof as a starting material, or production of vitamin-Dusing 7-dehydrocholesterol as provitamin Dor a dihydroxy derivative thereof as the starting material. The methods described herein comprise irradiating the starting material in a solution including an organic or inorganic base with light in the wavelength range 245-360 nanometers (nm) to obtain a product containing pre-vitamin-Dor pre-vitamin-D, and heating the product to convert the resulting pre-vitamin-Dor pre-vitamin-Dto vitamin Dor vitamin D. In various embodiments, these methods further comprise recovering vitamin Dor vitamin Dfrom this reaction as a purified product. 1. A method of production of vitamin-D2 using ergosterol or a dihydroxy derivative thereof as a starting material , or production of vitamin-D3 using 7-dehydrocholesterol or a dihydroxy derivative thereof as the starting material , comprising:{'sub': 2', '3, '(a) irradiating the starting material in a solution comprising an organic or inorganic base with ultraviolet light to obtain a product containing pre-vitamin-Dor pre-vitamin-D, and'}{'sub': 2', '3', '2', '3, '(b) heating the product to convert the pre-vitamin-Dor pre-vitamin-Dto vitamin Dor vitamin D.'}2. A method according to claim 1 , wherein the ultraviolet light comprises light of between about 245 and about 360 nanometers.3. A method according to claim 1 , wherein the base is an organic base.4. A method according to claim 1 , wherein the base is selected from the group consisting of an aliphatic amine or an aromatic amine.5. A method according to claim 4 , wherein the base is selected from the group consisting of methylamine claim 4 , ethylamine claim 4 , triethylamine claim 4 , isopropylamine claim 4 , ...

25-HYDROXYCHOLECALCIFEROL MONOHYDRATE CRYSTAL, PREPARATION METHOD THEREFOR AND MICROEMULSION USING SAME

A 25-hydroxycholecalciferol monohydrate crystal, a preparation method thereof, and a microemulsion using the 25-hydroxycholecalciferol monohydrate crystal. The X-ray powder diffraction spectrum of the 25-hydroxycholecalciferol monohydrate crystal of the present disclosure shows characteristic peaks at 2θ of 10.035°, 11.623°, 14.631°, 15.054°, 15.551°, 16.471°, 17.198°, 19.002°, 19.628°, 20.109°, 21.886°, 23.113°, 23.661°, 24.701°, 25.220°, 25.440°, and 28.527°. The 25-hydroxycholecalciferol monohydrate crystal can effectively enhance the stability of 25-hydroxycholecalciferol, and is more beneficial to the production and storage of related preparations, and thus biological characteristics of 25-hydroxycholecalciferol can be effectively utilized. 2. The 25-hydroxycholecalciferol monohydrate crystal according to claim 1 , wherein the organic solvent is selected from one or more of an ether solvent claim 1 , an alcohol solvent claim 1 , a ketone solvent claim 1 , and a chlorohydrocarbon solvent.3. The 25-hydroxycholecalciferol monohydrate crystal according to claim 2 , wherein a molar ratio of 25-hydroxycholecalciferol to water is 1:(0.6-2000).4. The 25-hydroxycholecalciferol monohydrate crystal according to claim 3 , wherein the molar ratio of 25-hydroxycholecalciferol to water is 1:(0.8-1.5).5. A preparation method of the 25-hydroxycholecalciferol monohydrate crystal according to claim 1 , comprising the following steps:1) heating and refluxing 25-hydroxycholecalciferol in an organic solvent until 25-hydroxycholecalciferol is dissolved to obtain a 25-hydroxycholecalciferol solution; and2) adding water to the 25-hydroxycholecalciferol solution until a solid is precipitated out to prepare the 25-hydroxycholecalciferol monohydrate crystal.6. The preparation method of the 25-hydroxycholecalciferol monohydrate crystal according to claim 5 , wherein the organic solvent is selected from one or more of an ether solvent claim 5 , an alcohol solvent claim 5 , a ketone solvent ...

Isolation of steroids containing a 5,7-diene functionality from a sterol mixture

본 발명은 5,7-디엔-함유 스테로이드, 특히 3β-올 및 3β-올의 에스테르를 스테롤 혼합물로부터 분리하는 방법을 제공한다. 본 방법은 (1)혼합물을 친디엔체로 처리하거나 산화제와 함께 산화될 수 있는 친디엔체 전구체로 처리하여 분리된 5,7-디엔의 디엘스-알데르 부가물을 생성시킨다음 (2)혼합물로부터 부가물을 제거하고 (3)적합한 환원제로 5,7-디엔을 재생시킴을 포함한다. 또한 본 발명은 연속되는 정제단계를 포함하고 디엘스-알데르 중간체의 중간체 변형을 포함하며, 여기서 디엘스-알데르 부가물의 화학적 전환은 5,7-디엔의 재생 이전에 수행한다. 본 발명은 신규한 화합물 5,7-디엔-함유 스테로이드의 디엘스-알데르 부가물을 생성시킨다. The present invention provides a process for separating 5,7-diene-containing steroids, in particular esters of 3β-ol and 3β-ol from a sterol mixture. The process comprises (1) treating the mixture with dienophiles or with dienophile precursors that can be oxidized with an oxidizing agent to produce an isolated 5,7-dienes-Alder adduct (2) Removing the adduct from and (3) regenerating the 5,7-diene with a suitable reducing agent. The present invention also includes a continuous purification step and includes intermediate modifications of the Diels-Alder intermediate, wherein the chemical conversion of the Diels-Alder adduct is carried out prior to the regeneration of the 5,7-dienes. The present invention produces diels-alder adducts of the novel compound 5,7-diene-containing steroids.

Isolation of 5,7-diene-functional steroids from sterol mixtures

Method for producing 1α, 25-dihydroxyvitamin D

ISOLATION OF STEROIDS CONTAINING A 5,7-DIENE FUNCTIONALITY FROM A STEROL MIXTURE

Adducts - aldehydes as intermediate products for synthesis of vitamin d derivatives

FIELD: organic chemistry. SUBSTANCE: product: adduct-aldehyde of the formula (I) where R 1 and R 2 - H, OH, possibly substituted with C 2 -C 5 -alkylchlorocarbonate, aromatic C 1 -C 4 -carboxylic acid, aliphatic saturated carboxylic acid or tri-C 1 -C 6 -alkylsilyl halide or tri-C 1 -C 6 -alkylsilylethoxymethyl halide, and R 1 can not be H; Z - sulfonyl or group of the formula (II) where A and B - C 1 -C 4 -alkoxy, or A and B together phenylimine, ortho-phenylene. EFFECT: improved method of synthesis. 069$ 0с П4 Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ” 2 036 904 ' 13) СЛ 50 МК С 07 С 401/00 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 4830151/04, 11.06.1990 (30) Приоритет: 15.06.1989 МЕ 8901513 (46) Дата публикации: 09.06.1995 (56) Ссылки: Ви. $0$. СП/.Тг. 1949, 501. Кегсией 74, 1955, р.788-792. (71) Заявитель: Дюфар Интернэшнл Рисерч Б.В. (МЕ) (72) Изобретатель: Себастьянус Й.Халкес(М!], Вильгельмус Р.М.Овербек МЕ] (73) Патентообладатель: Дюфар Интернэшнл Рисерч Б.В. (М) (54) АДДУКТЫ-АЛЬДЕГИДЫ В КАЧЕСТВЕ ПРОМЕЖУТОЧНЫХ ПРОДУКТОВ В СИНТЕЗЕ ПРОИЗВОДНЫХ ВИТАМИНА О (57) Реферат: Использование: В качестве промежуточных продуктов В синтезе производных витамина —Д. Сущность изобретения: аддукт-альдегид ф-лы 1, где Ка и В>-Н, ОН, возможно замещенная С 2-Сь алкилхлоркарбонатом, ароматической карбоновой кислотой С1-Сд алифатической насыщенной карбоновой кислотой или три С 1-Св — -алкилсилилгалоидом или три- С 1-Св -алкилсилилэтоксиметилгалоидом, причем Кл - не может быть Н, 2 - сульфонил или группа ф-лы 2, где А и В - С 1-С4 -алкокси, или А и В вместе -фенилимин, орто-фенилен. Структура ф-л 1 и 2036904 С1 КО 069$ 0с П4 Го КУЗЗАМ АСЕМСУ ГОК РАТЕМТ$ АМО ТКАОЕМАКК$ (19) 13) ВИ "” 2036 904 ' (51) пЁ. С1.6 С 07 С 401/00 СЛ 12) АВЗТКАСТ ОЕ 1МУЕМТОМ (21), (22) АррИсаНоп: 4830151/04, 11.06.1990 (30) Рпогйу: 15.06.1989 МЕ 8901513 (46) Рае о! рибИсаНоп: 09.06.1995 (71) АррИсапе: Отитаг И\егпейзпп! Ризегсй В.М. (МЕ) (72) |пуетог: Зебаз ...

Method for preparing vitamin d compounds

내용 없음. No content.

Process for the preparation of 1-alpha, 25-dihydroxy-vitamine d2 and the 24 epimer thereof

요약없음 No summary

The delivery formulations of vitamin D compounds

本发明涉及用于释放与维生素D-结合蛋白结合的维生素D化合物的试剂组合物，用于检测维生素D化合物的体外方法，其中通过使用该试剂组合物，使得所述维生素D化合物从维生素D-结合蛋白释放，且还涉及以该方式获得的试剂混合物。本发明还涉及所披露的用于释放维生素D化合物的试剂组合物的用途。所述方法以使用还原剂碳酸氢根离子(HCO 3 - )和碱化剂为基础。

24-Oxa derivatives in the vitamin D series

New 24-oxa derivatives in the vitamin D series of general formula I are described in which R 1 , R 2 and R 5 , independently of one another, mean a hydrogen atom or an acyl group with 1 to 9 carbon atoms, R 3 means a hydrogen atom or a linear or branched alkyl group with 1 to 4 carbon atoms and R 4 means a hydrogen atom each or a linear or branched alkyl group each with 1 to 4 carbon atoms. Pharmaceutical preparations which contain these compounds are also disclosed.

Side-chain homologous vitamin D derivatives, process for their production, pharmaceutical preparations containing these derivatives and their use as pharmaceutical agents

The invention discloses side-chain homologous vitamin D derivatives of formula I ##STR1## in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , B, and D have the meanings defined in the specification and either (1) A is a direct bond between carbon atoms 20 and 22 and X is an oxy alkylene radical, --(CH 2 ) n O-- where n is 1 to 3; (2) A is a methylene bridge, --CH 2 --, between carbon atoms 20 and 22 and X is either an alkylene radical, --(CH 2 ) n -- or an oxy alkylene radical, --(CH 2 ) n O--, where n is 1 to 3; or (3) if A is a direct bond and B and D together form a second bond, then X(R 5 ) (R 6 ) is ##STR2## The compounds possess proliferation-inhibiting and cell-differentiating activity.

Ferrocene compounds and uses thereof

Release reagent for vitamin D compounds

A reagent composition for releasing vitamin D compounds bound to vitamin D-binding protein and an in vitro method for the detection of a vitamin D compound in which the vitamin D compound is released from vitamin D-binding protein by the use of this reagent composition as well as the reagent mixture obtained in this manner. Also disclosed is the use of the reagent compositions to release vitamin D compounds as well as a kit for detecting a vitamin D compound.

New Vitamin D Homolog

본 발명은 화학식 I에 관한 것이다. The present invention relates to formula (I). 화학식 I Formula I 상기 화학식 I에서, In Formula I, X는 수소 또는 하이드록시이고, X is hydrogen or hydroxy, R 1 및 R 2 는 동일하거나 상이할 수 있고, 수소 또는 C 1 -C 3 알킬 라디칼이거나, R 1 and R 2 may be the same or different and are hydrogen or a C 1 -C 3 alkyl radical, or R 1 및 R 2 는 그룹 X를 갖는 탄소원자와 함께 C 3 -C 6 카보사이클릭 환을 형성할 수 있고, R 1 and R 2 may form a C 3 -C 6 carbocyclic ring with a carbon atom having a group X, R 3 은 C 1 -C 3 알킬 라디칼, 아릴 또는 아르알킬 라디칼 또는 YR 4 (여기서, Y는 -CO-S-, -CS-O- 또는 -CS-S- 라디칼이고, R 4 는 C 1 -C 3 알킬 라디칼 또는 아릴 또는 아르알킬 라디칼이다)이고, R 3 is a C 1 -C 3 alkyl radical, an aryl or aralkyl radical or YR 4 , wherein Y is a -CO-S-, -CS-O- or -CS-S- radical, and R 4 is C 1- C 3 alkyl radical or aryl or aralkyl radical), Q는 (CH 2 ) n (여기서, n은 1 내지 4이다)이고, Q is (CH 2 ) n (where n is 1 to 4), R 1 , R 2 및 Q는 하나 이상의 불소원자로 임의로 치환될 수 있는 화학식 I의 화합물에 관한 것이다. 당해 화합물은 면역조절 및 항염증성 효과 뿐만 아니라 특정 세포의 바람직하지 않은 증식을 예방하고 분화를 유도하는 강한 활성을 나타낸다. R 1 , R 2 and Q are directed to compounds of formula I which may be optionally substituted with one or more fluorine atoms. The compounds exhibit not only immunomodulatory and anti-inflammatory effects, but also strong activity of preventing undesirable proliferation of certain cells and inducing differentiation.

Release reagent for vitamin d compounds

본 발명은 비타민 D-결합 단백질에 결합한 비타민 D 화합물을 방출시키기 위한 시약 조성물, 비타민 D 화합물의 검출을 위한 시험관내 방법 (이때, 비타민 D 화합물은 이러한 시약 조성물을 사용하여 비타민 D-결합 단백질로부터 방출됨), 및 이러한 방식으로 수득되는 시약 혼합물에 관한 것이다. 또한, 이는 비타민 D 화합물을 방출시키기 위한 개시된 시약 조성물의 용도에 관한 것이다. 상기 방법은 수소 카르보네이트 이온 (HCO 3 - ), 환원제 및 알칼리화제를 사용하는 것을 기반으로 한다. The present invention is a reagent composition for releasing a vitamin D compound bound to a vitamin D-binding protein, an in vitro method for detection of a vitamin D compound (at this time, the vitamin D compound is released from the vitamin D-binding protein using such a reagent composition) , And reagent mixtures obtained in this way. It also relates to the use of the disclosed reagent compositions for releasing vitamin D compounds. The method is based on the use of hydrogen carbonate ions (HCO 3 − ), reducing agents and alkalizing agents.

Vitamin D3 analogues, process for preparing them and their use as antiproliferative and antitumor agents

Vitamin D 3 analogues of formula: wherein: W is a C 1 -C 3 alkyl group; A is selected from: a C 1 -C 3 alkylene group; an ethenylene group -CH=CH-; an ethynylene group -C#C-; and an oxygen atom -O-; B is selected from: a single bond; a C 1 -C 6 alkylene group optionally substituted by a hydroxy group or a halogen atom, preferably fluorine; a C 1 -C 4 alkenylene group; a C 1 -C 4 alkynylene group; a C 6 -C 10 arylene group; and a C 7 -C 9 arylalkylene group; T is selected from: a group, wherein R 1 and R 2 are, each independently, C 1 -C 4 alkyl groups, optionally substituted by one or more fluorine atoms, and X is hydrogen or hydroxy; and a cyclopropyl group. Such compounds are useful as antiproliferative and antitumor agents.

Process for reducing organic compounds

1,25-DIHYDROXYVITAMINES D2 AND METHODS FOR PREPARING THE SAME

L'INVENTION CONCERNE LA BIOCHIMIE. ELLE A POUR OBJET LA PREPARATION DE COMPOSES HYDROXYLES APPARTENANT A LA SERIE DE LA VITAMINE D, EN PARTICULIER UN PROCEDE POUR SYNTHETISER LA 1A,25-DIHYDROXYVITAMINE D, LA 1B,25-DIHYDROXYVITAMINE D, LEURS ISOMERES 5,6-TRANS CORRESPONDANTS ET LES EPIMERES EN C-24 DE CES COMPOSES. LES VITAMINES D HYDROXYLEES AINSI OBTENUES ONT UNE ACTIVITE VITAMINOIDE D ET PEUVENT REMPLACER LA VITAMINE D OU DIFFERENTS DE SES METABOLITES CONNUS. THE INVENTION CONCERNS BIOCHEMISTRY. ITS OBJECT THE PREPARATION OF HYDROXYL COMPOUNDS BELONGING TO THE VITAMIN D SERIES, IN PARTICULAR A PROCESS FOR SYNTHETIZING 1A, 25-DIHYDROXYVITAMINE D, 1B, 25-DIHYDROXYVITAMINE D, THEIR 5,6-CORRESPONDS AND THEIR ISOMERS SPIMERS IN C-24 OF THESE COMPOUNDS. THE HYDROXYLATED VITAMINS D THUS OBTAINED HAVE VITAMINOID D ACTIVITY AND MAY REPLACE VITAMIN D OR DIFFERENT FROM ITS KNOWN METABOLITES.

1,24-DIHYDROXY-22-VITAMINS D3 AND PROCESS FOR PREPARING THE SAME

L'INVENTION CONCERNE L'INDUSTRIE PHARMACEUTIQUE. ELLE A POUR OBJET DES COMPOSES QUI MANIFESTENT UNE ACTIVITE VITAMINOIDE D PAR LEUR APTITUDE A STIMULER LE TRANSPORT DU CALCIUM INTESTINAL, A AUGMENTER LE TAUX DE PHOSPHORE INORGANIQUE SERIQUE ET LA MINERALISATION OSSEUSE, CE QUI INDIQUE LEUR APPLICATION POUR LE TRAITEMENT DE DIFFERENTES AFFECTIONS METABOLIQUES DES OS. LES COMPOSES DE L'INVENTION, DU FAIT QU'ILS NE PROVOQUENT PAS LA MOBILISATION OSSEUSE, LES FAIT PREFERER EN COMBINAISON AVEC LA VITAMINE D POUR ASSURER UNE MINERALISATION OSSEUSE MENAGEE. THE INVENTION CONCERNS THE PHARMACEUTICAL INDUSTRY. ITS OBJECT OF COMPOUNDS WHICH MANIFEST A VITAMINOID ACTIVITY D BY THEIR ABILITY TO STIMULATE THE TRANSPORT OF INTESTINAL CALCIUM, TO INCREASE THE LEVEL OF INORGANIC PHOSPHORUS AND BONE MINERALIZATION, WHICH INDICATES THEIR APPLICATION FOR THE TREATMENT OF METABOLIC DISEASE. . THE COMPOUNDS OF THE INVENTION, BECAUSE THEY DO NOT INDUCE BONE MOBILIZATION, PREFERRED IN COMBINATION WITH VITAMIN D TO ENSURE A MENED BONE MINERALIZATION.

NOVEL ANALOGUES OF VITAMIN D AND PHARMACEUTICAL OR VETERINARY COMPOSITIONS CONTAINING THEM

L'INVENTION CONCERNE L'INDUSTRIE PHARMACEUTIQUE. ELLE A POUR OBJET DE NOUVEAUX DERIVES FLUORES DE LA VITAMINE D ET, EN PARTICULIER, LA 24-FLUORO-1A,25-DIHYDROXYVITAMINE D ET LA 24-FLUORO-1A, 25-DIHYDROXY-5,6,-TRANSVITAMINE D. UTILISATION DE CES COMPOSES POUR LA PROPHYLAXIE DE LA FIEVRE DE LAIT CHEZ LA VACHE LAITIERE A HAUTE PRODUCTIVITE PAR ADMINISTRATION DANS UN DELAI D'A PEU PRES 5JOURS AVANT LE VELAGE.

Patent FR2213053A1

Patent FR2126414A1

Process for obtaining from acetyl-cholesterol of oxo-7 and oxy-7-acetyl-3-cholesterol, raw materials of vitamin d3

New derivative of precalciferol and its process for obtaining

Patent FR2126414B1

Methods for improved production of vitamins D2 and D3

It is an object of the present invention to provide methods for producing vitamin D that gives improved yields and reduced side product contamination. In various aspects, these methods provide for production of vitamin-D 2 using ergosterol as provitamin D 2 or a dihydroxy derivative thereof as a starting material, or production of vitamin-D 3 using 7-dehydrocholesterol as provitamin D 3 or a dihydroxy derivative thereof as the starting material. The methods described herein comprise irradiating the starting material in a solution including an organic or inorganic base with light in the wavelength range 245-360 nanometers (nm) to obtain a product containing pre-vitamin-D 2 or pre-vitamin-D 3 , and heating the product to convert the resulting pre-vitamin-D 2 or pre-vitamin-D 3 to vitamin D 2 or vitamin D 3 . In various embodiments, these methods further comprise recovering vitamin D 2 or vitamin D 3 from this reaction as a purified product.

Crystals of vitamin D derivatives and process for the preparation thereof

本发明提供了下列式(I)所示化合物的结晶；经反相色谱法纯化维生素D衍生物的粗产物或初步纯化的产物，然后将纯化的衍生物于有机溶剂中析晶获得的维生素D衍生物结晶；维生素D衍生物合成过程中形成的作为副产物的新的化合物；以及维生素D衍生物或其前体的纯化方法。本发明所述方法使得以批量并且稳定地提供高纯度维生素D衍生物，特别是ED-71成为可能。

Crystals of vitamin d derivatives and process for the preparation thereof

A crystal of the compound of the structural formula (I); crystals of vitamin D derivatives prepared by purifying unpurified or roughly purified vitamin D derivatives by reversed phase chromatography and crystallizing the purified derivatives in organic solvents, novel by-products formed in the synthesis of vitamin D derivatives; and a process for the purification of vitamin D derivatives or intermediates thereof, which enables the constant and mass supply of high-purity vitamin D derivatives, particularly ED-71.

1,25-dihydroxyvitamin d2 compounds and methods for their preparation

Vitamin D derivative with substituent at the 2β-position

1α-hydroxy-vitamin D derivatives represented by formula ##STR1## wherein R 1 represents a hydrogen atom or a hydroxyl group; and R 2 represents a straight-chain or branched C 2 -C 7 alkyl, C 2 -C 7 alkenyl, or C 2 -C 7 alkynyl group. The compounds exhibit calcium metabolism regulating activity and differentiation stimulating activity on tumor cells, and are useful as treating agents for diseases caused by abnormal calcium metabolism, such as osteoporosis and osteomalacia, or as antitumor agents.

Ceutical compositions 10,19-dihydro-vitamin d derivatives preparation and pharma

Vitamin D3 analogs

A compound of the formula wherein R is hydrogen or hydroxy, each R 1 is ethyl, propyl, butyl, isopropyl or t-butyl, X is ═CH 2 , or when R is hydroxy, X is hydrogen or ═CH 2 , and A is —C≡C—, or —CH 2 —CH 2 —. These compounds are useful for the treatment of hyperproliferative disorders, skin diseases, and sebaceous gland diseases.

Novel method for the preparation of intermediates useful for the synthesis of vitamin d analogues

The present invention relates to novel methods for the preparation of intermediates which are useful in the synthesis of cacipotriol. The present invention relates further to the use of intermediates produced with said methods for making calcipotriol or calcipotriol monohydrate.

Process for the preparation of sodium salt of succinic mono-esther of vitamin d3

1-Hydroxyvitamin D derivatives

1-Hydroxyvitamin D esters of vitamin A acid are useful for preventing and treating osteoporosis, cutaneous ulcer and tumour.

METHOD FOR THE PREPARATION OF USEFUL INTERMEDIARIES FOR THE SYNTHESIS OF ANALOGS OF VITAMIN D

El uso de los intermediarios producidos con dichos métodos para la elaboracion del calcipotriol o calcipotriol monohidrato. Reivindicacion 1: Un método para la preparacion de un compuesto de la estructura general de formula (1), en la cual el carbono marcado con un asterisco está conectado por un enlace simple a un átomo de carbono del fragmento de análogo de la Vitamina D en C-17, o bien a un fragmento de un precursor para la síntesis de un análogo de la vitamina D en la posicion análoga C1-7, método que comprende la reaccion de un compuesto de la estructura general de formula (2), en la cual el carbono marcado con un asterisco está conectado por un enlace simple a un átomo de carbono del fragmento de análogo de la Vitamina D en C-17, o bien a fragmento de un precursor para la síntesis de un análogo de la Vitamina D en la posicion análogo C1-7, con un fosfonato de la estructura general de formula (3), en la cual R3 y R4 son iguales o diferentes y representan alquilo, haloalquilo, hidroxialquilo, alquenilo, alquinilo, aralquilo, aralquenilo, aralquinilo o arilo, cada uno de los cuales está optativamente sustituido con uno o más sustituyentes seleccionados del grupo conformado por alquilo, aralquilo, cicloalquilo, cicloalquenilo, haloalquilo, hidroxialquilo, alquenilo, alquinilo, aralquilo, aralquenilo, aralquinilo, arilo, oxo, alcoxicarbonilo, alquilcarboniloxi, halogeno, alcoxi, carboxi, sulfo o hidroxi, en presencia de una base. The use of intermediates produced with said methods for the preparation of calcipotriol or calcipotriol monohydrate. Claim 1: A method for the preparation of a compound of the general structure of formula (1), wherein the carbon marked with an asterisk is connected by a single bond to a carbon atom of the Vitamin D analog fragment in C-17, or a fragment of a precursor for the synthesis of a vitamin D analogue in the analogous position C1-7, a method comprising the reaction of a compound of the general structure of formula (2), in the which ...

Crystalline 1.alpha.-hydroxyvitamin d2 and method of purification thereof

A method of purifying 1.alpha.-hydroxyvitamin D2 to obtain 1.alpha.-hydroxyvitamin D2 in crystalline form. The method includes the steps of boiling a solvent selected from the group consisting of ethyl formate, ethyl acetate and a 2-propanol-hexane mixture under inert atmosphere, dissolving a product containing 1.alpha.-hydroxyvitamin D2 to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1.alpha.-hydroxyvitamin D2 crystals, and recovering the 1.alpha.-hydroxyvitamin D2 crystals. Optionally, petroleum ether may be added to the solvent after dissolving the product to be purified in the solvent.

PROCESS FOR PREPARING 1ALPHA-HYDROXYL COMPOUNDS

Process for the preparation of vitamin D3 and provitamin D3

Separation of vitamin D3 or provitamin D3 from mixtures with other components, e.g. dehydrocholesterol, lumisterol and tachysterol, is effected by column chromatography.

2-Halo-1,25-dihydroxycholecalciferols, pharmaceutical compositions, use as medicaments and process for the preparation of the cholecalciferols

2-Halo-1,25-dihydroxycholecalciferols, of the formula I <IMAGE> wherein X = chlorine or bromine and R1 = hydrogen or C1-C9-alkanoyl or benzoyl, and processes for their preparation. In addition to their vitamin D activity, the compounds have proliferation-inhibiting and cell-differentiating actions, that with respect to the cell differentiation being strongly dissociated compared with the hypercalcaemic action. The compounds are suitable for the preparation of medicaments.

Process for obtaining vitamin D derivatives from monohalogenovinyl compounds

(C20)-모노할로게노비닐 유도체를 금속 또는 유기금속 시약과 반응시키고, 반응시킨뒤, 다른 활성 시약과 반응시키는 단계를 포함하는 화학식 A reaction comprising reacting a (C20) -monohalogenovinyl derivative with a metal or organometallic reagent, and then reacting with another active reagent. 의 비타민 D 유도체를 획득하는 신규한 방법이 개시된다. A novel method of obtaining a vitamin D derivative of is disclosed. 비타민 D 유도체, 모노할로게노비닐 Vitamin D Derivatives, Monohalogenovinyl

Methods for producing paricalcitol

Compositions and methods for detecting vitamin d

Process for preparing 1a-hydroxyvitamin d compounds from 1a-hydroxy-3,5-cyclovitamin d compounds

16-ENE-VITAMIN D DERIVATE

PROCESS FOR PREPARING 1-ALFA-HYDROXYCHOLECALCIFEROL OR AN ACYLATE DERIVED THEREFROM

Method for synthesizing pre-vitamin D3 by using LED ultraviolet lamp

本发明涉及光反应设备领域，特别涉及一种LED紫外灯合成预维生素D3的方法。将合成预维生素D3光源改为LED紫外灯，并控制光反应的条件，通过本发明将7‑去氢胆固醇的一次性转化率提高至95％，同时将速甾醇的生成量控制在1％以内。

Crystals of a vitamin D derivative and a method for the preparation thereof

The present invention provides crystals of the compound represented by formula (I): crystals of a vitamin D derivative which are obtained by purifying a crude or preliminarily purified product of the vitamin D derivative through a reverse phase chromatography and then crystallizing the purified derivative from an organic solvent; novel compounds which are formed during the synthesis of a vitamin D derivative as by-product; and a method for purifying a vitamin D derivative or the precursor thereof. The method of the present invention makes it possible to supply a highly purified vitamin D derivative, especially ED-71, in bulk and steadily.

Method of preparing vitamin-d compounds usable as intermediates

Disclosed is a method of preparing vitamin-D of the general formula (III), wherein R is a hydrogen atom or an optionally etherified or esterified hydroxy group, R1 is an optionally etherified or esterified hydroxy group, and R2 is a branched or non-branched, saturated or unsaturated aliphatic hydrocarbyl or hydrocarbyloxy radical which comprises 1 to 14 carbon atoms and is optionally substituted, which method can be characterised in subjecting the above previtamin-D2 adduct of the general formula (II) to an oxidation, which is selective for the C22-C23 double bond, wherein Z is a residue of the formula (a) and A and B are equal or different and represent C1-C4 alkoxy groups or A and B together constitute a phenylimino group or an o-phenylene group. The aldehyde of the general formula (I) thereby obtained is subjected to a chain-extending reaction in which the aldehyde function is converted into the group R2, and then the group Z is removed. Also disclosed is aldehyde of the general formula (I) which is usable as an intermediate in the above method.

Vitamin D3 analogues,process for preparing them,and their use as antiproliferative and antitumour agents

Method for obtaining sulphonyl derivatives of cholecalcipherol and new compounds isolated during this process

Crystals of vitamin d derivatives and process for the preparation thereof

16-ene-vitamin d derivatives

A vitamin D derivative of general formula (1): wherein X represents an oxygen or sulfur atom, R 11 represents a saturated or unsaturated aliphatic hydrocarbon group which may be substituted by a hydroxyl group or a protected hydroxyl group, or a -COR 12 group where R 12 represents an alkyl, aryl or alkoxy group, R 2 represents - OR 9 or a hydrogen atom, and R 9 and R 10 each represent a hydrogen atom or a hydroxyl group.

METHOD OF PREPARING 9.beta.,10.alpha.-5.7-DIENE-STEROIDS

ABSTRACT: The invention relates to the preparation of 9.beta.,10.alpha.-5,7-dienesteroids by irradiating the corresponding 9.alpha.,10.beta. steroids with filtered ultraviolet light of an antimony lamp.

Epimerization of analogs of vitamin D

Provided is a method of general applicability of epimerizing a vitamin-D analog having an asymmetric allylic carbon atom at the C-24 position. The method is of particular utility in making calcipotriene.

Photochemical syntheses vitamin D in a kind of tubular reactor2、D3Method

本发明涉及一种管式反应器内光化学合成维生素D 2 、D 3 的方法，其特征在于，该方法利用不同波段紫外光合成成维生素D 2 、D 3 ，通过不与反应液互溶、不参与反应的液体分隔和运载麦角固醇、7‑去氢胆固醇反应液，强化反应液内部扰动，控制不同时间通入的反应液在管式反应器中的停留时间一致。本发明具有连续、稳定、光能利用率高的优势，其操作简便、过程可控。在光化学合成维生素D 2 、D 3 的工业化生产中具有巨大前景。

Monohalogenovinyl vitamin D derivative compounds

New vitamin D derivative compounds containing a monohalovinyl moiety at position C-20 are described. A process for obtaining the new compounds, consisting of reacting an aldehyde precursor with a haloform in the presence of Cr 2+ salts, is also described.

Vitamin d derivatives and a process for producing them

Highly crystalline vitamin D derivatives represented by the formula: (see formula I) (where R1 is a straight or branched C4 - C9 alkyl group optionally having a hydroxyl group; R2 and R3 which may be the same or different are each an acyl group), as well as a process for producing 22-oxavitamin D derivatives of high purity by hydrolyzing said compounds.

Efficient production process of vitamin D2

本发明公开了一种维生素D2的高效生产工艺，利用光电技术产生的单色性好的LED光作为光化学反应器的光源，促使原料麦角固醇发生光化学开环反应和光化学异构化反应获得预维生素D2，再经热异构化得维生素D2，是一种原料转化率及总产率更高、副产物更少、产物纯化简单、生产更高效的新工艺。

Epimerization of analogs of vitamin d

Provided is a method of general applicability of epimerizing a vitamin-D analog having an asymmetric allylic carbon atom at the C-24 position, which comprises the steps of: a) esterifying the hydroxyl group on the asymmetric allylic carbon atom at the 24 position with an esterifying agent, b) contacting a solution of the ester in a solvent with an epimerization-active solid, whereby the ester is epimerized, and c) hydrolysing the epimerized ester to obtain a mixture of C-24 epimers having a hydroxyl substituent on the asymmetric allylic carbon at position 24. The method is of particular utility in making calcipotriene.

Synthesis of 1α-hydroxy vitamin D

A method for 1α-hydroxylation of vitamin D compounds using the appropriate vitamin D as the starting material. The method requires no separatory procedures prior to the actual hydroxylation step.

PROCEDURE FOR OBTAINING VITAMIN DERIVATIVES FROM MONOHALOGENOVINYL COMPOUNDS.

Procedimiento para la obtención de derivados de vitamina D a partir de compuestos monohalogenovinílicos. Se describe un nuevo procedimiento para obtener derivados de vitamina D de fórmula **FIGURA** consistente en hacer reaccionar un derivado monohalogenovinílico en C20 con reactivos metálicos u organometálicos y, posteriormente, con otros reactivos activados. Procedure for obtaining vitamin D derivatives from monohalogenovinyl compounds. A new procedure for obtaining vitamin D derivatives of formula ** FIGURE ** is described, consisting of reacting a monohalogenovinyl derivative in C20 with metal or organometallic reagents and subsequently with other activated reagents.

Novel vitamin d analogs

Method for producing 24 (S) -hydroxyvitamin D2

(57)【要約】 本発明は、立体特異的合成である、24(S)-ヒドロキシビタミンＤ ２ の製造方法を提供する。

Process for preparing the potassium salt of the succinic mono-esther of vitamined2

1,25-dihydroxyvitamin D2 compounds

The invention is directed to the preparation of hydroxylated compounds of the vitamin D 2 series and specifically to a process for synthesizing 1α,25-dihydroxyvitamin D 2 , 1β,25-dihydroxyvitamin D 2 , their corresponding 5,6-trans isomers and the C-24 epimers of these compounds. The hydroxylated vitamin D 2 compounds obtained exhibit vitamin D-like activity and can be substituted for vitamin D 3 or various of its known metabolites where such compounds are applied.

Process for preparing 1α-hydroxylated compounds

An improved method for the preparation of 1α-hydroxylated vitamin D compounds involving directly introducing an oxygen function at carbon 1 of the vitamin D molecule or precursors or derivatives thereof, wherein the 1α-hydroxycyclovitamin D intermediate is solvolyzed directly, without first converting the 1-hydroxy group to a 1-O-acyl function as a protective measure.

Isolation of steroids containing a 5,7-diene functionality from a sterol mixture

A method is provided for isolating 5,7-diene-containing steroids, particularly 3 .beta.-ols and esters of 3 .beta.-ols, from a sterol mixture. The method involves (1) treating the mixture with a dienophile or with an oxidizable dienophile precursor in combina-tion with an oxidizing agent so as to provide a Diels-Alder adduct of the 5,7-diene to be isolated, followed by (2) removal of the adduct from the mixture and (3) regeneration of the 5,7-diene with a suitable reducing agent. The invention also encompasses subsequent purification steps and intermediate modification of the Diels-Alder intermediate, e.g., wherein chemical conversion of the Diels-Alder adduct is effected prior to regeneration of the 5,7-diene. Novel compounds which are Diels-Alder adducts of 5,7-diene-containing steroids are provided as well.