СОЕДИНЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩИЕ СВОЙСТВАМИ ВЫСВОБОЖДЕНИЯ ГОРМОНА РОСТА, СПОСОБСТИМУЛЯЦИИ ВЫДЕЛЕНИЯ ГОРМОНА РОСТА ИЗ ГИПОФИЗА МЛЕКОПИТАЮЩЕГО

Изобретение относится к новым соединениям формулы I или к фармацевтически приемлемым солям этих соединений и к содержащим их композициям, обладающим активностью в отношении высвобождения гормона роста. При этом R1 представляет водород или С1-6-алкил; R2представляет водород или С1-6-алкил; L представляет где R4 представляет водород или C1-6-алкил; р равно 0 или 1; r равно 1; q, s, t и u независимо друг от друга равны 0, 1, 2, 3 или 4; сумма q+r+s+t+u составляет 0, 1, 2, 3 или 4; R9, R10, R11 и R12независимо друг от друга представляют водород или C1-6-алкил; и Q представляет >N-R13, где R13 представляет водород или C1-6-алкил; или L представляет где r равно 0 или 1; q, s, t, u независимо друг от друга равны 0, 1, 2, 3 или 4; сумма q+r+s+t+u составляет 0, 1, 2, 3 или 4; R9, R10, R11 и R12 независимо друг от друга представляют водород или С1-6-алкил; Q представляет >N-R13 или где о равно 0, 1 или 2; Т представляет - N(R15)R16 или гидроксил; R13, R15 и R16 независимо друг от друга представляют ...

ПРОИЗВОДНЫЕ 1,5-БЕНЗОДИАЗЕПИНА, СПОСОБ ИХ ПОЛУЧЕНИЯ И СОДЕРЖАЩИЙ ИХ ФАРМАЦЕВТИЧЕСКИЙ СОСТАВ

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention relates to derivatives of 1,5-benzodiazepine of the formula (I) where X is H; R 1 - radical of the formula (II) or NR 4 R 5 ; R 2 - indole, benzofuran, thiophene, benzothiophene, indoline, quinoline or 4-oxobenzopyrane; phenyl possibly substituted with halogen atom, carboxy-, amino- or dimethylamino-group or NHR 11 ; R 11 is 7-indazolyl; R 3 - H, C 1-6 -alkyl, C 3-6 -cycloalkyl or phenyl and also their physiologically acceptable salts and solvates that show agonistic activity with respect to cholecystokinin-A receptors that ensures to use the indicated compounds for control of function of hormones gastrin and cholecystokinin in mammals. EFFECT: improved method of synthesis, agonistic activity of compounds to receptors. 10 cl, 9 tbl, 18 ex ЭзЗзу9егс ПЧ Го (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ” 2135 486 Сл (51) МПК 61 К 38/02, 31/55 С 070 243/12, С 07 К 5/02, А 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 95117974/04, 14.04.1994 (30) Приоритет: 15.04.1993 СВ 9307833.5 (46) Дата публикации: 27.08.1999 (56) Ссылки: МО 9006937 А, 1990. ЕР 0487207 А|, 1992. 4$ 4988692, 1991. $Ц 1362132 АЛ, 1987. 1$ 4517135 А, 1985. ОЕ 3731840 АЛ, 1988. ОЕ 3402507 А, 13985. (85) Дата перевода заявки РСТ на национальную фазу: 15.11.95 (86) Заявка РСТ: ЕР 94/01131 (14.04.94) (87) Публикация РСТ: М/О 94/24149 (27.10.94) (98) Адрес для переписки: 193036, Санкт-Петербург, а/я 24, Невинпат, Патентному поверенному Поликарпову А.В. (71) Заявитель: Глаксо Веллкам, Инк. (ЦЗ) (72) Изобретатель: Финч Хэрри (СВ), Карр Робин Артур Эллис (СВ), Сагг Элизабет Эллен (43), Аквайно Кристофер Джозеф (0$), Зевзик Джерзи Ризард (1$) (73) Патентообладатель: Глаксо Веллкам, Инк. (1$) (54) ПРОИЗВОДНЫЕ 1,5-БЕНЗОДИАЗЕПИНА, СПОСОБ ИХ ПОЛУЧЕНИЯ И СОДЕРЖАЩИЙ ИХ ФАРМАЦЕВТИЧЕСКИЙ СОСТАВ (57) Реферат: Производные 1,5-бензодиазепина формулы |, где Х=Н, В! - радикал формулы || или МВ\В°; В? - индол, бензофуран, тиофен, ...

ПРОИЗВОДНЫЕ 5-АМИНО-4-ОКСИГЕКСАНОВОЙ КИСЛОТЫ И СПОСОБ ИХ ПОЛУЧЕНИЯ

Использование: в медицине и биохимии. Сущность: производные 5-амино-4-оксигексановой кислоты ф-лы I: R1-B1-NH-CH(CH2R2 )-CH(OH)-CH2 -CH(CH2R3)-CO-A1-A2-N(R4,R5) с определенными буквенными значениями, способ их получения и производные 5-амино-4-оксигексановой кислоты, проявляющие активность при подавлении АSP-протеазы из ВИЧ-1. 3 табл.

ПРОЛЕКАРСТВА ДЕЙСТВУЮЩИХ ВЕЩЕСТВ ГЕТЕРОЦИКЛИЧЕСКИМИ ЛИНКЕРАМИ

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

Peptides, their preparation and use

A compound of the formula I in which A, R1, R2, R3, R4 and B have the meaning indicated in Claim 1, process for their preparation and their use as renin inhibitors and for the treatment of diseases caused by retroviruses.

1-AMINO-7-ISOCHINOLIN-DERIVATE ALS SERIN PROTEASE INHIBITOREN

New phosphinate-contg. peptide derivs. - as collagenase inhibitors e.g. for treating gangrene or dental infections

Peptide derivs. of formula R1-NH-CH(R2)-P(O)(OR3)-CH2-CH2-CO-R4-N(R5)-CH(R6)-CO-R7 (I) are new. R1 = H or an amino protecting gp. suitable for an alpha-amino acid or a gp. derived from an alpha-amino acid or a peptide bonded onto the NH via its CO end and having at its amino end, an H or an amino protecting gp. suitable for an alpha-amino acid; R2 = the side chain of an alpha-amino acid; R3 = H, a metal atom 1-5C alkyl or benzyl; R4 = a divalent gp. derived from an alpha-amino acid chosen from proline, hydroxyproline, thiazolidine and dehydroproline of the formulae (i)-(iv), bonded on the CO via their N atmos. R5 = H or 1-4C alkyl; R6 = 1-5C alkyl or the side chain of an alpha-amino acid; R7 = OR8; R8 = H, a metal atom, 1-5C alkyl or benzyl; or either R1 and R7 or R1 and R6 together form a divalent gp. derived from a alpha-amino acid or a peptide which contains 2-3 amino acid gps.. USE/ADVANTAGE - (I) are inhibitors of bacterial collagenases which belong to the class of Zn-contg. metal ...

ENKEPHALIN ANALOGUES

Derivatives of 1-aminocarbonylmethyl-3-amino-2,4-dioxo-1-5 benzodiazepines having CCKA agonist activity.

Novel benzodiazepine compounds of formualr ...

Novel opioid analogs that are 9 (delta) opioid receptor antagonists, their syntheis and their use as analgesic and immunosupressive compounds.

This invention is related to a new class of opiod peptide analogs that are 0 opioid receptor antagonists as well as to their synthesis and their use as analgesic and immunosuppressive compounds.

1,5 Benzodiazepine derivatives.

Compounds of the general formula ...

1,5 Benzodiaze pine derivatives

1,5 Benzodiaze pine derivatives

New peptides

Dipeptide derivative

This invention is directed to compounds of the formula (i)and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of owsteoporosis and/or fraily, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance os skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis and/or frailty when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from ghrp-6, hexarelin, ghrp-1, growth hormone releasing factor (grf), igf-1, igf-2 or b-ht920. The invention is also directed to intermediates useful in the preparation of compounds of formula i.

1,5 Benzodiazepine derivatives having cck antagonistic or agonistic activity

1,5 Benzodiazepine derivatives having cck and/or gastrin antagonistic activity

New peptides

1,5 Benzodiaze pine derivatives

1,5 Benzodiaze pine derivatives

CONNECTIONS WITH GROWTH-HORMONE-SETTING FREE CHARACTERISTICS

CONNECTIONS WITH GROWTH-HORMONE-SETTING FREE CHARACTERISTIC

MOLECULAR MIMETIKA OF MENINGOKOKKALEN B EPITOPEN

RETROVIRALE PROTEASE INHIBITORS

PEPTID ANALOGUES WITH RENININHIBIERENDER ACTIVITY.

NEUROKININ A ANTAGONIST.

NEW INHIBITORS OF FACTOR XA

PROCEDURE FOR THE POLYMERIZATION OF EPOXY CONNECTIONS.

PEPTIDE WITH ENDOTHELIN ANTAGONISTIC ACTIVITY, THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS

CIS EPOXIDE OF DERIVATIVES, USABLE AS IRREVERSIBLE ONES HIV PROTEASE INHIBITORS AND PROCEDURES AND INTERMEDIATE PRODUCTS TO YOUR PRODUCTION

RETROVIRUSPROTEASE INHIBITORS

PRODRUG DERIVATIVES OF ENZYME INHIBITORS WITH HYDROXYL GROUPS, PROCEDURES FOR THEIR PRODUCTION AND YOUR USE

FACTOR XA INHIBITORS

Inhibitors of farnesyl-protein transferase

HIV PROTEASE INHIBITING AGENTS

Inhibitors of memapsin 2 and use thereof

HIV protease inhibiting agents

Thrombin inhibitors

Inhibitors of farnesyl-protein transferase

Gamma-secretase inhibitors

Macrocyclic peptides useful in the treatment of thrombin related disorders

Cs-1 peptidomimetics, compositions and methods of using the same

NEUROKININ A ANTAGONISTS

Pyrrolidincarbonylamino cyclic disulfides

COMPOUNDS WITH GROWTH HORMONE RELEASING PROPERTIES

The invention relates to novel compounds, compositions containing them, and their use for treating medical disorders resulting from a deficiency in growth hormone.

PEPTIDASE INHIBITORS

This invention relates to analogs of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.

THERAPEUTICALLY USEFUL PSEUDOPEPTIDES, COMPOSITIONS CONTAINING THE SAME AND METHODS OF PREPARATION AND USE

VITRONECTIN RECEPTOR ANTAGONIST PHARMACEUTICALS

The present invention describes novel compounds of the formula: (Q)d-Ln-Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

COMPOUNDS WITH GROWTH HORMONE RELEASING PROPERTIES

Compounds of general formula (I), and their use for treating medical disorders resulting from a deficiency in growth hormone.

N-ACYLDIPEPTIDE DERIVATIVES AND THEIR USES

N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with a tumor, cancer, immune, nervous, vascular, musculoskeletal or cutaneous system, or other tissue or system in a subject.

FURTHER NOVEL 5-AMINO-4-HYDROXYHEXANOIC ACID DERIVATIVES AS THERAPEUTIC AGENTS

... 4-18787/A Further novel 5-amino-4-hydroxyhexanoic acid derivatives as therapeutic agents Described are compounds of the formula (1), wherein R1 is hydrogen, lower alkoxycarbonyl, heterocyclycarbonyl, benzyloxycarbonyl that is unsubstituted or substituted by up to three radicals which may be the same or different and are selected from fluorine, halo-lower alkyl, lower akanoyl, sulfo, lower alkylsulfonyl and cyano; heterocycloxycarbonyl wherein heterocyclyl is bonded by way of a carbon atom; one of the mentioned carbonyl radicals wherein the bonding carbonyl group has been replaced by a thiocarbonyl group; heterocyclylsulfonyl, lower alkyl-sulfonyl or N-(heterocyclyl-lower alkyl)-N-lower alkylaminocarbonyl, B1 is a bond or a bivalent radical of an .alpha.-amino acid, which radical is bonded N-terminally to R1 and C-terminally to the amino group at the R2-CH2-carrying carbon atom, each of R2 and R3, independently of the other, is phenyl or cyclohexyl, those radicals being unsubstituted or ...

ACETIC ACID DERIVATIVES

RAN 4045/12 Acetic acid derivatives of the formula H2N(NH)C-X-Y-CO-CH(Q1)COOQ2 I in which X, Y, Z, Q1 and Q2 have the meaning indicated in the description, and hydrates, solvates and physiologically utilisable salts thereof inhibit the binding of adhesive proteins to blood platelets and also inhibit blood platelet aggregation and cell-cell adhesion. They are prepared by removal of protecting groups in appropriate compounds containing ester groups and protected amidino groups.

ENZYME INHIBITORS

Disclosed herein are peptide derivatives which inhibit the activity of human immunodeficiency virus (HIV) protease. The peptide derivatives can be represented by general formula R1-R2-Y-R3-R4 wherein R1 is an optionally substituted 3-(1,2,3,4-tetrahydro-isoquinolyl)carbonyl residue, R2 and R3 are amino acid or analogous amino acid residues (R3 may optionally be absent), Y is a non-peptide linking unit, e.g. statyl, and R4 is ¢-NR17CH(R18)C(O)!p-2 wherein R17 is hydrogen or lower alkyl, R18 is an amino acid or analogous amino acid side chain, p is zero or 1 and 2 is a terminal group (e.g. hydroxy or amino), or R4 is -NR17CR18(R21)CH2OH wherein R17 and R18 are as noted hereinabove and R25 is hydrogen, lower alkyl or hydroxy(lower)alkyl. The derivatives also inhibit renin activity. Accordingly, the derivatives can be used for combating HIV infections or for treating hypertension or congestive heart failure.

RETROVIRAL PROTEASE INHIBITORS

Compounds represented by formula (I), wherein A represents R, R13 and radica ls represented by formulas (A1, A2, A3), B represents radicals represented by formula (II), (values for the variables given herein), are effective as retroviral protease inhibitors, and in particular as inhibitors of H1V protease.

MULTICATALYTIC PROTEASE INHIBITORS

Disclosed herein are inhibitors of the multicatalytic protease enzyme which are represented by general formula (I). Constituent members and preferred constituent members are disclosed herein. Methodologies for making and using the disclosed compounds are also set forth herein.

RAS FARNESYL TRANSFERASE INHIBITORS

Benzodiazepine derivatives are disclosed that act as potent inhibitors of ras farnesyl:protein transferase. Pharmaceutical compositions containing these benzodiazepines are provided for treatment of diseases for which inhibition of the ras farnesyl:protein transferase is indicated.

THERAPEUTICALLY EFFECTIVE ONES PSEUDOPEPTIDE AND THESE CONTAINING COMPOSITIONS.

PEPTIDE, YOUR PRODUCTION AND USE.

Compounds of formula I [wherein R1 and R4 are hydrophilic or hydrophobic side chains; R3 is hydrogen and R2 is amino or hydroxy or R3 and R2 together are oxo; and A and B have the significances given in claim 1] processes for the production thereof, and their use as a renin inhibitor (e.g. in the treatment of hypertension and cardiac insufficiency) and for the treatment of diseases caused by retroviruses.

Peptide analogs and mimetics, suitable for use in vivo of in treatment of diseases, associated with abnormal laying proteins in amyloid or amiloidpodobnye deposits, or their pathological precursors, enriched β-- folds

НОВЫЕ ИНГИБИТОРЫ γ-СЕКРЕТАЗЫ

Настоящее изобретение относится к новому соединению, которое обладает превосходным действием, направленным на ингибирование γ-секретазы и специфическое ингибирование продуцирования Аβ. Настоящее изобретение относится к соединению указанной ниже формулы (1) или к его фармацевтически приемлемой соли где R1 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода, или фенильную группу; R2 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода, которая может быть замещена одной или несколькими фенильными или галогенфенильными группами; R3 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода, которая может быть замещена одной или несколькими гидроксильными группами; R4 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода; и символ «*» означает хиральный центр.

СПОСОБЫ ЛЕЧЕНИЯ ИЛИ ПРОФИЛАКТИКИ РВОТЫ С ПОМОЩЬЮ АГЕНТОВ, УСИЛИВАЮЩИХ СЕКРЕЦИЮ ГОРМОНА РОСТА

Настоящее изобретение относится к способам лечения или профилактики рвоты и повышения оценок ASAS у субъекта путем введения указанному субъекту эффективного количества усиливающего выделение гормона роста соединения или его фармацевтически приемлемой соли, гидрата или сольвата.

MACROCYCLIC CONNECTIONS AS THE INHIBITORS OF PROTEASE NS3

ПЕПТИДНЫЕ АНАЛОГИ И МИМЕТИКИ, ПОДХОДЯЩИЕ ДЛЯ ПРИМЕНЕНИЯ IN VIVO ПРИ ЛЕЧЕНИИ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С АНОМАЛЬНОЙ УКЛАДКОЙ БЕЛКОВ В АМИЛОИДНЫЕ ИЛИ АМИЛОИДПОДОБНЫЕ ОТЛОЖЕНИЯ, ИЛИ ИХ ПАТОЛОГИЧЕСКИЕ ПРЕДШЕСТВЕННИКИ, ОБОГАЩЕННЫЕ b-СКЛАДКАМИ

... 1. Ингибиторный пептид, способный ингибировать образование β-складчатой структуры в амилоидном β-пептиде, представляющий собой аналог ингибиторного пептида болезни Альцгеймера iAβ5, состоящий из 5 остатков (SEQ ID NO:1 Leu-Pro-Phe-Phe-Asp), сконструированный путем химической модификации SEQ ID NO:1, при этом указанная химическая модификация достигается с помощью способа, выбранного из группы, состоящей из изменения N- и C-концов указанного ингибиторного пептида болезни Альцгеймера iAβ5; замены по меньшей мере одного остатка указанного ингибиторного пептида болезни Альцгеймера iAβ5 на α-аминоизомасляную кислоту (Aib); метилирования α-углеродного атома по меньшей мере одного остатка указанного ингибиторного пептида болезни Альцгеймера iAβ5; замены по меньшей мере одного L-энантиомерного остатка указанного ингибиторного пептида болезни Альцгеймера iAβ5 на D-энантиомерный остаток, проведения циклизации "голова-к-хвосту" указанного ингибиторного пептида болезни Альцгеймера iAβ5, замены амидных ...

ИНГИБИТОРЫ γ-СЕКРЕТАЗЫ

Настоящее изобретение относится к соединению, которое обладает превосходным действием, направленным на ингибирование γ-секретазы и специфическое ингибирование продуцирования Aβ. Настоящее изобретение относится к соединению формулы (1) или к его фармацевтически приемлемой соли где R1 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода, или фенильную группу; R2 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода, которая может быть замещена одной или несколькими фенильными или галогенфенильными группами; R3 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода, которая содержит одну или несколько гидроксильных групп; R4 представляет собой прямую или разветвленную алкильную группу, имеющую от 1 до 4 атомов углерода; и символ * означает хиральный центр.

Alpha -Ketoamide Inhibitors of 20S Proteasome, Pharmaceutical Preparations Containing the Same and Methods for Treatment

NOVEL PEPTIDE DERIVATIVES USEFUL AS INHIBITORS OF BACTERIAL COLLAGENASE.

The antagonists [...], process for their preparation and pharmaceutical compositions [...]

La présente invention concerne de nouveaux composés pseudo-bis-peptidiques antagonistes de la cholecystokinine de formule (I): (CF DESSIN DANS BOPI) leur procédé de préparation et les compositions pharmaceutiques les comprenant.

New amino acid derivatives and their therapeutic use

MACROCYCLIC COMPOUNDS AS HCV NS3 PROTEASE INHIBITORS

The present application describes macrocyclic compounds of formula (I) with NS3 protease inhibitory activity for treating hepatitis C virus infection.

PHOSPHONAMIDATE ESTER-CONTAINING PSEUDOPEPTIDES

A "capped" phosphonamide C1-C6 alkyl ester linkage unit for joining peptides is disclosed. The linkage unit is substantially isosteric and isocoulombic as compared to conventional peptide backbone structures. The "capping" of the phosphonamide by the C1-C6 alkyl ester causes the linkage unit to be acid stable. When incorporated into a peptide, the phosphonamide C1-C6 alkyl ester linkage unit becomes resistant to cleavage by aspartic proteinase. Accordingly, the phosphonamide C1-C6 alkyl ester linkage unit enhances and/or facilitates the aspartic proteinase inhibition activity of peptides into which it is incorporated.

HIV PROTEASE INHIBITORS CONTAINING GUANIDINE

Compounds of formula (I) wherein R1 and A are amino terminal groups: Z is O or N-R2; M is a dipeptide isostere; and D1 and D2 are optionally absent or amino acids; and pharmaceutically acceptable salts thereof, are potent inhibitors of the HIV-1 protease and are useful in the treatment of viral diseases such as Acquired Immune Deficiency Syndrome (AIDS).

MELANOCORTIN RECEPTOR LIGANDS

Disclosed are MC-4 and/or MC-3 receptor ligands, the ligands having a structure according to Formula (I): wherein R2, R4, R4', R5, R6, R6', R7, R8, R8', R9, R9', R10, Ar, Z1, Z2, Z3, X, B, D, p, q, r and s are as described in the specification and claims, and optical isomers, diastereomers or enantiomers thereof; pharmaceutically-acceptable salts, hydrates, and biohydrolyzable esters, amides or imides thereof. Also disclosed are pharmaceutical compositions comprising the ligands of Formula (I), as well as methods of treating diseases mediate by the MC-4/MC-3 receptors, as described in the Detailed Descriptions section of the specification.

ANTIMICROBIAL AGENTS

L'invention concerne des composés antimicrobiens représentés par la formule R¿1-X-R¿2. Dans cette formule, X représente un groupe comprenant environ 4 à 10 acides aminés, au moins l'une des liaisons amide (--CONH--) étant remplacée par --NR¿cCR¿aR¿b--; R¿a, R¿b, et R¿c représentent chacun indépendamment hydrogène, alkyle, (C¿1-C¿6), alcényle, (C¿2-C¿6), alkynyle(C¿2-C¿6), cycloalkyle(C¿3-C¿8), alcoxycarbonyle(C¿1-C¿6), aryle, ou hétérocycle; et R¿1 Et R¿2 représentent chacun indépendamment hydrogène, un saccharide, un lipide, un agent de solubilisation, ou un groupe protecteur approprié. L'invention concerne également un sel pharmaceutiquement acceptable de ces composés, ainsi que des compositions pharmaceutiques comprenant lesdits composés ou sels, et des techniques utilisant ces composés et ces sels pour traiter une infection bactérienne.

THROMBIN INHIBITORS

A compound which inhibits human thrombin and has structure (I) or (II) or (III) and pharmaceutically acceptable salts thereof, wherein compounds such as (IV) are useful for inhibiting formation of blood platelet aggregates in blood in a mammal.

RETROVIRAL PROTEASE INHIBITORS

Compounds represented by formula (I) or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein A represents radicals represented by formulae (A1, A2, A3) (values for the variables given herein), are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.

DIPEPTIDE HYDROXY ETHYLENE ISOSTERE SYNTHESIS AND INTERMEDIATES THEREFOR

The present invention provides processes and intermediates for one preparation of the hydroxy ethylene isostere dipeptide of leu-val which is itself useful in the preparation of renin inhibitory peptides. The process employs certain novel oxazolidenes.

Cycloalkyl-substituted glutaramide diuretic agents

... 2-Acylaminoalkyl-3-[1-(carboxycycloalkylcarbamoyl)cycloalkyl]propanoic acid derivatives (which may also be viewed as glutaramide derivatives) are useful in the treatment of hypertension, heart failure and renal insufficiency, based upon their inhibition of zinc-dependent, neutral endopiptidase.

Aminomethylene-peptides as immunosuppressants

Compounds which suppress human T-lymphocyte proliferation are disclosed. The active compounds essentially contain at least the following structure: см. иллюстрацию в PDF-документе wherein A, R1, R2, R3, n, X1 and Z are defined in the specification.

Tachykinin derivatives, their preparation and pharmaceutical compositions containing them

The invention relates to the derivatives of formula (I): in which: R1 or R2, which are identical or different, represent a hydrogen atom, an alkyl, cycloalkyl or benzyl group, B represents an aromatic amino acid residue, A represents a peptide residue containing from one to three amino acids, in cyclic or linear form.

5-Substituted amino-4-hydroxy-pentenoic acid derivatives and their use

A 5-substituted amino-4-hydroxy-pentenoic acid or its salt represented by the formula: wherein each of R1 and R² which may be the same or different is a hydrogen atom, a lower alkyl group, an aralkyl group, a lower alkoxycarbonyl group, an aryloxycarbonyl group, an aralkyloxycarbonyl group or a lower alkanoyl group which may be substituted by from one to three substituents selected from the group consisting of an amino group, a hydroxyl group, a carboxyl group, an aryloxy group, an aralkyloxycarbonylamino group, a lower alkoxycarbonylamino group and a group (wherein each of X1 and X² which may be the same or different is a hydrogen atom, a lower alkyl group, an aryl group or an aralkyl group, or X1 and X² form together with the adjacent nitrogen atom a 5- or 6-membered heterocyclic group which may further contain a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom) and which may further contain a double bond in its carbon chain ...

PYRROLIDINCARBOLYLAMINO CYCLIC DISULFIDES AS VCAM-VLA4 ANTAGONISTS

Compounds of formula (I) are described which have activity as anti-inflammatory agents. Cyclic disulfide compounds are provided which inhibit of binding of cells to endothelium. Such compounds are useful for treating inflammatory diseases, such as asthma, whose symptoms and/or damage are related to the binding of cell adhesion molecules to integrin expressing cells.

HIV protease inhibiting agents

Disclosed herein are compounds of the general formula X-A-B-C'-D-Y wherein X is a terminal group, for example, alkanoyl or phenylalkanoyl radicals, A is an amino acid residue having a lower alkyl or lower cycloalkyl side chain, e.g. Ala or val, B is a non-peptide linking unit, e.g. statyl or Phe [CH2NH]Leu, C' is an amino acid residue of -amino-ß-cycloalkylpropionic acid, glutamic acid or -aminoadipic acid, or a related derivative thereof, D is an amino-acid residue, for example, Phe or Val, and Y is hydroxy, alkoxy, amino, alkylamino or dialkylamino. The compounds inhibit the activity of human immunodeficiency virus (HIV) protease and interfere with HIV induced cytopathogenic effects in human cells. These properties render the compounds used for combating HIV infections.

5-Substituted amino-4-hydroxy-pentenoic acid derivatives and their use

Cis-epoxide derivatives useful as irreversible HIV protease inhibitors and process and intermediates for their preparation

CIS-OLEFIN COMPOUND AND ITS PRODUCTION

PROBLEM TO BE SOLVED: To obtain the subject compound useful as an intermediate for producing a HIV enzyme inhibitor by successively reacting phthalic acid N-(2- boromoethyl) with triethylphosphine and N-protecting-L-phenylalaninal and treating the reaction product with hydrazine. SOLUTION: This new cis-olefin compound is shown by formula I (R1 is a cycloalkyl or an aryl-substituted lower alkyl; Z' is t-butoxyalkyl) {e.g. 4S-1, 4-bis[(N-benzyloxycarbonyl)amino]-5-phenyl-(2, 3)-(Z)-pentene} and is useful as an intermediate for an irreversible inhibitor of human immunodeficiency virus(HIV) effective as a therapeutic agent for AIDS. The compound is obtained by reacting phthalic acid N-(2-boromoethyl) with triethylphosphine to give a compound of formula II (Ph is phenyl), reacting the compound with N- benzyloxycarbonyl-L phenylalaninal and treating the prepared compound of formula III with hydrazine. COPYRIGHT: (C)1998,JPO ...

БИОКОНЪЮГАЦИОННЫЕ КОМПЛЕКСЫ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ (ВАРИАНТЫ), ФЕНИЛБОРНОКИСЛЫЕ КОМПЛЕКСООБРАЗУЮЩИЕ РЕАГЕНТЫ, ФЕНИЛБОРНОКИСЛЫЕ ПОПЕРЕЧНО-СШИВАЮЩИЕ РЕАГЕНТЫ, НАБОР СРЕДСТВ ИЛИ СИСТЕМА, СПОСОБ ВЫДЕЛЕНИЯ ТРЕБУЕМОЙ ПОПУЛЯЦИИ КЛЕТОК

Изобретение относится к группе новых биоконъюгационных комплексов общей формулы А BAS-L-Bc-L'-(Bc'-L'')n-BAS', где BAS, BAS', BAS''- биоактивные ингредиенты, которые могут быть как одинаковыми, так и различными; Вс и Вс' - комплексы фенилборной кислоты; L, L', L'' - линкеры; n = 0 или 1, трем способам их получения, промежуточным продуктам, используемым в их синтезе и представляющим собой фенилборнокислые комплексообразующие реагенты и фенилборнокислые поперечно-сшивающие реагенты, способу выделения требуемой популяции клеток, а также набору или системе, содержащей биоконъюгат А, для выделения требуемой популяции клеток. 8 с. и 1 з.п. ф-лы.

2-АМИДО-4-АРИЛОКСИ-1-КАРБОНИЛПИРРОЛИДИНОВЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ СЕРИНПРОТЕАЗ, В ЧАСТНОСТИ ПРОТЕАЗЫ NS3-NS4A HCV

Настоящее изобретение относится к соединениям формулы I-A и I-B, которые ингибируют серинпротеазную активность, в частности активность протеазы NS3-NS4A вируса гепатита С. Соединения действуют, препятствуя жизненному циклу вируса гепатита С, и также применимы в качестве противовирусных средств. Изобретение также относится к композициям, содержащим указанные соединения, или для применения in vivo, или для введения пациенту, страдающему от заражения HCV. 6 н. и 29 з.п. ф-лы. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 440 368 (13) C2 (51) МПК C07K 5/10 (2006.01) A61K 38/55 (2006.01) A61P 31/14 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (72) Автор(ы): ПЕРНИ Роберт Б. (US), КОРТ Джон Дж. (US), БРИТТ Шон Д. (US), ПИТЛИК Янош (US), ВАН ДРИ Джон Х. (US) (21)(22) Заявка: 2006110934/04, 07.09.2004 (24) Дата начала отсчета срока действия патента: 07.09.2004 (43) Дата публикации заявки: 10.10.2007 Бюл. № 28 (73) Патентообладатель(и): ВЕРТЕКС ФАРМАСЬЮТИКАЛЗ ИНКОРПОРЕЙТЕД (US) 2 4 4 0 3 6 8 (45) Опубликовано: 20.01.2012 Бюл. № 2 (56) Список документов, цитированных в отчете о поиске: WO 01/40262 A1, 07.06.2001. WO 01/74768 A1, 11.11.2001. WO 9817679 A1, 30.04.1998. WO 01/02424 A2, 11.01.2001. WO 02/08256 A2, 31.01.2002. WO 03/087092 A2, 23.10.2003. RU 93036735 A, 27.04.1996. 2 4 4 0 3 6 8 R U (86) Заявка PCT: US 2004/029093 (07.09.2004) C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 05.04.2006 (87) Публикация заявки РСТ: WO 2005/035525 (21.04.2005) Адрес для переписки: 129090, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Е.Е.Назиной (54) 2-АМИДО-4-АРИЛОКСИ-1-КАРБОНИЛПИРРОЛИДИНОВЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ СЕРИНПРОТЕАЗ, В ЧАСТНОСТИ ПРОТЕАЗЫ NS3-NS4A HCV (57) Реферат: Настоящее изобретение относится к соединениям формулы I-A и I-B, которые ингибируют серинпротеазную активность, в частности активность протеазы NS3-NS4A вируса гепатита С. Соединения ...

ИМИДАЗОЛСОДЕРЖАЩИЕ ИНГИБИТОРЫ ФАРНЕЗИД-ПРОТЕИНТРАНСФЕРАЗЫ, СПОСОБ ЛЕЧЕНИЯ СВЯЗАННЫХ С НЕЙ ЗАБОЛЕВАНИЙ

Ингибирование фарнезил-трансферазы, которая представляет собой фермент, ответственный за экспрессию онкогена ras, осуществляют с помощью соединений общей формулы, данной в описании, или их энантиомеров, диастереомеров, фармацевтически приемлемых солей, пролекарственных предшественников, и сольватов.

2-АМИДО-4-АРИЛОКСИ-1-КАРБОНИЛПИРРОЛИДИНОВЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ СЕРИНПРОТЕАЗ, В ЧАСТНОСТИ, ПРОТЕАЗЫ NS3-NS4A HCV

... 1. Соединение формулы I где Ar представляет собой 5-10-членное ароматическое кольцо, содержащее до 4 гетероатомов, выбранных из О, S, N(H), SO и SO2, где 1-3 атома кольца, необязательно и независимо, замещены J; R1 и R2 представляют собой, независимо: (С1-С12)-алифатический радикал, (С3-С10)-циклоалкил- или -циклоалкенил-, [(C3-С10)-циклоалкил- или циклоалкенил]-(С1-С12)-алифатический радикал, (С6-С10)-арил-(С1-С12)-алифатический радикал, (С6-С10)-гетероарил-(С1-С12)-алифатический радикал, где до 3 алифатических атомов углерода в R1 и R2 могут быть заменены гетероатомами, выбранными из О, N, S, SO или SO2, в химически устойчивой структуре; где каждый из R1 и R2, независимо и необязательно, замещен заместителями, до 3, выбранными, независимо, из J; R3 и R3' представляют собой, независимо, водород или (С1-С12)-алифатический радикал, где любой атом водорода, необязательно, заменен галогеном; где любой концевой атом углерода группы R3, необязательно, замещен сульфгидрилом или гидрокси; или ...

2-АМИДО-4-АРИЛОКСИ-1-КАРБОНИЛПИРРОЛИДИНОВЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ СЕРИНПРОТЕАЗ, В ЧАСТНОСТИ ПРОТЕАЗЫ NS3 NS4A HCV

1. Соединение формулы Iгде Ar представляет собой 5-10-членное ароматическое кольцо, содержащее до 4 гетероатомов, выбранных из О, S, N(H), SO и SO, где 1-3 атома кольца, необязательно и независимо, замещены J;Rи Rпредставляют собой, независимо:(С1-С12)-алифатический радикал,(С3-С10)-циклоалкил- или -циклоалкенил-,[(C3-С10)-циклоалкил- или циклоалкенил]-(С1-С12)-алифатический радикал,(С6-С10)-арил-(С1-С12)-алифатический радикал,(С6-С10)-гетероарил-(С1-С12)-алифатический радикал,где до 3 алифатических атомов углерода в Rи Rмогут быть заменены гетероатомами, выбранными из О, N, S, SO или SO, в химически устойчивой структуре;где каждый из Rи R, независимо и необязательно, замещен заместителями, до 3, выбранными, независимо, из J;Rи Rпредставляют собой, независимо, водород или (С1-С12)-алифатический радикал, где любой атом водорода, необязательно, заменен галогеном; где любой концевой атом углерода группы R, необязательно, замещен сульфгидрилом или гидрокси; или Rпредставляет собой фенил или -СН-фенил, где указанная фенильная группа, необязательно, замещена заместителями, до 3, выбранными, независимо, из J; илиRи Rвместе с атомом, с которым они связаны, представляют собой 3-6-членное кольцо, содержащее до 2 гетероатомов, выбранных из N, NH, О, SO и SO; где кольцо имеет до 2 заместителей, выбранных, независимо, из J;Rи Rпредставляют собой, независимо:водород-,(С1-С12)-алифатический радикал,(С3-С10)-циклоалкил- или циклоалкенил-,(С3-С10)-циклоалкил-(С1-С12)-алифатический радикал,(С6-С10)-арил-,(С3-С10)-гетероциклил- или(С5-С10)-гетероарил-;где до двух алифатических атомов углерода в Rи Rмогут быть заменены гетероатомами, выбранными из О, N, S, SO и SO;где каждый из Rи R, независимо и необязательно, замещен замест� РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07K 5/10 (13) 2011 137 875 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2011137875/04, 14.09.2011 (71) Заявитель(и): ВЕРТЕКС ФАРМАСЬЮТИКАЛЗ ИНКОРПОРЕЙТЕД ( ...

Novel amino acid derivatives, process for their preparation and pharmaceutical compositions containing these compounds

The invention relates to novel amino acid derivatives of the formula I and their pharmaceutically acceptable salts, wherein the group R<2> is and R<1>, A, R<3>, R<4>, R<5>, R<6>, X, Y, Z, m and n have the meanings indicated in the description, and their preparation and use. The novel compounds are useful neurokinin (tachykinin) antagonists.

Dipeptide zur Förderung der Sekretion des Wachstumshormons

THERAPEUTIC AGENTS

PEPTIDE WITH ENDOTHELIN ANTAGONISTIC ACTIVITY. THEIR PRODUCTION AND PHARMACEUTICAL COMPOSITIONS

INHIBITORS OF RETROVIRALER PROTEASEN

TACHYKININDERIVATE, THEIR PRODUCTION AND THESE CONTAINING PHARMACEUTICAL COMPOSITIONS

ISOSTERI PEPTIDDERIVATE AGAINST HERPES

Methods of treating emesis using growth hormone secretagogues

The present invention relates to methods of treating or preventing emesis and improving a subject's ASAS score by administering to the subject an effective amount of a growth hormone secretagogue compound or a pharmaceutically acceptable salt, hydrate or solvate thereof.

Inhibition of memapsin 1 cleavage in the treatment of diabetes

Proteases such as memapsin-1 are import enzymes, playing roles in a variety of diseases including diabetes. The inventors have developed inhibitors of memapsin 1 and methods of use therefore in the treatment of disease.

Compounds, linker-drugs and ligand-drug conjugates

A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is provided. In formula (I), R1, R2 and R3 are each, independently, hydrogen, amino, nitro, halogen, hydroxyl, C1-C6 alkoxy, carboxylic acid, C1-C6 alkoxycarbonyl, C1-C6 amino, C1-C6 aminocarbonyl, C1-C6 alkyl, branched C1-C6 alkyl, C1-C6 cycloalkyl, C1-C6 heterocyclic, aryl or heteroaryl, provided at least one of R1 and R3 is an amino group. A linker-drug and a ligand-drug conjugate including the compound are also provided.

Novel Binder-Drug Conjugates (ADCs) and Use of Same

The present patent application relates to novel binder-drug conjugates (ADCs) of N,N-dialkylauristatins directed against the target epidermal growth factor receptor (EGFR, gene ID 1956), effective metabolites of these ADCs, methods for producing these ADCs, use of these ADCs for treatment and or prevention of diseases as well as the use of these ADCs to produce pharmaceutical drugs for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic diseases such as cancer, for example. Such treatments may be administered as monotherapy or in combination with other pharmaceutical drugs or other therapeutic measures.

COMPOUNDS, LINKER-DRUGS AND LIGAND-DRUG CONJUGATES

A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is provided. In formula (I), R1, R2 and R3 are each, independently, hydrogen, amino, nitro, halogen, hydroxyl, C1-C6 alkoxy, carboxylic acid, C1-C6 alkoxycarbonyl, C1-C6 amino, C1-C6 aminocarbonyl, C1-C6 alkyl, branched C1-C6 alkyl, C1-C6 cycloalkyl, C1-C6 heterocyclic, aryl or heteroaryl, provided at least one of R1 and R3 is an amino group. A linker-drug and a ligand-drug conjugate including the compound are also provided. 2. The compound as claimed in claim 1 , wherein R1 is hydrogen claim 1 , R2 is hydrogen claim 1 , carboxylic acid claim 1 , C1-C6 alkoxycarbonyl claim 1 , C1-C6 aminocarbonyl or C1-C6 alkyl claim 1 , and R3 is amino.6. The linker-drug as claimed in claim 3 , wherein -AAs- is the peptide unit selected from the group consisting of -Val-Cit- claim 3 , -Val-Lys- claim 3 , -Val-Arg- claim 3 , -Phe-Cit- claim 3 , -Phe-Lys- and -Phe-Arg-. This application is a Divisional of pending U.S. patent application Ser. No. 15/341,117, filed Nov. 2, 2016 and entitled “compounds, linker-drugs and ligand-drug conjugates”, which claims the benefit of U.S. Provisional Application No. 62/250,107, filed Nov. 3, 2015, the entirety of which is incorporated by reference herein.The technical field relates to an auristatine derivative, a novel linker, a linker-drug and a ligand-drug conjugate including the auristatine derivative.Antibodies have high-degree identification abilities with respect to their corresponding antigens, and many cytotoxic drug molecules cannot be used for cancer therapy because they cannot selectively kill cancer cells. Therefore, the connection of antibodies and highly toxic drugs (such as toxins) becomes a highly selective and specific conjugated drug. The concept of Antibody-Drug Conjugates (ADCs) was proposed more than 30 years ago. The world's major pharmaceutical companies and many small and medium-sized biotechnology companies are investing a lot of money and ...

HYDROXY-ETHYLENE DERIVATIVES FOR THE TREATMENT OF ARTHROSIS

The present invention relates to compounds of the formula I and in particular medicaments comprising at least one compound of the formula I for use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia. 2. Compounds according to in which{'sup': '1', 'Rdenotes isopropyl, 2-butyl or isobutyl'}{'sup': 1', '2', '3', '4', '5', '1', '2', '1', '2, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'and I, I, I, I, I, A, A, L, L, X, X′, Y, T, R, R′, m, n and Hal have the meanings indicated in , and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.'}3. Compounds according to in which{'sup': '1', 'Rdenotes isopropyl'}{'sup': 1', '2', '3', '4', '5', '1', '2', '1', '2, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'and I, I, I, I, I, A, A, L, L, X, X′, Y, T, R, R′, m, n and Hal have the meanings indicated in , and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.'}4. Compounds according to in which{'sup': '1', 'Rdenotes isopropyl, having an S configuration of the chiral centre to which the isopropyl group is bonded,'}{'sup': 1', '2', '3', '4', '5', '1', '2', '1', '2, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'and I, I, I, I, I, A, A, L, L, X, X′, Y, T, R, R′, m, n and Hal have the meanings indicated in , and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.'}5. Compounds according to in which{'sup': '1', 'sub': 2', '2, 'Adenotes 0 to 1 amino acid radicals, selected from alanine, glycine, cyclopropylglycine, cyclobutylglycine, cyclopentylglycine, cyclohexylglycine, 3-oxetanylglycine, 3- ...

PEPTIDE-OLIGOUREA CHIMERIC COMPOUNDS AND METHODS OF THEIR USE

The present description provides compositions and methods for producing therapeutic oligomeric compounds. In another aspect the description provides methods for administering the oligomeric compounds for the treatment and prevention of disease in a mammal. In particular, the invention relates to medicaments comprising various novel oligomeric compounds and pharmaceutically acceptable salts thereof. The compounds of the invention may optionally be administered with at least one of a pharmaceutically acceptable excipient, additional pharmacologically active agent or a combination thereof. 1. A peptide-oligourea chimeric compound comprising:a peptide portion including at least two consecutive α-amino acid residues, coupled to an oligourea portion including at least five consecutive peptidomimetic residues having N,N′-linked urea bridging unityes, wherein the peptidomimetic residues are selected from the group of substituted or unsubstituted N-2-aminoethylcarbamoyl residue, substituted and unsubstituted N-(2-aminoethyl)carbamothioyl residues, substituted and unsubstituted N-(2-aminoethyl)formamidinyl residues, substituted and unsubstituted 2-aminoethanoxycarbonyl and combinations thereof.2. The chimeric compound of claim 1 , wherein the oligourea portion is coupled to the amino terminus or carboxy terminus of the peptide portion3. The chimeric compound of claim 2 , wherein an oligourea sequence is coupled to both the amino and carboxy termini of the peptide portion.4. The chimeric compound of claim 1 , wherein the compound has at least six peptidomimetic residues having N claim 1 , N′-linked urea bridging units.6. A therapeutic composition comprising an effective amount of the compound of and a pharmaceutically acceptable carrier or excipient.7. A method of treating a disease in a patient comprising administering to an individual in need thereof claim 6 , and effective amount of the composition of claim 6 , wherein the composition is effective in ameliorating the ...

N-acyldipeptide Derivatives and Their Uses

Methods of treating aging related skin changes and of increasing skin thickness with topical administration of N-acyldipeptide derivatives are described. Compositions comprising N-acyldipeptide derivatives, are therapeutically effective for increasing skin thickness, and for treating extrinsic and intrinsic aging and aging related skin changes, such as fine lines, wrinkles, photoaging, hyperpigmentation, laxity, age spots, lentigines, mottled skin, and cellulite. 2. The composition of claim 1 , wherein AAB is Tyr and AAC is Tyr.3. The composition of claim 1 , wherein AAB is Val and AAC is Ala.4. The composition of claim 1 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Tyr-Tyr-NH claim 1 , N—Ac-Tyr-Tyr-OH claim 1 , N—Ac-Tyr-Tyr-OEt claim 1 , N—Ac-Tyr-Tyr-NHNH claim 1 , N—Ac-Tyr-Tyr-NHNHAc claim 1 , N—Ac-Tyr-Tyr-NHOH claim 1 , N—Pr-Tyr-Tyr-NH claim 1 , N—Pr-Tyr-Tyr-OH claim 1 , N—Pr-Tyr-Tyr-OEt claim 1 , N—Pr-Tyr-Tyr-NHNH claim 1 , and N—Pr-Tyr-Tyr-NHNHPr.5. The composition of claim 1 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Val-Ala-NH claim 1 , N—Ac-Val-Ala-OH claim 1 , N—Ac-Val-Ala-NHOH claim 1 , N—Pr-Val-Ala-NH claim 1 , and N—Pr-Val-Ala-OH.6. The composition of claim 1 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Tyr-Tyr-NHand N—Ac-Val-Ala-NH.7. The composition of claim 1 , wherein the dipeptide derivative is N—Ac-Val-Ala-NH.8. A method of treating aging related skin changes or changes associated with intrinsic or extrinsic aging claim 1 , or of increasing skin thickness in a subject in need thereof claim 1 , the method comprising topically administering to skin of the subject the composition of .9. The method of claim 8 , wherein the dipeptide derivative is selected from the group consisting of N—Ac-Tyr-Tyr-NH claim 8 , N—Ac-Tyr-Tyr-OH claim 8 , N—Ac-Tyr-Tyr-OEt claim 8 , N—Ac-Tyr-Tyr-NHNH claim 8 , N—Ac-Tyr-Tyr-NHNHAc claim 8 , N—Ac-Tyr-Tyr-NHOH claim 8 ...

N-acyldipeptide derivatives and their uses

N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for treating disorders and condition associated with the nervous system or musculoskeletal system, such as pain, weakness, numbness, arthritis, joint inflammation, weakness of muscles or joints, and myopia.

Potent and Efficient Cytotoxic Peptides and Antibody-Drug Conjugates thereof and Their Synthesis

The present invention provides a family of novel cytotoxic pentapeptides, which show potent antitumor activities against several cancer lines. The antibody-drug conjugates prepared from those pentapeptides can efficiently kill cancer cells. 7. A drug conjugate having the structure of{'br': None, 'sub': 'n', 'A-(L-D),'}whereA is an ligand, including antibody, peptide or small molecular ligand;{'claim-ref': {'@idref': 'CLM-00005', 'claim 5'}, 'L is a linker, according to the formula in ;'}andD is a drug; n is 1 to 4; wherein A is attached to a linker via thiol group of cysteine or amino group of lysine of A, but not to limited to those linkage types. The present application claims priority to U.S. Provisional Patent Application 61/975,046, filed Apr. 4, 2014, the entire contents of which is incorporated herein by reference.The present invention relates to the discovery and preparation of a family of novel cytotoxic pentapeptides. These compounds show potent antitumor activities against several cancer lines. The antibody-drug conjugates prepared from those pentapeptides can efficiently kill cancer cells.Since the introduction of the concept of antibody-drug conjugates (ADCs) three decades ago, this area has been advanced greatly along with improved ADC and linker technology. The approved drugs Adcetris (Brentuximabvedotin) in 2011 and Kadcyla (Trastuzumabemtansine) in 2013 have dramatically increased the interests and efforts on ADC drug discovery and development all over pharmaceutical, biopharmaceutical and research institutions worldwide. Success ratios of ADC drugs in clinical trials are largely dependent on ADC biomolecules's efficacy and toxicity, especially when the free drugs could not be cleaved and released from the whole ADC molecules in biological system before reaching the targeted cancer cells. So far there are only three main families of cytotoxins successfully used for ADC drugs developed in clinical trials. Among them, auristatin, such as ...

AMINO ACID DERIVATIVES

new ligand-drug conjugates (adcs) and their use

novos conjugados ligante-droga (adcs) e uso dos mesmos o presente se refere a novos conjugados ligante-rosa (adcs) de n,n-dialquilauristatinas que são direcionados contra o c4.4a alvo, a metabólicos ativos desses adcs, um processos para preparar esses adcs, ao uso desses adcs para tratar e/ou prevenir enfermidades, e também ao uso desses adcs para produzir medicamentos para tratar e/ou prevenir enfermidades, mais particularmente doenças proliferativas e/ou angiogênicas, tais como, por exemplo, doenças cancerosas. tais tratamentos podem ser praticados como uma monoterapia ou de outra forma em combinação com outros medicamentos ou medida terâpeuticas adicionais. novel ligand-drug conjugates (adcs) and use thereof The present refers to novel n, n-dialkyluristatine pink ligand conjugates (adcs) that are directed against the target c4.4a, to active metabolic of these adcs, a process for prepare such ADCs, the use of such ADCs to treat and / or prevent disease, and also the use of such ADCs to produce medicaments to treat and / or prevent disease, more particularly proliferative and / or angiogenic diseases such as, for example, cancerous diseases. . Such treatments may be practiced as a monotherapy or otherwise in combination with other medications or additional therapeutic measures.

抗體藥物複合物及其製造方法

本揭露提供一種具有化學式(I)之抗體藥物複合物(ADC)或其藥學上可接受鹽類或溶劑化物。於化學式(I)中，p為介於1~26之整數，A為一抗體，且-(L-D)為一連接子-藥物單元。其中，L為一具有醣胜肽的連接子單元，且D為一藥物單元。其中，抗體藉由抗體之一半胱氨酸殘基連接至連接子單元。本揭露也提供一種抗體藥物複合物(ADC)的製造方法。 A-(L-D) p (I)

Compounds, linker-drugs and ligand-drug conjugates

A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is provided. In formula (I), R1, R2 and R3 are each, independently, hydrogen, amino, nitro, halogen, hydroxyl, C1-C6 alkoxy, carboxylic acid, C1-C6 alkoxycarbonyl, C1-C6 amino, C1-C6 aminocarbonyl, C1-C6 alkyl, branched C1-C6 alkyl, C1-C6 cycloalkyl, C1-C6 heterocyclic, aryl or heteroaryl, provided at least one of R1 and R3 is an amino group. A linker-drug and a ligand-drug conjugate including the compound are also provided.

Compounds, linker-drugs and ligand-drug conjugates

A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is provided. In formula (I), R1, R2 and R3 are each, independently, hydrogen, amino, nitro, halogen, hydroxyl, C1-C6 alkoxy, carboxylic acid, C1-C6 alkoxycarbonyl, C1-C6 amino, C1-C6 aminocarbonyl, C1-C6 alkyl, branched C1-C6 alkyl, C1-C6 cycloalkyl, C1-C6 heterocyclic, aryl or heteroaryl, provided at least one of R1 and R3 is an amino group. A linker-drug and a ligand-drug conjugate including the compound are also provided.

Antibody-drug conjugate (ADC) and method for forming the same

An antibody-drug conjugate (ADC) of formula (I) or a pharmaceutically acceptable salt or solvate thereof is provided. In formula (I), p is an integer ranging from 1 to 26, A is an antibody, and -(L-D) is a linker-drug unit. L is a linker unit having a glycopeptide, and D is a drug unit. The antibody is conjugated to the linker unit through a cysteine residue of the antibody. A method for forming an antibody-drug conjugate (ADC) is also provided. A-(L-D) p   (I)

Aza-peptide epoxides

The present invention provides compositions for inhibiting proteases, methods for synthesizing the compositions, and methods of using the disclosed protease inhibitors. Aspects of the invention include aza-peptide epoxide compositions that inhibit proteases, for example cysteine proteases, either in vivo or in vitro. The disclosed compounds, pharmaceutically acceptable salts, pharmaceutically acceptable derivatives, prodrugs, or combinations thereof can be used to treat disease or pathological conditions related to the activity of proteases associated with a specific disease or condition. Such treatable conditions include viral infections, stroke, neurodegenerative disease, and inflammatory disease, among others.

New conjugates binding compound - active compound (adc) and use thereof

FIELD: medicine. SUBSTANCE: present invention relates to novel conjugates of binding compound – active compound of (ADC) N,N-alkylauristatins targeted against target C4.4a, active metabolites of said ADC conjugates, method of obtaining said ADC conjugates, use of said ADC conjugates for treating and/or preventing diseases, as well as use of these ADC conjugates to produce medicinal agents for treating and/or preventing diseases, more specifically hyperproliferative and/or angiogenic diseases, such as, for example, cancer. EFFECT: such drug treatment can be used in form of single agent therapy or, in another version, in combination with other drugs or additional other therapeutic measures. 52 cl, 6 tbl, 128 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 610 336 C2 (51) МПК C07K 7/02 (2006.01) C07K 16/28 (2006.01) C07K 16/30 (2006.01) A61K 47/48 (2006.01) A61K 38/08 (2006.01) A61P 35/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ФОРМУЛА (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2013151600, 20.04.2012 (24) Дата начала отсчета срока действия патента: 20.04.2012 Дата регистрации: Приоритет(ы): (30) Конвенционный приоритет: (45) Опубликовано: 09.02.2017 Бюл. № 4 (56) Список документов, цитированных в отчете о поиске: WO 2006071441 A2, 06.07.2006. WO 2 6 1 0 3 3 6 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 21.11.2013 R U (73) Патентообладатель(и): СИЭТЛ ДЖЕНЕТИКС, ИНК. (US) 2005081711 A2, 09.09.2005. WO 2009099728 A1, 13.08.2009. RU 2436796 C2, 20.12.2011. (86) Заявка PCT: EP 2012/057247 (20.04.2012) (87) Публикация заявки PCT: WO 2012/143497 (26.10.2012) Адрес для переписки: 105064, Москва, а/я 88, "Патентные поверенные Квашнин, Сапельников и партнеры" (54) НОВЫЕ КОНЪЮГАТЫ СВЯЗЫВАЮЩЕЕ СОЕДИНЕНИЕ - АКТИВНОЕ СОЕДИНЕНИЕ (ADC) И ИХ ПРИМЕНЕНИЕ (57) Формула изобретения 1. Конъюгат связывающее соединение - активное соединение общей формулы (Ia) Стр.: 1 C 2 C 2 (43) Дата публикации заявки: 27.05.2015 Бюл. № 15 2 6 1 0 3 ...

Новые конъюгаты связывающее соединение-активное соединение (adc) и их применение

1. Конъюгат связывающее соединение - активное соединение общей формулы (Ia)гдеn представляет собой число от 1 до 50,AK обозначает связывающее соединение, предпочтительно химерное гуманизированное или человеческое антитело, особенно предпочтительно антитело к EGFR,группа §-G-L1-B-L2-§§ обозначает линкер,где§ обозначает точку связывания с группой AK, 觧 обозначает точку связывания с атомом азота,D представляет собой группу формулыгде#обозначает точку связывания с атомом азота,Rпредставляет собой водород или метил,Rпредставляет собой изобутил, сек-бутил, трет-бутил, фенил, бензил, 1-гидроксиэтил, 4-гидроксибензил, 4-гидроксил-3-нитробензил, 4-гидроксил-3-аминобензил, 1-фенилэтил, дифенилметил, 1H-имидазол-4-илметил или 1H-индол-3-илметил,илиRи Rвместе с атомом углерода, к которому они присоединены, образуют (1S,2R)-2-фенил-циклопропан-1,1-диил формулыгде#обозначает точку связывания с соседним атомом азота,#обозначает точку связывания с карбонильной группой,кольцо А с присутствующей на нем группой N-O представляет собой моно- или бициклический, возможно содержащий заместители гетероцикл формулыгде#обозначает точку связывания с карбонильной группой,Rпредставляет собой водород, гидрокси или бензилокси,Rпредставляет собой водород или метил,Rпредставляет собой изобутил, сек-бутил, трет-бутил, фенил, бензил, 1-гидроксиэтил, 4-гидроксибензил, 4-гидроксил-3-нитробензил, 4-гидроксил-3-аминобензил, 1-фенилэтил, дифенилметил, 1H-имидазол-4-илметил или 1H-индол-3-илметил,илиRи Rвместе с атомом углерода, к которому они присоединены, образуют (1S,2R)-2-фенил-циклопропан-1,1-диил формулыгде#обозначает точку связывания с соседним атомом азота,#обозначает точку свя РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК A61K 47/48 (13) 2013 151 599 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2013151599/04, 20.04.2012 (71) Заявитель(и): СИЭТЛ ДЖЕНЕТИКС, ИНК. (US) Приоритет(ы): (30) Конвенционный приоритет: 11163474.7; 11163467.1; ...

Gamma Secretase Inhibitors

아미노산서열 Val-Val-Ile-Ala-Thr-Val-Ile-Val-Ile-Thr-Leu-Val-Met-Leu-Lys-Lys-Lys에 있어서, 제11번째 Leu를 포함하는 연속된 적어도 3개의 아미노산으로 되는 아미노산서열로 되고, 상기 Leu와 그의 직전 및/또는 직후에 위치하는 아미노산 사이에 펩티드 결합 대신에 히드록시에틸렌기를 가지며, N말단에, 페닐기 또는 나프틸기로 치환되어 있어도 되는 C1~10 알킬을 기반으로 하는 알킬옥시카르보닐기를 가지고, C말단이, 페닐기 또는 나프틸기로 치환되어 있어도 되는 C1~10 알킬에 의한 알킬에스테르화 또는 알킬아미드화되어 있으며, 제10번째 Thr의 히드록실기의 수소가 탄소수 1~4의 소수성기 또는 Z기에 의해 치환되어 있어도 되는 것인 화합물 또는 그의 염이 감마 세크레타제 활성을 저해하는 화합물로서 개시되어 있다. 감마 세크레타제 저해제, 아밀로이드 전구체 단백질, 아미노산서열, 펩티드 결합, 소수성 아미노산

Novel binder-drug conjugates (ADCs) and their use

本发明涉及针对靶标表皮生长因子受体(EGFR，基因ID1956)的N，N-二烷基耳他汀的新的结合剂-药物缀合物(ADC)，涉及这些ADC的活性代谢物，涉及合成这些ADC的方法，涉及这些ADC用于治疗和/或预防疾病的用途，以及涉及这些ADC用于生产药物的用途，所述药物用于治疗和／或预防疾病，尤其是过度增生性疾病和／或血管生成性疾病，例如癌症。此类治疗可以作为单一疗法或者与其它药物或其它治疗性措施联用来实施。

Factor Xa inhibitor

NAMPT protein degradation targeting chimera and preparation method and application thereof

本发明涉及医药技术领域，具体地说，是一种NAMPT蛋白降解靶向嵌合体，所述的NAMPT蛋白降解靶向嵌合体为通式(i)和/或(ii)的化合物或它们药学上可接受的盐。本发明还涉及上述NAMPT蛋白降解靶向嵌合体的制备方法和应用。本发明的化合物表现出良好的NAMPT酶抑制活性，能通过泛素蛋白酶体途径下调细胞内和细胞外NAMPT蛋白水平，实现对肿瘤的抑制，具有一定广谱的抗肿瘤活性，能够明显的抑制肿瘤生长，可以应用于NAMPT介导的肿瘤疾病。

Prodrugs of active substances with heterocyclic linkers

FIELD: pharmaceutics. SUBSTANCE: invention relates to prodrugs of opioid active substance, which provide controlled release of active substance by enzymatic decomposition with further intramolecular cyclization. Invention also relates to compositions, containing prodrugs, and methods for using them. EFFECT: composition can optionally include trypsin inhibitor, which interacts with enzyme, which is mediator in release of active substance from prodrugs in order to attenuate enzymatic splitting of prodrug. 16 cl, 17 dwg, 15 tbl, 49 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 608 305 C2 (51) МПК C07K 5/062 (2006.01) C07D 489/02 (2006.01) A61K 38/05 (2006.01) A61K 47/48 (2006.01) A61P 25/04 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ФОРМУЛА (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2013144368, 08.03.2012 (24) Дата начала отсчета срока действия патента: 08.03.2012 (72) Автор(ы): ДЖЕНКИНС Томас Э. (US), ХАСФЕЛД Крэйг О. (US) (73) Патентообладатель(и): СИГНИЧЕР ТЕРАПЬЮТИКС, ИНК. (US) Дата регистрации: (56) Список документов, цитированных в отчете о поиске: RU 2562583 C2, 10.09.2015. US Приоритет(ы): (30) Конвенционный приоритет: R U 17.01.2017 20070123468 A1, 31.05.2007. WO 2011007247 A1, 20.01.2011. 09.03.2011 US 61/451,019; 05.01.2012 US 61/583,523 (45) Опубликовано: 17.01.2017 Бюл. № 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 02.10.2013 (86) Заявка PCT: US 2012/028367 (08.03.2012) 2 6 0 8 3 0 5 (43) Дата публикации заявки: 10.04.2015 Бюл. № 10 Адрес для переписки: 109012, Москва, ул. Ильинка, 5/2, ООО "Союзпатент" (54) ПРОЛЕКАРСТВА ДЕЙСТВУЮЩИХ ВЕЩЕСТВ ГЕТЕРОЦИКЛИЧЕСКИМИ ЛИНКЕРАМИ (57) Формула изобретения 1. Соединение формулы: R U 2 6 0 8 3 0 5 WO 2012/122422 (13.09.2012) C 2 C 2 (87) Публикация заявки PCT: где: X выбран из: остатка кетонсодержащего опиоида, где атом водорода соответствующей гидроксильной группы енольного таутомера кетона замещен ковалентной связью с -С Стр.: 1 (О)-N[(цикл A)-Yc]-(CR1R2)a- ...

Novel binder-drug conjugates (adcs) and their use

The present application relates to novel, anti-Target Epidermal Growth Factor Receptor (EGFR, GeneID1956) binder-drug conjugates (ADCs) of N,N-dialkyl auristatins, to effective metabolites of said ADCs, to methods for producing said ADCs, to the use of said ADCs for treating and/or preventing diseases, and to the use of said ADCs for producing pharmaceuticals for treating and/or preventing diseases, in particular hyperproliferative and/or angiogenic diseases, such as cancers. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

Novel binder-drug conjugates (adcs) and their use

The present application relates to novel, anti-carboanhydrase IX (carboanhydrase IX, CAIX, CA9, G250) binder-drug conjugates (ADCs) of N,N-dialkyl auristatins, to effective metabolites of said ADCs, to methods for producing said ADCs, to the use of said ADCs for treating and/or preventing diseases, and to the use of said ADCs for producing pharmaceuticals for treating and/or preventing diseases, in particular hyperproliferative and/or angiogenic diseases, such as cancers. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

Novel binder-drug conjugates (adcs) and their use

The present application relates to novel, anti-mesothelin binder-drug conjugates (ADCs) of N,N-dialkyl auristatins, to effective metabolites of said ADCs, to methods for producing said ADCs, to the use of said ADCs for treating and/or preventing diseases, and to the use of said ADCs for producing pharmaceuticals for treating and/or preventing diseases, in particular hyperproliferative and/or angiogenic diseases, such as cancers. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

HIV protease inhibiting compounds

A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

Irrevesible hiv protease inhibitors with anti-aids effect, process for the preparation thereof and compositions containing the same

본 발명은 HIV 프로테아제의 억제제로서 유용한 신규 화합물 및 그의 제조방법 및 이를 포함하는 조성물에 관한 것으로서, 하기의 일반식(Ⅰ)의 시스-에폭사이드 구조를 갖는 화합물 및 그의 약학적으로 허용되는 염, 수화물 또는 용매화물은, HIV 프로테아제의 비가역적 억제제로서 억제 효과는 높은 반면 그 세포독성은 낮기 때문에, 에이즈 또는 HIV 감염의 치료 또는 예방용 제제로서 유용하게 사용될 수 있다. The present invention relates to a novel compound useful as an inhibitor of HIV protease, a method for preparing the same, and a composition comprising the same, the compound having a cis-epoxide structure of the following general formula (I) and a pharmaceutically acceptable salt and hydrate thereof Alternatively, solvates can be usefully used as agents for the treatment or prevention of HIV or HIV infection because of their high inhibitory effect and low cytotoxicity as irreversible inhibitors of HIV proteases. 상기식에서, R 1 , R 2 및 R 3 는 명세서중에서 정의한 바와 같다. Wherein R 1 , R 2 and R 3 are as defined in the specification.

Compounds to treat Alzheimer's disease

The present invention is directed toward substituted hydroxyethylene compounds of formulas (XII) (XIII), and (XIV) useful in treating Alzheimer's disease and other similar diseases.

COMPOUNDS AND METHOD FOR THE TREATMENT OF ALZHEIMER'S DISEASE

Peptide aldehydes as antithrombotic agents

Dipeptides which promote release of growth hormone

Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis.

Potent and efficient cytotoxic peptides and antibody-drug conjugates thereof and their synthesis

The present invention provides a family of novel cytotoxic pentapeptides, which show potent antitumor activities against several cancer lines. The antibody-drug conjugates prepared from those pentapeptides can efficiently kill cancer cells.

Melanocortin receptor ligands

본 발명은 MC-4 및/또는 MC-3 수용체 리간드를 개시하며, 상기 리간드는 하기 화학식 I 에 따른 구조를 갖는 화합물, 또는 그의 광학 이성질체, 부분입체이성질체 (diastereomer) 또는 거울상이성질체 (enantiomer); 그의 약학적으로 수용가능한 염, 수화물 또는 생가수분해성 에스테르, 아미드 또는 이미드이다: The present invention discloses MC-4 and / or MC-3 receptor ligands, which ligands have a structure according to formula (I), or optical isomers, diastereomers or enantiomers thereof; Pharmaceutically acceptable salts, hydrates or biohydrolysable esters, amides or imides thereof: [화학식 I] [Formula I] [식중, R 2 , R 4 , R 4' , R 5 , R 6 , R 6' , R 7 , R 8 , R 8' , R 9 , R 9' , R 10 , Ar, Z 1 , Z 2 , Z 3 , X, B, D, p, q, r 및 s 는 본원 명세서 및 특허청구범위 내에 설명되어 있음]. [Wherein, R 2 , R 4 , R 4 ' , R 5 , R 6 , R 6' , R 7 , R 8 , R 8 ' , R 9 , R 9' , R 10 , Ar, Z 1 , Z 2 , Z 3 , X, B, D, p, q, r and s are described in the specification and claims. 또한, 본 발명은 상기 화학식 I의 리간드를 포함하는 약학적 조성물, 및 본원 명세서의 상세한 설명 부분에 기재한 바와 같은 MC-4/MC-3 수용체에 의해 매개되는 질환의 치료 방법을 개시한다. The present invention also discloses pharmaceutical compositions comprising the ligands of Formula I, above, and methods of treating diseases mediated by the MC-4 / MC-3 receptor as described in the detailed description herein.

Dipeptides which promote release of growth hormone

式1化合物是拟生长激素释放肽，它们适用于治疗和预防骨质疏松。

CS-1 peptidomimetics, compositions and methods of using same

The present invention contemplates a compound defined by the following formula: ##STR1## that inhibits the binding between the VLA-4 and the fibronectin CS-1 compound. Pharmaceutical compositions containing a contemplated compound and methods for treating immunoinflammatory conditions using the compound are also disclosed.

Inhibitors of xa factor

FIELD: organic chemistry. SUBSTANCE: invention describes compound of unnatural origin that inhibits activity of Xa factor and has the general formula (I): A1-A2-(A3) m -B where m = 0 or 1; A1 means R 1 -R 2 -R 3 ; A3 means A3; R 7 -R 8 -R 9 is taken among the group including R 1 ; where X means N and and are taken independently among the group including H, alkyl, acyl, aryl, arylalkyl and groups protecting amino-group; R 2 means -CR 99 R 100 where R 99 and R 100 are taken independently among the group including H, alkyl, arylalkyl, heteroarylalkyl and heteroaryl; R 3 means -C(O)- or -CH 2 -;R 4 means -NR 50 - where R 50 means H; R 5 means -CR 201 R 202 where R 201 and R 202 are taken independently among the group including H, alkyl, aryl and arylalkyl; R 6 means -C(O)- or -CH 2 -; R 7 means -NR 51 where R 51 means H; R 8 means -CR 210 R 211 - where R 210 and R 211 are taken independently among the group including H, alkyl, arylalkyl and heterocycle being alkyl, alkylaryl and heterocycle can be substituted with Q or -(CH 2 ) n -Q where n = 1-5 and Q is taken among the group including amine-, amidine-, imidazole- or guanidine-group that can be substituted and mono-, di-, tri- or tetraalkylammonium of pharmaceutically acceptable salt, its isoureide or isothioureide; R 9 means -C(O)- or -CH 2 -; B means -NHR 52 where R 52 is taken among the group including H, alkyl, arylalkyl, heteroarylalkyl, heteroaryl, one amino acid or two amino acids, or its pharmaceutically acceptable salt, amide, ester, alcohol or aldehyde. Compound of the formula (I) prevents blood clot formation and it is the specific low-molecular inhibitor of Xa factor. EFFECT: enhanced effectiveness of compound, absence of nondesirable adverse effects, valuable pharmacological properties. 28 cl, 5 tbl, 4 dwg, 38 ex тУ6бсчс ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) ВИ” 2 152 954 ' (51) МПК? 13) СЛ К 38/06, 38/08, А 61 Р 7/02 С 07К 5/08, 5/10, 7/02, А 61 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ ...

Compound, connexon medicine and ligand drug coupling body

本揭露提供一种具有式(I)的化合物或其药学上可接受的盐类或溶剂化物。式(I)中，每一R1、R2与R3独立地为氢、胺基、硝基、卤素、羟基、C1‑C6烷氧基、羧基、C1‑C6烷氧基羰基、C1‑C6胺基、C1‑C6胺基羰基、C1‑C6烷基、C1‑C6分支型烷基、C1‑C6环烷基、C1‑C6杂环基、芳基或杂芳基，R1与R3至少其中之一为胺基。本揭露亦提供一种包含该化合物的连接子‑药物及配体‑药物耦合体。

Peptide inhibitors of hematopoietic cell proliferation

2-amido-4-aryloxy-1-carbonylpyrrolidine derivatives and pharmaceutical compositions containing the same

Compounds

Peptides and pseudopeptides derived from tachykinine, their preparation and their pharmaceutical compositions

Peptide derivs. of formula (I) A-B-N(R1)(R2), their enantiomers, diastereomers, epimers, and addn. salt with acids or bases, are new. In (I), R1 and R2 are H, 1-6C alkyl, 3-7C cycloalkyl or benzyl; B is aromatic amino acid (AA) residue; A is P-A6-A5-A4-; A4 is residue of 2-azabicyclo(2.2.2)octane-3-carboxylic acid (Abo) or 2-naphthylamine (Nal); A5 is bond, Phe, Nal, or Abo; A6 is bond, Trp (opt. protected by CHO or Me) or Abo; P is H, benzyloxycarbonyl (Z), tert.-butoxycarbonyl (Boc), 3-indolylcarbonyl, benzhydrylcarbonyl or 9-fluorenylmethyoxycarbonyl (Fmoc); a peptide bond between A5 and A6 may be replaced by CH2NH or CH2S; all AA are optically pure with D or L configuration.

Low molecular weight peptide-like growth hormone release promoter

(57)【要約】 本発明は、下垂体から成長ホルモンの放出を生じさせ得る成長ホルモン放出ペプチド／ペプチド様物質（ＧＨＲＰ）に関する。本発明のＧＨＲＰ類を含む組成物は、単独でまたは他の成長促進化合物、特に、ＩＧＦ−１と組み合わせてのいずれかで、哺乳動物の成長を促進するために用いられ得る。本発明の方法において、ＩＧＦ−１と組み合わせたＧＨＲＰ類はII型糖尿病の治療に用いられ得る。本発明の化合物の例として下記のものが挙げられる。

Use of peptide isosteres as retroviral protease inhibitors

Use of peptide isosteres as retroviral protease inhibitors Abstract The invention relates to the use of compounds of the renin inhibitor type or related aspartate proteinase inhibitors as gag protease inhibitors. It relates especially to the use of those compounds for the manufacture of pharmaceutical preparations for use as gag protease inhibitors, there being used compounds of the formula wherein AAN is a bivalent radical, consisting of from one to five bivalent .alpha.-amino acid residues, which is bonded N-terminally to the radical R2 and C-terminally to the radical Q, AAC is a bond or a bivalent radical, consisting of from one to five bivalent .alpha.-amino acid residues, which is bonded N-terminally to the radical Q and C-terminally to the radical R1, R1 is hydroxy, etherified hydroxy, amino or substituted amino with the exception of an amino radical derived from an .alpha.-amino acid, R2 is hydrogen or an acyl radical with the exception of an unsubstituted or N-substituted acyl radical of a natural amino acid, and Q is a bivalent radical that is an isostere of a dipeptide, and salts thereof.

Aminomethylene-peptides as immunosuppressants

ABSTRACT Compounds which suppress human T-lymphocyte proliferation are disclosed. The active compounds essentially contain at least the following structure:

Patent FR2677361B1

Molecular mimetics of meningococcal b epitopes

Molecular mimetics of unique epitopes of Neisseria meningitidis serogroup B ("MenB") are disclosed. Compositions containing such molecular mimetics can be used to prevent MenB or E. coli K1 disease without the risk of evoking autoantibody responses.

Hemiasterlin derivatives and uses thereof

The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.

NOVEL PEPTIDES AND PSEUDOPEPTIDES, TACHYKININ DERIVATIVES, PROCESS FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.

L'invention concerne les dérivés de formule (I): (CF DESSIN DANS BOPI) dans laquelle R1 ou R2 identiques ou différents représentent un atome d'hydrogène, un groupement alkyle, cycloalkyle ou benzyle, B représente un résidu d'amino-acide aromatique, A représente un résidu peptidique comportant de un à trois aminoacides, sous forme cyclique ou linéaire. Médicaments. The invention relates to the derivatives of formula (I): (CF DRAWING IN BOPI) in which R1 or R2 which are identical or different represent a hydrogen atom, an alkyl, cycloalkyl or benzyl group, B represents an amino acid residue aromatic, A represents a peptide residue comprising from one to three amino acids, in cyclic or linear form. Medicines.

Cs-1 peptidomimetics, compositions and methods of using the same

The present invention contemplates a peptide that inhibits the binding between the VLA-4 receptor expressed on inflammatory leukocytes and the fibronectin CS-1 peptide expressed on endothelial cells that are involved in immunoinflammatory disease states. Pharmaceutical compositions containing a contemplated peptide and processes for treating immunoinflammatory conditions using a binding-inhibitory peptide are also disclosed.

NOVEL PEPTIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS

LA PRESENTE INVENTION A POUR OBJET LES COMPOSES DE FORMULE : (CF DESSIN DANS BOPI) DANS LAQUELLE A, R, R, R, R ET B SIGNIFIENT DES RESTES ORGANIQUES VARIES. CES COMPOSES PEUVENT ETRE UTILISES COMME MEDICAMENTS. THE PRESENT INVENTION RELATES TO COMPOUNDS OF FORMULA: (CF DRAWING IN BOPI) IN WHICH A, R, R, R, R AND B MEAN VARIOUS ORGANIC REMAINS. THESE COMPOUNDS CAN BE USED AS A MEDICINAL PRODUCT.

Polypeptide analogs

Peptoids are provided which are polymers comprised of monomer units wherein the monomer units include at least some substitute amino acids and may include conventional amino acids. The peptoids can be synthesized in large numbers so as to provide libraries of peptoids which can be screened in order to isolate peptoids of desired biological activity. Certain peptoids are designed to mimic as closely as possible the activity of known proteins. Other peptoids are designed so as to have greater or lesser activity than known proteins and may be designed so as to block known receptor sites and/or elicit a desired immunogenic response and thereby act as vaccines. A range of different amino acid substitutes are disclosed, as are their methods of synthesis and methods of using such amino acid substitutes in the synthesis of peptoids and peptoid libraries. Methods of screening the libraries in order to obtain desired peptoids of a particular biological activity are also disclosed. The peptoids are preferably linked to a pharmaceutically active drug forming a conjugate with increased binding affinity to a particular biological receptor site.

Indole-containing peptide and process for preparing the same

There are disclosed an indole-containing peptide represented by the formula (I):    wherein R represents hydrogen atom, a lower alkyl group or formyl group; and X represents oxygen atom or sulfur atom, an ester thereof or pharmaceutically acceptable salts thereof, and a process for preparing the same.

Opioid peptides

Opioid peptides including those of formula (I), in which A1 is the identifying group of an amino acid selected from 3,4-dihydroxyphenylalanine, 3,4-dimethoxyphenylalanine, azatyrosine, and 2,6-dimethyltyrosine; A2 is the identifying group of an amino acid selected from D-Ala and D-Arg; A3 is H, or the identifying group of an amino acid selected from 3,4-dihydroxyphenylalanine and 3,4-dimethoxyphenylalanine, A4 is H, cyclohexylmethyl, the identifying group of an amino acid selected from 3,4-dihydroxyphenylalanine, 3,4-dimethoxyphenylalanine, Phe, and substituted Phe with its benzene ring substituted by halogen, NO2, OH, or CH3; A5 is the identifying group of a D- or L-amino acid selected from Leu, Nle, Lys, Met and Met(O), or is deleted together with R4-CH attached thereto; each R1 and R2 is -H, -C(NH2) = NH, or C1-12 alkyl; R3 is -(a) or (b); R4 is (c); (d), or (e); and R5 is -(CH2)n+1OH, (f), or (g); wherein m is 0-6, n is 0-6, and X is H, C1-12 alkyl, C6-12 aryl, C7-18 aralkyl, C7-18 alkaryl, C7-18 alkaryl, C6-17 pyridylalkyl, or C6-17 alkylpyridyl; provided that when one of R1 and R2 is -C(NH2) = NH, the other must be H; or a pharmaceutically acceptable salt thereof.

Irreversible HIV Protease Inhibitor with Anti-Aids (AIDS) Effect, Preparation Method thereof, and Composition Comprising the Same

본 발명은 HIV 프로테아제의 억제제로서 유용한 신규 화합물 및 그의 제조방법 및 이를 포함하는 조성물에 관한 것으로서, 하기의 일반식(Ⅰ)의 시스-에폭사이드 구조를 갖는 화합물 및 그의 약학적으로 허용되는 염, 수화물 또는 용매화물은, HIV 프로테아제의 비가역적 억제제로서 억제 효과는 높은 반면 그 세포독성은 낮기 때문에, 에이즈 또는 HIV감염의 치료 또는 예방용 제제로서 유용하게 사용될 수 있다. 상기 식에서, A, B 및 D는 명세서중에서 정의한 바와 같다.

NOVEL PEPTIDE DERIVATIVES USEFUL AS INHIBITORS OF BACTERIAL COLLAGENASES.

L'invention concerne de nouveaux dérivés de peptides, utilisables comme inhibiteurs des collagénases bactériennes. Ces dérivés répondent à la formule: (CF DESSIN DANS BOPI) dans laquelle R1 est un atome d'hydrogène, un groupe bloquant ou un radical dérivé d'un aminoacide ou d'un peptide éventuellement protégé par un groupe bloquant, R2 est la chaîne latérale d'un alpha-aminoacide, R3 est H, un métal, un groupe alkyle ou benzyle, R4 est dérivé de la proline, de l'hydroxyproline, de la thiazolidine ou de la déshydroproline, R5 est H ou un alkyle, R4 est la chaîne latérale d'un aminoacide, et R7 est OR8 avec R8 étant H, un métal, alkyle ou benzyle, ou dans laquelle R1 et R7 forment ensemble un radical bivalent dérivé d'un aminoacide ou d'un peptide. Les dérivés dans lesquels R3 est un métal ou l'hydrogène sont utilisables comme inhibiteurs des collagénases bactériennes.

Novel binder-drug conjugates (adcs) and their use

The present application relates to novel, anti-C4,4a binder-drug conjugates (ADCs) of N,N-dialkyl auristatins, to effective metabolites of said ADCs, to methods for producing said ADCs, to the use of said ADCs for treating and/or preventing diseases, and to the use of said ADCs for producing pharmaceuticals for treating and/or preventing diseases, in particular hyperproliferative and/or angiogenic diseases, such as cancers. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

Compounds with growth hormone releasing properties

Compounds of general formula (I), and their use for treating medical disorders resulting from a deficiency in growth hormone.

Novel binder-drug conjugates (ADCs) and their use

Il:\grs\Interwovn\NRPortbl\DCC\GRS757809_l.docx-9 06/2017 Novel binder-drug conjugates (ADCs) and their use Abstract The present application relates to novel, anti-C4.4a binder-drug conjugates (ADCs) of N,N-dialkyl auristatins, to effective metabolites of said ADCs, to methods for producing said ADCs, to the use of said ADCs for treating and/or preventing diseases, and to the use of said ADCs for producing pharmaceuticals for treating and/or preventing diseases, in particular hyperproliferative and/or angiogenic diseases, such as cancers. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

Phenylboronic acid complexing reagents derived from aminosalicyclic acid

The present invention relates to a novel class of phenylboronic acid complexing reagents useful for the preparation of bioconjugates, and the method of making and using such reagents. In the present invention, in the place of prior art Avidin-Biotin and Digoxigenin-anti-Digoxigenin systems, phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents (many of which are known in the prior art) to facilitate chemical conjugation without the use of intermediary biological macromolecules. Reagents suitable for the modification of a bioactive species for the purpose of incorporating a phenylboronic acid complexing moiety for subsequent conjugation to a different bioactive species having pendant phenylboronic acid moieties are of General Formula I or General Formula II. ##STR1## wherein group X is selected from either H, OH, NH 2 , NHCH 3 , NHOH and NHOCH 3 , wherein group Y is selected from either O, S and NH, and wherein group Z comprises a spacer which either separates the boronic acid complexing moiety from group R, as in General Formula I, or seperates two boronic acid complexing moieties, as in General Formula II. Group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the phenylboronic acid complexing reagent with a bioactive species.

Compounds, linker-drugs and ligand-drug conjugates

本揭露提供一種具有式(I)的化合物或其藥學上可接受的鹽類或溶劑化物。式(I)中，每一R1、R2與R3獨立地為氫、胺基、硝基、鹵素、羥基、C1-C6烷氧基、羧基、C1-C6烷氧基羰基、C1-C6胺基、C1-C6胺基羰基、C1-C6烷基、C1-C6分支型烷基、C1-C6環烷基、C1-C6雜環基、芳基或雜芳基，R1與R3至少其中之一為胺基。本揭露亦提供一種包含該化合物的連接子-藥物及配體-藥物耦合體。

Amino acid derivatives

Abstract Compounds of the formula I wherein R1 represents alkoxycarbonyl, aralkoxy-carbonyl, alkanoyl, aralkanoyl, aroyl, cycloalkyl-carbonyl, heterocyclylcarbonyl, heterocyclyl-alkanoyl, 6-(dibenzylcarbamoyl)-4-oxohexanoyl or an acyl group of an .alpha.-amino acid in which the amino group is substituted by alkoxycarbonyl, aralkoxycarbonyl, diaralkylcarbamoyl, diaralkylalkanoyl or aralkanoyl: R2 represents alkyl, cycloalkylalkyl or aralkyl: R3 represents hydrogen or alkyl; R4 represents alkyl: and one of R5 and R6 represents hydrogen and the other represents hydrogen, alkyl, aryl, aralkyl, l-alkoxycarbonyl-2-phenylethyl, l-alkoxy-carbonyl-2-(imidazol-4-yl)ethyl, 2-(imidazol-1-yl)-ethyl, indanyl, heterocyclyl-alkyl, carboxyalkyl, alkoxycarbonylalkyl, aryloxycarbonylalkyl, aralkoxy-caebonylalkyl ne a group of the formula -A-N(Ra)(Rb) in which A represents alkylene and Ra and Rb each represent alkyl or Ra and Rb together represent a pentamethylene group in which one methylene group can be replaced by NH, N-alkyl, N-alkanoyl, N-aralkoxy-carbonyl, O, S, SO or SO2; or R5 and R6 together with the nitrogen atom to which they are attached represent a l,2,3,4-tetrahydcoisoquinoline ring: one of W and X represents hydrogen and the other represents hydroxy or amino or W and X together represent hydroxyimino and Y represents hydrogen or, where one of W and X represents hydroqen and the other represents hydroxy, Y can also represent hydroxy, and pharmaceutically acceptable acid addition salts thereof can be used as medicaments for the treatment and prophylaxis of viral infections, particularly of infections caused by HIV and other retroid viruses. They can be manufactured according to generally known procedures.

HIV PROTEASE INHIBITORS USED TO TREAT AIDS

Dipeptide derivatives

This invention is directed to compounds of the formula and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis and/or frailty, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis and/or frailty when used in combination with: a bisphosphonate compound such as alendronate; estrogen, conjugated estrogens, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2 or B-HT920. The invention is also directed to intermediates useful in the preparation of compounds of Formula I.

Hemiasterlin derivatives and uses thereof

The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.

Irreversible HIV protease inhibitors, intermediates, compositions and processes for the preparation thereof

Method of preparing intermediates useful in synthesis of retroviral protease inhibitors

A synthesis is described for intermediates which are readily amenable to the large scale preparation of hydroxyethylurea-based chiral HIV protease inhibitors. The method includes forming a diastereoselective epoxide from a chiral alpha amino aldehyde.

Novel peptidase inhibitors

N-acyldipeptide derivatives and their uses

N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with a tumor, cancer, immune, nervous, vascular, musculoskeletal or cutaneous system, or other tissue or system in a subject.

Retroviral protease inhibitors

Compounds represented by formula (I) wherein A represents radicals represented by formulae (A1, A2, A3) (values for the variables given herein), are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.

Method for preparing intermediates useful in synthesis of retroviral protease inhibitors

A synthesis is described for intermediates which are readily amenable to the large scale preparation of hydroxyethylurea-based chiral HIV protease inhibitors. The method includes forming a diastereoselective epoxide from a chiral alpha amino aldehyde.

FACTOR XA INHIBITORS

Novel peptides and pseudopeptides derived from tachykinin, process for their preparation and the pharmaceutical compositions containing these

Inhibitors of farnesyl protein transferase

TITLE OF THE INVENTION INHIBITORS OF FARNESYL PROTEIN TRANSFERASE ABSTRACT OF THE DISCLOSURE The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemothera peutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

Quinolone vitronectin receptor antagonist pharmaceuticals

The present invention describes novel compounds of the formula: (Q) d —L n —C h , useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

Irreversible HIV protease inhibitors, intermediates, compositions and processes for the preparation thereof

Novel cis-epoxide compounds of formula (I) are useful for treating or preventing diseases caused by HIV infection: wherein A, B, R 1 to R 4 and n have the same meanings as defined in the specification. The novel HIV protease inhibitor of the formula (I) has a specific structure to form a stable bonding with the enzyme active site, which entails a highly enhanced irreversible inhibition against HIV protease.

Inhibitors of serine proteases, particularly HCV NS3-NS4A protease

The present invention relates to compounds of formula I-A and I-B that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

Aminoacid derivatives

5-amino-4-hydroxyvaleryl derivatives,their manufacture and pharmaceutical compositions containing them

Opioid peptides

Opioid peptides including those of the formula ##STR1## in which A 1 is the identifying group of an amino acid selected from 3,4-dihydroxyphenylalanine, 3,4-dimethoxyphenylalanine, azatyrosine, and 2,6-dimethyltyrosine; A 2 is the identifying group of an amino acid selected from D-Ala and D-Arg; A 3 is H, or the identifying group of an amino acid selected from of 3,4-dihydroxyphenylalanine and 3,4-dimethoxyphenylalanine, A 4 is H, cyclohexylmethyl, the identifying group of an amino acid selected from 3,4-dihydroxyphenylalanine, 3,4-dimethoxyphenylalanine, Phe, and substituted Phe with its benzene ring substituted by halogen, NO 2 , OH, or CH 3 ; A 5 is the identifying group of a D- or L-amino acid selected from Leu, Nle, Lys, Met and Met(O), or is deleted together with R 4 --CH attached thereto; each R 1 and R 2 is --H, --C(NH 2 )═NH, or C 1-12 alkyl; R 3 is ##STR2## R 4 is ##STR3## and R 5 is --(CH 2 ) n+1 OH, ##STR4## wherein m is 0-6, n is 0-6, and X is H, C 1-12 alkyl, C 6-12 aryl, C 7-18 aralkyl, C 7-18 alkaryl, C 7-18 alkayl, C 6-17 pyridylalkyl, or C 6-17 alkylpyridyl; provided that when one of R 1 and R 2 is --C(NH 2 )═NH, the other must be H; or a pharmaceutically acceptable salt thereof.

Compounds to treat Alzheimer's disease

The present invention is directed toward substituted hydroxyethylene compounds of formula (XII) useful in treating Alzheimer's disease and other similar diseases.

Inhibitors of retroviral proteases

The invention relates to compounds of the formula <IMAGE> in which AAN is a divalent radical which consists of one to five divalent alpha -amino acid residues and which is connected at the N terminus to the radical R<2> and at the C terminus to the group NH-, AAC is a divalent radical which consists of one or two divalent alpha -amino acid residues and which is connected at the N terminus to the group -C=O and at the C terminus to the radical R<1>, R<1> is hydroxyl, etherified hydroxyl, amino or substituted amino with the exception of an amino radical derived from an alpha -amino acid, and R<2> is hydrogen or an acyl radical with the exception of an optionally N-substituted acyl radical of a natural amino acid, and salts of such compounds with salt-forming groups. The compounds are suitable as gag protease inhibitors.

Gamma-secretase inhibitors

Disclosed, as a γ-secretase inhibitor, is a compound consisting of an amino acid sequence which consists of at least three consecutive amino acids of the amino acid sequence Val-Val-Ile-Ala-Thr-Val-Ile-Val-Ile-Thr-Leu-Val-Met-Leu-Lys-Lys-Lys including Leu at position 11, wherein, between the Leu and one or both amino acids located immediately before or after it, the peptide bond, —CO—NH—, is replaced with a hydroxyethylene group, —CHOH—CH 2 —, wherein the N terminus has an alkyloxycarbonyl group based on C1-10 alkyl that may carry phenyl or naphthyl as a substituent group, wherein the C terminus is converted to alkyl ester or alkyl amide based on C1-10 alkyl that may carry phenyl or naphthyl as a substituent group, and wherein the hydrogen atom of the hydroxyl group of the Thr at position 10 may be replaced with a C1-4 hydrophobic group or a Z group, or a pharmaceutically acceptable salt thereof.

Tachykinin denved peptides and pseudopeptides, process for their preparation and pharmaceutical compositions containing them

PRECIS NOUVEAUX PEPTIDES ET PSEUDOPEPTIDES, DERIVES DE TACHYKININES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT ADIR ET COMPAGNIE L'invention concerne les dérivés de formule (I) : (I) dans laquelle : R1 ou R2 identiques ou différents représentent un atome d'hydrogène, un groupement alkyle, cycloalkyle ou benzyle, B représente un résidu d'amino-acide aromatique, A représente un résidu peptidique comportant de un à trois amino-acides, sous forme cyclique ou linéaire. Médicaments. SPECIFIC NEW PEPTIDES AND PSEUDOPEPTIDES, TACHYKININ DERIVATIVES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM ADIR AND COMPANY The invention relates to the derivatives of formula (I): (I) in which : R1 or R2, identical or different, represent a hydrogen atom, a alkyl, cycloalkyl or benzyl group, B represents an aromatic amino acid residue, A represents a peptide residue comprising from one to three amino-acids, in cyclic or linear form. Medicines.

Retroviral protease inhibitors

Compounds represented by formula (I) wherein A represents R, R13 and radicals represented by formula (II), B represents R5 and radicals represented by formula (III) (values for the variables given herein) are effective as retroviral protease inhibitors and in particular as inhibitors of HIV protease.

Hydroxyethylene derivatives for the treatment of arthrosis

The invention relates to compounds of formula (1),

Cis epoxy derivatives useful as irreversible HIV protease inhibitors and methods and intermediates for their

Novel binder-drug conjugates (adcs) and their use

The present application relates to novel, anti-Target Epidermal Growth Factor Receptor (EGFR, GeneID1956) binder-drug conjugates (ADCs) of N,N-dialkyl auristatins, to effective metabolites of said ADCs, to methods for producing said ADCs, to the use of said ADCs for treating and/or preventing diseases, and to the use of said ADCs for producing pharmaceuticals for treating and/or preventing diseases, in particular hyperproliferative and/or angiogenic diseases, such as cancers. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

Binder-drug conjugates (ADCs) and use thereof

The present application relates to new binder-drug conjugates (ADCs) of N,N-dialkylauristatins that are directed against the target C4.4a, to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for treating and/or preventing illnesses, and also to the use of these ADCs for producing medicaments for treating and/or preventing illnesses, more particularly hyperproliferative and/or angiogenic diseases such as, for example, cancer diseases. Such treatments may be practiced as a monotherapy or else in combination with other medicaments or further therapeutic measures.

METHOD FOR THE PREPARATION OF NEW PEPTIDASE INHIBITORS

Peptides retroviral protease inhibitors comprising 2-amino-2-methylpropionic acid

Antiviral peptides of the formula ##STR1## in which W is an amino protecting group, A,B,D,E and L each independently is a direct bond, or a radical of the formula ##STR2## R 1 and R 2 each independently is cycloakyl or optionally substituted alkyl or alkenyl, Y is --NHR 10 , and R 10 is cycloalkyl or optionally substituted alkyl, and their physiologically acceptable salts. The formula includes a 2-amino-2-methylpropionic acid (AiB) residue, which may optionally be protected, as the N-terminal α-amino acid. The peptides are expected to be useful as medicaments, in particular as antiviral agents in human and veterinary medicine. The peptides are shown to inhibit aspartyl proteases including human immunodeficiency virus (HIV) protease, to have anti-HIV activity and to inhibit the proliferation of HIV in HIV-I infected human lymphocytes. The peptides are expected to be useful in treating patients having HIV related disorders such as ARC and AIDS.