НОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ПРОТИВОВОСПАЛИТЕЛЬНЫХ, ИММУНОМОДУЛИРУЮЩИХ И ПРОТИВОПРОЛИФЕРАТИВНЫХ АГЕНТОВ

Соединение общей формулы (I) и его соли где А является неароматической кольцевой системой, содержащей пять атомов углерода, где кольцевая система содержит, по крайней мере, одну двойную связь и где один или более атомов углерода в кольце могут быть замещены на группу X, где Х выбран из группы, состоящей из S, О, N, NR4, SO или SO2 и где один или более атомов углерода в кольце могут иметь заместитель R1; D представлет собой О, S, SO2, NR4 или СН2; Z1 и Z независимо друг от друга являются О, S или NR5; R1 независимо является Н, галогеном, галогеналкилом, галогеналкилокси или алкилом; R2 является Н, OR6 или NHR7; R3 является Н, алкилом, циклоалкилом, арилом, арилалкилом, алкокси, O-арилом; O-циклоалкилом, галогеном, аминоалкилом, алкиламино, гидроксиламино, гидроксилалкилом, галогеналкилом, галогеналкилокси, гетероарилом, алкилтио, S-арилом или S-циклоалкилом; R4 является Н, алкилом, циклоалкилом, арилом или гетероарилом; R5 является Н, ОН, алкокси, O-арилом, алкилом или арилом; R6 является ...

НОВЫЕ СОЕДИНЕНИЯ, ИСПОЛЬЗУЕМЫЕ В КАЧЕСТВЕ ОТКРЫВАТЕЛЕЙ КАЛИЕВЫХ КАНАЛОВ

N-Phenpropylclopentyl-substituted glutaramide derivatives as NEP inhibitors for FSAD.

The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R1 is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C1-6alkoxy, -NR2R3 or -NR4SO2R5; X is the linkage -(CH2)n-or-(CH2)q-O-(wherein y is attached to the oxygen); wherein in one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy; hydroxy; hydroxy(C1-3alkyl); C3-7cycloalkyl; carbocyclyl; heterocyclyl; or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6 or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R8 groups on adjacent carbon atoms together with the interconnnecting carbon atoms may form a fused optionally substituted 5- or 6-membered carbocyclic or heterocyclyic ring.

N-phenpropylcyclopen-tyl-substituted glutaramide derivatives as nep inhibitors for fsad

N-Phenpropylcyclopentyl-substituted glutaramide derivatives as NEP inhibitors for FSAD.

N-phenpropylcyclopen-tyl-substituted glutaramide derivatives as nep inhibitors for fsad

N-phenpropylcyclopen-tyl-substituted glutaramide derivatives as nep inhibitors for fsad

NPYY5-ANTAGONISTEN

HERBICIDES ACYLIERTE AMINO (PHENYL OR PYRIDINYL OR THIENYL) PHENYL OF DERIVATIVES

Novel compounds useful as potassium channel openers

The present invention discloses novel compounds which are useful as potassium channel openers, in particular as openers of the Kv7.4 potassium channel. The novel compounds are compounds according to formula (I), wherein - n = 0 or 1, - RL is a substituent selected from the group consisting of unsubstituted or substituted cycloalkyl groups, in particular bicycloalkyl groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted thienyl groups or cyclopentathienyl groups, and unsubstituted or substituted indanyl groups, which optionally contain heteroatoms, and - RR is a substituent selected from the group consisting of unsubstituted or substituted phenyl groups or unsubstituted or substituted benzyl groups, which optionally contain heteroatoms, - or a stereoisomer, a tautomer, a prodrug or a salt, preferably pharmaceutically acceptable salt thereof.

PLANT GROWTH REGULATING AND HERBICIDAL CYCLOALKANE CARBOXYLIC ACID DERIVATIVES

PLANT GROWTH REGULATING AND HERBICIDAL CYCLOALKANE CARBOXYLIC ACID DERIVATIVES

Novel phenylalanine derivatives

PPAR-(GAMMA) AGONISTS AS AGENTS FOR THE TREATMENT OF TYPE II DIABETES

Disclosed are compounds of formula (I) or the pharmaceutically acceptable non- toxic salts thereof wherein: Z is aryl or heteroaryl; n and m are 0, 1 or 2; A is a carboxylic acid or ester; or A is formula (II) where D, F and G are hydrogen, (un)substituted amino, (un)substituted alkoxy, methylene or an (un)substituted sulfide; X is N, O, CH2, S, SO or SO2; R4 is oxo, hydrogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyl, keto, acyl, or sulfonyl; Y is hydrogen, (un)substituted amino, (un)substituted alkoxy, methylene, an (un)substituted sulfide, (un)substituted sulfonyl or an (un)substituted sulfoxide; and R5, R6 and R8 are hydrogen, lower alkyl, lower alkoxy, cycloalkyl, keto, acyl, or sulfonyl; or R5 and R6 together form a ring. The compounds are highly selective agonists for the PPAR-.gamma. receptor or prodrugs of agonists for the PPAR-.gamma. receptor. Thus these compounds are useful in the treatment Type II diabetes (NIDDM).

COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISEASE ASSOCIATED WITH TRP-P8 EXPRESSION

Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp- p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.

PROCESS OF MAKING PROSTACYCLIN COMPOUNDS WITH LINKER THIOL AND PEGYLATED FORMS

A process provides for producing chiral prostacyclin derivatives of Formula (I) in high yield from meso anhydrides.

INDUSTRIAL PROCESS FOR THE PREPARATION OF (5S,10S)-10-BENZYL-16-METHYL-11,14,18-TRIOXO-15,17,19-TRIOXA-2,7,8-TRITHIA-12-AZAHENICOSAN-5-AMINIUM (E)-3-CARBOXYACRYLATE SALT

ABCA-1 ELEVATING COMPOUNDS

NOVEL COMPOUNDS AS ANTI-INFLAMMATORY, IMMUNOMODULATORY AND ANTI-PROLIFERATORY AGENTS

The present invention relates to compounds of the general formula (I); or salts thereof, as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

NPY Y5 antagonist

The present invention provides a pharmaceutical composition for use as an NPY Y5 receptor antagonist comprising a compound of the formula (I): wherein R1 is lower alkyl, cycloalkyl or the like, R2 is hydrogen, lower alkyl or the like, n is 1 or 2, X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, Y is CONR7, CSNR7, NR7CO, NR7CS or the like, Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like and R7 is hydrogen or lower alkyl, prodrug, pharmaceutically acceptable salt or solvate thereof ...

NPYY5 ANTAGONISTS

ИНГИБИТОР АКТИВНОСТИ ХОЛЕСТЕРИН ЭТЕРИФИЦИРОВАННОГО ТРАНСПОРТНОГО БЕЛКА, ПРОФИЛАКТИЧЕСКОЕ ИЛИ ТЕРАПЕВТИЧЕСКОЕ СРЕДСТВО, ПРОИЗВОДНЫЕ БИС-(2-АМИДОФЕНИЛ)ДИСУЛЬФИДА ИЛИ АМИДОТИОФЕНОЛА

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention relates to an inhibitor of activity of cholesterol esterified transport protein comprising as an active component the compound presented by the formula (I) where R means direct or branched alkyl group; lower halogenalkyl group; substituted or unsubstituted cycloalkyl group; substituted or unsubstituted cycloalkylalkyl group; substituted or unsubstituted aryl group, or substituted or unsubstituted heterocyclic group; X 1 , X 2 , X 3 , X 4 can be similar or different and each means hydrogen atom, halogen atom, lower alkyl group, lower halogenalkyl group; lower alkoxy-group; cyano-group; nitro-group; Y means CO- and Z means hydrogen atom or mercapto-protecting group, or its pharmaceutically acceptable salt or hydrate, or solvate. Compounds presented by the formula (I) can increase the level of high density lipoproteins (HDL) and in the same time decrease the level of low density lipoproteins (LDL) by selective inhibition of activity of cholesterol esterified transport protein and therefore as suggested they can be used as prophylactic or therapeutic agents of new type for treatment of atherosclerosis or hyperlipidemia. EFFECT: new compounds indicated above, valuable medicinal properties. 24 cl, 48 tbl (19) 13) ВО” 2 188 631” С2 ОМК’ А бл К 31/165, 31/44, С 07 С 323/40, 323/63, 323/65, С 07 0 с эз8з с ПЧ сэ РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 211/62, 213/81, А 61 Р 3/06 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 99119494/04, 10.02.1998 (24) Дата начала действия патента: 10.02.1998 (30) Приоритет: 12.02.1997 /Р 9/44836 05.06.1997 УР 9/165085 23.01.1998 УР 10/26688 (43) Дата публикации заявки: 21.07.2001 (46) Дата публикации: 10.09.2002 (56) Ссылки: ЗИ 499261, А, 06.07.1976. ММО 95/01326, АЛ, 12.01.1995. \МО 9203412, АЛ, 05.03.1992. КУ 94046149, СЛ, 27.11.1996. ММО 9203408, АЛ, 05.03.1992. (85) Дата перевода заявки РСТ на национальную фазу: 13.09.1999 (86) Заявка РСТ: ...

АНТАГОНИСТ NPY Y5

FIELD: medicine, pharmacology. SUBSTANCE: the present innovation deals with applying pharmaceutical composition as an antagonist of NPY Y5 receptor that contains the compound of formula I , moreover, it deals with compounds of formula I and method for treating obesity and suppressing food intake, as well. EFFECT: higher efficiency of therapy. 18 cl, 13 ex, 6 tbl ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (51) ÌÏÊ 7 (11) 2 264 810 (13) C2 A 61 K 31/18, 31/341, 31/415, 31/44, 31/495, 31/535, C 07 C 311/06, 311/07, 311/08, C 07 D 265/30, 307/02, 211/08, 241/02, ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) 261/08, A 61 P 3/04 ÎÏÈÑÀÍÈÅ ÈÇÎÁÐÅÒÅÍÈß Ê ÏÀÒÅÍÒÓ (21), (22) Çà âêà: 2002117021/15, 21.11.2000 (72) Àâòîð(û): ÊÀÂÀÍÈÑÈ ßñóþêè (JP), ÒÀÊÅÍÀÊÀ Õèäåþêè (JP), ÕÀÍÀÑÀÊÈ Êîõäçè (JP), ÎÊÀÄÀ Òåöóî (JP) (24) Äàòà íà÷àëà äåéñòâè ïàòåíòà: 21.11.2000 (30) Ïðèîðèòåò: 26.11.1999 JP 11-336469 14.12.1999 JP 11/353786 (45) Îïóáëèêîâàíî: 27.11.2005 Áþë. ¹ 33 2 2 6 4 8 1 0 (56) Ñïèñîê äîêóìåíòîâ, öèòèðîâàííûõ â îò÷åòå î ïîèñêå: RU 2126382, C1, 20.02.1999. US 5962530, A, 05.10.1999. US 5939462, A, 17.08.1999. (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 26.06.2002 Àäðåñ äë ïåðåïèñêè: 129010, Ìîñêâà, óë. Á.Ñïàññêà , 25, ñòð.3, ÎÎÎ "Þðèäè÷åñêà ôèðìà Ãîðîäèññêèé è Ïàðòíåðû", ïàò.ïîâ. Å.Å.Íàçèíîé (54) ÀÍÒÀÃÎÍÈÑÒ NPY Y5 (57) Ðåôåðàò: Èçîáðåòåíèå îòíîñèòñ ê îáëàñòè ìåäèöèíû è ôàðìàêîëîãèè è êàñàåòñ ôàðìàöåâòè÷åñêîé êîìïîçèöèè â êà÷åñòâå àíòàãîíèñòà ðåöåïòîðà NPY Y5, ñîäåðæàùåé ñîåäèíåíèå ôîðìóëû I, ñîåäèíåíèé ôîðìóëû I è ñïîñîáà ëå÷åíè îæèðåíè è ïîäàâëåíè ïîòðåáëåíè ïèùè ñ ïîâûøåííîé ýôôåêòèâíîñòüþ 8 í. è 10 ç.ï. ô-ëû, 6 òàáë. R U 2 2 6 4 8 1 0 (87) Ïóáëèêàöè PCT: WO 01/37826 (31.05.2001) C 2 C 2 (86) Çà âêà PCT: JP 00/08197 (21.11.2000) Ñòðàíèöà: 1 RU R U (73) Ïàòåíòîîáëàäàòåëü(ëè): ÑÈÎÍÎÃÈ ÝÍÄ ÊÎ., ËÒÄ. (JP) (43) Äàòà ïóáëèêàöèè çà âêè: 27.01.2004 RUSSIAN FEDERATION (19) RU (51) Int. Cl. 7 (11) 2 264 810 (13) C2 A 61 K 31/18, 31/341, 31/415, 31/44, 31/495, ...

НОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ПРОТИВОВОСПАЛИТЕЛЬНЫХ, ИММУНОМОДУЛИРУЮЩИХ И ПРОТИВОПРОЛИФЕРАТИВНЫХ АГЕНТОВ

FIELD: organic chemistry, pharmaceuticals. SUBSTANCE: invention relates to compounds of general formula I and salt thereof, wherein F is non-aromatic ring system containing five carbon atoms and at least one double bond wherein one ring carbon atom is optionally substituted with X group, such as S, O, or SO 2 , and one or more ring carbon atoms are optionally substituted with R 1 ; D represents S, O, SO 2 , NR 4 , or CH 2 ; Z 1 and Z 2 are independently O; Y is steryl, mono- or polycyclic non-substituted ring system, containing one or more X group such as S, O, SO 2 , N; m, n, p, r and q = 0 or 1; meanings of the rest substituents are as defined in specification. Also invention relates to compounds of general formula I , wherein m, n, and q = 0; r = 1. Disclosed is pharmaceutical composition having inhibitory activity in relates to dihydroorotate dehydrogenase (DHODH) containing effective amount of said compound in free form or in form of pharmaceutically acceptable salts together with pharmaceutically acceptable diluents or carriers. Compounds of formula I are useful as drug inhibiting DHODH for treatment of disease or therapeutic condition in which inhibition of DHODH is beneficial. EFFECT: new compounds as anti-inflammatory, immunomodulating, and anti-proliferative agents. 13 cl, 1 tbl, 1 dwg, 76 ex ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (11) 2 309 946 (13) C2 (51) ÌÏÊ C07C 233/60 C07C 233/58 C07C 233/59 C07C 233/62 C07C 255/60 ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ C07D 335/12 ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ,C07D 333/38 ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ C07D 333/60 C07D 307/30 A61K 31/167 (12) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) A61K 31/341 (2006.01) A61K 31/381 (2006.01) ÎÏÈÑÀÍÈÅ ÈÇÎÁÐÅÒÅÍÈß Ê ÏÀÒÅÍÒÓ (21), (22) Çà âêà: 2004103741/04, 09.07.2002 (24) Äàòà íà÷àëà îòñ÷åòà ñðîêà äåéñòâè ïàòåíòà: 09.07.2002 (30) Êîíâåíöèîííûé ïðèîðèòåò: 10.07.2001 (ïï.1-13) EP PCT/EP01/07948 (43) Äàòà ïóáëèêàöèè çà âêè: 20.06.2005 2 3 0 9 9 4 6 R U (56) ...

СПОСОБ ПОЛУЧЕНИЯ АРОМАТИЧЕСКИХ ТИОЛЬНЫХ ПРОИЗВОДНЫХ ПРИ ГИДРИРОВАНИИ ДИСУЛЬФИДОВ

FIELD: chemistry. SUBSTANCE: invention relates to methods of producing thiophenols during reaction of corresponding disulphide with hydrogen in presence of a heterogeneous hydrogenation catalyst based on a transition metal. In particular, method of producing a compound of formula (I') involves reaction of a compound of formula (II'), wherein R is H or with H 2 in presence of a heterogeneous hydrogenation catalyst based on a transition metal, where heterogeneous hydrogenation catalyst based on a transition metal is a Raney catalyst, Pd/C, Pd(OH) 2 /C, nanoparticles of palladium (0), micro-encapsulated in a polyurea matrix, Au/TiO 2 , Rh/C, Ru/Al 2 O 3 , Ir/CaCO 3 , Pt/C or mixture thereof. When reaction is carried out in presence of an acylating reagent, such as anhydride or halide of carboxylic acid, acylated thiophenol is obtained. EFFECT: pharmaceutically active compound S-[2-[1-(2-ethylbutyl)cyclohexylcarbonylamino]-phenyl]-2-methylthiopropionate is obtained during said method. 20 cl, 16 ex, 1 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (51) МПК C07C 319/06 C07C 323/40 C07C 327/30 C07D 277/64 (11) (13) 2 607 636 C2 (2006.01) (2006.01) (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ФОРМУЛА (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2013131443, 12.12.2011 (24) Дата начала отсчета срока действия патента: 12.12.2011 Дата регистрации: (73) Патентообладатель(и): Ф. ХОФФМАНН-ЛЯ РОШ АГ (CH) Приоритет(ы): (30) Конвенционный приоритет: 16.12.2010 EP 10195294.3 (56) Список документов, цитированных в отчете о поиске: С.Сalais et al. "Selective Reduction of Diphenyldisulfides Catalysed by Sulfides -; Influence of the Nature of the Catalyst"; Journal of Catalysis, 144, p. 160-174, 1993;Н. Shinkai "Bis(2-(Acylamino)phenyl)Disulfides, 2-(Acylamino)benzenethiols, and S-(2-(Acylamino)phenyl) Alkanethioates as Novel Inhibitors of Cholesteryl Ester Transfer Protein"; (см. прод.) (45) Опубликовано: 10.01.2017 Бюл. № 1 (85) Дата начала ...

Антагонист NPY Y5

... 1. Фармацевтическая композиция для применения в качестве антагониста рецептора NPY Y5, содержащая соединение формулы (I) где R1 представляет необязательно замещенный низший алкил, необязательно замещенный циклоалкил или необязательно замещенный арил; R2 представляет водород или низший алкил, и R1 и R2, взятые вместе, могут образовывать низший алкилен; n равно 1 или 2; Х представляет необязательно замещенный низший алкилен, необязательно замещенный низший алкенилен, необязательно замещенный -СО-(низший алкилен), необязательно замещенный -СО-(низший алкенилен) или где R3, R4, R5 и R6, каждый независимо, представляют водород или низший алкил, представляет собой необязательно замещенный циклоалкилен, необязательно замещенный циклоалкенилен, необязательно замещенный бициклоалкилен, необязательно замещенный арилен или необязательно замещенный гетероциклдиил, и р и q, каждый независимо, равен 0 или 1, -NR2-X- может представлять где представляет пиперидиндиил, пиперазиндиил, пиридиндиил, пиразиндиил ...

НИЗКОМОЛЕКУЛЯРНЫЕ МОДУЛЯТОРЫ АКТИВНОСТИ Trp-p8

... 1. Соединение формулы I: ! , ! где R1 выбирают из H, алкила, гетероалкила, арилалкила и арила, или R1 и R2 вместе с группой азота могут образовывать циклическую или гетероциклическую группу, самое большее, из 25 атомов; ! R2 выбирают из арила и арилалкила; ! R3 выбирают из алкила, гетероалкила и арилалкила; ! R4 выбирают из H, алкила, гетероалкила и арилалкила; и ! R3 и R4 вместе с группой азота образуют алифатический амин. ! 2. Соединение формулы I-A: ! , ! где A, B, C и D независимо выбирают из CR2 и N; где, по меньшей мере, один из A, B, C и D представляет собой CR2; где R2 представляет собой остаток, выбранный из H, алкила, гетероалкила, арила, галогена и арилалкила, R6O- и R6S-, где R6 представляет собой алкил; при этом, когда два соседних остатка A, B, C и D представляют собой CR2, два R2 могут объединяться с образованием единой арильной, циклоалкильной или гетероциклоалкильной группы; и ! R1 выбирают из H, алкила, гетероалкила, арила и арилалкила; ! R3 выбирают из алкила, гетероалкила ...

КЕТОНОВЫЕ ИНГИБИТОРЫ ЛИЗИН-СПЕЦИФИЧНОГО ГИНГИПАИНА

INHIBITOREN DER CETP-AKTIVITÄT

CYCLOBUTAN-DERIVATE ALS INHIBITOREN DER SQUALEN-SYNTHETASE UND DER PROTEIN-FARNESYLTRANSFERASE

NPYY5-ANTAGONISTEN

Bisaryl compounds and cancer remedies containing the same

Bisaryl compounds and cancer remedies containing the same

Derivatives of cycloalkyl- and cycloalkenyl-1,2-dicarboxylic acid compounds having formyl peptide receptor like-1 (FPRL-1) agonist or antagonist activity

The invention provides well defined compounds having FPRL-1 agonist or antagonist activity. As such, the compounds of the invention are useful for treating a variety of ocular disorders.

Novel compounds useful as potassium channel openers

Abstract The present invention discloses novel compounds which are useful as potassium channel openers, in particular as openers of the Kv7.4 potassium channel. The novel compounds are compounds according to formula I, wherein -n = 0 or 1, - RL is a substituent selected from the group consisting of unsubstituted or substituted cycloalkyl groups, in particular bicycloalkyl groups, unsubstituted or 5 substituted phenyl groups, unsubstituted or substituted thienyl groups or cyclopentathienyl groups, and unsubstituted or substituted indanyl groups, which optionally contain heteroatoms, and - RR is a substituent selected from the group consisting of unsubstituted or substituted phenyl groups or unsubstituted or substituted benzyl groups, which 0 optionally contain heteroatoms, - or a stereoisomer, a tautomer, a prodrug or a salt, preferably pharmaceutically acceptable salt thereof.

SUBSTITUTED 1, 3, 5-TRIAZINES AND PYRIMIDINES AS ABCA-1 ELEVATING COMPOUNDS AGAINST CORONARY ARTERY DISEASE OR ATHEROSCLEROSIS

The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

N-Phenpropylcyclopentyl-Substituted Glutaramide Derivatives as Inhibitors of Neutral Endopeptidase Enzyme (NEP) for Treating Female Sexual Dysfunction (FSAD)

1. Technical Result Increase in treatment efficiency. 2. Essence N-phenpropylcyclopentyl -substituted glutara- mide derivatives of formula 1 wherein R1, X, Y are provided in the description, pharmaceutically acceptable salts thereof, solvates, polymorphs or prodrugs thereof as inhibitors of neutral endopeptidase (NEP) for treatment of the disorders of Female Sexual Dysfunction (FSAD), methods for its production and pharmaceutical compositions on its basis. 3. Field of Application Medicine, pharmacology.

N-ФЕНПРОПИЛЦИКЛОПЕНТИЛ-ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ГЛУТАРАМИДА В КАЧЕСТВЕ NEP ИНГИБИТОРОВ ПРИ FSAD

Данное изобретение относится к соединениям формулы (I) для лечения, например, сексуальной дисфункции, где R1 представляет собой возможно замещенный C1-6 алкил, возможно замещенный карбоциклил, возможно замещенный гетероциклил, водород, С1-6алкокси, -NR2R3 или -NR4SO2R5; X является связью -(СН2)n- или -(CH2)q-O- (причем Y присоединен к кислороду); где один или более чем один водородный атом в связи Х может быть независимо заменен С1-4алкокси; гидрокси; гидрокси(С1-3алкилом); С3-7 циклоалкилом; карбоциклилом; гетероциклилом или С1-4 алкилом, возможно замещенным одной или более чем одной фторо- или фенильной группой; n равно 3, 4, 5, 6 или 7; и q равно 2, 3, 4, 5 или 6; и Y представляет собой фенил или пиридил, каждый из которых может быть замещен; или две группы R8 на соседних атомах углерода вместе с соединяющими атомами углерода могут образовывать конденсированное, возможно замещенное 5- или 6-членное карбоциклическое или гетероциклическое кольцо.

OF N-FENPROPILTsIKLOPENTIL-SUBSTITUTED DERIVATIVES OF SUBSTITUTED GLUTARAMIDE AS NEP INHIBITORS FOR FSAD

SPHINGOSINE KINASE INHIBITORS

The invention relates to substituted adamantane compounds of formula (I), pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, imflammatory disease, or angiogenic disease. © KIPO & WIPO 2008 ...

링커 티올 및 PEG화된 형태를 갖는 프로스타시클린 화합물의 제조 방법

... 본 발명은 메소 무수물로부터 하기 화학식 I의 키랄 프로스타시클린 유도체를 고수율로 제조하는 방법을 제공한다. <화학식 I> ...

Pharmaceutical composition for treating or preventing diseases attributed to CETP activity

The present invention provides a CETP activity inhibitor comprising as an active ingredient a compound represented by the formula (I), wherein R represents a straight chain or branched alkyl group; a straight chain or branched alkenyl group; a lower haloalkyl group; a substituted or unsubstituted cycloalkyl group; a substituted or unsubstituted cycloalkenyl group; a substituted or unsubstituted cycloalkylalkyl group; a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, X1, X2, X3, and X4 may be the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group; a lower alkoxy group; a cyano group; a nitro group; an acyl group; or an aryl group, Y represents -CO- or -SO2-, and Z represents a hydrogen atom or a mercapto-protecting group, or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. The compounds represented by the formula (I) can increase HDL and at ...

SUBSTITUTED 1, 3, 5-TRIAZINES AND PYRIMIDINES AS ABCA-1 ELEVATING COMPOUNDS AGAINST CORONARY ARTERY DISEASE OR ATHEROSCLEROSIS

The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

BISARYL COMPOUNDS AND CANCER REMEDIES CONTAINING THE SAME

Cancer remedies, each containing a compound of the following general formula (I): Ar?1-S-R1-S-Ar2¿ [wherein RP represents a non-metallic connecting group; Ar?1 and Ar2¿ each independently represents aryl or heteroaryl having 1 to 3 hydroxyls which may be substituted with a monovalent group on the ring thereof (and optionally having 1 to 3 substituents other than the hydroxyl on the ring thereof)] or a physiologically acceptable salt thereof; and compounds of the following general formula (XII): Ar?23-S-R22-N(R24)-R23-S-Ar24¿ [wherein R?22 and R23¿ each independently represents a divalent group; R24 represents a monovalent group or atom, or R24 may be bonded to R22 and/or R23 to form a cyclic structure and further bonded to one or two C¿1-4? alkylene groups to form a divalent group; and Ar?23 and Ar24¿ each independently represents aryl or heteroaryl (optionally having 1 to 3 substituents other than hydroxyl on the ring thereof) having 1 to 3 hydroxyls which may be substituted with a monovalent group; excluding specified compounds] and salts thereof.

CETP ACTIVITY INHIBITORS

CYCLOBUTANE DERIVATIVES AS INHIBITORS OF SQUALENE SYNTHETASE AND PROTEIN FARNESYLTRANSFERASE

PPAR (GAMMA) AGONISTEN FOR THE TREATMENT OF TYPE II DIABETES

NEW CONNECTIONS AS ENTZÜNDUNGSHEMMENDE ONES, IMMUNE-MODULATING AND ANTIPROLIFERATIVE MEANS

INHIBITORS OF THE CETP ACTIVITY

NON-STEROIDAL FXR AGONISTS

Npyy5 antagonists

NOVEL COMPOUNDS AS ANTI-INFLAMMATORY, IMMUNOMODULATORY AND ANTI-PROLIFERATORY AGENTS

The present invention relates to compounds of the general formula (I); or salts thereof, as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

NPY Y5 ANTAGONIST

NPYY5 receptor antagonists which contain compounds represented by general formula (I), prodrugs thereof, pharmaceutically acceptable salts thereof or solvates of the same wherein R1 represents lower alkyl, cycloalkyl, etc.; R2 represents hydrogen, lower alkyl, etc.; n is 1 or 2; X represents lower alkylene, lower alkenylene, arylene, cycloalkylene, etc.; Y represents CONR7, CSNR7, NR7CO, NR7CS, etc. (wherein R7 represents hydrogen or lower alkyl); and Z represents lower alkyl, an optionally substituted hydrocarbon cycle, an optionally substituted heterocycle, etc.

PROCESS FOR PREPARING 1-(2-ETHYL-BUTYL)-CYCLOHEXANECARBOXYLIC ACID

The present invention relates to a process for the preparation of 1 -(2-cthyl-butyl)-cyclohexanecarboxylic acid which is useful as an intermediate in the preparation of, pharmaceutical active compounds, comprising reacting cyclohexanecarboxylic acid derivative of formula (II) wherein Y is an alkali metal, with an alkylating agent, in the presence of a secondary amine and (C1-C6)alkyllithium, (C3-C6)cycloalkyllithium or phenyllithium.

Novel amide derivatives and medicinal use thereof

本发明涉及具有C5a受体拮抗活性的式(1)的酰胺衍生物：

compound or solvate, hydrate or pharmaceutically acceptable salt thereof, pharmaceutical composition, process, and, methods of inhibiting sphingosine kinase in a patient in need of such inhibition, treating a disorder and disease

Antagonista de y5 para npy

NPYY5 antagonists

НИЗКОМОЛЕКУЛЯРНЫЕ МОДУЛЯТОРЫ АКТИВНОСТИ Trp-p8

Настоящее изобретение относится к области органической химии, а именно к соединению формулы I или его фармацевтически приемлемой соли, где Rпредставляет собой Н или Rи Rвместе с группой азота могут образовыватьгде А, В, С и D независимо выбирают из группы, состоящей из CRи N; где, по меньшей мере, один из А, В, С и D представляет собой CR; где Rвыбирают из группы, состоящей из Н, -OR, -SR, -S(O)R, -C(O)NRRи CF, где Rвыбран из группы, состоящей из метила, этила, пропила, гидроксиэтила, гидроксипропила, 2-оксо-2-фенилэтила, бутила, ацетонитрила и бензила; R, Rи Rпредставляет собой метил; Rи Rнезависимо выбраны из группы, состоящей из Н, метила, этила, гидроксиэтила, гидроксипропила, диэтиламиноэтила, фенила, пиридинила, метоксиэтила, гидроксиэтоксиэтила, бензила, фенилэтила, 2-гидрокси-1-гидроксиметил-2-фенилэтила и карбамоилметила, или Rи Rвместе образуют морфолин или сложный этиловый эфир пиперазина; Rвыбирают из группы, состоящей из фенила, нафтила, пиразолила и С-Салкиленфенила; Rпредставляет ...

НОВЫЕ СОЕДИНЕНИЯ, ИСПОЛЬЗУЕМЫЕ В КАЧЕСТВЕ ОТКРЫВАТЕЛЕЙ КАЛИЕВЫХ КАНАЛОВ

AS WELL AS REDUCING KOSMETIKUM FOR THE DAUERWELLE, A DERIVATIVE THE N-MERCAPTO-ALKYL-SUCCINAMSAEURE ONES OR A N-MERCAPTO-ALKYL-SUCCINIMIDS CONTAINS ITS USE IN A HAIR CONTINUOUS WAVING PROCEDURE.

CYCLOBUTANE DERIVATIVES AS INHIBITORS OF THE SQUALEN SYNTHETASE AND THE PROTEIN FARNESYLTRANSFERASE ONES

NEW AMIDE CONNECTIONS AND THEIR MEDICAL USE

Ketone inhibitors of lysine gingipain

The present invention provides compounds according to Formula (I) as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium ...

AMIDE DERIVATIVES, THEIR PRODUCTION PROCESSES AND THEIR COMPOSITIONS FOR THE CONTROL OF INSECT PESTS

Sphingosine kinase inhibitors

Compounds for inhibiting insulin secretion and methods related thereto

HERBICIDAL ACYLATED AMINO-(PHENYL- OR PYRIDINYL- OR THIENYL-)-PHENYL DERIVATIVES

SPHINGOSINE KINASE INHIBITORS

The invention relates to substituted adamantane compounds of formula (I), pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, imflammatory disease, or angiogenic disease.

PROCESS FOR PREPARING 1-(2-ETHYL-BUTYL)-CYCLOHEXANECARBOXYLIC ACID

The present invention relates to a process for the preparation of 1 -(2-cthyl-butyl)-cyclohexanecarboxylic acid which is useful as an intermediate in the preparation of, pharmaceutical active compounds, comprising reacting cyclohexanecarboxylic acid derivative of formula (II) wherein Y is an alkali metal, with an alkylating agent, in the presence of a secondary amine and (C1-C6)alkyllithium, (C3-C6)cycloalkyllithium or phenyllithium.

N-PHENPROPYLCYCLOPENTYL-SUBSTITUTED GLUTARAMIDE DERIVATIVES AS NEP INHIBITORS FOR FSAD

The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R1 is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C1- 6alkoxy, -NR2 R3 or - NR4SO2R5; X is the linkage -(CH2)n- or -(CH2)q-O- (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy; hydroxy; hydroxy(C1- 3alkyl); C3-7cycloalkyl; carbocyclyl; heterocyclyl; or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6, or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5- or 6- membered carbocyclic or heterocyclyic ring.

SMALL-MOLECULE MODULATORS OF TRP-P8 ACTIVITY

Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp- p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.

REDUCTIVE STEP PERMANENT COSMETIC COMPOSITION CONTAINING A DERIVATIVE OF N - (MERCAPTO-ALKYLPHENYL) - SUCCINAMIC OR N (THE MERCAPTO-ALKYL) A SUCCINIMIDE, AND ITS USE IN A METHOD FOR PERMANENT DEFORMATION OF HAIR.

PROCESS OF OBTAINING OF the ACID 1 (2-ETIL-BUTIL) - CICLOHEXANOCARBOXILICO

La presente se refiere a un proceso para la obtencion del ácido 1-(2-etil-butil)-ciclohexanocarboxílico que es util como compuesto intermedio para la obtencion de compuestos activos farmacéuticos. Reivindicacion 1:Un proceso para la obtencion del ácido 1-(2-etil-butil)-ciclohexanocarboxílico de la formula (1) que consiste en hacer reaccionar el derivado ácido ciclohexanocarboxílico derivado de la formula (2), en la que Y es un metal alcalino, con un agente alquilante, en presencia de una amina secundaria y alquil C1-6-litio, cicloalquil C3-6-litio o fenil-litio.

ABCA-1 ELEVATING COMPOUNDS

The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

ABCA-1 ELEVATING COMPOUNDS

The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

CETP ACTIVITY INHIBITORS

The present invention provides a CETP activity inhibitor comprising as an active ingredient a compound represented by the formula (I): wherein R represents a straight chain or branched alkyl group; a straight chain or branched alkenyl group; a lower haloalkyl group; a substituted or unsubstituted cycloalkyl group; a substituted or unsubstituted cycloalkenyl group; a substituted or unsubstituted cycloalkylalkyl group; a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, X1, X2, X3, and X4 may be the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group; a lower alkoxy group; a cyano group; a nitro group; an acyl group; or an aryl group, Y represents CO or SO2, and Z represents a hydrogen atom or a mercapto-protecting group, or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. The compounds represented by the formula (I) can increase HDL and at the ...

ABCA-1 elevating compounds

The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

NOVEL COMPOUNDS USEFUL AS POTASSIUM CHANNEL OPENERS

The present invention discloses novel compounds which are useful as potassium channel openers, in particular as openers of the Kv7.4 potassium channel. The novel compounds are compounds according to formula I, wherein n=0 or 1, RL is a substituent selected from the group consisting of unsubstituted or substituted cycloalkyl groups, in particular bicycloalkyl groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted thienyl groups or cyclopentathienyl groups, and unsubstituted or substituted indanyl groups, which optionally contain heteroatoms, and RR is a substituent selected from the group consisting of unsubstituted or substituted phenyl groups or unsubstituted or substituted benzyl groups, which optionally contain heteroatoms, or a stereoisomer, a tautomer, a prodrug or a salt, preferably pharmaceutically acceptable salt thereof.

Sphingosine kinase inhibitors

The invention relates to substituted adamantane compounds, pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease.

ИНГИБИТОРЫ СФИНГОЗИНКИНАЗЫ

FIELD: medicine, pharmaceutics. SUBSTANCE: present invention refers to new compounds of formula I or their pharmaceutically acceptable salts showing an ability to inhibit sphingosine kinase, to a based pharmaceutical composition, to a method of inhibiting sphingosine kinase and a method of treating diseases specified in breast cancer, diabetic retinopathy, arthritis and colitis. , wherein X represents -C(R 3 ,R 4 )N(R 5 )-, -C(O)N(R 4 )-; R 1 represents phenyl unsubstituted or substituted by 1 or 2 halogens. The values of R 2 , R 3 , R 4 , R 5 substitutes are such as specified in the patent claim. EFFECT: preparation of new compounds. 17 cl, 24 dwg, 9 tbl, 26 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 447 060 (13) C2 (51) МПК C07C C07C C07C C07C C07D C07D C07D ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИC07D C07D C07D 233/57 255/44 317/32 323/23 317/58 207/02 295/13 295/32 213/24 265/30 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) C07D C07D C07D C07D C07D C07D C07D A61K A61K A61K 233/54 (2006.01) 277/46 (2006.01) 263/58 (2006.01) 277/82 (2006.01) 257/04 (2006.01) 209/88 (2006.01) 473/34 (2006.01) 31/33 (2006.01) 31/16 (2006.01) 31/13 (2006.01) (см. прод.) (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ Приоритет(ы): (30) Конвенционный приоритет: 17.06.2005 US 60/691,563 (73) Патентообладатель(и): ЭПОУДЖИ БИОТЕКНОЛОДЖИ КОРПОРЕЙШН (US) 2 4 4 7 0 6 0 (43) Дата публикации заявки: 27.07.2009 Бюл. № 21 2 4 4 7 0 6 0 R U (56) Список документов, цитированных в отчете о поиске: US 4053509 А, 11.10.1977. US 5595995 А, 21.01.1997. US 4332806 А, 01.06.1982. US 3663565 A, 16.05.1972. US 4349552 A, 14.09.1982. US 6649600 B1, 18.11.2003. US 3657273 A, 18.04.1972. WO 99/26927 A2, 03.06.1999. WO 2004/089470 A2, 21.10.2004. SU 1574586 A1, 30.06.1990. SU 1367194 A1, 10.04.1996. RU 2197467 C2, 27.01.2003. SU 451691 A, 09.07.1975. (см. прод.) C 2 C 2 (45) Опубликовано: 10.04.2012 Бюл. № 10 (85) Дата начала рассмотрения заявки PCT на ...

ПРОИЗВОДНЫЕ БЕНЗОЛА И ИХ ФАРМАЦЕВТИЧЕСКОЕ ПРИМЕНЕНИЕ

ЗАМЕЩЕННЫЕ 1,3,5-ТРИАЗИНЫ И ПИРИМИДИНЫ В КАЧЕСТВЕ ПОВЫШАЮЩИХ АВСА-1 СОЕДИНЕНИЙ ПРОТИВ ЗАБОЛЕВАНИЯ КОРОНАРНОЙ АРТЕРИИ ИЛИ АТЕРОСКЛЕРОЗА

СПОСОБ ПОЛУЧЕНИЯ АРОМАТИЧЕСКИХ ТИОЛЬНЫХ ПРОИЗВОДНЫХ ПРИ ГИДРИРОВАНИИ ДИСУЛЬФИДОВ

1. Способ получения соединения формулы (I''):где X, X, Xи Xнезависимо друг от друга представляют собой водород, (C-C)алкил, арил, гетероарил, -OR, -О-C(=O)R, -NHR, -NH-C(=O)Rили; илидва соседних заместителя (т.е. Xи Xили Xи Xили Xи X) вместе с атомами углерода, к которым они присоединены, образуют четырех, пяти или шестичленное циклоалкильное кольцо, которое возможно включает дополнительный гетероатом, выбранный из О, NH и S, где указанное четырех, пяти или шестичленное циклоалкильное кольцо возможно замещено одним-тремя заместителями, независимо выбранными из (C-C)алкила или арила;R, R, Rи Rнезависимо представляют собой (C-C)алкил, (C-C)циклоалкил, арил или гетероарил;каждый Rнезависимо представляет собой водород, (C-C)алкил или арил;согласно которому подвергают взаимодействию соединение формулы (II''):где X, X, Xи Xнезависимо друг от друга представляют собой водород, (C-C)алкил, арил, гетероарил, -OR, -О-C(=O)R, -NHR, -NH-C(=O)Rили; илидва соседних заместителя (т.е. Xи Xили Xи Xили Xи X) вместе с атомами углерода, к которым они присоединены, образуют четырех, пяти или шестичленное циклоалкильное кольцо, которое возможно включает дополнительный гетероатом, выбранный из О, NH и S, где указанное четырех, пяти или шестичленное циклоалкильное кольцо возможно замещено одним-тремя заместителями, независимо выбранными из (C-C)алкила или арила; иR, R, R, R, R, X, X, Xи Xявляются такими, как определено выше, с Hв присутствии гетерогенного катализатора гидрирования на основе переходного металла.2. Способ по п.1 получения соединения формулы (I''')где X, X, Xи Xнезависимо друг от друга представляют собой водород, (C-C)алкил, арил, гетероарил, -OR, -О-C(=O)R, -NHR, -NH-C(=O)Rили; илидва соседних заместителя (т.е. Xи Xили Xи Xили X

PPAR-(GAMMA) AGONISTEN ZUR BEHANDLUNG VON TYPE II DIABETES

THERAPEUTIC AGENTS

Small-molecule modulators of Trp-p8 activity

Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp-p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.

CETP ACTIVITY INHIBITORS

The present invention provides a CETP activity inhibitor comprising as an active ingredient a compound represented by the formula (I): wherein R represents a straight chain or branched alkyl group; a straight chain or branched alkenyl group; a lower haloalkyl group; a substituted or unsubstituted cycloalkyl group; a substituted or unsubstituted cycloalkenyl group; a substituted or unsubstituted cycloalkylalkyl group; a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, X1, X2, X3 and X4 may be the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group; a lower alkoxy group; a cyano group; a vitro group; an acyl group; or an aryl group, Y represents -CO- or -SO2-, and Z represents a hydrogen atom or a mercapto-protecting group, or a prodrug compound, a pharmaceutically acceptable salt, or hydrate or solvate thereof. The compounds represented by the formula ( I ) can increase HDL ...

Novel amide derivatives and medicinal use thereof

Amide derivatives represented by the following general formula (1) which have a C5 alpha receptor antagonism, wherein each symbol has the meaning as defined in the description. These amide derivatives, optically active isomers thereof or pharmaceutically acceptable salts of the same are useful as preventives and remedies for diseases or syndromes caused by inflammation induced by C5 alpha [for example, immunological diseases such as rheumatism and systemic lupus erythematosus, allergic diseases such as sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease and asthma, atherosclerosis, heart infarction, brain infarction, psoriasis, Alzheimer's disease and important organistic breakdown (for example, pneumonia, nephritis, hepatitis, pancreatitis) induced by leukocyte activation caused by ischemic reperfusion, burn or surgical invasion]. Moreover, they are useful as preventives and remedies for infection with bacteria and viruses mediated by C5 alpha receptor.

Process for preparing 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid

NOVEL AMIDE DERIVATIVES AND MEDICINAL USE THEREOF

N-PHENPROPYLCYCLOPENTYL-SUBSTITUTED GLUTARAMIDE DERIVATIVES AS NEP INHIBITORS FOR FSAD

The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R1 is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C1-6alkoxy, -NR2 R3 or - NR4SO2R5; X is the linkage -(CH2)n- or -(CH2)q-O- (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy; hydroxy; hydroxy(C1-3alkyl); C3-7cycloalkyl; carbocyclyl; heterocyclyl; or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6, or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5- or 6-membered carbocyclic or heterocyclyic ring.

DERIVATIVES OF CYCLOALKYL- AND CYCLOALKENYL-1,2-DICARBOXYLIC ACID COMPOUNDS HAVING FORMYL PEPTIDE RECEPTOR LIKE-1 (FPRL-1) AGONIST OR ANTAGONIST ACTIVITY

The invention provides well defined compounds having FPRL-1 agonist or antagonist activity. As such, the compounds of the invention are useful for treating a variety of ocular disorders.

BISARYL COMPOUNDS AND CANCER REMEDIES CONTAINING THE SAME

A medicament for treatment of cancer comprising a compound represented by the following general formula (I) or a physiologically acceptable salt thereof: wherein R1 represents a nonmetal bridging group; Ar1 and Ar2 independently represent a group selected from the group consisting of an aryl group which has, on its ring, one to three hydroxyl groups optionally substituted with a monovalent group and said aryl group may have one to three substituents other than hydroxyl group on its ring; and a heteroaryl group which has, on its ring, one to three hydroxyl groups optionally substituted with a monovalent group, and said heteroaryl group may have one to three substituents other than hydroxyl group on its ring.

ИНГИБИТОРЫ СФИНГОЗИНКИНАЗЫ

... 1. Соединение формулы I ! ! и его фармацевтически приемлемая соль, гидрат или сольват, где ! L представляет собой связь или -С(R3,R4)-; ! Х представляет собой -C(R3,R4)N(R5)-, -C(O)N(R4)-, -N(R4)C(O)-, -C(R4,R5)-, -N(R4)-, -O-, -S-, -C(O)-, -S(O)2-, -S(O)2N(R4)- или -N(R4)S(O)2-; ! R1 представляет собой Н, алкил, циклоалкил, циклоалкилалкил, алкенил, алкинил, гетероалкил, арил, алкиларил, алкениларил, гетероциклил, гетероарил, алкилгетероарил, гетероциклоалкил, алкилгетероциклоалкил, ацил, ароил, галоген, галогеналкил, алкокси, галогеналкокси, гидроксиалкил, алканоил, -СООН, -ОН, -SH, -S-алкил, -CN, -NO2, -NH2, -СO2(алкил), -ОС(O)алкил, карбамоил, моно или диалкиламинокарбамоил, моно или диалкилкарбамоил, моно или диалкиламино, аминоалкил, моно- или диалкиламиноалкил, тиокарбамоил, или моно или диалкилтиокарбамоил; ! R2 представляет собой Н, алкил, циклоалкил, циклоалкилалкил, алкенил, алкинил, гетероалкил, арил, алкиларил, алкениларил, гетероциклил, гетероарил, алкилгетероарил, гетероциклоалкил ...

HYPOGLYCAEMIC AMIDINES AND GUANIDINES

Compounds of formula I and their salts in which n = 0 or 1, R1 and R2 are each aliphatic or cyloallkyl or NR1R2 is an optionally substituted heterocyclic ring, R3 is alkyl, cycloalkyl or optionally substituted amino, R5 is H or an aliphatic group, R6 is H, an optionally substituted aliphatic group or a cycloalkyl group, or R3 and R5 together with the nitrogen and carbon atoms to which they are attached form an optionally substituted heterocyclic ring or R5 and R6 together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted by alkyl and R7 is hydrogen, halogen, optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkoxycarbonyl, trifluoromethyl or cyano have utility as hypoglycaemic agents and may be incorporated into pharmaceutical compositions.

HYPOGLYCAEMIC AMIDINES AND GUANIDINES

Cyclobutane derivatives and their use as inhibitors of prote in farnesyltransferase

KETONE INHIBITORS OF LYSINE GINGIPAIN

The present invention provides compounds according to Formula I as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium . Also described are gingipain activity probe compounds and methods for assaying gingipain activity are also described, as well as methods for the treatment of disorders associated with infection, including brain disorders such as Alzheimer's disease. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of Ccycloalkyl claim 1 , Calkyl claim 1 , Caryl claim 1 , and 5- to 12-membered heteroaryl each of which is optionally substituted with one or more Rsubstituents claim 1 , and each Ris independently selected from the group consisting of halogen claim 1 , —N claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Chaloalkoxy claim 1 , —N(R) claim 1 , —N(R) claim 1 , and —NRC(O)R.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris Calkyl substituted with Calkoxy.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.67-. (canceled)8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHR claim 1 , Ris —O—R claim 1 , and Ris Chaloalkyl.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHR claim 1 , Ris —O—R claim 1 , and Ris 5- to 12-membered heteroaryl claim 1 , which is optionally substituted with one or more members independently selected from the group consisting of halogen and Calkyl.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of —N(R) claim 1 , 5- to 12-membered heteroaryl claim 1 , and 3- to 12-membered heterocyclyl claim 1 , wherein:{'sub': 1-3', '1-3, '5- to 12-membered heteroaryl is optionally substituted with one or more members ...

PROCESS OF MAKING PROSTACYCLIN COMPOUNDS WITH LINKER THIOL AND PEGYLATED FORMS

A process provides for producing chiral prostacyclin derivatives of Formula (I) 2. The process of claim 1 , wherein Ris a benzyl claim 1 , tertiary-butyl claim 1 , dimethoxy benzyl claim 1 , nitrobenzyl or a dinitrobenzyl group.3. The process of claim 1 , wherein the chiral ligand is a quinine or quinidine derivative.4. The process of claim 3 , wherein the quinine or quinidine derivative is hydroquinine anthraquinone-1 claim 3 ,4-diyl diether ((DHQ)AQN) claim 3 , hydroquinidine anthraquinone-1 claim 3 ,4-diyl diether ((DHQD)AQN).5. The process of claim 1 , wherein the hydrolyzing agent is trimethyltin hydroxide.6. The process of claim 1 , wherein the compound of Formula VIII is deprotected using an acid.7. The process of claim 6 , wherein the acid is trifluoroacetic acid.9. The process of claim 8 , wherein Ris a benzyl claim 8 , tertiary-butyl claim 8 , dimethoxy benzyl claim 8 , nitrobenzyl or a dinitrobenzyl group.10. The process of claim 8 , wherein Ris a tetrahydropyranyl claim 8 , benzyl claim 8 , methoxybenzyl claim 8 , nitrobenzyl claim 8 , tertiary butyl dimethyl silyl or a tertiary methyl dimethyl silyl group.11. The process of claim 8 , wherein the compound of Formula VII is deprotected using an acid.12. The process of claim 11 , wherein the acid is trifluoroacetic acid.14. The process of claim 13 , wherein Ris a benzyl claim 13 , tertiary-butyl claim 13 , dimethoxy benzyl claim 13 , nitrobenzyl or a dinitrobenzyl group.15. The process of claim 13 , wherein Ris a tetrahydropyranyl claim 13 , benzyl claim 13 , methoxybenzyl claim 13 , nitrobenzyl claim 13 , tertiary butyl dimethyl silyl or a tertiary methyl dimethyl silyl group.16. The process of claim 13 , wherein Ris a Calkyl group.17. The process of claim 1 , wherein the purity of compound of Formula I is at least 90%.18. The process of claim 1 , wherein the purity of compound of Formula II is at least 90%.19. The process of claim 1 , wherein the polyethylene glycol maleimide compound is a 4-arm 20 KDa ...

KETONE INHIBITORS OF LYSINE GINGIPAIN

The present invention provides compounds according to Formula I as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium . Also described are gingipain activity probe compounds and methods for assaying gingipain activity are also described, as well as methods for the treatment of disorders associated with infection, including brain disorders such as Alzheimer's disease. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of Ccycloalkyl claim 1 , Calkyl claim 1 , Caryl claim 1 , 5- to 12-membered heteroaryl claim 1 , and 3- to 12-membered heterocyclyl claim 1 , each of which is optionally substituted with one or more Rsubstituents.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently selected from the group consisting of halogen claim 1 , —N claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Chaloalkoxy claim 1 , —N(R) claim 1 , —N(R) claim 1 , and —NRC(O)R.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —O-phenyl claim 1 , wherein phenyl is substituted with 1-5 halogens.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of 2 claim 1 ,3 claim 1 ,6-trifluorophenoxy; 2 claim 1 ,3 claim 1 ,5-trifluorophenoxy; 2 claim 1 ,3 claim 1 ,4-trifluorophenoxy; 3 claim 1 ,4 claim 1 ,5-trifluorophenoxy; 2 claim 1 ,3-difluorophenoxy; 2 claim 1 ,4-difluorophenoxy; 2 claim 1 ,5-difluorophenoxy; 2 claim 1 ,6-difluorophenoxy; 3 claim 1 ,4-difluorophenoxy; 3 claim 1 ,5-difluorophenoxy; 2-fluorophenoxy; 3-fluorophenoxy; and 4-fluorophenoxy.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHR claim 1 , Ris —O ...

Process For Preparation Of Vortioxetine Hydrobromide

The present invention provides a process for preparation of Vortioxetine hydrobromide (I). The present invention also relates to the novel intermediate and its use in preparation of vortioxetine hydrobromide (I). 4. The process of claim 2 , wherein reduction is carried out in presence of a reducing agent selected from lithium aluminum hydride (LiAlH); Sodium bis(2-methoxyethoxy) aluminumhydride (trade names Red-Al or vitride); Borane-dimethyl sulfide (Borane-DMS); a combination of borohydride and a lewis acid claim 2 , wherein borohydride is selected from sodium borohydride (NaBH) claim 2 , lithium borohydride (LiBH) claim 2 , and sodium cyanoborohydride (NaCNBH) and the lewis acid is selected from ZnCl claim 2 , AlCl claim 2 , MgCl claim 2 , BFand TiCl; and a combination of borohydride and other reagent claim 2 , wherein borohydride is selected from sodium borohydride (NaBH) claim 2 , lithium borohydride (LiBH) claim 2 , and sodium cyanoborohydride (NaCNBH) and the other reagent is selected from acetic acid claim 2 , pyridine claim 2 , POCl claim 2 , trimethylsilyl.5. The process of claim 1 , wherein said protecting group Pr is selected from tertbutyloxycarbonyl (boc) claim 1 , triphenylmethyl (trityl) claim 1 , benzyloxycarbonyl (cbz) claim 1 , benzyl claim 1 , trifluoroacetyl (COCF) claim 1 , acetyl claim 1 , silyl or any other N-protecting or O-protecting group.7. (canceled)8. (canceled)10. (canceled)11. (canceled)12. The process of claim 9 , wherein said protecting group PROC is selected from methane sulfonyl claim 9 , p-toluene sulfonyl claim 9 , nosyl claim 9 , COCF(trifluoro acetyl) claim 9 , acetyl claim 9 , acyl claim 9 , benzyl claim 9 , substituted benzyl claim 9 , benzoyl claim 9 , trimethylsilyl claim 9 , tert butyl dimethyl silyl (TBDMS) claim 9 , trifluoromethylsulfonate (OTf).13. The process of claim 1 , wherein step (e) deprotection is carried out by hydrolysis or hydrogenation depending on the protecting group.14. The process of claim 1 , wherein ...

Compositions and methods for the treatment of disease associated with trp-p8 expression

Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Tip-p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Tip-p8 expression.

MODULATORS OF THE INTEGRATED STRESS PATHWAY

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions. 2. The compound of claim 1 , wherein D is a bridged bicyclic cycloalkyl or a bridged bicyclic heterocyclyl claim 1 , each of which is optionally substituted with 1-4 Rgroups.3. The compound of any one of - claim 1 , wherein D is a bridged 5-8 membered bicyclic cycloalkyl or heterocyclyl claim 1 , each of which is optionally substituted with 1-4 Rgroups.4. The compound of any one of - claim 1 , wherein D is selected from cubane claim 1 , bicyclo[1.1.1]pentane claim 1 , bicyclo[2.2.2]octane claim 1 , bicyclo[2.1.1]hexane claim 1 , bicyclo[3.1.1]heptane claim 1 , bicyclo[2.2.1]heptane claim 1 , bicyclo[3.2.1]octane claim 1 , 2-azabicyclo[2.2.2]octane claim 1 , or 2-oxabicyclo[2.2.2]octane claim 1 , each of which is optionally substituted with 1-4 Rgroups.8. The compound of any one of - claim 1 , wherein D is substituted with 0 R.10. The compound of any one of - claim 1 , wherein D is substituted with 1 or 2 R.12. The compound of any one of - claim 1 , wherein each Ris independently selected from the group consisting of oxo claim 1 , —OH claim 1 , —C(O)OH claim 1 , —C(O)OR claim 1 , halo claim 1 , and hydroxy-C-Calkyl.13. The compound of any one of - claim 1 , wherein at least one of Land Lis independently 2-7-membered heteroalkylene optionally substituted by 1-5 R.14. The compound of any one of - claim 1 , wherein Lis 2-7-membered heteroalkylene and Lis C-Calkylene or 2-7-membered heteroalkylene claim 1 , wherein each alkylene and heteroalkylene is optionally substituted by 1-5 R.15. The compound of any one of - claim 1 , wherein Lis CHO—* or CHCHO—* claim 1 , wherein “-*” indicates the attachment point to A.16. The compound of any one of - claim 1 , wherein Lis selected from the group consisting of —CH—* claim 1 , —CHCH—* claim 1 , CHCHCH—* claim 1 , —CH(CH)—* claim 1 , —CH(CH)CH—* claim 1 , — ...

INDUSTRIAL PROCESS FOR THE PREPARATION OF (5S, 10S)-10-BENZYL-16-METHYL-11, 14, 18-TRIOXO-15, 17, 19-TRIOXA-2,7,8-TRITHIA-12-AZAHENICOSAN-5-AMINIUM(E)-3-CARBOXYACRYLATE SALT

The present invention relates to an industrial process for the preparation of (5S,10S)-10-benzyl-16-methyl-11,14,18-trioxo-15,17,19-trioxa-2,7,8-trithia-12-azahenicosan-5-aminium (E)-3-carboxyacrylate salt of following formula (I): wherein X is fumarate. This process comprises the following successive key steps: a kinetic resolution, formation of disulfide compound, peptide coupling, and anion exchange reaction to obtain the desired product of formula (I). 2. Industrial process according to claim 1 , wherein crystallization in step 1b comprises the following successive steps:1b.1) dissolution of quinine salt at solubilizing temperature, then;1b.2) cooling the mixture obtained in step 1 b.1, until temperature ranging from 10° C. to 20° C.;1b.3) isolating quinine salt obtained after step 1 b.2 by filtration.3. Industrial process claim 1 , according to claim 1 , wherein in step 1a is solvent is ethyl acetate.5. Industrial process claim 1 , according to claim 1 , further comprising after step 1d.1 claim 1 , the following successive steps:1d.2.1) Alkaline hydrolysis in polar and protic solvent, then1d.2.2) Acidic treatment, then;1d.2.3) Extraction of compound (E) with organic solvent.6. Industrial process according to claim 1 , wherein the recovering of quinine in step 1e comprises the following successive steps:1e.1) Combining the aqueous phases obtained in step 1d.2.1 and in step 1d.2.2, then;1e.2) Adding 20% by weight of aqueous solution of NaOH in water to adjust the pH to 12, then;1e.3) Extracting the resulting mixture obtained in step 1e.2 with AcOEt, then;1e.4) Concentrating under vacuum the resulting organic layer obtained in step 1e.3, then;1e.5) Adding petroleum ether at temperature ranging from 10° C. to 20° C., then;1e.6) Filtrating the resulting solid obtained at the end of step 1e.5 and recovering quinine.7. Industrial process according to claim 1 , further comprising after step 2b and before step 3 the following successive steps:2b.1) adding water ...

Process of making prostacyclin compounds with linker thiol and pegylated forms

본 발명은 메소 무수물로부터 하기 화학식 I의 키랄 프로스타시클린 유도체를 고수율로 제조하는 방법을 제공한다. <화학식 I> The present invention provides a method for preparing a chiral prostacycline derivative of formula (I) from meso anhydride in high yield. <Formula I>

用作抗炎、免疫调节及抗增殖药剂的新化合物

本发明涉及用作抗炎、免疫调节及抗增殖药剂的通式(I)的化合物或其盐。

Bisaryl compound and medicament for cancer treatment comprising the same

A medicament for treatment of cancer comprising a compound represented by the following general formula (I) or a physiologically acceptable salt thereof: Ar 1 —S—R 1 —S—Ar 2 wherein R 1 represents a nonmetal bridging group; Ar 1 and Ar 2 independently represent a group selected from the group consisting of an aryl group which has, on its ring, one to three hydroxyl groups optionally substituted with a monovalent group and said aryl group may have one to three substituents other than hydroxyl group on its ring; and a heteroaryl group which has, on its ring, one to three hydroxyl groups optionally substituted with a monovalent group, and said heteroaryl group may have one to three substituents other than hydroxyl group on its ring.

Isothiazole derivatives as insecticidal compounds

The present invention provides compounds of formula (I). The invention also provides methods of controlling insects, acarines, nematodes or molluscs using the compounds of formula 1.

Inhibitors of protein farnesyltransferase and squalene synthase

The present invention provides a compound of the formula ##STR1## or a pharmaceutically acceptable salt thereof, which are useful in inhibiting protein farnesyltransferase and the farnesylation of the oncogene protein Ras or inhibiting de novo squalene production resulting in the inhibition of cholesterol biosynthesis, processes for the preparation of the compounds of the invention in addition to intermediates useful in these processes, a pharmaceutical composition, and to methods of using such compounds.

Small­molecule modulators of trp­p8 activity

본 발명은 Trp-p8 작용제 및 Trp-p8 길항제를 포함하는, 소-분자 Trp-p8 조절자, 및 소-분자 Trp-p8 작용제를 포함하는 조성물을 비롯한 신규한 소-분자 Trp-p8 조절자를 확인하고 특성을 결정하기 위한 방법 및 Trp-p8 발현 세포의 생존도를 감소시키고/시키거나 상기 세포의 성장을 억제시키기 위한 방법, Trp-p8-매개성 양이온 유입을 활성화시키기 위한 방법, 아폽토시스 및/또는 괴사를 자극하기 위한 방법을 제공하며, Trp-p8 발현과 관련된, 암, 예컨대 폐암, 유방암, 대장암, 및/또는 전립선암을 비롯한 기타 질병, 예컨대 양성 전립선 비대증을 포함하는, 질병의 치료를 위한 관련 방법과 관련이 있다.

Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents

본 발명은 다음 화학식 1의 화합물 또는 이의 염에 관한 것이다: The present invention relates to a compound of formula (I) or a salt thereof: 상기 식에서, Where A는 5개의 탄소원자를 함유하는 비방향족 환 시스템이고, 여기에서 이러한 환 시스템은 하나 이상의 이중 결합을 포함하고, 이 환에서 탄소원자중의 하나 이상은 그룹 X 에 의해 치환될 수 있으며, X 는 S, O, N, NR 4 , SO 또는 SO 2 로 이루어진 그룹으로부터 선택되고, 이 환의 탄소원자중의 하나 이상은 치환체 R 1 을 수반할 수 있고, A is a non-aromatic ring system containing five carbon atoms, wherein such ring system comprises at least one double bond, wherein at least one of the carbon atoms in the ring may be substituted by group X, X is S, Is selected from the group consisting of O, N, NR 4 , SO or SO 2 , at least one of the carbon atoms of this ring may carry a substituent R 1 , D 는 O, S, SO 2 , NR 4 또는 CH 2 이고, D is O, S, SO 2 , NR 4 or CH 2 , Z 1 및 Z 2 는 서로 독립적으로 O, S 또는 NR 5 이고, Z 1 and Z 2 are independently of each other O, S or NR 5 , R 1 은 독립적으로 H, 할로겐, 할로알킬, 할로알킬옥시 또는 알킬이고, R 1 is independently H, halogen, haloalkyl, haloalkyloxy or alkyl, R 2 는 H 또는 OR 6 이고, R 2 is H or OR 6 , R 3 은 H, 알킬, 사이클로알킬, 아릴, 알콕시, O-아릴, O-사이클로알킬, 할로겐, 아미노알킬, 알킬아미노, 하이드록실알킬, 할로알킬옥시, 헤테로아릴, 알킬티오, S-아릴, S-사이클로알킬, 아릴알킬 또는 할로알킬이다. R 3 is H, alkyl, cycloalkyl, aryl, alkoxy, O-aryl, O-cycloalkyl, halogen, aminoalkyl, alkylamino, hydroxylalkyl, haloalkyloxy, heteroaryl, alkylthio, S-aryl, S -Cycloalkyl, arylalkyl or haloalkyl. 소염제, 면역조절물질, 세포 증식, 류마티즘, 면역학적 질환, 디하이드로오로테이트 데하이드로제나제, 피리미딘 생합성, 생리학적으로 관능성인 유도체 Anti-inflammatory agents, immunomodulators, cell proliferation, rheumatism, immunological disorders, dehydroorotate dehydrogenase, pyrimidine biosynthesis, physiologically functional derivatives

Production of ethylene glycol

(57)【要約】 （修正有） 【解決手段】一般式（Ｉ） （式中、Ｒは直鎖又は分枝状のアルキル基；直鎖又は分 枝状のアルケニル基；低級ハロアルキル基などであり、 Ｘ 1 、Ｘ 2 、Ｘ 3 、Ｘ 4 は同一又は異なっていてもよく、水 素原子；ハロゲン原子；低級アルキル基；低級ハロアル キル基；低級アルコキシ基；シアノ基；ニトロ基；アシ ル基又はアリール基であり、Ｙは−ＣＯ−又は−ＳＯ 2 −であり、Ｚは水素原子又はメルカプト保護基である） で表わされる化合物、そのプロドラッグ化合物、その医 薬上許容し得る塩、又はその水和物若しくは溶媒和物を 有効成分としてなるＣＥＴＰ活性阻害剤。 【効果】上記の化合物は、ＣＥＴＰの活性を選択的に阻 害することにより、ＨＤＬを増加させると同時にＬＤＬ を低下させることのできる新しいタイプの動脈硬化若し くは高脂血症の予防又は治療薬として有用性が期待され る。

Patent RU2019111188A3

`” ВУ“? 2019111188” АЗ Дата публикации: 14.01.2021 Форма № 18 ИЗИМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2019111188/04(02 1741) 15.09.2017 РСТЛ52017/051912 15.09.2017 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 62/395,938 16.09.2016 05 2. 62/459,456 15.02.2017 05 Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) КЕТОНОВЫЕ ИНГИБИТОРЫ ЛИЗИН-СПЕЦИФИЧНОГО ГИНГИПАИНА Заявитель: КОРТЕКСИМ, ИНК., 05 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты (см. Примечания) [ ] приняты во внимание следующие пункты: [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) Аб/1К 31/16 (2006.01) А6б1К 45/06 (2006.01) С07С 323/42 (2006.01) Аб/1К 31/165 (2006.01) Аб1Р 25/00 (2006.01) С07С 381/00 (2006.01) Аб1К 31/167 (2006.01) Аб1Р 31/4 (2006.01) С07В 59/00 (2006.01) Аб/1К 31/41 (2006.01) С07С 233/62 (2006.01) (070 213/70 (2006.01) Аб1К 31/42 (2006.01) С07С 233/78 (2006.01) (070 213/65 (2006.01) Аб/1К 31/44 (2006.01) С07С 235/10 (2006.01) (070 213/68 (2006.01) Аб1К 31/4402 (2006.01) С07С 235/50 (2006.01) (070 213/651 (2006.01) Аб1К 31/4406 (2006.01) С07С 237/42 (2006.01) (070 213/82 (2006.01) Аб/1К 31/4409 (2006.01) ...

Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents

The present invention relates to compounds of the general formula (I), wherein A is a non-aromatic ring system containing 4 to 8 carbon atoms, wherein the ring system comprises at least one double bond and wherein one or more of the carbon atoms in the ring can be substituted by a group X, wherein X is selected from the group consisting of S, O, N, NH, NHR4, SO or SO¿2?, and wherein one or more of the carbon atoms of the ring can carry a substituent R?1¿; D is O, S, SO¿2?, NH, NHR?4¿, or CH¿2; R?1 is independently H, halogen, CF¿3?, OCF3, or C1-C5-alkyl; R?2¿ is H, OH, OR6, NH2, NHR7; R6 is H, alkyl, cycloalkyl, aryl, arylalkyl, alkylaryl, alkoxyalkyl, acylmethyl, (acyloxy)alkyl, non-symmetrical(acyloxy)alkyldiester, dialkylphosphate; R7 is H, alkyl, aryl, O-alkyl, O-aryl, cycloalkyl or O-cycloalkyl; R8 is hydrogen or alkyl; R3 is H, cycloalkyl, aryl, O-alkyl, O-aryl or O-cycloalkyl; R4 is C1-C5-alkyl or an unsaturated or saturated carbocycle selected from the group consisting of cyclopentyl, cyclohexyl or aryl; Z?1 and Z2¿ are independent from each other O, S, NH or NR5; R5 is OH, O-alkyl, O-aryl, alkyl or aryl; Ar is a monocyclic or polycyclic substituted or unsubstituted ring system which may contain one or more groups X and which contains at least one aromatic ring; Y is hydrogen, halogen, CF¿3?, OCF3, substituted or unsubstituted alkyl; substituted or unsubstituted cycloalkyl, Ar, O-substituted or unsubstituted Ar, O-substituted or unsubstituted alkylaryl, O-substituted or unsubstituted arylalkyl or (Formula); m is 0 or 1; and q is 0 to 10; with the proviso that when ring A is an unsubstituted carbocyclus containing five carbon atoms and one double bond between the CZ?1 and CZ2-¿substituents with Z1 = Z2 = O and R2 = OH, the following compounds are excluded: q = 0; Y = hydrogen; Ar = phenylene or naphthylene, phenylene substituted with one or two chlorine atoms or with 2-methyl, 4-methyl, 4-methoxy, 4-ethoxy, 2, 6-diethyl, 2-chloro-4-methyl, 4-bromo, 4-cyano, 2 ...

PERMANENTLY REDUCING COSMETIC COMPOSITION CONTAINING SUCCINAMIC N- (MERCAPTO ALKYL) ACID OR N- (MERCAPTO ALKYL) SUCCINIMIDE DERIVATIVE, AND USE THEREOF IN A METHOD OF PERMANENTLY DEFORMING HAIR.

Composition cosmétique pour le traitement des cheuveux. Cette composition contient, dans un véhicule approprié un agent réducteur ayant la formule générale suivante: (CF DESSIN DANS BOPI) dans laquelle: n est 2 ou 3 A représente un radical divalent choisi parmi: (CF DESSIN DANS BOPI) R3 et R4 , identiques ou différents, représentant un radical alkyle ayant de 1 à 4 atomes de carbone ou R3 et R4 forment ensemble, avec les atomes de carbone adjacents, un cycle cyclohexane, et (CF DESSIN DANS BOPI) R5 et R6 , identiques ou différents, représentant un atome d'hydrogène, un radical alkyle ayant de 1 à 4 atomes de carbone ou R5 et R6 forment ensemble, avec les atomes de carbone adjacents, un cycle benzénique, R1 représente un atome d'hydrogène et R2 représente un radical hydroxy ou R1 et R2 pris ensemble forment une liaison simple, et les sels d'une base organique ou minérale desdits composés sous forme acide libre. Utilisation de la composition pour le premier temps d'une opération de déformation permanente des cheveux.

Process for the preparation of cyclohexanecarboxylic acid derivatives

A process for the preparation of a compound of formula (I): which is useful as an intermediate in the preparation of pharmaceutically active compounds.

Sphingosine kinase inhibitors

Compuesto de fórmula**Fórmula** o una sal farmaceuticamente aceptable, hidrato o solvato del mismo, en la que: Y es -N(R4)-; R1 es fenilo, sustituido con 1 ó 2 halogenos, R2 es arilo, -alquilarilo, heterocicloalquilo, -alquil-heterocicloalquilo, heteroarilo o -alquil-heteroarilo opcionalmente sustituido; R3 es H, alquilo u oxo; en la que la parte de alquilo y anillo de cada uno de los grupos R2 y R3 anteriores esta opcionalmente sustituida con hasta 5 grupos que son independientemente alquilo (C1-C6), halógeno, haloalquilo, -0C(0)(alquilo C1-C6), -C(0)0(alquilo C1-C6), -CONR'R", -0C(0)NR' R", -NR'C(0)R", -CF3, -0CF3, -OH, alcoxilo hidroxialquilo, -CN, -CO2H, -SH, -S-alquilo, -SOR'R", -SO2R', -NO2 o NR'R", en la que R' y R" son independientemente H o alquilo (C1-C6), y en la que cada parte de alquilo de un sustituyente esta opcionalmente sustituida adicionalmente con 1, 2 1:5 3 grupos seleccionados independientemente de halógeno, CN, OH y NH2; y R4 es H o alquilo (C1-C6). Compound of formula ** Formula ** or a pharmaceutically acceptable salt, hydrate or solvate thereof, in which: Y is -N (R4) -; R1 is phenyl, substituted with 1 or 2 halogens, R2 is aryl, -alkylaryl, heterocycloalkyl, -alkyl-heterocycloalkyl, heteroaryl or -alkyl-heteroaryl optionally substituted; R3 is H, alkyl or oxo; wherein the alkyl and ring portion of each of the above R2 and R3 groups is optionally substituted with up to 5 groups that are independently (C1-C6) alkyl, halogen, haloalkyl, -0C (0) (C1-C6 alkyl ), -C (0) 0 (C1-C6 alkyl), -CONR'R ", -0C (0) NR 'R", -NR'C (0) R ", -CF3, -0CF3, -OH, hydroxyalkyl alkoxy, -CN, -CO2H, -SH, -S-alkyl, -SOR'R ", -SO2R ', -NO2 or NR'R", in which R' and R "are independently H or (C1 alkyl) -C6), and in which each alkyl part of a substituent is optionally further substituted with 1, 2 1: 5 3 groups independently selected from halogen, CN, OH and NH2; and R4 ...

Abca-1 elevating compounds against coronary artery disease or atherosclerosis

The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

Process of making prostacyclin compounds with linker thiol and pegylated forms

ABSTRACT A process provides for producing chiral prostacyclin derivatives of Formula (I) ÇIìiCiiiI"WO (I) 0 0 X COOH _____________________________ S N ¨ PEG H \ /1-0 in high yield from meso anhydrides. A process involves coupling a meso anhydride of Formula III with an ester compound in the presence of a chiral ligand, to provide a compound of Formula V, which is coupled with a compound of Formula VI to form a thiol and the thiol is hydrolyzed with a hydrolyzing agent to form a compound of Formula VIII. The compound of Formula VIII is deprotected to form the compound of Formula II, which is coupled with a PEG-maleimide compound to form the compound of Formula I. Alternate processes begin with desymmeterizing a meso anhydride of Formula III using an alcohol to provide an hemiester of Formula IX, which undergoes various reaction steps to form the compound of Formula II, which is coupled with a PEG-maleimide compound to form the compound of Formula I. Date recu/Date received 2020-06-16

N-Phenylpropylcyclopentyl- substituted glutaramide derivatives as NEP inhibitors for FSAD

The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R<1> is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C1-6alkoxy, -NR2 R<3> or - NR<4>SO2R<5>; X is the linkage -(CH2)n- or -(CH2)q-O- (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy; hydroxy; hydroxy(C1-3alkyl); C3-7cycloalkyl; carbocyclyl; heterocyclyl; or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6, or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R<8> groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5- or 6-membered carbocyclic or heterocyclyic ring.

Therapeutic agents

Npyy5 antagonists

하기 화학식 Ⅰ 로 표시되는 화합물, 그의 전구 약물, 그의 약제학적 허용가능 염 또는 그의 용매화물을 함유하는, NPY Y5 수용체 길항제: [화학식 Ⅰ] [식 중, R 1 은 저급 알킬, 시클로알킬 등이고; R 2 는 수소, 저급 알킬 등이며; n 은 1 또는 2 이고; X 는 저급 알킬렌, 저급 알케닐렌, 아릴렌, 시클로알킬렌 등이며; Y 는 CONR 7 , CSNR 7 , NR 7 CO, NR 7 CS (R 7 은 수소 또는 저급 알킬임)등이고; Z 는 저급 알킬, 치환될 수 있는 카르보시클릴, 치환될 수 있는 헤테로시클릴 등이다].

Novel amide derivatives and medicinal use thereof

The present invention relates to an amide derivative of the formula (1), having a C5a receptor antagonistic action (see formula 1) wherein each symbol is as defined in the specification. The above-mentioned amide derivative, an optically active form thereof and a pharmaceutically acceptable salt thereof are promising as an agent for the treatment or prophylaxis of diseases or syndromes caused by inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia reperfusion, trauma, burn, surgical invasion and the like]. Moreover, they are useful as a therapeutic or prophylactic agent for the infectious diseases caused by bacteria and virus that invade via a C5a receptor.

Abca-1 elevating compounds against coronary artery disease or atherosclerosis

The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

Npyy5 antagonists

NPYY5 receptor antagonists which contain compounds represented bygeneral formula (I), prodrugs thereof, pharmaceutically acceptable salts thereof or solvates of the same wherein R1 represents lower alkyl, cycloalkyl, etc.; R2 represents hydrogen, lower alkyl, etc.; n is 1 or 2; X represents lower alkylene, lower alkenylene, arylene, cycloalkylene, etc.; Y represents CONR?7, CSNR7, NR7CO, NR7¿CS, etc. (wherein R7 represents hydrogen or lower alkyl); and Z represents lower alkyl, an optionally substituted hydrocarbon cycle, an optionally substituted heterocycle, etc.

Hypoglycaemic phenylamidines and phenylguanidines

Compounds of formula I (see formula I) and their salts in which n = 0 or 1, R1 and R2 are each aliphatic or cycloalkyl or NR1R2 is an optionally substituted heterocyclic ring, R3 is alkyl, cycloalkyl or optionally substituted amino, R5 is an aliphatic group, R6 is H, an optionally substituted aliphatic group or a cycloalkyl group, or R3 and R5 together with the nitrogen and carbon atoms to which they are attached form an optionally substituted heterocyclic ring or R5 and R6 together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted by alkyl and R7 is optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkoxycarbonyl, trifluoromethyl or cyano have utility as hypoglycaemic agents.

NPY-Y5 ANTAGONISTS.

Uso de un compuesto de la fórmula (I): (Ver fórmula) en la que R 1 es alquilo C1-C10 opcionalmente sustituido, o cicloalquilo C3-C8 opcionalmente sustituido, R 2 es hidrógeno o alquilo C1-C10, y R 1 y R 2 juntos pueden formar un alquileno C1-C6, incluido el caso, en el que (Ver fórmula) es (Ver fórmula) n es el número 1 ó 2, X es alquileno C1-C6 opcionalmente sustituido, alquenileno C2-C6 opcionalmente sustituido, -CO-alquileno C1-C6 opcionalmente sustituido, -CO-alquenileno C2-C6 opcionalmente sustituido o (Ver fórmula) en la que R 3 , R 4 , R 5 y R 6 con independencia entre sí son hidrógeno o alquilo C1-C10, (Ver fórmula) es cicloalquileno C3-C8 opcionalmente sustituido, cicloalquenileno C3-C8 opcionalmente sustituido, bicicloalquileno C3-C8 opcionalmente sustituido, arileno opcionalmente sustituido elegido entre un grupo bivalente formado por exclusión de un hidrógeno del fenilo, naftilo, antrilo, fenantrilo, indanilo, indenilo, bifenililo, acenaftilo, tetrahidronaftilo y fluorenilo, arileno o heterociclodiilo opcionalmente sustituido y p y q con independencia entre sí son el número 0 ó 1, -NR 2 -X- puede ser (Ver fórmula) en el que (Ver fórmula) es piperidinadiilo, piperazinadiilo, piridinadiilo, pirazinadiilo, pirrolidinadiilo o pirroldiilo y U es un enlace sencillo, alquileno C1-C6 o alquenileno C2-C6, Y es OCON-R 7 , -CONR 7 , CSNR 7 , NR 7 CO o NR 7 CS; R 7 es hidrógeno o alquilo C1-C10 y Z es alquilo C1-C10 alquilo opcionalmente sustituido, alquenilo C2-C10 opcionalmente sustituido, amino opcional-mente sustituido, alcoxi C1-C10 opcionalmente sustituido, carbociclilo opcionalmente sustituido o heterociclilo opcionalmente sustituido, dicho heterociclilo se elige entre un heteroarilo de 5 ó 6 eslabones elegido entre pirrolilo, imidazolilo, pirazolilo, piridilo, piridazinilo, pirimidinilo, oxazolilo, oxadiazolilo, isotiazolilo, tiazolilo, tiadiazolilo, furilo y tienilo; un heterociclilo fusionado que contiene dos anillos elegidos entre indolilo, isoindolilo, ...

Abca-1 elevating compounds

Ketone inhibitors of lysine gingipain

KETONE INHIBITORS OF LYSINE GINGIPAIN Abstract FIG.2 Brucella blood medium Conc. (pg/ml) M n to M ' to Ci r7 0 0 r W CD 6 6 a 73 5 2 The present invention provides compounds according to Formula (I) as described herein, and their use for inhibiting the lysine gingipain protease (Kgp) from the bacterium Porphyromonas gingivalis. Also described are gingipain activity probe compounds and methods for assaying gingipain activity are also described, as well as methods for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease.

Novel amide derivatives and medicinal use thereof ugs

The present invention relates to an amide derivative of the formula (1), having a C5a receptor antagonistic action wherein each symbol is as defined in the specification. The above-mentioned amide derivative, an optically active form thereof and a pharmaceutically acceptable salt thereof are promising as an agent for the treatment or prophylaxis of diseases or syndromes caused by inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia reperfusion, trauma, burn, surgical invasion and the like]. Moreover, they are useful as a therapeutic or prophylactic agent for the infectious diseases caused by bacteria and virus that invade via a C5a receptor.

Benzene derivatives and medicinal use thereof

Benzene derivatives represented by general formula (I) or pharmaceutically acceptable salts thereof; and AP-1 activation inhibitors, NF-kappa B activation inhibitors, inflammatory cytokine production inhibitors, matrix metalloprotease production inhibitors, inflammatory cell adhesion factor expression inhibitors, anti-inflammatory agents, antirheumatic agents, immunosuppressive agents, cancerous metastasis inhibitors, remedies for arteriosclerosis or antiviral agents containing the above compounds as the active ingredient.__________________________________________________

Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents

The present invention relates to compounds of the general formula (I); or salts thereof, as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

Cetp activity inhibitor

Modulators of the integrated stress pathway

Provided herein are compounds of formula (I) and (II), compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

Substituted 1, 3, 5-triazines and pyrimidines as ABCA-1 elevating compounds against coronary artery disease or atherosclerosis

Novel amide derivatives and medicinal use thereof

本发明涉及具有C5a受体拮抗活性的式(1)的酰胺衍生物：其中每个符号如说明书中所定义。上述酰胺衍生物、其旋光型和其药用盐有望成为用于治疗或预防由C5a引起的炎症而导致的疾病或综合症的药物，所述疾病或综合症例如有自身免疫性疾病，例如风湿病和系统性红斑狼疮等；脓毒病；成人呼吸窘迫综合症；慢性阻塞性肺病；过敏性疾病如哮喘等；动脉粥样硬化；心肌梗塞；脑梗塞；牛皮癣；阿尔茨海默氏病；和由于局部缺血再灌注、外伤、烧伤、手术侵害等引起的白细胞激活造成的严重的器官损伤(例如肺炎，肾炎，肝炎和胰腺炎等)。并且，它们用作通过C5a受体侵袭的细菌和病毒引起的感染疾病的治疗或预防药物。

Abca-1 elevating compounds against coronary artery disease or atherosclerosis

本发明提供了提高ABCA－1基因的细胞表达，促进胆固醇从细胞流出，增加哺乳动物特别是人的血浆中的HDL水平的化合物。该化合物用于治疗冠状动脉疾病。

Substituted 1, 3,5-triazines and pyrimidines as ABCA-1 elevating compounds against coronary artery disease or atherosclerosis

Substituted 1, 3,5-triazines and pyrimidines that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal are disclosed. These compounds are useful for treating coronary artery disease.

NPY Y5 antagonists

Described is the use of a sulfonamide compound of formula (I) in the manufacture of medicaments for use as NPY Y5 receptor antagonists, particularly for treating and/or preventing obesity, wherein the substituents are defined herein.

N-phenpropylcyclopentyl-substituted glutaramide derivatives as NEP inhibitors for FSAD

Sphingosine kinase inhibitors

The invention relates to substituted adamantane compounds of formula (I), pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, imflammatory disease, or angiogenic disease.

Industrial process for the preparation of (5S,10S)-10-benzyl-16-methyl-11,14,18-trioxo-15,17,19-trioxa-2,7,8-trithia-12-azahenicosan-5-aminium (E)-3-carboxyacrylate salt

本發明係關於一種用來製備下列式(I)的(5S,10S)-10-苄基-16-甲基-11,14,18-三側氧基-15,17,19-三氧雜-2,7,8-三噻基-12-氮二十一烷基-5-銨基(E)-3-羧基丙烯酸鹽之工業方法：□其中X-係反丁烯二酸鹽。此方法包含下列相繼關鍵步驟：動力學離析、形成二硫醚化合物、胜肽耦合及陰離子交換反應，以獲得式(I)之想要的產物。

Process for preparing aromatic thiol derivatives by hydrogenation of disulfides.

Mevcut buluş, yararlı farmasötik aktif bileşik olan S-[2-[1-(2-etilbutil)sikloheksilkarbonilamino]-fenil]2-metiltiyopropiyonatın hazırlanması için bir yöntem ile ilgilidir. The present invention relates to a method for the preparation of the useful pharmaceutical active compound S- [2- [1- (2-ethylbutyl) cyclohexylcarbonylamino] phenyl] 2-methylthiopropionate.

NPYY5 antagonists

Sphingosine kinase inhibitors

본 발명은 하기 화학식 (I)의 치환된 아다만탄 화합물, 그의 약제학적으로 허용가능한 염, 그의 제조 방법, 및 스핑고신 키나제 저해 방법 및 과증식성 질환, 염증성 질환 또는 혈관형성 질환을 치료 또는 예방하는 방법에 관한 것이다. The present invention provides a method for treating or preventing a substituted adamantane compound of formula (I), a pharmaceutically acceptable salt thereof, a method for preparing the same, and a method for inhibiting sphingosine kinase and hyperproliferative disease, inflammatory disease or angiogenic disease. It is about a method. <화학식 I> (I) 스핑고신 키나제, 과증식성 질환, 염증성 질환, 혈관형성 질환, 아다만탄 화합물 Sphingosine kinases, hyperproliferative diseases, inflammatory diseases, angiogenic diseases, adamantane compounds

Small-molecule modulators of trp-p8 activity

Jedinjenje formule I-E:gde su A, B, C i D nezavisno izabrani od CR1 i N; gde je najmanje jedan od A, B, C i D jednak CR1 ;gde je R1 izabran od H, alkil, heteroalkil, aril, arilalkil, halogen grupe; i gde kada su dvasusedna od A, B, C i D jednaka CR1, dva R1 mogu da se spoje tako da formiraju jednu aril,cikloalkil ili heterocikloalkil grupu;R2 je izabran od alkil, heteroalkil i arilalkil grupe;R3 je izabran od H, alkil, heteroalkil i arilalkil grupe; iR2 i R3 uzeti zajedno sa azotovom grupom formiraju alifatični amin.Prijava sadrži još 17 patentnih zahteva. Compounds of formula I-E: wherein A, B, C and D are independently selected from CR1 and N; wherein at least one of A, B, C and D is CR1, wherein R1 is selected from H, alkyl, heteroalkyl, aryl, arylalkyl, halogen groups; and wherein when two adjacent A, B, C and D are equal to CR1, the two R1 may be joined to form one aryl, cycloalkyl or heterocycloalkyl group, R2 is selected from alkyl, heteroalkyl and arylalkyl groups, R3 is selected from H, alkyl, heteroalkyl and arylalkyl groups; iR2 and R3 taken together with the nitrogen group form an aliphatic amine. The application contains 17 more claims.

Sphingosine Kinase Inhibitors

The invention relates to substituted adamantane compounds, pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease.

Processes for the preparation of s-[2-[1-(2-ethylbutyl) cyclcohexanecarbonylamino]phenyl] 2-methylthiopropionate and derivativesthereof by hydrogenation of disulfide precursors

The present invention relates to a process for the preparation of S-[2-[1-(2-ethylbutyl) cyclohexylcarbonylamino]-phenyl] 2-methylthiopropionate which is a useful pharmaceutical active compound. The process involves the preparation of a compound of formula (I') or formula (Ia): (see above formula)

New compounds as anti-inflammatory, immunomodulatory and anti-hypoplastic agents

Η παρούσα εφεύρεση σχετίζεται με ενώσεις του γενικού χημικού τύπου (Ι)• ή με άλατα εξ αυτών, ως αντι-φλεγμονώδεις, ανασοτροποποιητικοί και αντι-υπερπλαστικοί παράγοντες. The present invention relates to compounds of the general formula (I) or to salts thereof as anti-inflammatory, anti-inflammatory and anti-hyperplastic agents.

Non-steroidal farnesoid x receptor modulators and methods for the use thereof

The efficient regulation of cholesterol synthesis, metabolism, acquisition, and transport is an essential component of lipid homeostasis. The farnesoid X receptor (FXR) is a transcriptional sensor for bile acids, the primary product of cholesterol metabolism. Accordingly, the development of potent, selective, small molecule agonists, partial agonists, and antagonists of FXR would be an important step in further deconvoluting FXR physiology. In accordance with the present invention, the identification of novel potent FXR activators is described. Two derivatives of invention compounds, bearing stilbene or biaryl moieties, contain members that are the most potent FXR agonists reported to date in cell-based assays. These compounds are useful as chemical tools to further define the physiological role of FXR as well as therapeutic leads for the treatment of diseases linked to cholesterol, bile acids and their metabolism and homeostasis.

N-phenpropylcyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase

The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R 1 is optionally substituted C 1-6 alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C 1-6 alkoxy, —NR 2 R 3 or —NR 4 SO 2 R 5 ; X is the linkage —(CH 2 ) n — or —(CH 2 ) q —O— (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C 1-4 alkoxy; hydroxy; hydroxy(C 1-3 alkyl); C 3-7 cycloalkyl; carbocyclyl; heterocyclyl; or by C 1-4 alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6 or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R 8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5- or 6-membered carbocyclic or heterocyclyic ring.

Sphingosine kinase inhibitor compounds, compositions comprising them and uses thereof for preparing a medicament for treating disorders characterized by abnormal activation of spingosine kinase

The invention relates to substituted adamantane compounds, pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, inflammatory disease, or angiogenic disease. [WO2006138660A2]

Color light-sensitive material

A color light sensitive material which provides a positive dye image having high density, good color reproducibility and which exhibits excellent preservability before use. The material comprises a support having provided thereon a light-sensitive silver halide, a binder, a reducible dye donating compound, and at least one reducing agent selected from the group consisting of a compound represented by formula (IA) and a compound represented by formula (IB): ##STR1## wherein the substituents have the meanings indicated in the specification.

CEPT ACTIVITY INHIBITORS

Herbicides

Novel herbicides Abstract: Cycloalkanecarboxylic acid derivatives of formula I (I), wherein W is (W1), (W2), (W3), (W4), (W5), (W6), (W7), (Ws) (W9) or (W10); and A is CO-R3 or CN; Rl is hydrogen or fluorine; R2 is halogen or cyano; R3 is chlorine, X-R5, amino, Cl-C4alkylamino, di-Cl-C4alkylamino, C2-C4haloalkyl-amino, di-C2-C4haloalkylamino, Cl-C4hydroxyalkylamino, di-Cl-C4hydroxyalkylamino, C3-C4alkenylamino, diallylamino, -N-pyrrolidino, -N-piperidino, -N-morpholino, -N-thiomorpholino, -N-piperidazino, the group -O-N=C-(R9)R10 or the group -N-R6(OR6); each of R4 and R14, independently of the other, is hydrogen, fluorine, chlorine, bromine, Cl-C4alkyl or trifluoromethyl; R5 is hydrogen, Cl-C10alkyl, Cl-C4alkoxy-C1-C4alkyl, halo-C1-C8alkyl, Cl-C10-alkylthio-C1-C4alkyl, di-Cl-C4alkylamino-Cl-C4alkyl, cyano-Cl-C8alkyl, C3-C8alkenyl, halo-C3-C8alkenyl, C3-C8alkynyl, C3-C7cycloalkyl, C3-C7cycloalkyl-Cl-C4alkyl or halo-C3-C7cycloalkyl, or benzyl which is unsubstituted or substituted at the phenyl ring by up to three identical or different substituents selected from halogen, Cl-C4alkyl, halo-Cl-C4alkyl, halo-C1-C4alkoxy or Cl-C4alkoxy, or is an alkali metal ion, an alkaline earth metal ion or an ammonium ion, the group -[CHR6-(CH2)m]-COOR7, or the group [CHR6-(CH2),-Si(R8)3]; R6 is hydrogen or Cl-C4alkyl; R7 is hydrogen, Cl-C6alkyl, C3-C8alkenyl, C3-C8alkynyl, Cl-C8alkoxy-C2-C8alkyl, Cl-C8alkylthio-C2-C8alkyl or C3-C7cycloalkyl; R8 is Cl-C4alkyl; R9 is Cl-C4alkyl; R10 is Cl-C4alkyl or phenyl; or R9 and R10, together with the carbon atom to which they are bonded, form a cyclohexane ring; R11 is C1-C8alkyl; R12 is hydrogen or C1-C8alkyl; R13 is hydrogen, Cl-C6alkyl, C3-C7cycloalkyl, Cl-C4alkoxy-C1-C4alkyl, C1-C4alkylthio-C1-C4alkyl, halo-C1-C7alkyl, C3-C7alkenyl or C3-C7alkynyl; X is oxygen or sulfur; Y is oxygen or sulfur; Y1 is oxygen or sulfur; Y2 is oxygen or sulfur; Y3 is oxygen or sulfur; Y4 is oxygen or sulfur; Z1 is oxygen or sulfur, Z2 is oxygen or sulfur; n is 0, ...

Therapeutic agents

Compounds of formula I and their salts in which n = 0 or 1, R1 and R2 are each aliphatic or cyloallkyl or NR1R2 is an optionally substituted heterocyclic ring, R3 is alkyl, cycloalkyl or optionally substituted amino, R5 is H or an aliphatic group, R6 is H, an optionally substituted aliphatic group or a cycloalkyl group, or R3 and R5 together with the nitrogen and carbon atoms to which they are attached form an optionally substituted heterocyclic ring or R5 and R6 together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted by alkyl and R7 is hydrogen, halogen, optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkoxycarbonyl, trifluoromethyl or cyano have utility as hypoglycaemic agents and may be incorporated into pharmaceutical compositions.

Npyy5 antagonists

NPYY5 receptor antagonists which contain compounds represented bygeneral formula (I), prodrugs thereof, pharmaceutically acceptable salts thereof or solvates of the same wherein R1 represents lower alkyl, cycloalkyl, etc.; R2 represents hydrogen, lower alkyl, etc.; n is 1 or 2; X represents lower alkylene, lower alkenylene, arylene, cycloalkylene, etc.; Y represents CONR?7, CSNR7, NR7CO, NR7¿CS, etc. (wherein R7 represents hydrogen or lower alkyl); and Z represents lower alkyl, an optionally substituted hydrocarbon cycle, an optionally substituted heterocycle, etc.

Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

Photosensitive color material.

Reductive cosmetic composition for permanent containing an n-(mercapto alkyl) succinamic acid or an n-(mercapto alkyl) succinimide acid derivative and its use in 2 process of permanent waving of the hair

This composition contains, in a suitable vehicle, a reducing agent having the following general formula: <IMAGE> in which: n is 2 or 3 A represents a divalent radical chosen from: (i) -(CH2)m-, m being 2 to 3, <IMAGE> R3 and R4, which may be identical or different, representing an alkyl radical having from 1 to 4 carbon atoms, or R3 and R4, together with the adjacent carbon atoms, form a cyclohexane ring, and <IMAGE> R5 and R6, which may be identical or different, representing a hydrogen atom or an alkyl radical having from 1 to 4 carbon atoms, or R5 and R6, together with the adjacent carbon atoms, form a benzene ring, R1 represents a hydrogen atom, and R2 represents a hydroxyl radical, or R1 and R2, taken together, form a single bond, and the salts with an organic or inorganic base of the abovementioned compounds in free acid form. <??>Use of the composition for the first stage of a permanent hair shaping operation.

Small-molecule modulators of trp-p8 activity

Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp-p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.

Npyy5 antagonists

하기 화학식 Ⅰ 로 표시되는 화합물, 그의 전구 약물, 그의 약제학적 허용가능 염 또는 그의 용매화물을 함유하는, NPY Y5 수용체 길항제: NPY Y5 receptor antagonist, containing a compound represented by Formula I, a prodrug thereof, a pharmaceutically acceptable salt thereof, or a solvate thereof: [화학식 Ⅰ] [Formula I] [식 중, R 1 은 저급 알킬, 시클로알킬 등이고; [Wherein, R 1 is lower alkyl, cycloalkyl or the like; R 2 는 수소, 저급 알킬 등이며; R 2 is hydrogen, lower alkyl and the like; n 은 1 또는 2 이고; n is 1 or 2; X 는 저급 알킬렌, 저급 알케닐렌, 아릴렌, 시클로알킬렌 등이며; X is lower alkylene, lower alkenylene, arylene, cycloalkylene and the like; Y 는 CONR 7 , CSNR 7 , NR 7 CO, NR 7 CS (R 7 은 수소 또는 저급 알킬임)등이고; Y is CONR 7 , CSNR 7 , NR 7 CO, NR 7 CS (R 7 is hydrogen or lower alkyl) and the like; Z 는 저급 알킬, 치환될 수 있는 카르보시클릴, 치환될 수 있는 헤테로시클릴 등이다]. Z is lower alkyl, substituted carbocyclyl, substituted heterocyclyl, and the like.

Abca-1 elevating compounds

본 발명은 ABCA-1 유전자의 세포성 발현을 증가시켜, 세포로부터 콜레스테롤 유출을 촉진시키고, 포유동물, 특히 인간의 혈장에서 HDL 수준을 증가시키는 화합물을 제공한다. 화합물은 관상동맥 질환의 치료에 유용하다.

Sphingosine kinase inhibitors

The invention relates to substituted adamantane compounds of formula (I), pharmaceutical compositions thereof, processes for their preparation, and methods for inhibiting sphingosine kinase and for treating or preventing hyperproliferative disease, imflammatory disease, or angiogenic disease.

Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents

The present invention relates to compounds of the general formula (I); or salts thereof, as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

NPY Y5 antagonists

Disclosed are compounds of formula (I), wherein: X is alkylene or alkenylene, R1 is optionally substituted alkyl or cycloalkyl, R2 is H or lower alkyl, or R1 and R2 are taken together to form alkylene, n is 1 or 2, Y is OCONR7, CONR7, CSNR7, NR7CO or NR7CS, R7 is H or alkyl, and Z is optionally substituted alkyl, alkenyl, amino, alkoxy, carbocyclyl or heterocyclyl. The compounds are used for the manufacture of medicaments for use as NPY Y5 receptor antagonist, particularly as anti-obestic agents.

Hypoglycaemic phenylamidines and phenylguanidines

Compounds of formula I (see formula I) and their salts in which n = 0 or 1, R1 and R2 are each aliphatic or cycloalkyl or NR1R2 is an optionally substituted heterocyclic ring, R3 is alkyl, cycloalkyl or optionally substituted amino, R5 is an aliphatic group, R6 is H, an optionally substituted aliphatic group or a cycloalkyl group, or R3 and R5 together with the nitrogen and carbon atoms to which they are attached form an optionally substituted heterocyclic ring or R5 and R6 together with the nitrogen to which they are attached form a heterocyclic ring optionally substituted by alkyl and R7 is optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkoxycarbonyl, trifluoromethyl or cyano have utility as hypoglycaemic agents.

Industrial process for the preparation of the (E) -3-carboxyacrylate salt of (5S, 10S) -10-benzyl-16-methyl-11,14,18-trioxo-15,17,19-trioxa-2,7 , 8-tritia-12-azahenicosan-5-aminium

Proceso industrial para la preparación de sal de (E)-3-carboxiacrilato de (5S,10S)-10-bencil-16-metil-11,14,18- trioxo-15,17,19-trioxa-2,7,8-tritia-12-azahenicosan-5-aminio de la fórmula (I) siguiente: **(Ver fórmula)** que comprende las etapas sintéticas sucesivas siguientes realizadas en solventes orgánicos desgasificados polares o apolares, próticos o apróticos: 1) preparar el compuesto (E) de la fórmula siguiente con un exceso enantiomérico superior a 95% **(Ver fórmula)** 1a) haciendo reaccionar el compuesto (A) de la fórmula siguiente **(Ver fórmula)** con 0.5 - 0.6 equivalentes molares de quinina en solventes orgánicos polares y apróticos, preferentemente en acetato de etilo; 1b) cristalizar la sal de quinina resultante a una temperatura que varía de 10°C a 20°C, en el mismo solvente orgánico que el utilizado en la etapa 1a, en el que la cristalización se inicia añadiendo unos cuantos cristales de la sal de enantiómero deseada para iniciar la cristalización, a continuación; 1c) recristalizar la sal obtenida después de la etapa 1b al mismo intervalo de temperatura y el mismo solvente que el utilizado en la etapa 1b; 1d) recuperar el compuesto (E): 1d.1)recuperando el compuesto (D) de la fórmula siguiente **(Ver fórmula)** 1d.2)desproteger el tiolacetato en un solvente polar y prótico tal como MeOH; 1e) recuperar la quinina; 2) preparar el compuesto (F) de la fórmula siguiente **(Ver fórmula)** 2a) haciendo reaccionar los primeros 1.1 equivalentes molares de dicho compuesto (E) con 1 equivalente molar de cloruro de clorocarbonil sulfenilo, en un solvente polar y aprótico, a continuación; 2b) hacer reaccionar el intermedio obtenido después de la etapa 2a con 0.9 equivalentes molares del compuesto (B) de la fórmula siguiente **(Ver fórmula)** en solución con 1 equivalente molar de Et3N en el mismo solvente que el utilizado en la etapa 2a; 3) preparar el compuesto (G) de la fórmula siguiente **(Ver fórmula)** haciendo reaccionar dicho compuesto (F) con el amino-é ...

Modulators of the integrated stress pathway

Modulators of the integrated stress pathway.

Se proporcionan en la presente compuestos de fórmula (I) y (II), composiciones y métodos de utilidad para modular la respuesta al estrés integrada (ISR) y para tratar enfermedades, trastornos y condiciones relacionados.

N-phenpropylcyclopentyl-substituted glutaramide derivatives as NEP inhibitors for FSAD

Compounds of formula (I) that are suitable for treating for example sexual dysfunction are disclosed, wherein R1 is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C1- 6alkoxy, -NR2R3 or - NR4SO2R5; X is the linkage -(CH2)n- or -(CH2)q-O- (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C1-4alkoxy; hydroxy; hydroxy(C1- 3alkyl); C3-7cycloalkyl; carbocyclyl; heterocyclyl; or by C1-4alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6, or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring.

N-phenpropylcyclopentyl-substituted glutaramide derivatives as NEP inhibitors of FSAD

Inhibitors of CETP activity

Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents

The present invention relates to compounds of the general formula (I); or salts thereof, as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

NPY Y5 antagonist

The present invention provides a pharmaceutical composition for use as an NPY Y5 receptor antagonist comprising a compound of the formula (I): wherein R 1 is lower alkyl, cycloalkyl or the like, R 2 is hydrogen, lower alkyl or the like, n is 1 or 2, X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, Y is CONR 7 , CSNR 7 , NR 7 CO, NR 7 CS or the like, Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like and R 7 is hydrogen or lower alkyl, prodrug, pharmaceutically acceptable salt or solvate thereof

Inhibitors of farnesyltransferase

GLUTARAMIDE DERIVATIVES REPLACED WITH N-FENPROPILCICLOPENTILO AS NEP INHIBITORS FOR FSAD

LA INVENCION SE REFIERE A COMPUESTOS DE FORMULA (I) PARA TRATAR, POR EJEMPLO, DISFUNCION SEXUAL, EN LA QUE R1 ES ALQUILO C1-6 OPCIONALMENTE SUSTITUIDO, CARBOCICLILO OPCIONALMENTE SUSTITUIDO, HETEROCICLILO OPCIONALMENTE SUSTITUIDO, HIDROGENO, ALCOXI C1-6, -NR2R3 O -NR4SO2R5, X ES EL ENLACE -(CH2)n- o -(CH2)q-O- (DONDE Y ESTA UNIDO AL OXIGENO); DONDE UNO O MAS ATOMOS DE HIDROGENO EN EL ENLACE X SE PUEDEN REEMPLAZAR, INDEPENDIENTEMENTE, POR ALCOXI C1-4; HIDROXI; HIDROXI(ALQUILO C1-3); CICLOALQUILO C3-7; CARBOCICLILO; HETEROCICLILO; O POR ALQUILO C1-4 OPCIONALMENTE SUSTITUIDO CON UNO O MAS GRUPOS FLUORO O FENILO; n ES 3, 4, 5, 6 ó 7; Y q ES 2, 3, 4, 5 ó 6; E Y ES FENILO O PIRIDILO, CADA UNO DE LOS CUALES PUEDE ESTAR SUSTITUIDO; O DOS GRUPOS R8 EN LOS ATOMOS DE CARBONO ADYACENTES JUNTO CON LOS ATOMOS DE CARBONO QUE LOS INTERCONECTAN PUEDEN FORMAR UN ANILLO CARBOCICLICO O HETEROCICLICO, CONDENSADO, DE 5 ó 6 MIEMBROS, OPCIONALMENTE SUSTITUIDO.

Novel phenylalanine derivatives

Phenylalanine derivatives of the following formula and analogues thereof have an antagonistic activity to α 4 β 7 integrin and a selectivity toward α 4 β 1 integrin. They are used as therapeutic agents for various diseases to which α 4 β 7 integrin relates.

Manufacturing process of prostacyclin compounds with binding thiol and pegylated forms

Procedimiento para la preparación de un compuesto de fórmula I, o una sal farmacéuticamente aceptable del mismo: **Fórmula** comprendiendo el procedimiento: acoplar un anhídrido meso de fórmula III con un compuesto de éster de fórmula IV en presencia de un ligando quiral, para proporcionar un compuesto de fórmula V: **Fórmula** acoplar el compuesto de fórmula V con un compuesto de fórmula VI para formar un tiol, hidrolizar el tiol con un agente hidrolizante para formar un compuesto de fórmula VIII; **Fórmula** desproteger el compuesto de fórmula VIII para formar el compuesto de fórmula II: **Fórmula** acoplar el compuesto de fórmula II con un compuesto de PEG-maleimida para formar el compuesto de fórmula I; en las que X es O o CH2; Z es O o CH2; **Fórmula** L es p>=0 o 1; r>=1-8; t>=1, 2 o 3; w>=1, 2 o 3; PEG es un resto de polietilenglicol; R1 representa un grupo protector de ácido; y R4 representa un grupo de protección de tiol. Procedure for the preparation of a compound of formula I, or a pharmaceutically acceptable salt thereof: ** Formula **, the procedure comprising: coupling a meso anhydride of formula III with an ester compound of formula IV in the presence of a chiral ligand, to provide a compound of formula V: ** Formula ** coupling the compound of formula V with a compound of formula VI to form a thiol, hydrolyzing the thiol with a hydrolyzing agent to form a compound of formula VIII; ** Formula ** deprotect the compound of formula VIII to form the compound of formula II: ** Formula ** couple the compound of formula II with a PEG-maleimide compound to form the compound of formula I; where X is O or CH2; Z is O or CH2; ** Formula ** L is p> = 0 or 1; r> = 1-8; t> = 1, 2 or 3; w> = 1, 2 or 3; PEG is a polyethylene glycol residue; R1 represents an acid protecting group; and R4 represents a thiol protection group.

Modulators of the integrated stress pathway