ЗАМЕЩЕННЫЕ 1-АМИНОАЛКИЛЛАКТАМЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ИХ ПОЛУЧЕНИЯ

Изобретение относится к органической химии и может найти применение в медицине. Описывается соединение, имеющее общую формулу I, где R1 и R2 означают независимо в каждом случае водород, галоген, (С1-С6)алкил, -OR', -SR', -NR'R", -SOR', -SO2R'. -COOR', -OCOR'-, -OCONR'R", -OSO2R', -OSO2NR'R", -NR'SO2R", -NR'COR", -SO2NR'R", -SO2(СН2)1-3 - CONR'R", -CONR'R", циангруппу, галоидалкил или нитрогруппу; или R' и R" означают независимо в каждом случае водород, (С1 -С6)алкил, замещенный (С1-С6)алкил, арил, гетероциклил, гетероарил, арил(С1-С3)-алкил, гетероарил(С1-С3)алкил, гетероциклил(С1-С3)алкил, циклоалкил-алкил, циклоалкил, или R' и R" вместе с атомом азота, с которым они связаны, могут также образовывать 5-7-членное кольцо, необязательно включающее дополнительный кольцевой гетероатом, выбранный из N, О или S(О)0-2; R3 независимо в каждом случае означает (С1-С6)алкил, (С1-С6)алкенил, (С1-С6)алкинил или циклоалкил; или один из X, Y или Z означает независимо -О- или >N-R4, другие означают -СН2 ...

Способ получения гексагидро-1,4-ОКСАзЕпиНОВ или иХ СОлЕй

Improvements in or relating to heterocyclic sulphonyl-urea compounds and pharmaceutical compositions containing them

The invention comprises compounds of the formula and pharmacologically acceptable acid addition salts thereof, wherein R is a C1-4 alkyl group and is a saturated heterocyclic amino radical having from 5 to 9 ring atoms, Z being a polymethylene, oxapolymethylene, thiapolymethyllene or azapolymethylene radical, which may bear one or more alkyl substituents, and their preparation by reacting an alkanoylbenzenesulphonyl urethane with an N-amino-heterocyclic amine H2N.N=Z. Preferably the group -N=Z is a piperidino, pyrrolidino, morpholino or hexamethyleneimino radical. Alkanoylbenzenesulphonyl urethanes used as starting materials are made by treating an alkanoylbenzenesulphonamide with ethyl chlorocarbonate in the presence of an alkalimetal carbonate. The alkanoylbenzenesulphonamide, RCO.C6H4.SO2NH2, is suitably prepared by treating an aminophenyl alkyl ketone with nitrous acid, reacting the resulting diazonium salt with sulphur dioxide and cupric ...

N-(2-(cyclic amine)ethyl) benzamide derivatives asP2X7 inhibitors

Aralkyl and aralkylidene heterecyclic lactams and imides.

The present invention relates to compounds of the formula wherein R1, R2, R3, X, Y and the dashed line are defined as in the specification, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. These compounds are useful as psychotherapeutic agents.

(2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE I INHIBITORS

Aralkyl and aralklidene heterocyclic lactams and imides

N-(2-(cyclic amine)ethyl) benzamide derivatives asP2X7 inhibitors

Aralkyl and aralkylidene heterocyclic lactams and imides

(2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE I INHIBITORS

Aralkyl and aralklidene heterocyclic lactams and imides

(2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE I INHIBITORS

N-(2-(cyclic amine)ethyl) benzamide derivatives asP2X7 inhibitors

PROCEDURE FOR THE PRODUCTION OF NEW ONES MORPHOLIN, OXAZEPIN AND OXAZOCIN DERIVATIVES AND THEIR SALTS

VERFAHREN ZUR HERSTELLUNG VON NEUEN MORPHOLIN-, OXAZEPIN- UND OXAZOCIN-DERIVATEN UND DEREN SALZEN

HEXAHYDRO-1,4-OXAZEPINE, PROCEDURE FOR THEIR PRODUCTION AND THESE CONTAINING DRUGS.

SUBSTITUTED 1-AMINOALKYL-LACTAME AND THEIR USE AS an MUSCARINREZEPTOR ANTAGONIST

PROCEDURE FOR the PRODUCTION OF NEW CYCLI, N-SUBSTITUTING 1,4-BENZOLDISULFONAMID-DERIVATEN AND YOUR SALTS

PROCEDURE FOR the PRODUCTION OF NEW ONE 1,4-OXAZEPINEN AND/OR - DIAZEPINEN

ALANIN-2,6-DIALKOXYPHENYLESTERDERIVATE AS HYPNOTICS

DISUBSTITUIERTE MORPHOLIN, OXAZEPIN OR THIAZEPINDERIVATE, THEIR PRODUCTION AND USE AS DOPAMIN-D4-REZEPTORANTAGONISTEN

SUBSTITUTED 1-AMINOALKYL-LACTAME AND YOUR USE AS MUSCARINREZEPTOR an ANTAGONIST

Substituted aniline derivatives

3-aryl-4-amido-bicyclic (4,5,0) hydroxamic acids as HDAC inhibitors

The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, ...

(2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamides as dipeptidyl peptidase I inhibitors

The present disclosure relates to certain (2 ...

Aralkyl and aralkylidene heterocyclic lactams and imides

Benzyl (idene)-lactams and their use as 5ht1-receptor ligands

COMPOUNDS USEFUL IN THE TREATMENT OF INFLAMMATORY DISEASES

There are provided according to the invention, novel compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, X a, b, and Z are as defined in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

7-PHENYL-7-PHENOXYMETHYL-HEXAHYDRO-1,4-OXAZEPINES, THEIR PREPARATION AND THEIR USE

... 7-phenyl-7-phenoxymethyl-hexahydro-1,4-oxazepines of the formula I where R1 is hydrogen, chlorine or methoxy and R2 is hydrogen or methyl, and their salts with physiologically tolerated acids, and their preparation, are described. The substances are useful for treating depression.

SUBSTITUTED 1-AMINOALKYL-LACTAMS AND THEIR USE AS MUSCARINIC RECEPTOR ANTAGONISTS

This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula (1) wherein one of X, Y, or Z is independently -S-, -O-, or > N-R4, the others are-CH2-; (p) is an integer from 0 to 3 inclusive; m is an integer from 0 to 3 inclusive; n is an integer from 1 to 6 inclusive; R3 is (C1-6)-alkyl, (C1-6)-alkenyl, (C 1-6)- alkynyl or cycloalkyl; and R1, R2 and R3 are hydrogen or specified substituents. These compounds are useful for treating diseases associated with smooth muscle disorders.

SUBSTITUTED ANILINE DERIVATIVES

The present invention relates to novel analine derivatives and their use in therapy, in particular their use in the treatment of fungal infections. ...

N-(2-(CYCLIC AMINE)ETHYL)BENZAMIDE DERIVATIVES AS P2X7 INHIBITORS

The present invention is directed to N-(2-(cyclic amine)ethyl)benzamide derivatives of formula (I), as P2X7 inhibitors, pharmaceutical compositions comprising said compounds and uses of the compounds to treat pain, inflammation, neurological disorders, or neuropsychiatric disorders.

MORPHOLINE AND 1,4-OXAZEPANE AMIDES AS SOMATOSTATIN RECEPTOR SUBTYPE 4 (SSTR4) AGONISTS

The invention relates to morpholine and 1,4-oxazepane amide derivatives of general formula (I), which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture of the compounds according to the invention.

1,4-OXAZEPINES AS BACE1 AND/OR BACE2 INHIBITORS

This invention relates to compounds of the formula wherein and R1 to R3 are as described below, or to pharmaceutically acceptable salts thereof. These compounds are BACE1 and/or BACE2 inhibitors and can be used as medicaments for the therapeutic and/or prophylactic treatment of diseases such as Alzheimer's disease, diabetes, particularly type 2 diabetes, and other metabolic disorders.

GUANIDINE COMPOUND

... [Problem] To provide a compound which is useful as an active ingredient of a pharmaceutical composition, especially of a pharmaceutical composition for the prophylaxis and/or treatment of VAP-1 associated diseases. [Solution] As a result of intensive studies on a compound having VAP-1 inhibitory activity, the inventors have achieved the present invention by discovering that a compound of the present invention or a salt thereof has excellent VAP-1 inhibitory activity and is thus useful for the prophylaxis and/or treatment of VAP-1 associated diseases, especially for the prophylaxis and/or treatment of diabetic nephropathy or diabetic macular edema. The present invention also relates to a pharmaceutical composition, particularly a pharmaceutical composition for the prophylaxis and/or treatment of VAP-1 associated diseases, said pharmaceutical composition containing a compound of the present invention or a salt thereof and an excipient.

Verfahren zur Herstellung von Dihydronaphthalinen

PROCEDURE FOR THE PRODUCTION OF NEW OF TRICYCLI CONNECTIONS.

PROCEDURE FOR THE PRODUCTION OF NEW TRICYCLI CONNECTIONS.

Pesticides containing N-alkyl-N-aminosulphenyl- N'-phenylformamidine derivates as active ingredient

The pesticide contains, as active ingredient, a novel compound of the formula (I) in which R1 denotes an optionally mono-, di- or trisubstituted phenyl group and R2 denotes a C1-C4-alkyl group, while R3 and R4 independently of one another denote a C1-C8-alkyl, (C3-C6-cycloalkyl)-methyl or C3-C6-cycloalkyl group; or together with the nitrogen atom to which they are bonded form a 5- to 8-membered heterocyclic ring which is optionally substituted by C1-C4-alkyl and optionally interrupted by an oxygen or sulphur atom. The agent is employed, in particular, for controlling insects or representatives of the order Acarina.

1-(3-Trifluoromethylphenyl)-2-(homo)morpholinopropanes - with anorectic activity

... 2-(Homo)morpholinopropanes of formula (I) and their acid addn. salts are new: (where R is H or halogen; R1 is lower alkyl; R3 and R4 are H, lower alkyl or phenyl; R5 is H or lower alkyl; n = 1 or 2). Cpds. (I) are anorectic agents with a high anorectic/CNS depressant activity ratio (no details given).

Heterocyclic aminocyclopentanealkenoic acids and their esters, their preparation, and pharmaceutical preparations

Compounds of the formula (and salts and hydrates) in which X, Y, R<1> and R<2> have the definitions given in Patent Claim 1. These compounds inhibit the aggregation of blood platelets and bronchial constriction and can be formulated for use as antithrombotic and antiasthmatic agents.

GUANIDINE COMPOUNDS USEFUL FOR PREVENTING AND/OR TREATING DIABETIC NEPHROPATHY OR DIABETIC MACULAR EDEMA

CYCLIC AMINES

guanidinovoe compound

DERIVATIVES OF 1.4 - OKSAZEPANA

GUANIDINE COMPOUND

SUBSTITUTED BENZAMIDE DERIVATIVES

(2S) - N-- [(1S) - OF 1 - CYANO - OF 2 - PHENYLETHYL] - OF 1, OF 4 - OKSAZEPAN - OF 2 - CARBOXAMIDES AS INHIBITORS OF DIPEPTIDYL PEPTIDASE I OF

Morpholine and 1,4-oxazepane amides as somatostatin receptor subtype 4 (SSTR4) agonists

PROCEEDED OF PRODUCTION OF COMPOSE OF MORPHOLINE AND NEW PRODUCTS THUS OBTAINED, HAS ACTIVITY ON THE CENTRAL NERVOUS SYSTEM

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

The invention relates to the compound 5-(4-isopropylsulfonylphenyl) -3-[3-[4-[(3R)-morpholin-3-yl]phenyl]isoxazol-5-yl]pyrazine-2-amine and pharmaceutically acceptable salts thereof. The compounds are useful as inhibitors of ATR kinase.

OXAZINE DERIVATIVES AND THEIR USE AS BACE INHIBITORS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS

The invention relates to novel heterocyclic compounds of the formula (I) in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their medical use as BACE inhibitors for the treatment of Alzheimer and to medicaments comprising them.

3-alkyl-4-amido-bicyclic [4,5,0] hydroxamic acids as HDAC inhibitors

The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with an HDAC, e.g., HDAC6, having a Formula I: where R, L, X1, X2, X3, X4, Y1, Y2, Y3, and Y4are described herein.

Cysteine prodrugs

Novel cysteine prodrugs and their use in the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of the Central Nervous System (CNS), including but not limited to schizophrenia, drug craving, drug addiction, bipolar disorder, anxiety, depression, Parkinson's disease, Alzheimer's disease, cognitive dysfunction, multiple sclerosis, Amyotrophic lateral sclerosis (ALS), ischemic stroke, HIV dementia, and Huntington's disease.

"AMINOCYCLOPENTANALKENSAEUREN UND ESTER UND IHRE HERSTELLUNG SOWIE PHARMAZEUTISCHE PRAEPARATE"

VERBINDUNGEN VERWENDBAR FÜR DIE BEHANDLUNG VON ENTZÜNDUNGSKRANKHEITEN

ALKYLAMINO ETHYNYL ALANINE AMINODIOLVERBINDUNGE WITH MORPHOLINO/THIOMORPHOLINOENDGRUPPEN AS RENIN INHIBITORS

Procedures for the production of new 1,3-Aminoketone and 1,3-Aminoalkohole von Äthern, Estern, N-Oxide, Säureadditionssalzen, optically isomers forms and quaternären ammonium halides of it

NEW LACTAMS AND THEIR USES

VERFAHREN ZUR HERSTELLUNG VON NEUEN CYCLISCHEN, N-SUBSTITUIERTEN 1,4-BENZOLDISULFONAMID-DERIVATEN UND IHREN SALZEN

VERFAHREN ZUR HERSTELLUNG VON NEUEN 1,4-OXAZEPINEN BZW. -DIAZEPINEN

PROCEDURE FOR THE PRODUCTION OF NEW ONES MORPHOLIN, OXAZEPIN AND OXAZOCIN DERIVATIVES AND THEIR SALTS

PROCEDURE FOR the PRODUCTION OF NEW ONE 1,4-OXAZEPINEN AND/OR - DIAZEPINEN

PROCEDURE FOR the PRODUCTION OF NEW CYCLI, N-SUBSTITUTING 1,4-BENZOLDISULFONAMID-DERIVATEN AND YOUR SALTS

SUBSTITUTED CAPROLACTAME AND THEIR DERIVATIVES USABLE FOR THE TREATMENT OF THE HIV ILLNESS

ARALKYL AND ARALKYLIDEN HETERO-CYCLIC LACTAMS AND IMIDES

MORPHOLINE DERIVATIVES

(2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE I INHIBITORS

The present disclosure relates to certain (2S)-N- [(IS)-1 -cyano-2-phenylethyl] -1,4 oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), 5 (Formula (I)) that inhibit dipeptidyl peptidase 1(DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

(2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE I INHIBITORS

The present disclosure relates to certain (2S)-N-[(S)--cyano-2-phenylethyl]-1,4 oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), 5 (Formula (I)) that inhibit dipeptidyl peptidase 1(DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Azepane derivatives and methods of treating hepatitis B infections

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

MORPHOLINE DERIVATIVES AND PRODUCTION THEREOF

MORPHOLINE DERIVATIVES AND PRODUCTION THEREOF

Novel morpholine compounds of the formula: wherein R2 is hydrogen, methyl, ethyl, isopropyl, allyl, 2,2,2-trifluoroethyl, 2-hydroxyethyl, propargyl, benzyl, cyclopropylmethyl, A is straight chain C2 or C3 alkylene group, B is -CH2-CH2-, -CH-CH- , , , -CH2-O-, -CH2-S-, -S- or -O-, ?D-E- is ?CH-CH2- or ?C=CH- and C1 and C2 are each 1,2-phenylene optionally substituted with chlorine and their non-toxic salts, which are useful as antidepressants and can be produced by various methods.

(2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE I INHIBITORS

The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4- oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), (Formula (I)) that inhibit dipeptidyl peptidase 1(DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

1,4-OXAZEPANE DERIVATIVES

ПИПЕРАЗИНИЛ-БЕНЗИЛИДЕНИЛ ЛАКТАМОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ АГОНИСТОВ И АНТАГОНИСТОВ 5-НТ1А И 5-НТ1D РЕЦЕПТОРОВ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ ИЛИ ПРОФИЛАКТИКИ НАРУШЕНИЯ ИЛИ СОСТОЯНИЯ, СВЯЗАННЫХ С НЕДОСТАТОЧНОЙ СЕРОТОНЕРГИЧЕСКОЙ НЕЙРОТРАНСМИССИЕЙ У МЛЕКОПИТАЮЩЕГО

... 1. Пиперазинил-бензилиденил лактамовые соединения формулы где R1 представляет пиперазин-1-ил или пиперазин-1-ил, замещенный в положении 4 (C1-C4) алкилом; R2представляет водород; R представляет-(СН2)m В, где m равно 0 или 1 и В представляет водород, фенил, необязательно замещенный одним или несколькими заместителями, независимо выбранными из галогена, (C1-C6)алкила или трифторметила; Х представляет водород или галоген; Y представляет гетероалкильный мостик, который, вместе с атомами, к которым он присоединен, образует пяти- или шестичленный гетероцикл, содержащий два гетероатома, выбранный из группы, включающей 1,3-тиазолидин-2,4-дион-5-ил, 1,3-имидазолидин-2,4-дион-5-ил, морфолин-3-ил и тиоморфолин-3-он-2-ил, или их фармацевтически приемлемые соли. 2. Соединение по п.1, где R1представляет где R6представляет метил. 3. Соединение по п.2, где Y вместе с атомами, к которым он присоединен, образует тиоморфолин-3-он-2-ил. 4. Соединение по п.1, где R3представляет необязательно замещенный фенил ...

AMINOMETILBIARILNYE DERIVATIVES-INHIBITORS COMPLEMENT FACTOR D AND THEIR APPLICATION

ARALKILIARALKILIDEN - HETEROCYCLIC LACTAMS AND IMIDES

MORFOLINI 1.4 - OKSAZEPAN - AMIDES AS AGONISTS OF SOMATOSTATINOVOGO RECEPTOR SUBTYPE 4 (SSTR4)

DERIVATIVES OF AZEPANE DERIVATIVES AND METHODS FOR TREATMENT OF HEPATITIS B INFECTIONS

ПРОИЗВОДНЫЕ ОКСАЗИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ИНГИБИТОРОВ BACE ДЛЯ ЛЕЧЕНИЯ НЕВРОЛОГИЧЕСКИХ НАРУШЕНИЙ

В заявке описаны новые гетероциклические соединения формулы в которой все переменные являются такими, как определено в описании, в свободной форме или в форме соли, их получение, их применение в медицине и содержащие их лекарственные средства.

PROCEEDED OF PRODUCTION OF COMPOSE OF MORPHOLINE AND NEW PRODUCTS THUS OBTAINED, HAS ACTIVITY ON THE CENTRAL NERVOUS SYSTEM

ACIDS AMINOCYCLOPENTANE-ALCENOIQUES AND THEIR ESTERS, THEIR PREPARATION AND USE IN PHARMACEUTICAL COMPOSITIONS

L'INVENTION CONCERNE DES ESTERS ET ACIDES AMINOCYCLOPENTANE ALCENOIQUES. LES COMPOSES REPONDENT A LA FORMULE GENERALE: (CF DESSIN DANS BOPI) OU X REPRESENTE UN GROUPE CIS OU TRANS -CHCH-; R EST UN GROUPE ALKYLE EN C-C A TERMINAISON -COOR OU R EST H, ALKYLE EN C-C OU ARALKYLE EN C-C; Y REPRESENTE UN GROUPE AMINO HETEROCYCLIQUE SATURE A 5, 8CHAINONS CYCLIQUES; ET R REPRESENTE UN GROUPE ALCANOYLE EN C-C, ALCENYLE EN C-C, ALKYLE EN C-C, PHENYLALKYLE, THIENYLALKYLE, FURANNYLALKYLE, BIPHENYLALKYLE OU NAPHTYLALKYLE. CES COMPOSES INHIBENT LA THROMBO-AGGLUTINATION ET LA BRONCHOCONSTRICTION. THE INVENTION CONCERNS ESTERS AND AMINOCYCLOPENTANE ALCENOIC ACIDS. THE COMPOUNDS MEET THE GENERAL FORMULA: (CF DRAWING IN BOPI) OR X REPRESENTS A CIS OR TRANS -CHCH- GROUP; R IS A C-C ALKYL GROUP WITH -COOR TERMINATION OR R IS H, C-C ALKYL OR C-C ARALKYL; REPRESENTS A SATURATED HETEROCYCLIC AMINO GROUP WITH 5, 8 CYCLIC CHAINS; AND R REPRESENTS A GROUP C-C ALKANOYL, C-C ALKENYL, C-C ALKYL, PHENYLALKYL, THIENYLALKYL, FURANNYLALKYL, BIPHENYLALKYL OR NAPHTYLALKYL. THESE COMPOUNDS INHIBIT THROMBO-AGGLUTINATION AND BRONCHOCONSTRICTION.

PROCEDURE FOR the 2,4-DIAMINO-6-CHLORINE PRODUCTION COMPOUND DE

(2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE I INHIBITORS

Process for benzazepine intermediates

A process is disclosed for providing benzazepine intermediates of the formulae см. иллюстрацию в PDF-документе wherein R3, R4 and Y are as defined herein, which intermediates are useful in a process for the preparation of pharmaceutically useful benzazepine derivatives.

Azepane derivatives and methods of treating hepatitis B infections

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Benzocycloalkylenylamine derivatives as muscarinic receptor antagonists

This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula I:wherein X, Y, and Z are O, S, or NR4, and the other substituents are as defined in the specification; and prodrugs, individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents.

Thiazolidinyl terminated alkylamino ethynyl alanine amino diol compounds for treatment of hypertension

Compounds characterized generally as thiazolidinyl-terminated alkylamino ethynyl alanine amino diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I (I) wherein A is selected from CO and SO2; wherein X is selected from oxygen atom and methylene; wherein B is a thiazolidinyl group; wherein R1 is selected from hydrido, methyl, ethyl, isopropyl and n-propyl; wherein R2 is phenylmethyl; wherein each of R3 and R5 is hydrido; wherein R4 is selected from methyl; wherein R6 is cyclohexylmethyl; wherein R7 is selected from isobutyl, cyclopropyl and cyclopropylmethyl; wherein q is a number selected from zero through three, inclusive; and wherein n is a number selected from zero through three, inclusive; or a pharmaceutically-acceptable salt thereof.

Cyclic amidine analogs as inhibitors of nitric oxide synthase

Disclosed herein are compounds of Formula I I and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These disease and disorders include hypotension, septic shock, toxic shock syndrom, hemodialysis, IL-2 therapy such as in cancer patients, cachexia, immunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn or psoriasis and respiratory conditions such as bronchitis, asthma, and acure respiratory distress (ARDS), myocarditis, heart failure, atherosclerosis, arthritis, rheumatoid arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis. Compounds of ...

Heterocyclic analgesic compounds and methods of use thereof

One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including opiate receptors, other G-protein-coupled receptors, and ion channels. An additional aspect of the present invention relates to the use of the novel heterocyclic compounds as analgesics.

ЗАМЕЩЕННЫЕ БЕНЗАМИДНЫЕ ПРОИЗВОДНЫЕ

Изобретение относится к соединению формулы (I), где R представляет собой водород или Салкил; Rпредставляет собой -(СН)-(О)-5-7-членный гетероциклоалкил, содержащий 1-2 гетероатома, выбранных из N и О, за исключением пиперазина, где указанная гетероциклоалкильная группа возможно замещена Салкилом, гидрокси или галогеном; n равно 0, 1 или 2; о равно 0 или 1; Rпредставляет собой CF, С3-6-циклоалкил, возможно замещенный Cалкокси или галогеном, или представляет собой индан-2-ил, или представляет собой 6-членный гетероциклоалкил, содержащий 1-2 гетероатома, выбранных из N и О, возможно замещенный пиримидинилом, или представляет собой 5-6 моно- или 9-10-членный бициклический гетероарил, содержащий 1-2 гетероатома, выбранных из N, О и S, где гетероарил не является тиазолом и где указанное ароматическое кольцо возможно замещено одним или двумя заместителями, выбранными из Cалкила, галогена, 5-6-членного гетероарила, содержащего 1-2 гетероатома, выбранных из N и О, гидрокси, CF, OCF, OCHCF, ОСН-циклоалкила ...

2,5,6,7-ТЕТРАГИДРО-[1,4]ОКСАЗЕПИН-3-ИЛАМИНЫ ИЛИ 2,3,6,7-ТЕТРАГИДРО-[1,4]ОКСАЗЕПИН-5-ИЛАМИНЫ

FIELD: medicine, pharmaceutics. SUBSTANCE: invention relates to formula compounds, possessing properties of BACE1 (enzyme 1, cleaving β-site of protein-precursor of β-amyloid) and/or BACE2 inhibitors, and their pharmaceutically acceptable salts, as well as to based on them pharmaceutical composition, their application and method of therapeutic and/or preventive impact on such diseases as Alzheimer's disease, type 2 diabetes. In general formula (I) A represents O, and B represents -CR 8 R 9 -; or B represents O and A represents -CR 8 R 9 -; R 1 is selected from hydrogen and C 1-7 -alkyl; R 2 is selected from hydrogen and C 1-7 -alkyl; R 3 is selected from hydrogen and halogen; R 4 is selected from hydrogen and halogen; R 5 represents C 1-7 -alkyl; or R 3 and R 5 together with C atom, which they are bound to, form cyclopropyl ring; R 6a , R 6b , R 6c and R 6d are selected from hydrogen and halogen; R 7 represents -(CO)-R 10 or R 11 , where R 10 is selected from the group, consisting of 5-6-membered heteroaryl with 1-3 heteroatoms, selected from N, O and S, with said heteroaryl being non-substituted or substituted with one-two groups, selected from the group, consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, -COO-CH 2 -CH 3 , halogen-C 1-7 -alkyl, C 3-7 -cycloalkyl, with said cycloalkyl being non-substituted or substituted with one-four groups, selected from C 1-7 -alkyl, halogen or halogen-C 1-7 -alkyl, and C 1-7 -alkoxy-C 1-7 -alkyl, R 11 is selected from C 1-7 -alkyl and C 3-7 -cycloalkyl; R 8 and R 9 independently on each other are selected from hydrogen, C 1-7 -alkyl and phenyl. EFFECT: obtaining medication for therapeutic and/or preventive impact on such diseases as Alzheimer's disease, type 2 diabetes. 25 cl, 7 tbl, 118 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 413/12 C07D 417/12 A61K 31/553 A61P 25/28 (13) 2 570 796 C2 (2006.01) (2006.01) (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ...

НОВЫЕ СОЕДИНЕНИЯ И КОМПОЗИЦИИ В КАЧЕСТВЕ ИНГИБИТОРОВ КАТЕПСИНА

... 1. Соединение, имеющее структуру формулы (I) где A представляет собой или ; X1 представляет собой метилен, этилен или связь; X2 представляет собой CN, CHO, C(O)R6, C(O)C(O)NR7R7, C(O)C(O)NR7R8 , C(O)C(O)R13, C(O)C(O)OR13, C(O)CH2X3R13; X3 выбран из группы, состоящей из O, S(O)n, CO, CONH, NHCO, NHSO2 и SO2NH; X4 представляет собой CH(R12) или CH(R12)-CH2; X5 представляет собой метилен, этилен, пропилен или связь; X6 представляет собой связь или (C1-2)алкилен; R1 представляет собой R13C(O)-, R13 S(O)2-, R13OC(O)-, R8R7NC(O)-, R8R7NS(O)2-; R13S(O)2NC(O)- или R13C(O)NS(O)2 -; R2 выбран из группы, состоящей из водорода, (C1-6)алкила, (C3-12)циклоалкил(C0-6)алкила, гетеро(C5-12)циклоалкил(C0-6 )алкила, (C6-12)арил(C0-6)алкила и гетеро(C5-13)арил(C0-6)алкила; R3 выбран из группы, состоящей из H, (C1-6)алкила, (C3-12)циклоалкил(C0-6)алкила, гетеро(C5-12)циклоалкил(C0-6)алкила, (C6-12)арил(C0-6)алкила или гетеро(C5-13)арил(C0-6)алкила, необязательно замещенных 1-5 радикалами, независимо выбранными ...

Naphtho-fused lactams that stimulate release of growth hormone

The present invention is directed to certain naphtho-fused lactams of the general structural formula: wherein and R1, R1a, R1b, R2a, R2b, R3a, R4, R5, R6, A, L, X, n, p and w are as defined herein. These compounds promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Combination therapy with bisphosphonate compounds is also disclosed.

7-PHENYL-7-PHENOXYMETHYL-HEXAHYDRO-1,4-OXAZEPIN, YOUR PRODUCTION AND USE.

PROCEDURE FOR THE PRODUCTION OF NEW AMINOCYCLOPENTANALKENSAEUREDERIVATEN AS WELL AS OF THEIR SALTS AND HYDRATES

PYRROLIDIN-1,2-DICARBONSÄURE-1 (PHENYLAMID) - 2 (- (3-OXO-MORPHOLIN-4-YL) - PHENYLAMID) DERIVATIVES AND USED CONNECTIONS AS INHIBITORS of the COAGULATION FACTOR XA FOR the TREATMENT OF THROMBOEMBOLI ILLNESSES

Process for producing 2-hydroxymethylmorpholine salt

The invention relates to a production method of a 2-hydroxymethylmorpholine salt, which includes crystallization from a solution containing 2-hydroxymethylmorpholine of formula (1) 1,4-oxazepane compound of formula (2) and an acid.

Compounds Useful as Inhibitors of ATR Kinase

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. A method for treating cancer in a patient comprising administering a compound of or a pharmaceutically acceptable derivative thereof.4. The method of claim 3 , further comprising administering to said patient an additional therapeutic agent selected from a DNA-damaging agent; wherein said additional therapeutic agent is appropriate for the disease being treated; and said additional therapeutic agent is administered together with said compound as a single dosage form or separately from said compound as part of a multiple dosage form.56-. (canceled)76. The method of claim claim 3 , wherein said DNA-damaging agent is selected from ionizing radiation claim 3 , a platinating agent claim 3 , a Topo I inhibitor claim 3 , a Topo II inhibitor claim 3 , an antimetabolite claim 3 , an alkylating agent claim 3 , or an alkyl sulphonates.816-. (canceled)176. The method of claim claim 3 , wherein the DNA-damaging agent is selected from one or more of the following: Cisplatin claim 3 , Carboplatin claim 3 , gemcitabine claim 3 , Etoposide claim 3 , Temozolomide claim 3 , or ionizing radiation.18. (canceled)19. The method of claim 3 , wherein said cancer is selected from a cancer of the ...

BIARYL AMIDE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

Disclosed is a novel biaryl amide derivative represented by formula (1) and having an affinity for the aldosterone receptor; also disclosed is a pharmaceutically acceptable salt thereof. (In the formula, A is any of the groups represented by formula (a); L is —CONH—, etc.; Ris a substitutable aminosulfonyl group, etc.; Ris a hydrogen atom, etc.; Ris a hydrogen atom, etc.; Ris a hydrogen atom, a halogen atom, hydroxy group, a substitutable amino group, a substitutable Calkoxy group, a substitutable 4- to 7-membered cyclic amino group, etc.; R, Rand Rare each independently hydrogen atoms, etc.; Ris a halogen atom, a cyano group, etc.; Rand Rare each independently a hydrogen atom, etc.; and m is an integer such as 0.) 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is a group of formula (a).3. The compound of either claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —NHCO—.4. The compound of either claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —CONH—.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris [{'sub': '1-6', 'claim-text': [{'sub': '1-6', '(i) amino (in which the amino may be optionally substituted with the same or different 1 to 2 Calkyl),'}, {'sub': '1-6', '(ii) Calkoxy, or'}, '(iii) 4- to 7-membered cyclic amino),, '(a) Calkyl (in which the group may be optionally substituted with'}, {'sub': '1-6', '(b) Calkylcarbonyl,'}, '(c) aminocarbonyl, and', {'sub': '2', '(d) —C(═NH)—NH),'}], '1: aminosulfonyl group (in which the amino may be optionally substituted with the same or different 1 to 2 groups selected from the group consisting of'}{'sub': '1-6', '2: Calkylsulfonyl group, or'}{'sub': '1-6', '3: Calkylsulfonylamino group, or a pharmaceutically acceptable salt thereof.'}6. The compound of claim 5 , wherein Ris aminosulfonyl group claim 5 , or a pharmaceutically acceptable salt thereof.7. The compound of claim ...

Guanidine compound

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

APOPTOSIS PROMOTERS

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member. 19-. (canceled)10. A compound , or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(2,4-dimenthyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;4-(((1R)-3-(bis(2-methoxyethyl)amino)-1 ...

1,4-OXAZEPANE DERIVATIVES

Provided is a compound having a monoamine reuptake inhibitory activity, which is represented by the formula (I) wherein ring A is an optionally substituted 6-membered aromatic ring, ring B is the substituents on ring A are optionally bonded to form, together with ring A, an optionally substituted 9- or 10-membered aromatic fused ring, and other symbols are as defined in the specification, or a salt thereof. 3. The compound according to claim 2 , wherein ring A is an optionally substituted benzene ring claim 2 , or a salt thereof.7. N-{[(6S claim 2 ,7R)-7-(3 claim 2 ,4-Dichlorophenyl)-1 claim 2 ,4-oxazepan-6-yl]methyl}-2-methoxyacetamide claim 2 , or a salt thereof.8. N-[(6R claim 2 ,7S)-7-(3 claim 2 ,4-Dichlorophenyl)-1 claim 2 ,4-oxazepan-6-yl]acetamide claim 2 , or a salt thereof.9. N-{[(6S claim 2 ,7R)-7-(4-Chloro-3-fluorophenyl)-1 claim 2 ,4-oxazepan-6-yl]methyl}-2-[(H)methyloxy]acetamide claim 2 , or a salt thereof.10. 1-{[(6S claim 2 ,7R)-7-(4-Chloro-3-fluorophenyl)-1 claim 2 ,4-oxazepan-6-yl]methyl}-2-oxo-1 claim 2 ,2-dihydropyridine-3-carboxylic acid claim 2 , or a salt thereof.11. (1S)-1-[(6R claim 2 ,7R)-6-(3 claim 2 ,4-Dichlorophenyl)-1 claim 2 ,4-oxazepan-7-yl]ethane-1 claim 2 ,2-diol claim 2 , or a salt thereof.12. [(7S)-7-(3 claim 2 ,4-Dichlorophenyl)-1 claim 2 ,4-oxazepan-7-yl]methanol claim 2 , or a salt thereof.13. A medicament comprising the compound according to claim 1 , or a salt thereof.14. The medicament according to claim 13 , which is a monoamine reuptake inhibitor.15. The medicament according to claim 13 , which is a prophylactic or therapeutic drug for depression claim 13 , anxiety claim 13 , attention deficit hyperactivity disorder claim 13 , climacteric disorder claim 13 , pain claim 13 , stress urinary incontinence or mixed urinary incontinence.16. A method for the prophylaxis or treatment of depression claim 1 , anxiety claim 1 , attention deficit hyperactivity disorder claim 1 , climacteric disorder claim 1 , pain claim 1 , stress ...

METHOD FOR PRODUCING N-SUBSTITUTED AMINE COMPOUNDS THROUGH CATALYZED ALKYLATION

The invention relates to a method for producing a N-substituted amine compound by catalyzed alkylation. The method uses amine and alcohol or two kinds of amines as the reaction materials, employs composite metal oxides catalyst at a reaction temperature of 80-180° C. to catalyze the reaction for 6-36 hours, so as to produce the N-substituted amine compound. The reaction condition of the method of the invention is relatively moderate, using a catalyst made of cheap non-noble metals, which is non-caustic and easy to be separated and reused. The reaction does not need any medium and has relatively high conversion rate and selectivity. 2. The method of claim 1 , wherein the molar ratio of Cu to Ni is from 10:1 to 1:10 claim 1 , and the molar ratio of Cu to Fe is from 10:1 to 1:10 in CuO—NiO—FeO.3. The method of claim 1 , wherein the molar ratio of Ni to Fe in NiO—FeOis from 10:1 to 1:10.4. The method of claim 1 , wherein the molar ratio of Cu to Fe in CuO—FeOis from 10:1 to 1:10.5. The method of claim 1 , wherein the molar ratio of Cu to Ni in CuO—NiO is from 10:1 to 1:10.6. (canceled)7. The method of claim 1 , wherein the mass ratio between the composite metal oxide catalyst and the amine is from 0.01:1 to 1.2:1.8. The method of claim 1 , wherein the composite metal oxide catalyst is produced by the following steps:{'sub': 3', '2', '3', '2', '3', '3', '3', '3, '1) adding an aqueous solution of any two or three nitrates selected from Cu(NO), Ni(NO), and Fe(NO), and an aqueous Al(NO)solution, to an aqueous alkali metal oxide or hydroxide solution, aqueous ammonia, or aqueous carbamide solution which functions as a precipitator to coprecipitate;'}2) after step 1), providing a crude catalyst by washing, drying in the air, calcining, and reducing in hydrogen gas;{'sub': 3', '4', '3', '4', '3', '4, '3) using an aqueous alkali metal hydroxide solution to remove any alumina in the crude catalyst obtained in steps 1) and 2) to provide a composite metal oxides catalyst CuO—NiO— ...

2,5,6,7-Tetrahydro-[1,4]oxazepin-3-ylamine or 2,3,6,7-tetrahydro-[1,4]oxazepin-5-ylamine compounds

This invention relates to compounds of the formula 2. A compound according to claim 1 , wherein A is O and B is —CRR—.3. A compound according to claim 1 , wherein B is O and A is —CRR—.4. A compound according to claim 1 , wherein Rand Rare independently from each other hydrogen or C-alkyl.5. A compound according to claim 1 , wherein Rand Rare hydrogen.6. A compound according to claim 1 , wherein Rand Rare independently from each other selected from the group consisting of hydrogen claim 1 , halogen claim 1 , and C-alkyl.7. A compound according to claim 1 , wherein Rand Rare independently from each other hydrogen or fluoro.8. A compound according to claim 1 , wherein Rand Rare fluoro.9. A compound according to claim 1 , wherein Ris methyl or ethyl.10. A compound according to claim 1 , wherein Rand Rtogether with the C atom to which they are attached form a cyclopropyl ring.11. A compound according to claim 1 , wherein Ris hydrogen or fluoro and R claim 1 , Rand Rare hydrogen.12. A compound according to claim 1 , wherein Ris —(CO)—Rand Ris selected from the group consisting of{'sub': 1-7', '1-7', '1-7', '1-7', '1-7, 'aryl, said aryl being unsubstituted or substituted by one, two or three groups selected from the group consisting of C-alkyl, halogen, halogen-C-alkyl, C-alkoxy, halogen-C-alkoxy, cyano, hydroxy-C-alkyl, oxo and phenyl,'}{'sub': 1-7', '1-7', '1-7', '1-7', '1-7, 'heteroaryl, said heteroaryl being unsubstituted or substituted by one, two or three groups selected from the group consisting of C-alkyl, halogen, halogen-C-alkyl, C-alkoxy, halogen-C-alkoxy, cyano, hydroxy-C-alkyl, oxo and phenyl, and'}{'sub': 3-7', '1-7', '1-7, 'C-cycloalkyl, said cycloalkyl being unsubstituted or substituted by one, two, three or four groups selected from the group consisting of C-alkyl, halogen and halogen-C-alkyl.'}13. A compound according to claim 12 , wherein Ris selected from the group consisting of{'sub': 1-7', '1-7', '1-7', '1-7', '1-7, 'heteroaryl, said heteroaryl being ...

Guanidine compound

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

Azepane derivatives and methods of treating hepatitis b infections

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject. 4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare claim 1 , independently at each occurrence claim 1 , —C-Calkyl claim 1 , phenyl claim 1 , pyridyl claim 1 , benzyl claim 1 , or pyridylmethyl.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare claim 1 , independently at each occurrence claim 1 , —C-Calkyl claim 1 , wherein the —C-Calkyl groups join to form a 3- to 7-membered ring.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris claim 1 , independently at each occurrence claim 1 , halo and x is 1 claim 1 , 2 claim 1 , or 3.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris claim 1 , independently at each occurrence claim 1 , halo claim 1 , OH claim 1 , —C-Calkyl claim 1 , or —O—C-Calkyl claim 1 , wherein the alkyl group is optionally substituted 1-3 times with halo or OH.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris claim 1 , independently at each occurrence claim 1 , halo or —C-Calkyl-OH and y is 1 or 2.11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Ris claim 1 , independently at each occurrence claim 1 , OR claim 1 , wherein Ris claim 1 , independently at each occurrence claim 1 , —C-Calkyl or —C-Ccycloalkyl claim 1 , wherein the alkyl and cycloalkyl groups are optionally substituted 1-2 times with halo or OH.1236-. (canceled)37. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof ...

CERTAIN (2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE 1 INHIBITORS

The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), 412.-. (canceled)14. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , diluent or carrier.15. A pharmaceutical composition comprising a compound of claim 3 , and a pharmaceutically acceptable adjuvant claim 3 , diluent or carrier.16. A pharmaceutical composition comprising a compound of claim 3 , and a pharmaceutically acceptable adjuvant claim 3 , diluent or carrier.17. A pharmaceutical composition comprising a compound of claim 13 , and a pharmaceutically acceptable adjuvant claim 13 , diluent or carrier.18. A method of treating an obstructive disease of the airway in a patient in need thereof claim 1 , comprising administering to the patient a therapeutically effective amount of the compound of .19. A method of treating an obstructive disease of the airway in a patient in need thereof claim 2 , comprising administering to the patient a therapeutically effective amount of the compound of .20. A method of treating an obstructive disease of the airway in a patient in need thereof claim 3 , comprising administering to the patient a therapeutically effective amount of the compound of .21. A method of treating an obstructive disease of the airway in a patient in need thereof claim 13 , comprising administering to the patient a therapeutically effective amount of the compound of .22. The method of claim 18 , wherein the administering comprises oral administration.23. The method of claim 19 , wherein the administering comprises oral administration.24. The method of claim 20 , wherein the administering comprises oral administration.25. The method of claim 21 , wherein the administering comprises oral administration. This application is a continuation of U.S. application Ser. No. 15/708,634, filed on Sep. 19, 2017, which is a continuation ...

INHIBITING NEUROTRANSMITTER REUPTAKE

This document relates to compounds as well as methods and materials involved in modulating neurotransmitter reuptake. For example, compounds, methods for synthesizing compounds, and methods for inhibiting neurotransmitter reuptake are provided. Specifically gamma-amino alcohol derivatives that inhibit the reuptake of neurotransmitters such as dopamine, serotonin, epinephrine or norepinephrine are provided as therapeutic agents for the treatment of depression or anxiety in a mammalian subject. 17-. (canceled)9. The compound of claim 8 , wherein Ris optionally substituted with one or two substituents.11. The compound of claim 10 , wherein at least two of R claim 10 , R claim 10 , R claim 10 , R claim 10 , and Rare hydrogen.12. The compound of claim 11 , wherein the remaining R claim 11 , R claim 11 , R claim 11 , R claim 11 , and Rare independently selected from ethyl claim 11 , chloro claim 11 , and bromo.13. The compound of claim 10 , wherein R claim 10 , R claim 10 , and Rare hydrogen; and Rand Rare independently selected from ethyl claim 10 , chloro claim 10 , and bromo.15. The compound of claim 14 , wherein each of Rand Ris not hydrogen.17. The compound of claim 16 , wherein Ris selected from hydrogen claim 16 , lower alkyl claim 16 , halo claim 16 , hydroxyl claim 16 , lower alkoxy claim 16 , methylsulfanyl claim 16 , and methsulfonyl; and Ris selected from hydrogen claim 16 , lower alkyl claim 16 , halo claim 16 , dimethylamino claim 16 , methylsulfanyl claim 16 , and 1 claim 16 ,1 claim 16 ,1-trifluoromethanesulfonamide.1826-. (canceled) This application claims the benefit of U.S. Provisional Application Ser. No. 61/783,122, filed Mar. 14, 2013. The disclosure of the prior application is considered part of (and is incorporated by reference in) the disclosure of this application.1. Technical FieldThis document relates to compounds as well as methods and materials involved in modulating neurotransmitter reuptake.2. Background InformationNeuronal signals are ...

Cyclic Amines

The present invention is directed to novel cyclic amines which inhibit the P2Xreceptor. 2. The compound of claim 1 , wherein Ris optionally substituted phenyl.3. The compound of claim 1 , wherein Ris optionally substituted pyridyl.4. The compound of claim 1 , wherein Ris optionally substituted pyrazinyl.5. The compound of claim 1 , wherein Ris optionally substituted pyrimidyl.6. The compound of claim 1 , wherein Ris optionally substituted 5 membered heteroaryl.7. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted piperazinyl.8. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted piperidinyl.9. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted morpholinyl.10. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted pyrrolidinyl.11. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted pyrrolo.12. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted imidazo.13. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted 6 to 10 membered spiro(heterocyclyl).14. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted homomorpholinyl15. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted homopiperidinyl16. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted homopiperazinyl17. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form ...

Compounds Useful for Treating a Mannheimia Haemolytica or Histophilus Somni Infection

The present invention discloses compounds that are useful in the treatment of respiratory diseases of animals, especially Bovine or Swine Respiratory disease (BRD and SRD). 2. A compound according to claim 1 , wherein R claim 1 , Rare independently selected from the group consisting of{'sub': 1-6', '2-6', '3-10', '1-6', '1-6', '1', '6', '1', '6', '2, 'sup': 6', '7, 'H, C-alkyl, C-alkenyl, C-cycloalkyl, C-alkyloxy-C-alkyl, C-C-alkyl substituted with aryl, C-C-alkyl substituted with heteroaryl, or NRRis NOor'}{'sup': 6', '7, 'claim-text': {'sup': 6', '7, 'wherein the alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, alkyloxy or the heterocyclic ring formed by R, Rtogether with the N atom to which they are attached is optionally substituted with a substituent selected from the group consisting of'}, 'R, Rtogether with the N atom to which they are attached can form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 1 ring atom is N and wherein 0, 1, 2, or 3 further ring atoms are selected from N, S, and O;'}{'sub': 1-6', '3-8', '1-6', '1-6', '1-6', '1-6', '1', '6', '2', '2', '1-6, 'sup': 9', '10', '9', '8', '8', '9', '10', '9', '10, 'C-alkyl, C-cycloalkyl, C-alkyloxy, —NRR, carbonyl, —C(═O)—OR, halogen atom, C-alkyl substituted with halo, C-alkyloxy-C-alkyl, aryl, heteroaryl, C-C-alkyl substituted with aryl, cyano, hydroxy, —SR, —SOR, —SONRR, —C(═O)NRR, C-alkyl substituted with hydroxyl.'}3. A compound according to anyone of - claim 1 , wherein L is selected from the group consisting of{'sub': 1-6', '2-6', '2-6', '3-10, 'sup': 'L3', 'C-alkyl, C-alkenyl, C-alkynyl, C-cycloalkyl, —NR—,'} [{'sup': 'L3', 'R, is selected from the group consisting of'}, {'sub': 1-6', '1-6', '1', '6', '1', '6', '1', '6', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'H, C-alkyl, halo-C-alkyl, C-C-alkyl substituted with aryl, C-C-alkyl substituted with heteroaryl, C-C-alkyl substituted with heterocyclyl, preferably wherein L is selected from the group consisting of — ...

Novel compounds

The present invention relates to substituted N-biphenyl-3-acetylamino-benzamides and N-[3-(acetylamino)phenyl]-biphenyl-carboxamides of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyperproliferative disorder, as a sole agent or in combination with other active ingredients.

TRNA SYNTHETASE INHIBITORS

Disclosed herein are secondary amine compounds that inhibit tRNA synthetase. The compounds of the invention are useful in inhibiting tRNA synthetase in Gram-negative bacteria and are useful in killing Gram-negative bacteria. The secondary amine compounds of the invention are also useful in the treatment of tuberculosis. 215-. (canceled)1726-. (canceled)28. The compound of claim 27 , wherein at least three of R claim 27 , R claim 27 , R claim 27 , and Rare H.29. The compound of claim 27 , wherein R claim 27 , R claim 27 , Rand Rare each H.30. The compound of claim 27 , wherein Ris H.31. The compound of claim 27 , wherein Ris (C-C)alkyl.32. (canceled)33. The compound of claim 27 , wherein Ris optionally substituted cyclohexyl or cyclohexenyl.34. The compound of claim 27 , wherein Ris optionally substituted cyclohexyl.35. The compound of claim 27 , wherein Ris H.36. The compound of claim 27 , wherein R claim 27 , independently for each occurrence claim 27 , is selected from H and (C-C)alkyl.37. The compound of claim 27 , wherein each occurrence of Ris H.38. The compound of claim 27 , wherein each occurrence of Ris methyl claim 27 , or one Ris methyl or ethyl claim 27 , and the other Ris H.39. The compound of claim 27 , wherein one Ris selected from one of (a)-(d):(a) optionally substituted —C(O)alkyl;{'sub': 3', '10, '(b) optionally substituted —C(O)NH—(C-C)cycloalkyl;'}{'sub': 1', '8, '(c) optionally substituted (C-C)alkyl; or'}(d) optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heterocyclyl.40. The compound of claim 39 , wherein one Ris —C(O)CH(NH)CHCHMe.41. (canceled)42. The compound of claim 39 , wherein one Ris —C(O)NH— cyclohexyl claim 39 , optionally substituted with methyl.43. (canceled) .44. The compound of claim 39 , wherein one Ris selected from —CHCH(OH)CHOH claim 39 , —CHC(O)NHCHCOOH claim 39 , —CHC(O)NHCHCOOH claim 39 , —CHCHOMe claim 39 , —CHCOOH claim 39 , —CH(Me)COOH claim 39 , and —CH-furanyl.45. (canceled) . ...

SUBSTITUTED BENZAMIDES

The invention relates to compounds of formula 2. The compound of claim 1 , wherein X is NR′ and R′ is hydrogen.3. The compound of claim 2 , selected from the group consisting of(RS)-1-(4-Butyl-2-methyl-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;1-(3,4-Dichloro-phenyl)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-urea;(RS)-1-(3,4-Dichloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(4-Chloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-Phenyl-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(2,4-Dichloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(3-Chloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(4-Pyrrolidin-3-yl-phenyl)-3-(4-trifluoromethyl-phenyl)-urea;(RS)-1-(5-Chloro-pyridin-2-yl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(6-Chlor-pyridin-3-yl)-3-(4-piperidin-3-yl-phenyl)-urea;(RS)-1-(5-Chloro-pyridin-2-yl)-3-(4-piperidin-3-yl-phenyl)-urea; and(RS)-1-(5-Chloro-pyridin-2-yl)-3-[4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-urea.4. The compound of claim 2 , selected form the group consisting of(RS)-1-(4-Chloro-phenyl)-3-[4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-urea;(RS)-1-(4-Chloro-phenyl)-3-[4 (2-piperidin-3-yl-ethyl)-phenyl]-urea;(RS)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea;(RS)-1-(4-Chiorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(4-(Morpholin-2-yl)phenyl)-3-p-tolylurea;(RS)-1-(6-Chloropyridin-3-yl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(3-Chlorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(4-(Morpholin-2-yl)phenyl)-3-m-tolylurea;(RS)-1-(2-Chlorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(4-Methylbenzyl)-3-(4-(morpholin-2-yl)phenyl)urea;(R)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea; and(S)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea.5. The compound of claim 1 , wherein X is a bond.6. The compound of claim 5 , selected from the group consisting of(RS)—N-(4-Pyrrolidin-3-yl-phenyl)-benzamide;(RS)-4-Chloro-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;(RS)—N-(4-Pyrrolidin-3-yl-phenyl)-4- ...

Certain (2s)-n-[(1s)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamides as dipeptidyl peptidase 1 inhibitors

The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

SUBSTITUTED BENZAMIDES

The invention relates to compounds of formula 132-. (canceled)34. The method according to claim 33 , wherein X is NR′ and R′ is hydrogen.35. The method according to claim 33 , wherein X is a bond.36. The method according to claim 33 , wherein X is —(CH)—O—.37. The method according to claim 33 , wherein X is —O(CHR″)—.38. The method according to claim 33 , wherein X is —CHR″—.39. The method according to claim 33 , wherein X is —CHCH—.40. The method according to claim 33 , wherein said compound is selected from the group consisting of:(RS)-1-(4-Butyl-2-methyl-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;1-(3,4-Dichloro-phenyl)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-urea;(RS)-1-(3,4-Dichloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(4-Chloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-Phenyl-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(2,4-Dichloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(3-Chloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(4-Pyrrolidin-3-yl-phenyl)-3-(4-trifluoromethyl-phenyl)-urea;(RS)-1-(5-Chloro-pyridin-2-yl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;(RS)-1-(6-Chloro-pyridin-3-yl)-3-(4-piperidin-3-yl-phenyl)-urea;(RS)-1-(5-Chloro-pyridin-2-yl)-3-(4-piperidin-3-yl-phenyl)-urea;(RS)-1-(5-Chloro-pyridin-2-yl)-3-[4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-urea;(RS)-1-(4-Chloro-phenyl)-3-[4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-urea;(RS)-1-(4-Chloro-phenyl)-3-[4-(2-piperidin-3-yl-ethyl)-phenyl]-urea;(RS)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea;(RS)-1-(4-Chlorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(4-(Morpholin-2-yl)phenyl)-3-p-tolylurea;(RS)-1-(6-Chloropyridin-3-yl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(3-Chlorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(4-(Morpholin-2-yl)phenyl)-3-m-tolylurea;(RS)-1-(2-Chlorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;(RS)-1-(4-Methylbenzyl)-3-(4-(morpholin-2-yl)phenyl)urea;(R)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea;(S)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-( ...

Cysteine Prodrugs

Novel cysteine prodrugs and their use in the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of the Central Nervous System (CNS), including but not limited to schizophrenia, drug craving, drug addiction, bipolar disorder, anxiety, depression, Parkinson's disease, Alzheimer's disease, cognitive dysfunction, multiple sclerosis, Amyotrophic lateral sclerosis (ALS), ischemic stroke, HIV dementia, and Huntington's disease.

Hdac6 inhibitors and uses thereof

Provided herein are compounds that inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and/or compositions described herein.

Aminomethyl-Biaryl Derivatives Complement Factor D inhibitors and uses thereof

The present invention provides a compound of formula (I), a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject. 135-. (canceled)37. A pharmaceutical composition comprising a compound of claim 36 , or a pharmaceutically acceptable salt thereof claim 36 , together with a pharmaceutically acceptable carrier.38. A method of treating an HBV infection in an individual in need thereof claim 36 , comprising administering to the individual a therapeutically effective amount of a compound of .3945-. (canceled)46. The method of claim 38 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of a HBV polymerase inhibitor claim 38 , immunomodulatory agents claim 38 , pegylated interferon claim 38 , viral entry inhibitor claim 38 , viral maturation inhibitor claim 38 , literature-described capsid assembly modulator claim 38 , reverse transcriptase inhibitor claim 38 , a cyclophilin/TNF inhibitor claim 38 , a TLR-agonist claim 38 , an HBV vaccine claim 38 , and a combination thereof.47. The method of claim 46 , wherein the therapeutic agent is a reverse transcriptase inhibitor claim 46 , and is at least one of Zidovudine claim 46 , Didanosine claim 46 , Zalcitabine claim 46 , 2′ claim 46 ,3′-dideoxyadenosine claim 46 , Stavudine claim 46 , Lamivudine claim 46 , Abacavir claim 46 , Emtricitabine claim 46 , Entecavir claim 46 , Apricitabine claim 46 , Atevirapine claim 46 , ribavirin claim 46 , acyclovir claim 46 , famciclovir claim 46 , valacyclovir claim 46 , ganciclovir claim 46 , valganciclovir claim 46 , Tenofovir claim 46 , Adefovir claim 46 , cidofovir claim 46 , Efavirenz claim 46 , Nevirapine claim 46 , Delavirdine claim 46 , and Etravirine.48. The method of claim 46 , wherein the therapeutic agent is a TLR agonist claim 46 , and wherein the TLR agonist is selected from the group consisting ...

AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject. 3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein each Ris claim 2 , independently at each occurrence claim 2 , halo.4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein each Ris claim 2 , independently at each occurrence claim 2 , halo or —C-Calkyl claim 2 , wherein the alkyl is optionally substituted 1-3 times with halo.7. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , together with a pharmaceutically acceptable carrier.8. A method of treating an HBV infection in an individual in need thereof claim 1 , comprising administering to the individual a therapeutically effective amount of a compound of .9. A method of reducing the viral load associated with an HBV infection in an individual in need thereof claim 1 , comprising administering to the individual a therapeutically effective amount of a compound of .10. A method of reducing reoccurrence of an HBV infection in an individual in need thereof claim 1 , comprising administering to the individual a therapeutically effective amount of a compound of .11. A method of inducing remission of hepatic injury from an HBV infection in an individual in need thereof claim 1 , comprising administering to the individual a therapeutically effective amount of a compound of .12. The method of claim 8 , further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of a HBV polymerase inhibitor claim 8 , immunomodulatory agents claim 8 , pegylated interferon claim 8 , viral entry inhibitor claim 8 , viral maturation inhibitor claim 8 , literature-described capsid assembly modulator claim 8 , ...

SSAO INHIBITORS AND USES THEREOF

Described herein are compounds that are semicarbazide-sensitive amine oxidase (SSAO) inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in treating or preventing a liver disease or condition. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein m is 0.5. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein n is 0.6. The compound of claim 5 , or a pharmaceutically acceptable salt or solvate thereof claim 5 , wherein X is —O—.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris H.8. The compound of claim 7 , or a pharmaceutically acceptable salt or solvate thereof claim 7 , wherein Z is F.9. The compound of claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein p is 1.10. The compound of claim 9 , or a pharmaceutically acceptable salt or solvate thereof claim 9 , wherein Ris —OR claim 9 , —N(R)C(O)R claim 9 , —N(R)C(O)N(R)(R) claim 9 , —N(R)S(O)R claim 9 , —C(O)R claim 9 , —C(O)N(R)(R) claim 9 , or —S(O)N(R)(R).11. The compound of claim 10 , or a pharmaceutically acceptable salt or solvate thereof claim 10 , wherein Ris —C(O)N(R)(R).12. The compound of claim 11 , or a pharmaceutically acceptable salt or solvate thereof claim 11 , wherein Ris selected from H claim 11 , Calkyl claim 11 , Ccycloalkyl claim 11 , and Cheterocycloalkyl claim 11 , wherein Calkyl claim 11 , Ccycloalkyl and Cheterocycloalkyl are optionally substituted with one claim 11 , two claim 11 , or three R.13. The compound of claim 12 , or a pharmaceutically acceptable salt or solvate thereof claim 12 , wherein Ris selected from H claim 12 , Calkyl claim 12 , and Cheterocycloalkyl claim 12 , wherein Calkyl and Cheterocycloalkyl are optionally substituted with one claim 12 , two claim 12 , or three R.14. The compound of ...

CERTAIN (2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE 1 INHIBITORS

The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), 3. A compound according to either or whereinX is O;{'sup': '6', 'sub': '1-3', 'Ris Calkyl; and'}{'sup': '7', 'Ris hydrogen; or a pharmaceutically acceptable salt thereof.'}4. A compound of the formula (I) according to selected from:(2S)-N-[(1S)-1-Cyano-2-(4′-cyanobiphenyl-4-yl)ethyl]-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4-(3,7-dimethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;4′-[(2S)-2-Cyano-2-{[(2S)-1,4-oxazepan-2-ylcarbonyl]amino}ethyl]biphenyl-3-yl methanesulfonate;(2S)-N-{(1S)-1-Cyano-2-[4-(3-methyl-1,2-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4′-(trifluoromethyl)biphenyl-4-yl]ethyl1-1,4-oxazepane-2-carboxamide;(2S)-N-[(1S)-1-Cyano-2-(3′,4′-difluorobiphenyl-4-yl)ethyl]-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4-(6-cyanopyridin-3-yl)phenyl]ethyl1-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4-(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4-(3-ethyl-7-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;(2S)-N-[(1S)-1-Cyano-2-{4-[3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl}ethyl]-1,4-oxazepane-2-carboxamide;(2S)-N-[(1S)-1-Cyano-2-{4-[3-(2,2-difluoroethyl)-7-fluoro-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl]phenyl}ethyl]-1,4-oxazepane-2-carboxamide;(2S)-N-[(1S)-1-Cyano-2-(4-{3-[2-(dimethylamino)ethyl]-2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl}phenyl)ethyl]-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4-(3,3-difluoro-1-methyl-2-oxo-2,3-dihydro-1H-indol-6-yl)phenyl]ethyl}-1,4-oxazepane-2-carboxamide;(2S)-N-{(1S)-1-Cyano-2-[4-(7-fluoro-3- ...

DUAL NAV1.2/5HT2a INHIBITORS FOR TREATING CNS DISORDERS

Compounds of formula I: 2. A compound according to wherein Q is an optionally substituted nitrogenous aliphatic monocycle chosen from pyrrolidine claim 1 , piperidine claim 1 , morpholine claim 1 , piperazine claim 1 , azepane claim 1 , oxazepane claim 1 , thiazapane and diazepane.34-. (canceled)5. A compound according to wherein Q is an optionally substituted nitrogenous aliphatic bicycle chosen from diazabicycloheptane and diazabicyclooctane.6. (canceled)7. A compound according to wherein Q is an optionally substituted nitrogenous aliphatic spirocycle chosen from diazaspiro[4.4]nonane and diazaspiro[4.5]decane.8. (canceled)9. A compound according to wherein Q is an optionally substituted nitrogenous aliphatic spirocycle chosen from oxazaspiro[3.4]octane claim 1 , oxazaspiro[3.4]octene claim 1 , azaspiro [4.4]nonane claim 1 , and oxazaspiro [4.5]decane.10. (canceled)13. A compound according to wherein Ris an optionally substituted monocycle chosen from benzene claim 1 , cyclohexane claim 1 , tetrahydropyridazine and tetrahydropyran.14. A compound according to wherein Ris an optionally substituted fused bicycle containing an aromatic 6-membered ring and a non-aromatic 5-membered ring.15. (canceled)17. A compound according to wherein Ris an optionally substituted fused bicycle containing an aromatic 6-membered ring and a non-aromatic 6-membered ring.18. (canceled)19. A compound according to wherein Ris an optionally substituted fused bicycle containing two aromatic 6-membered rings.20. (canceled)21. A compound according to wherein Ris an optionally substituted fused bicycle containing an aromatic 6-membered ring and a non-aromatic 7-membered ring.2226-. (canceled)27. A compound according to wherein Lis —O—CHCH(OH)CH—.2829-. (canceled)30. A compound according to wherein Lis —CH—.3132-. (canceled)33. A compound according to wherein Lis —CHCH—.3435-. (canceled)36. A compound according to wherein Lis —OCHCH—.37. (canceled)38. A compound according to wherein Ris chosen ...

CERTAIN (2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE 1 INHIBITORS

The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), 112.-. (canceled)21. The method of claim 13 , wherein the compound is present in a sterile solution claim 13 , suspension or emulsion.22. The method of claim 19 , wherein the compound is present in a sterile solution claim 19 , suspension or emulsion.23. The method of claim 22 , wherein administering comprises parenteral administration.24. The method of claim 23 , wherein the parenteral administration is intravenous claim 23 , subcutaneous claim 23 , intramuscular claim 23 , intravascular or infusion administration.25. The method of claim 24 , wherein the parenteral administration is intravenous administration.26. The method of claim 13 , wherein administering comprises oral administration.27. The method of claim 19 , wherein administering comprises oral administration. This application is a continuation of U.S. application Ser. No. 16/855,522, filed Apr. 22, 2020, which is a continuation of U.S. application Ser. No. 16/358,091, filed Mar. 19, 2019, now U.S. Pat. No. 10,669,245, which is a continuation of U.S. application Ser. No. 15/708,634, filed Sep. 19, 2017, now U.S. Pat. No. 10,287,258, which is a continuation of U.S. application Ser. No. 15/346,411, filed Nov. 8, 2016, now U.S. Pat. No. 9,815,805, which is a continuation of U.S. application Ser. No. 14/601,371, filed Jan. 21, 2015, now U.S. Pat. No. 9,522,894, which claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 61/931,090, filed Jan. 24, 2014. The contents of the foregoing application are hereby incorporated by reference in their entirety.The technical field relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof) that inhibit dipeptidyl peptidase 1 (DPP1; EC 3.4.14.1) activity, to their utility in ...

Azepane derivatives and methods of treating hepatitis b infections

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

1,4 OXAZEPINES AS BACE1 AND/OR BACE2 INHIBITORS

This invention relates to compounds of the formula 2. The compound of claim 1 , wherein Ris F.3. The compound of claim 1 , wherein Ris H.4. The compound of claim 1 , wherein Ris Me.5. The compound of claim 1 , wherein Ris Et.6. The compound of claim 1 , wherein Ris C-cycloalkyl-C-alkyl-.7. The compound of claim 6 , wherein Ris cyclopropyl-CH—.8. The compound of claim 7 , which is (5R claim 7 ,6R)-5-[5-(Cyclopropylmethyl-amino)-2-fluoro-phenyl]-6-fluoro-5-methyl-2 claim 7 ,5 claim 7 ,6 claim 7 ,7-tetrahydro-[1 claim 7 ,4]oxazepin-3-ylamine.9. The compound of claim 1 , wherein Ris —(C═O)—R.10. The compound of claim 9 , wherein Ris pyridinyl substituted by one halogen and one amidyl.11. The compound of claim 10 , which is (R)—N2-(3-(3-amino-6 claim 10 ,6-difluoro-5-methyl-2 claim 10 ,5 claim 10 ,6 claim 10 ,7-tetrahydro-1 claim 10 ,4-oxazepin-5-yl)-4-fluorophenyl)-3-fluoropyridine-2 claim 10 ,5-dicarboxamide formate.12. The compound of claim 9 , wherein Ris pyridinyl substituted by one substituent selected from the group consisting of C-cycloalkyl-C-alkoxy- claim 9 , C-cycloalkyl-C-alkynyl- claim 9 , C-alkoxy-C-alkynyl- claim 9 , unsubstituted heteroaryl and unsubstituted C-cycloalkyl.13. The compound of claim 12 , selected from the group consisting of(R)—N-(3-(3-amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenyl)-6-(cyclopropylmethoxy)picolinamide formate,(R)—N-(3-(3-amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenyl)-5-(thiazol-2-yl)picolinamide formate,(R)—N-(3-(3-amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenyl)-5-(cyclopropylethynyl)picolinamide formate,(R)—N-(3-(3-amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenyl)-5-cyclopropylpicolinamide formate, and(R)—N-(3-(3-amino-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenyl)-5-β-methoxyprop-1-ynyl)picolinamide formate.14. The compound of claim 9 , wherein Ris pyrazinyl ...

NOVEL VIRAL REPLICATION INHIBITORS

The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds. 6. The compound of claim 1 , wherein{'sup': 1', '1a', '1b', '1c', '2', '3', '3', '4', '5', '4', '5', '4', '2', '4', '2', '3', '2', '4', '5, 'sub': 2', '2', '1-6', '1-6', '1-6, 'claim-text': {'sub': 1-6', '1-6', '2', '3', '3', '2', '1-4', '2', '1-4', '1-6, 'and wherein said Calkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, ═O, —O—C(O)Me, cyano, —C(O)OH, —C(O)OCalkyl, —NH, —NHCH; —N(CH), —NH—C(═O)O—Calkyl; —S(O)Calkyl, and —O—Calkyl;'}, 'each Z, Z, Z, and Zis independently selected from the group consisting of halogen, hydroxyl, —OZ, —O—C(═O)Z, ═O, —S(═O)Z, —S(═O)NZZ, trifluoromethyl, trifluoromethoxy, —NZZ, —NZC(═O)Z, —NZC(═O)—OZ, cyano, —C(═O)Z, —C(═O)OZ, —C(═O)NZZ, Calkyl, heteroCalkyl, aryl, heterocycle, and heterocycle-Calkyl;'}{'sup': '2', 'sub': 1-6', '1-6, 'claim-text': {'sub': 1-6', '1-6', '2', '1-4', '1-4', '2', '3', '2, 'wherein said Calkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, —O—Calkyl, —S(═O)Calkyl, —C(═O)OH, —C(═O)O—Calkyl, —NH, and —N(CH), pyrrolidinyl, piperidinyl, and piperazinyl;'}, 'each Zis independently selected from ...

CERTAIN (2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE 1 INHIBITORS

The present disclosure relates to certain (2S)-N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), 112-. (canceled)14. A pharmaceutical composition comprising a compound of formula (I) as claimed in and a pharmaceutically acceptable adjuvant claim 13 , diluent or carrier.15. A method of treating an obstructive disease of the airway claim 13 , which comprises administering to the patient a therapeutically effective amount of a compound of formula (I) as claimed in .16. A method of treating asthma or chronic obstructive pulmonary disease in a patient suffering from said disease claim 13 , which comprises administering to the patient a therapeutically effective amount of a compound of formula (I) as claimed in .17. The method of claim 15 , wherein administering comprises oral administration.18. The method of claim 16 , wherein administering comprises oral administration. This application is a continuation of U.S. application Ser. No. 15/346,411, now U.S. Pat. No. 9,815,805, filed on Nov. 8, 2016, which is a continuation of U.S. application Ser. No. 14/601,371, now U.S. Pat. No. 9,522,894, filed on Jan. 21, 2015, which claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 61/931,090, filed Jan. 24, 2014. The contents of the foregoing applications are hereby incorporated by reference in their entirety.The technical field relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof) that inhibit dipeptidyl peptidase 1 (DPP1; EC 3.4.14.1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.Dipeptidyl peptidase 1 (DPP1; EC 3.4.14.1), also ...

SUBSTITUTED BENZAMIDES

The invention relates to compounds of formula 2. The compound of claim 1 , wherein X is NR′ and R′ is hydrogen.34-. (canceled)5. The compound of claim 1 , wherein X is a bond.622-. (canceled)23. The compound of claim 1 , wherein X is —(CH)—O—.2425-. (canceled)26. The compound of claim 1 , wherein X is —O(CHR″)—.27. (canceled)28. The compound of claim 1 , wherein X is —CHR″—.29. (canceled)30. The compound of claim 1 , wherein X is —CHCH—.3132-. (canceled)33. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically suitable acid addition salt thereof claim 1 , and a pharmaceutically acceptable carrier.34. A compound according to claim 1 , wherein said compound is:(RS)-2-Methyl-N-(4-(morpholin-2-yl)phenyl)thiazole-4-carboxamide hydrochloride;(S)-6-Methyl-N-(4-(piperidin-3-yl)phenyl)nicotinamide hydrochloride;(S)-5-Methyl-N-(4-(piperidin-3-yl)phenyl)pyrazine-2-carboxamide hydrochloride;(R)-6-Methyl-N-(4-(piperidin-3-yl)phenyl)nicotinamide hydrochloride;(S)-5-Ethyl-N-(4-(piperidin-3-yl)phenyl)pyrazine-2-carboxamide hydrochloride;(S)—N-(4-(Piperidin-3-yl)phenyl)-5-propylpyrazine-2-carboxamide hydrochloride;(S)—N-(4-(Piperidin-3-yl)phenyl)-6-propylnicotinamide;(RS)-2-Methyl-N-(4-(morpholin-2-yl)phenyl)isonicotinamide dihydrochloride;(RS)-2,6-Dimethyl-N-(4-(morpholin-2-yl)phenyl)isonicotinamide dihydrochloride; or(S)-6-Ethyl-N-(4-(piperidin-3-yl)phenyl)nicotinamide.35. A pharmaceutical composition claim 34 , comprising a therapeutically effective amount of a compound according to claim 34 , or a pharmaceutically suitable acid addition salt thereof claim 34 , and a pharmaceutically acceptable carrier. This application claims the benefit of European Patent Application No. 09180504.4, filed Dec. 22, 2009, which is hereby incorporated by reference in its entirety.Some of the physiological effects (i.e. cardiovascular effects, hypotension, induction of sedation) which have been reported for ...

CERTAIN (2S)-N-[(1S)-1-CYANO-2-PHENYLETHYL]-1,4-OXAZEPANE-2-CARBOXAMIDES AS DIPEPTIDYL PEPTIDASE 1 INHIBITORS

The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), 112.-. (canceled)21. The method of claim 13 , wherein the obstructive disease of the airway is due to a coronavirus infection.22. The method of claim 13 , wherein the obstructive disease of the airway is due to an influenza infection.23. The method of claim 14 , wherein the obstructive disease of the airway is due to a coronavirus infection.24. The method of claim 14 , wherein the obstructive disease of the airway is due to an influenza infection.25. The method of claim 15 , wherein the obstructive disease of the airway is due to a coronavirus infection.26. The method of claim 15 , wherein the obstructive disease of the airway is due to an influenza infection.27. The method of claim 16 , wherein the obstructive disease of the airway is due to a coronavirus infection.28. The method of claim 16 , wherein the obstructive disease of the airway is due to an influenza infection.29. The method of claim 17 , wherein the obstructive disease of the airway is due to a coronavirus infection.30. The method of claim 17 , wherein the obstructive disease of the airway is due to an influenza infection.31. The method of claim 18 , wherein the obstructive disease of the airway is due to a coronavirus infection.32. The method of claim 18 , wherein the obstructive disease of the airway is due to an influenza infection.33. The method of claim 19 , wherein the obstructive disease of the airway is due to a coronavirus infection.34. The method of claim 19 , wherein the obstructive disease of the airway is due to an influenza infection.35. The method of claim 20 , wherein the obstructive disease of the airway is due to a coronavirus infection.36. The method of claim 20 , wherein the obstructive disease of the airway is due to an influenza infection.37. The method of claim 21 , wherein the coronavirus is a SARS coronavirus. ...

THERAPEUTIC COMPOUNDS AND COMPOSITIONS

Provided are aryl sulfonamide diarylurea derivative compounds that are inhibitors of mutant isocitrate dehydrogenase 1/2 (IDH 1/2), useful for treating cancer. Also provided are methods of treating cancer comprising administering to a subject in need thereof a compound described herein. Cancers that are treatable by the compounds of the invention are glioblastoma, myelodysplastic syndrome, myeloproliferative neoplasm, acute myelogenous leukemia, sarcoma, melanoma, non-small cell lung cancer, chondrosarcoma, and non-Hodgkin's lymphoma (NHL). 5. The compound of claim 1 , wherein the compound is selected from Table 1.6. The compound of claim 1 , wherein the compound is selected from Table 2.7. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.8. The composition of claim 7 , further comprising a second therapeutic agent useful in the treatment of cancer.9. A method of treating a cancer characterized by the presence of an IDH2 mutation claim 7 , wherein the IDH2 mutation results in a new ability of the enzyme to catalyze the NAPH-dependent reduction of α-ketoglutarate to R(−)-2-hydroxyglutarate in a patient claim 7 , comprising the step of administering to the patient in need thereof a composition of .10. The method of claim 9 , wherein the IDH2 mutation is an IDH2 R140Q or R172K mutation.11. The method of claim 10 , wherein the IDH2 mutation is an IDH2 R140Q mutation.12. The method of claim 11 , wherein the cancer is selected from glioblastoma (or glioma) claim 11 , myelodysplastic syndrome (MDS) claim 11 , myeloproliferative neoplasm (MPN) claim 11 , acute myelogenous leukemia (AML) claim 11 , sarcoma claim 11 , melanoma claim 11 , non-small cell lung cancer claim 11 , chondrosarcoma claim 11 , cholangiocarcinomas or angioimmunoblastic non-Hodgkin's lymphoma (NHL).13. A method of treating a cancer characterized by the presence of an IDH1 mutation claim 7 , wherein the IDH1 mutation results in a new ability of the ...

NOVEL VIRAL REPLICATION INHIBITORS

The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds. 4. (canceled)6. (canceled)7. A method of treatment or prevention of a flavivirus infection in an animal claim 1 , mammal or human claim 1 , comprising administrating an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , optionally in combination with one or more other medicines claim 1 , to an animal claim 1 , mammal or human in need thereof.8. (canceled)12. (canceled)14. (canceled)15. The method according to claim 9 , wherein the flavivirus infection is an infection with a Dengue virus or a yellow fever virus.16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier claim 1 , and as active ingredient an effective amount of the compound according to or a pharmaceutically acceptable salt thereof.17. A method for the preparation of the compound according to comprising the step ofreacting an imine with an aldehyde under umpolung conditions in the presence of a thiazolium catalyst to obtain the desired compounds of the invention; orreacting a ketone derivative having a methylene adjacent to the carbonyl under halogenation conditions to obtain an alpha-halogenoketone, andsubstitute the previously obtained alpha- ...

Cyclic amines

The present invention is directed to novel cyclic amines which inhibit the P2X7 receptor.

MORPHOLINE AND 1,4-OXAZEPANE AMIDES AS SOMATOSTATIN RECEPTOR SUBTYPE 4 (SSTR4) AGONISTS

The invention relates to morpholine and 1,4-oxazepane amide derivatives of general formula (I), which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture of the compounds according to the invention.

MORPHOLINE AND 1,4-OXAZEPANE AMIDES AS SOMATOSTATIN RECEPTOR SUBTYPE 4 (SSTR4) AGONISTS

The invention relates to morpholine and 1,4-oxazepane amide derivatives of general formula (I), which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture of the compounds according to the invention. 115-. (canceled)17. The compound according to claim 16 , or a pharmaceutically acceptable salt thereof claim 16 , wherein A is H.18. The compound according to claim 16 , or a pharmaceutically acceptable salt thereof claim 16 , wherein{'sup': '3', 'W is selected from the group consisting of a monocyclic aryl, a monocyclic heteroaryl and a monocyclic heterocyclyl, wherein each of these ring systems is optionally substituted with one or more R, and wherein the heteroaryl comprises up to 4 heteroatoms and one or two 5- or 6-membered ring(s).'}21. The compound according to claim 16 , or a pharmaceutically acceptable salt thereof claim 16 , whereinm is 0, p is 1 and q is 1, orm is 1, p is 1 and q is 1.22. The compound according to claim 16 , or a pharmaceutically acceptable salt thereof claim 16 , wherein{'sup': '3', 'sub': 1-3', '3-6', '1-3, 'claim-text': [{'sup': 3', '3, 'sub': 1-3', '3-6, 'wherein, in case Ris connected to N-atoms of W, Ris selected from the group consisting of C-alkyl and C-cycloalkyl,'}, {'sub': 1-3', '3-6', '1-3, 'wherein the C-alkyl, C-cycloalkyl, and the C-alkyl-O-substituents are optionally substituted with halogens.'}], 'Ris selected from the group consisting of C-alkyl, C-cycloalkyl, C-alkyl-O—, halogen, NC—,'}23. The compound according to claim 16 , or a pharmaceutically acceptable salt thereof claim 16 , wherein{'sup': '3', 'sub': 3', '3, 'claim-text': {'sup': 3', '3, 'sub': '3', 'wherein, Ris HC— when Ris connected to N-atoms of W.'}, 'Ris selected from the group consisting of HC—, F— and FC—,'}24. The compound according to claim 16 , or a ...

Compounds Useful for Treating a Mannheimia Haemolytica or Histophilus Somni Infection

The present invention discloses compounds of formula (I) that are useful in the treatment of respiratory diseases of animals, especially Bovine or Swine Respiratory disease (BRD and SRD). 120-. (canceled)22. The compound according to claim 21 , wherein R claim 21 , Rare independently selected from the group consisting of{'sub': 1-6', '2-6', '3-10', '1-6', '1-6', '1', '6', '1', '6', '2, 'sup': 6', '7, 'H, C-alkyl, C-alkenyl, C-cycloalkyl, C-alkyloxy-C-alkyl, C-C-alkyl substituted with aryl, C-C-alkyl substituted with heteroaryl, or NRRis NOor'}{'sup': 6', '7, 'claim-text': {'sup': 6', '7, 'wherein the alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, alkyloxy or the heterocyclic ring formed by R, Rtogether with the N atom to which they are attached is optionally substituted with a substituent selected from the group consisting of'}, 'R, Rtogether with the N atom to which they are attached can form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein 1 ring atom is N and wherein 0, 1, 2, or 3 further ring atoms are selected from N, S, and O;'}{'sub': 1-6', '3-8', '1-6', '1-6', '1-6', '1-6', '1', '6', '2', '2', '1-6, 'sup': 9', '10', '9', '8', '8', '9', '10', '9', '10, 'C-alkyl, C-cycloalkyl, C-alkyloxy, —NRR, carbonyl, —C(═O)—OR, halogen atom, C-alkyl substituted with halo, C-alkyloxy-C-alkyl, aryl, heteroaryl, C-C-alkyl substituted with aryl, cyano, hydroxy, —SR, —SOR, —SONRR, —C(═O)NRR, C-alkyl substituted with hydroxyl.'}23. The compound according to claim 21 , wherein L is selected from the group consisting of{'sub': 1-6', '2-6', '2-6', '3-10, 'sup': 'L3', 'C-alkyl, C-alkenyl, C-alkynyl, C-cycloalkyl, —NR—,'} [{'sup': 'L3', 'R, is selected from the group consisting of'}, {'sub': 1-6', '1-6', '1', '6', '1', '6', '1', '6, 'H, C-alkyl, halo-C-alkyl, C-C-alkyl substituted with aryl, C-C-alkyl substituted with heteroaryl, C-C-alkyl substituted with heterocyclyl.'}], 'wherein'}24. The compound according to f claim 21 , wherein L is selected from ...

Substituted 1-aminoalkyllactams and their use as muscarinic receptor antagonists

This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula I: wherein X, Y, and Z are O, S or NR<SUP>5</SUP>, and the other substituents are as defined in the specification; and prodrugs, individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents.

Substituted 1-aminoalkyl lactames, pharmaceutical composition based on thereof and method for their preparing

FIELD: organic chemistry, medicine. SUBSTANCE: invention describes a compound of the general formula (I): wherein R 1 , R 2 and R 3 mean independently in each case hydrogen, halogen atom, (C 1 -C 6 )-alkyl, -OR', -SR', -NR'R'', -SOR', -SO 2 R', -COOR', -OCOR', -OCONR'R'', -OSO 2 R', -OSO 2 NR'R'', -NR'SO 2 R''. -NR'COR'', -SO 2 NR'R'', -SO 2 (CH) 1-3 CONR'R'', -CONR'R'', cyano-group, halogenalkyl or nitro-group; or if R 1 and R 2 if there are adjacent then in common with carbon atom to which they are bound can form 5-7-membered aromatic, saturated or unsaturated cycle optionally comprising one or two ring heteroatoms taken among nitrogen atom (N), S(O) 0-2 or oxygen atom (O), and optionally substituted with (C-C 6 )-alkyl, halogen atom, cyano-group or (lower)-alkoxy-group; R' and R'' mean independently in each case hydrogen atom, (C 1 -C 6 )-alkyl, substituted (C 1 -C 6 )-alkyl, (C 0 -C 3 )-alkylalkoxy-group, aryl, heterocyclyl, heteroaryl, aryl-(C 1 -C 3 )-alkyl, heteroaryl-(C 1 -C 3 )-alkyl, heterocyclyl-(C 1 -C 3 )-alkyl, cycloalkylalkyl, cycloalkyl; or R' and R'' in common with nitrogen atom to which they are bound can form also 5-7-membered cycle optionally comprising one additional ring heteroatom taken among nitrogen (N), oxygen (O) atom or S(O) 0-2 ; in each case R 4 means (C 1 -C 6 )-alkyl; R 5 means independently in each case (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkenyl or cycloalkyl; one among X, Y or Z means independently -S-, -O-, -CH 2 - or ›N-R 6 and others mean -CH 2 -; R 6 means hydrogen atom, (C 1 -C 6 )-alkyl, halogen alkyl, aryl-(C 1 -C 6 )-alkyl, heteroaryl-(C 1 -C 6 )-alkyl, -(C 1 -C 6 )-CR'R'R', -COOR', -SO 2 R', -C(O)R', -SO 2 (CH 2 ) 0-3 -NR'R'', -CONR'R'', -C(O)OCH 2 OC(O)R', -C(O)-CH 2 -S-C(O)R' or PO(OR') 2 wherein R&# ...

胍化合物

本发明提供作为药物组合物、特别是作为VAP-1相关疾病的预防和／或治疗用药物组合物的有效成分有用的化合物。本发明人对于具有VAP-1抑制活性的化合物进行了广泛深入的研究，结果发现，本发明化合物或其盐显示优异的VAP-1抑制活性，对于VAP-1相关疾病、特别是糖尿病性肾病或糖尿病性黄斑水肿的预防和／或治疗有用，并完成了本发明。另外，本发明涉及含有本发明化合物或其盐和赋形剂的药物组合物，特别是VAP-1相关疾病的预防和／或治疗用药物组合物。

3-hydroxybutyric acid polymers

Guanidine compound

본 발명은, 의약 조성물, 특히, VAP-1 관련 질환의 예방 및/또는 치료용 의약 조성물의 유효 성분으로서 유용한 화합물을 제공한다. 본 발명자들은, VAP-1 저해 활성을 갖는 화합물에 대해서 예의 검토한 결과, 본 발명 화합물 또는 그의 염이, 우수한 VAP-1 저해 활성을 나타내어, VAP-1 관련 질환, 특히 당뇨병성 신증 혹은 당뇨병성 황반 부종의 예방 및/또는 치료에 유용한 것을 발견하여, 본 발명을 완성하였다. 또한, 본 발명은, 본 발명 화합물 또는 그의 염, 및 부형제를 함유하는 의약 조성물, 특히, VAP-1 관련 질환의 예방 및/또는 치료용 의약 조성물에 관한 것이다. The present invention provides a compound useful as an active ingredient of a pharmaceutical composition, particularly, a pharmaceutical composition for the prevention and / or treatment of VAP-1 related diseases. The present inventors have intensively studied a compound having VAP-1 inhibitory activity and found that the compound of the present invention or a salt thereof exhibits excellent VAP-1 inhibitory activity and is useful as a therapeutic agent for VAP-1 related diseases, particularly diabetic nephropathy or diabetic macular Which is useful for prevention and / or treatment of edema, thereby completing the present invention. The present invention also relates to a pharmaceutical composition containing the compound of the present invention or a salt thereof and an excipient, and particularly to a pharmaceutical composition for the prevention and / or treatment of VAP-1 related diseases.

Apoptosis promoters

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member.

Apoptosis promoters

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member.

Substituted 1-aminoalkyl-lactams compound and their use as muscarinic receptor antagonists

本发明涉及通常是M2/M3毒蕈碱受体拮抗剂的通式(I)化合物，其中X、Y或Z当中有一个独立地为-S-、-O-、-CH 2 -或＞N-R 4 ，其它的为-CH 2 -；p是0-3并包括0和3的整数；m是0-3并包括0和3的整数；n是1-6并包括1和6的整数；R 3 是(C 1-6 )-烷基、(C 1-6 )-链烯基、(C 1-6 )-炔基或环烷基；且R 1 、R 2 和R 3 是氢或特定的取代基。这些化合物可用于治疗与平滑肌障碍有关的疾病。

Patent IN139006B

Substituted 1-aminoalkyl-lactams and their use as muscarinic receptor antagonists

본 발명은 일반적으로 무스카린성 M2/M3 수용체 길항제로서 하기 화학식 I의 화합물에 관한 것이다: 화학식 I 상기 식에서, X, Y 또는 Z중 하나는 독립적으로 -S-, -O- 또는 >N-R 4 이고 나머지 둘은 -CH 2 -이고; p는 0 내지 3의 정수이고; m은 0 내지 3의 정수이고; n은 1 내지 6의 정수이고; R 3 은 (C 1-6 )-알킬, (C 1-6 )-알케닐, (C 1-6 )-알키닐 또는 사이클로알킬이고; R 1 , R 2 및 R 3 은 수소 또는 특정한 치환체이다. 상기 화합물은 평활근 장애와 관련된 질병을 치료하는데 유용하다.

Novel viral replication inhibitors

The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.

P38α mitogen-activated protein kinase inhibitors

Disclosed herein are p38α mitogen-activated protein kinase inhibitors, pharmaceutical compositions thereof, and therapeutic methods of using the p38α mitogen-activated protein kinase inhibitors.

Viral replication inhibitors

The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.

p38α mitogen-activated protein kinase inhibitors

Disclosed herein are p38α mitogen-activated protein kinase inhibitors, pharmaceutical compositions thereof, and therapeutic methods of using the p38α mitogen-activated protein kinase inhibitors.

Antagonists of the GPR39 protein

인간 GPR39 단백질에 대한 길항제로서 작용하는 신규 화합물이 개시되어 있다. 인간 GPR39 단백질에 대한 길항제의 제약 조성물 및 사용 방법이 개시된다. 특히, 심혈관 상태, 내분비계 및 호르몬 장애, 암 장애, 대사 질환, 위장 및 간 질환, 혈액 장애, 신경계 장애 및 호흡기 질환을 비롯한 질환 또는 상태의 치료에서 길항제를 사용하는 방법이 본원에 개시된다.

2,5,6,7-tetrahydrochysene-[Isosorbide-5-Nitrae] oxygen azepine *-3-base amine or 2,3,6,7-tetrahydrochysene-[Isosorbide-5-Nitrae] oxygen azepine *-5-ylamine compounds

本发明涉及式(I)的化合物或其药用盐，其中A、B和R 1 至R 7 如下所述。这些化合物是BACE1和/或BACE2抑制剂，并且可以用作用于疾病如阿尔茨海默病、糖尿病、尤其是II型糖尿病，以及其他代谢性疾病的治疗性和/或预防性治疗的药物。

Substituted 1-aminoalkyl-lactams compound and their use as muscarinic receptor antagonists

本发明涉及通常是M2/M3毒蕈碱受体拮抗剂的式(I)化合物，其中X、Y或Z当中有一个独立地为-S-、-O-、-CH 2 -或＞N-R 6 ，其它的为-CH 2 -；m是0-3并包括0和3的整数；n是1-6并包括1和6的整数；R 4 是(C 1-6 )-烷基；R 5 在每次出现时分别独立地为(C 1-6 )-烷基、(C 1-6 )-链烯基、(C 1-6 )-炔基或环烷基；且R 1 、R 2 和R 3 是氢或特定的取代基。这些化合物可用于治疗与平滑肌障碍有关的疾病。

Substituted benzamide derivatives

本発明は、式［式中、 Ｒは、水素または低級アルキルであり； Ｒ １ は、−（ＣＨ ２ ） ｎ −（Ｏ） ｏ −ヘテロシクロアルキル又は−Ｃ（Ｏ）−ヘテロシクロアルキル（ここで、ヘテロシクロアルキル基は、低級アルキル、ヒドロキシ、ハロゲンで、又は−（ＣＨ ２ ） ｐ −アリール）で、場合により置換されている）であり； ｎは、０、１又は２であり； ｏは、０又は１であり； ｐは、０、１又は２であり； Ｒ ２ は、ＣＦ ３ 、低級アルコキシ若しくはハロゲンで場合により置換されているシクロアルキルであるか、又はインダン−２−イルであるか、ヘテロアリールで場合により置換されているヘテロシクロアルキルであるか、又は、 アリール又はヘテロアリール（ここで芳香族環は、低級アルキル、ハロゲン、ヘテロアリール、ヒドロキシ、ＣＦ ３ 、ＯＣＦ ３ 、ＯＣＨ ２ ＣＦ ３ 、ＯＣＨ ２ −シクロアルキル、ＯＣＨ ２ Ｃ（ＣＨ ２ ＯＨ）（ＣＨ ２ Ｃｌ）（ＣＨ ３ ）、Ｓ−低級アルキル、低級アルコキシ、ＣＨ ２ −低級アルコキシ、低級アルキニルもしくはシアノから選択される１つもしくは２つの置換基で、又はＣ（Ｏ）−フェニル、−Ｏ−フェニル、−Ｏ−ＣＨ ２ −フェニル、フェニルもしくは−ＣＨ ２ −フェニルで、場合により置換されており、そしてここでフェニル環は、ハロゲン、−Ｃ（Ｏ）−低級アルキル、−Ｃ（Ｏ）ＯＨ又は−Ｃ（Ｏ）Ｏ−低級アルキルで、場合により置換されていてよく、 あるいは芳香族環は、低級アルキルで場合により置換されている、ヘテロシクロアルキル、ＯＣＨ ２ −オキセタン−３−イル又はＯ−テトラヒドロピラン−４−イルで、場合により置換されている）であり； Ｘは、結合、−ＮＲ’−、−ＣＨ ２ ＮＨ−、−ＣＨＲ”−、−（ＣＨＲ”） ｑ −Ｏ−、−Ｏ−（ＣＨＲ”） ｑ −又は−（ＣＨ ２ ） ２ −であり； Ｙは、結合又は−ＣＨ ２ −であり、 Ｒ’は、水素又は低級アルキルであり、 Ｒ”は、水素、低級アルキル、ＣＦ ３ 、低級アルコキシであり、 ｑは、０、１、２又は３である］の化合物又はその薬学的に適切な酸付加塩に関する。 式Ｉの化合物が、微量アミン関連受容体（ＴＡＡＲ）、特にＴＡＡＲ１に対し、良好な親和性を有することが今や見出された。本化合物は、鬱病、不安障害、双極性障害、注意欠陥多動性障害（ＡＤＨＤ）、ストレス関連障害、精神障害、例えば統合失調症、神経疾患、例えばパーキンソン病、神経変性障害、例えば、アルツハイマー病、癲癇、偏頭痛、高血圧、物質濫用、並びに代謝性障害、例えば、摂食障害、糖尿病、糖尿病合併症、肥満、脂質異常症、エネルギー消費及び同化の障害、体温恒常性の障害及び機能不全、睡眠及び概日リズムの障害、並びに心血管障害の処置のために使用し得る。

Substituted benzamide derivatives

【課題】中枢神経に関連した疾患の治療等に有効な微量アミン関連受容体（ＴＡＡＲ）、特にＴＡＡＲ１に対し、良好な親和性を有する化合物の提供。 【解決手段】式（Ｉ）で表される置換されたベンズアミド誘導体。 【効果】前記ベンズアミド誘導体は、アドレナリン受容体よりもＴＡＡＲ１受容体に対して選択性を有し、鬱病、不安障害、双極性障害、注意欠陥多動性障害（ＡＤＨＤ）、ストレス関連障害、精神障害、例えば統合失調症、神経疾患、例えばパーキンソン病、神経変性障害、例えば、アルツハイマー病、癲癇、偏頭痛、高血圧、物質濫用、並びに代謝性障害、例えば、摂食障害、糖尿病、糖尿病合併症、肥満、脂質異常症、エネルギー消費及び同化の障害、体温恒常性の障害及び機能不全、睡眠及び概日リズムの障害、並びに心血管障害の処置のために使用し得る。 【選択図】なし

Substituted benzamides

The invention relates to compounds of formula wherein R, R 1 , R 2 , X, and Y are as defined herein and to a pharmaceutically suitable acid addition salt thereof. Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

Bleaching compositions and additives comprising bleach activators having alpha-modified lactam leaving-groups

Improved cleaning and/or bleaching compositions including fabric laundry and bleaching compositions, automatic dishwashing compositions, hard surface cleaners, bleach additives and the like, suitable for domestic use, comprising improved bleach activators having particular alpha-modified lactam leaving groups leading to improved in-use performance of bleaching agents such as perborate even under wash conditions less alkaline than those typically encountered or when hydrogen peroxide source is at low levels in a cleaning operation.

2-morpholino or homomorpholino 1-3-trifluoromethylphenyl propanes

1394001 2 - (Morpholino or homomorpholino) - 1 - (3 - trifluoromethylphenyl) propanes PFIZER Ltd 19 Dec 1973 [22 Dec 1972] 59360/72 Heading C2C Novel compounds of the Formula I in which R is hydrogen or halogen; R<SP>1</SP> is alkyl; R<SP>3</SP> and R<SP>4</SP> each are hydrogen, alkyl or phenyl; R<SP>5</SP> is hydrogen or alkyl and n is 1 or 2 wherein alkyl groups are C 1-4 groups and non-toxic acid addition salts thereof may be prepared by (1) reacting a compound II with an appropriately substituted morpholine or homomorpholine followed by reduction of the intermediate ethylene derivative; (2) reacting a compound VI wherein X is halogen or an alkyl or arylsulphonyloxy group with the morpholine or homomorpholine; (3) reacting a compound VIII with a 2,2<SP>1</SP>-dichlorodiethyl ether or a substituted derivative thereof ClCHR<SP>5</SP>CHR<SP>4</SP>OCHR<SP>3</SP>CH 2 Cl; (4) reacting a compound of the Formula XVIII with a chloracetylchloride ClCHR 3 COCl, to yield a compound XIX followed by dehydrohalogenation to cyclize to the compound XX followed by reduction of the keto group; (5) reacting a compound of the Formula XVIII with an epoxide X followed by dehydration of the product of the Formula XVI or other equivalent processes. 1 - (3 - Trifluoromethylphenyl) - 2 - p - toluene sulphonyloxypropane may be prepared by esterification of 1 - (3 - trifluoromethylphenyl)- propan-2-ol with p-toluenesulphonylchloride. Pharmaceutical compositions of the compounds I alone or with the usual excipients may be administered orally or parenterally to reduce the appetite.

Guanidine compound

Morpholine and 1,4-oxazepane amides as somatostatin receptor subtype 4 (SSTR4) agonists

The invention relates to morpholine and 1,4-oxazepane amide derivatives of general formula (I), which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture of the compounds according to the invention.

Substituted 1-aminoalkyl-lactams compound and their use as muscarinic receptor antagonists

本发明涉及通常是M2/M3毒蕈碱受体拮抗剂的式(I)化合物，其中X、Y或Z当中有一个独立地为－S－、－O－、－CH 2 －或＞N－R 6 ，其它的为－CH 2 －；m是0－3并包括0和3的整数；n是1－6并包括1和6的整数；R 4 是(C 1－6 )－烷基；R 5 在每次出现时分别独立地为(C 1－6 )－烷基、(C 1－6 －链烯基、(C 1－6 )－炔基或环烷基；且R 1 、R 2 和R 3 是氢或特定的取代基。这些化合物可用于治疗与平滑肌障碍有关的疾病。

Nitric oxide synthase inhibitors derived from cyclic amidines

Compounds having formula (I) wherein R1, R5, R6 and R7 are hydrogen or certain specified substituents; R8 and R9 are independently hydrogen, hydroxy or alkoxy; and X, A and B are independently NR2, O, S, SO, SO2, CH=CH or (CH2)p, p being 0-6; are useful as nitric oxide synthase inhibitors.

AMINOCYCLOPENTANE-ALKENOIC ACIDS AND THEIR ESTERS, THEIR PREPARATION AND THEIR USE IN PHARMACEUTICAL COMPOSITIONS

METHOD FOR PREPARING NEW 7,7-DIPHENYL-HEXAHYDRO-1,4-OXAZEPINES

Patent FR2211251A1

1.3-amino alcohols, their intermediates and derivatives and process for their preparation

1, 4-OXAZEPINES AS BACE1 AND (OR) BACE2 INHIBITORS

1. Соединение формулыв которомRпредставляет собой H или F;Rпредставляет собой C-алкил; иRпредставляет собой -(C=O)-Rили R, гдеRпредставляет собой гетероарил, содержащий один заместитель, выбранный из группы, включающей C-циклоалкил-C-алкоксигруппу, C-циклоалкил-C-алкинил-, C-алкокси-C-алкинил-, незамещенный гетероарил, незамещенный C-циклоалкил и C-алкил-S-, илиRпредставляет собой гетероарил, содержащий в качестве заместителя один галоген и один амидил;Rпредставляет собой C-циклоалкил-C-алкил-;или его фармацевтически приемлемая соль.2. Соединение по п.1, в котором Rпредставляет собой F.3. Соединение по п.1, в котором Rпредставляет собой Н.4. Соединение по п.1, в котором Rпредставляет собой Me.5. Соединение по п.1, в котором Rпредставляет собой Et.6. Соединение по п.1, в котором Rпредставляет собой C-циклоалкил-C-алкил.7. Соединение по п.1, в котором Rпредставляет собой циклопропил-CH.8. Соединение по п.7, представляющее собой (5R,6R)-5-[5-(циклопропилметил-амино)-2-фторфенил]-6-фтор-5-метил-2,5,6,7-тетрагидро-[1,4]оксазепин-3-иламин.9. Соединение по п.1, в котором Rпредставляет собой -(C=O)-R.10. Соединение по п.9, в котором Rпредставляет собой пиридинил, содержащий в качестве заместителя галоген и один амидил.11. Соединение по п.9, представляющее собой (R)-N2-(3-(3-амино-6,6-дифтор-5-метил-2,5,6,7-тетрагидро-1,4-оксазепин-5-ил)-4-фторфенил)-3-фторпиридин-2,5-дикарбоксамид формиат.12. Соединение по п.9, в котором Rпредставляет собой пиридинил, содержащий один заместитель, выбранный из группы, включающей C-циклоалкил-C-алкоксигруппу, C-циклоалкил-C-алкинил, C-алкокси-C-алкинил, незамещенный гетероарил и незамещенный C-циклоалкил.13. Соединение по п.12, выбранное из группы, включающей(R)-N-(3-(3-амино-6,6-дифт РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 267/10 (13) 2013 139 998 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2013139998/04, 13.02.2012 (71) Заявитель(и): Ф.ХОФФМАНН-ЛЯ РОШ АГ (CH), СИЕНА ...

Patent FR2195449B1

Substituted 1−aminoalkyl−lactams and their use as muscarinic receptor antagonists

This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula (I) wherein one of X, Y or Z is independently -S-,-0- CH2- or >N-R<6>, the others are -CH2-; m is an integer from 0 to 3 inclusive; n is an integer from 1 to 6 inclusive; R<4> is (C1-6)-alkyl; R<5> is independently in each occurrence (C1-6)-alkyl, (C1-6)-alkenyl, (C1-6)- alkynyl or cycloalkyl; and R<1>, R<2>, and R<3> are hydrogen or specified substituents. These compounds are useful for treating diseases associated with smooth muscle disorders.

AMINOCYCLOPENTANONE AMIDES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

L'INVENTION CONCERNE DES AMIDES. LES COMPOSES CONFORMES A L'INVENTION REPONDENT A LA FORMULE(1), DANS LAQUELLE R REPRESENTE UN GROUPE CINNAMYLE, NAPHTYL-, THIENYL- OU PHENYL-ALKYLE SUBSTITUE OU NON, R REPRESENTE H, UN GROUPE METHYLE OU ALKYLE SUBSTITUE PAR UN GROUPE ALCOXY OU -COOH, W REPRESENTE UN GROUPE ALKYLENE, X REPRESENTE UN GROUPE CIS OU TRANS -CHCH- OU -CHCH- ET Y REPRESENTE UN GROUPE AMINO HETEROCYCLIQUE SATURE A 5-8CHAINONS, AINSI QUE LES SELS ET SOLVATES DE CES COMPOSES. CES COMPOSES INHIBENT LA THROMBO-AGGLUTINATION ET LA BRONCHOCONSTRICTION ET SERVENT D'AGENTS ANTI-THROMBOTIQUES ET ANTI-ASTHMATIQUES. (CF DESSIN DANS BOPI) THE INVENTION RELATES TO AMIDS. THE COMPOUNDS CONFORMING TO THE INVENTION RESPOND TO FORMULA (1), IN WHICH R REPRESENTS A CINNAMYL, NAPHTYL-, THIENYL- OR PHENYL-ALKYL GROUP SUBSTITUTES OR NOT, R REPRESENTS H, A METHYL OR ALKYL GROUP SUBSTITUTED BY A METHYL OR ALKYL GROUP SUBSTITUTED BY AN ALCOYL GROUP OR -COOH, W REPRESENTS AN ALKYLENE GROUP, X REPRESENTS A CIS OR TRANS -CHCH- OR -CHCH- GROUP AND REPRESENTS A 5-8 CHAIN SATURATED HETEROCYCLIC AMINO GROUP, AS WELL AS THE SALTS AND SOLVATES OF THESE COMPOUNDS. THESE COMPOUNDS INHIBIT THROMBO-AGGLUTINATION AND BRONCHOCONSTRICTION AND SERVE AS ANTI-THROMBOTIC AND ANTI-ASTHMATIC AGENTS. (CF DRAWING IN BOPI)

New imidazoline derivatives and their preparation

Process for preparing aminocyclopentane alkenoic acids and esters thereof

Aminocyclopentane alkenoic acid of formula (1) and their salts and solvates are new. X is cis or trans -CH=CH-; R1 is (CH2)nCOOR3; n is 2-4; R3 is H or C1-3 alkyl; Y is piperidino, morpholino, thiaamorpholino, dioxomorpholino, or homomorpholino; R2 is ph-substd. C3-6 alkenyl or C3-6 alkenyl; R'a is (CH2)nCOOR3, -(CH2)nCH2OH or - (CH2)nCHO; n is 2-4 ; R3 is H or C1-3 alkyl. (I) were prepd. by the oxidation of (II) for use as blood platelet aggregation inhibitors and bronchodilators.

ENANTIOPUR HETEROCYCLIC COMPOUND

Composé hétérocyclique énantiopur de formule (I)dans laquelle J est choisi parmi C, N, O et S ; Z est H ou un groupement protecteur de la fonction amino, R3 désigne H ou un résidu organique m vaut 0, 1 ou 2 et n vaut 0, 1 ou 2 et dans laquelle l'hétérocycle est de préférence substitué par au moins un substituant autre que CH2-COOR3. Enantiopure heterocyclic compound of formula (I) in which J is selected from C, N, O and S; Z is H or a protecting group for the amino function, R3 denotes H or an organic residue m is 0, 1 or 2 and n is 0, 1 or 2 and in which the heterocycle is preferably substituted by at least one other substituent than CH2-COOR3.

Morpholine and 1,4-oxazepane amides as somatostatin receptor subtype 4 (SSTR4) agonists

The invention relates to morpholine and 1,4-oxazepane amide derivatives of general formula (I), which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture of the compounds according to the invention.

Substituted 1-aminoalkyl-lactams and their use as muscarinic receptor antagonists

This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula (I) wherein one of X, Y or Z is independently -S-,-0- CH2- or >N-R6, the others are -CH2-; m is an integer from 0 to 3 inclusive; n is an integer from 1 to 6 inclusive; R4 is (C1-6)-alkyl; R5 is independently in each occurrence (C1-6)-alkyl, (C1-6)-alkenyl, (C1-6)- alkynyl or cycloalkyl; and R1, R2, and R3 are hydrogen or specified substituents. These compounds are useful for treating diseases associated with smooth muscle disorders.

Substituted 1-aminoalkyl-lactams and their use as muscarinic receptor antagonists

THIS INVENTION RELATES TO COMPOUNDS WHICH ARE GENERALLY MUSCARINIC M2/M3 RECEPTOR ANTAGONISTS AND WHICH ARE REPRESENTED BY FORMULAWHEREIN X, Y, AND Z ARE -0-, -8- OR >N-R5, AND THE OTHER SUBSTITUENTS ARE AS DEFINED IN THE SPECIFICATION; OR PRODRUGS, INDIVIDUAL ISOMERS, RACEMIC OR NON- RACEMIC MIXTURES OF ISOMERS, AND PHARMACEUTICALLY ACCEPTABLE SALTS OR SOLVATES THEREOF. THE INVENTION FURTHER RELATES TO PHARMACEUTICAL COMPOSITIONS CONTAINING SUCH COMPOUNDS, PROCESSES FOR THEIR PREPARATION AND THEIR USE FOR TREATING DISEASES ASSOCIATED WITH SMOOTH MUSCLE DISORDERS.

MORPHOLINE DERIVATIVES AND THEIR MANUFACTURE

Cyclic amines

The present invention is directed to novel cyclic amines which inhibit the P2X7 receptor.

Antiseptic

本发明涉及抗菌剂。本发明提供式(I)的抗菌化合物，以及其立体异构体、医药学上可接受的盐、酯和前药；包含这些化合物的医药组合物；通过投与这些化合物来治疗细菌感染的方法；以及制备这些化合物的方法。

1,4-OXAZEPINES AS BACE1 AND (OR) BACE2 INHIBITORS

1. Соединение формулы Iгде Rвыбирают из группы, включающейi) водород,ii) галоген иiii) C-алкил;Rвыбирают из группы, включающейi) водород,ii) C-алкил иiii) галоген-C-алкил;Rвыбирают из группы, включающейi) галоген,ii) водород иiii) C-алкил;Rвыбирают из группы, включающейi) водород иii) галоген;Rвыбирают из группы, включающейi) водород иii) C-алкил;Rвыбирают из группы, включающейi) водород иii) C-алкил;Rвыбирают из группы, включающейi) галоген иii) C-алкил;n равно 0 или 1;Rвыбирают из группы, включающейi) гетероарил,ii) гетероарил, содержащий 1-4 заместителя, индивидуально выбранных из группы, включающей цианогруппу, циано-C-алкил, галоген, галоген-C-алкил, галоген-C-алкоксигруппу, C-алкоксигруппу и C-алкил;iii) гетероарил-CH-,iv) гетероарил-CH-, содержащий 1-4 заместителя, индивидуально выбранных из группы, включающей цианогруппу, циано-C-алкил, галоген, галоген-C-алкил, галоген-C-алкоксигруппу, C-алкоксигруппу и C-алкил;v) арил,vi) арил, содержащий 1-4 заместителя, индивидуально выбранных из группы, включающей цианогруппу, циано-C-алкил, галоген, галоген-C-алкил, галоген-C-алкоксигруппу, C-алкоксигруппу и C-алкил,vii) гетероциклил иviii) гетероциклил, содержащий 1-4 заместителя, индивидуально выбранных из группы, включающей цианогруппу, циано-C-алкил, галоген, галоген-C-алкил, галоген-C-алкоксигруппу, C-алкоксигруппу и C-алкил;или его фармацевтически приемлемые соли.2. Соединение формулы Ia по п.1где Rвыбирают из группы, включающейi) водород,ii) галоген иiii) C-алкил;Rвыбирают из группы, включающейi) водород,ii) C-алкил иiii) галоген-C-алкил;Rвыбирают из группы, включающейi) галоген,ii) водород иiii) C-алкил;Rвыбирают из группы, включающейi) водород иii) галоген;Rвыбирают из группы, включающейi) водород иii РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 267/10 (13) 2013 143 746 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2013143746/04, 15.03.2012 (71) Заявитель(и): Ф. ХОФФМАНН-ЛЯ РОШ АГ (CH), СИЕНА ...

Aminocyclopentane alkenoic acid and esters thereof,manufacture and drug composition

Novel keto-oxadiazole derivatives as cathepsin inhibitors

Disclosed are compounds of formula (Ib), wherein the substituents are as defined in the specification. The compounds are cathepsin inhibitors useful in the treatment of juvenile onset diabetes, multiple sclerosis, pemphigus vulgaris, Graves' disease, myasthenia gravis, systemic lupus erythemotasus, irritable bowel disease, rheumatoid arthritis, Hashimoto's thyroiditis, asthma, obstructive pulmonary disease, emphysema and bronchiolitis.

Novel viral replication inhibitors.

La presente invención se refiere a una serie de compuestos novedosos, métodos para prevenir o tratar infecciones virales en animales utilizando los compuestos novedosos y a compuestos novedosos para su uso como un medicamento, más preferiblemente para su uso como una medicina para tratar o prevenir infecciones virales, particularmente infecciones por virus de ARN, más particularmente infecciones por virus pertenecientes a la familia Flaviviridae, e incluso más particularmente infecciones por el virus del dengue. Más aun, la presente invención se refiere a composiciones farmacéuticas o preparaciones de combinación de los compuestos novedosos, a las composiciones o preparaciones para su uso como un medicamento, más preferiblemente para la prevención o tratamiento de infecciones virales. La invención también se refiere a procesos para la preparación de los compuestos.

2 and 3 substituted-4-heterocyclic aminosulfonyl benzene sulfonamides as vasodilators

PROCEDURE FOR THE PREPARATION OF AMINOCYCLOPENTANIC ACID ACID OR ESTERS THEREOF

Antibacterial agents

Antibacterial compounds of formula (I) are provided, as well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.

NEW LACTAME AND ITS USES

Morpholinone compounds as factor ixa inhibitors

The present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt or a solvate thereof. The present invention also provides pharmaceutical compositions comprising one or more said com-pounds, and methods for using said compounds for treating or preventing a thromboses, embolisms, hypercoagulability or fibrotic changes.

Substituted 1-aminoalkyllactams and their use as muscarinic receptor antagonists

(57)【要約】 本発明は、一般的にムスカリン性Ｍ２／Ｍ３受容体アンタゴニストであり、式（Ｉ）（式中、Ｘ、Ｙ又はＺのうちの１個は、独立して−Ｓ−、−Ｏ−、−ＣＨ 2 −又は＞Ｎ−Ｒ 6 であり、その他は−ＣＨ 2 −であり；ｍは、０〜３の整数であり；ｎは、１〜６の整数であり；Ｒ 4 は（Ｃ 1-6 ）アルキルであり；Ｒ 5 は、それぞれの場合に独立して（Ｃ 1-6 ）アルキル、（Ｃ 1-6 ）アルケニル、（Ｃ 1-6 ）アルキニル又はシクロアルキルであり；そしてＲ 1 、Ｒ 2 及びＲ 3 は、水素又は特定の置換基である）で表される化合物に関する。これらの化合物は、平滑筋障害に関連する疾患の処置に有用である。