2-АМИНОБЕНЗОКСАЗОЛКАРБОКСАМИДЫ В КАЧЕСТВЕ МОДУЛЯТОРОВ 5-НТ3

Изобретение относится к соединениям общей формулы II, где R1, R2 и R3 независимо выбраны из группы, состоящей из водорода, галогена и низшего алкила, содержащего 1-6 атомов углерода; R4 представляет собой остаток, представленный в формуле изобретения; R5 представляет собой водород или метил; R10 выбран из группы, состоящей из: (i) водорода; (ii) (C1-С10)алкила; (iii) (С1-С10)алкила, замещенного одним или несколькими заместителями, независимо выбранными из группы, состоящей из -N(СН3)2, морфолинила, (C1-C4)алкокси, гидроксила, -CON(CH3)2 и галогена; (iv) моноциклического (С3-C8)циклоалкила, содержащего один гетероатом N; (v) 9-метил-9-азабицикло[3.3.1]нонана; (vi) фенила; (vii) фенила, замещенного одним или несколькими (С1-С4)алкокси; R11 выбран из группы, состоящей из водорода и (С1-С10)алкила; или R10, R11 и атом азота, к которому они присоединены, взятые вместе, образуют азотистый гетероцикл или замещенный азотистый гетероцикл, такие, как представлены в формуле изобретения. Также изобретение ...

ЛИГАНДЫ ДЛЯ G-БЕЛОК СОПРЯЖЕННЫХ РЕЦЕПТОРОВ

Изобретение относится к соединению общей формулы (I), его солям и сольватам в качестве лигандов для G-белок сопряженных рецепторов ! ! а также к библиотеке, состоящей из элементов, которые представляют собой соединения формулы (I). В общей формуле (I) у равно 1 или 2; z равно 0; X представляет собой -CO-(Y)k-(R1)n или SO2-(Y)k-(R1)n; k равно 0; каждый R1 независимо выбран из водорода или алкила, галоалкила, алкокси, галоалкокси, алкенила, алкинила, алкиламино, алкиламиноалкила, алкиламинодиалкила, имеющего заряд алкиламинотриалкила или имеющего заряд алкилкарбоксилата из 1-20 атомов углерода; или каждый R1 независимо выбран из фтора, хлора, брома, йода, гидрокси, оксиалкила, амино, аминоалкила, аминодиалкила, имеющего заряд аминотриалкила или карбоксилат радикала; n является целым числом от 1 до m, где m представляет собой максимальное число допустимых заместителей; R1 содержит атом углерода, следующий за карбонильной группой карбонамида или сульфонильной группой сульфаниламида, который ...

ПРОИЗВОДНЫЕ 1,2,5-ТИАДИАЗОЛА, ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ, СПОСОБЫ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ

Описываются новые производные 1,2,5-тиадиазола или его кватернизованная форма, выбранные из соединений, имеющих общую формулу I, в которой W представляет кислород или серу; R выбран из группы, состоящей из водорода, галогена, R4, -OR4, -SR4, -SO2R4 и -Z-C4-12-(циклоалкилалкила); R4 выбран из группы, состоящей из C1-15-алкила, С2-15-алкенила и С2-15-алкинила, каждый из которых необязательно замещен одним или более заместителями, независимо выбранными из группы, состоящей из галогена, -CF3, фенила и фенокси, в которой фенил и фенокси необязательно замещен одним или более заместителями, независимо выбранными из группы, состоящей из галогена, - CN, С1-4 -алкила, C1-4-алкокси, -OF3, -СF3; или R выбран из группы, состоящей из -OR5Y, -SR5Y, OR5-Z-Y, -SR5ZY, -O-R5 Z-R4 и Z представляет кислород или серу; R5 представляет С1-15-алкил; Y представляет 5- или 6-членную гетероциклическую группу, выбранную из тиенила, пиридила и тиазолидонила; G выбран из азациклических или азабициклических кольцевых ...

ПТЕРИДИНОВЫЕ СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ ПСОРИАЗА

... 1. Соединение формулы (I) или его фармацевтически приемлемая соль или сольват в которой А представляет собой группу формулы (а) или (b) R1 представляет собой С3-С7 карбоциклическую, C1-C8 алкильную, С2-С6 алкенильную или C2-C6 алкинильную группу, последние четыре группы необязательно замещены одним или более заместителей, независимо выбранных из атомов галогенов, -OR4, -NR5R6, -CONR5R6, -COOR7, -NR8COR9, -SOR10, -SO2R10, -SO2NR5R6, -NR8SO2R10, арильную или гетероарильную группу, каждая из которых может быть необязательно замещена одним или более заместителей, независимо выбранных из атомов галогенов, циано, нитро, -OR4, -NR5R6, -CONR5R6, -COOR7, -NR8COR10, -SR10, -S02R10, -SO2NR5R6, -NR8SO2 R10, C1-С6 алкильной или трифторметильной групп; один из R2 и R3 представляет собой водород, а другой представляет собой С3-С4 алкил, замещенный одной или более гидроксильными группами; R4 представляет собой водород, C1-C6 алкильную или фенильную группу, из которых две последние могут быть необязательно ...

1,1-DIARYL-1-OXADIAZOL-ALKYLAMINE

VERFAHREN ZUR SYNTHESE VON N-ALKYLIERTER ALPHA-AMINOSAEURE UND DEREN ESTERN, VERWENDUNG BEI DER SYNTHESE VON CARBOXYALKYLDIPEPTIDEN.

Oxadiazole zur Verwendung in der Behandlung von Dementia Senilis.

VERFAHREN ZUR HERSTELLUNG VON BASISCHEN ACYLAMIDEN VON (5-AMINO-1,3-DIALKYLPYRAZOL-4-YL) (ARYL)METHANONEN

Tricyclische Verbindungen.

PYRAZOLIDIN-1,2-DICARBONSÄURE-1-((PHENYL)-AMID)-2-((PHENYL)-AMID) DERIVATE ALS KOAGULATIONSFAKTOR XA INHIBITOREN ZUR BEHANDLUNG VON THROMBOSEN

Spirocyclische Verbindungen mit zwei Heteroatome enthaltenden fünfgliedrigen Ringen.

SUBSTITUIERTE HARNSTOFFE, HERSTELLUNG UND VERWENDUNG

AZABICYCLOVERBINDUNG, MATRIXMETALLPROTEASEINHIBITOR UND ZUBEREITUNG FÜR HAUT

Verfahren zur Herstellung von neuen N'-substituierten N-Arylsulfonylharnstoffen

Isochinuclidinderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende therapeutische Mittel gegen Hypercholesterinämie

Die Erfindung betrifft neue therapeutische Mittel aus Isochinuclidinderivaten, die durch die folgende Formel dargestellt werden DOLLAR F1 oder ihre pharmakologisch verträglichen Salze, insbesondere ihre Hydrochloridsalze (worin R¶1¶ Wasserstoff, eine Carboxylgruppe, eine Ethoxycarbonylgruppe, eine 4-(Ethoxycarbonyl)phenylgruppe, eine 4-(Carboxy)phenylgruppe, eine 2-(Carboxy)thiophen-5-ylgruppe, eine Chinolin-5-ylgruppe, eine 4-(Chinolin-5-yl)phenylgruppe oder eine 4-(3-Oxo-2-azabicyclo[2.2.2]octan-2-yl)phenylgruppe bedeutet, R¶2¶ Wasserstoff oder eine Allylgruppe bedeutet, beide Substituenten X¶1¶ und X¶2¶ Wasserstoff bedeuten oder X¶1¶ und X¶2¶ eine Oxogruppe bilden können, m für eine ganze Zahl von 0 bis 2 steht). DOLLAR A Diese Verbindungen besitzen ausgezeichnete inhibitorische Aktivitäten gegenüber Squalensynthese und sind als Behandlungsmittel für Hypercholesterinämie nützlich.

CHINOLIN- UND CHINOXALIN-VERBINDUNGEN DIE DEN VON BLUTPLÄTTCHEN ABSTAMMMENDEN WACHSTUMSFAKTOR UND/ODER PDGF- UND P56lck-TYROSIN-KINASE HEMMEN

Verfahren zur Herstellung von Arylsulfonylharnstoffen und Arylsulfonylthioharnstoffen

1,4-ETHANO-2,3-DIHYDROQUINOLINE DERIVATIVES

... 1382785 1,4-Ethano-2,3-dihydroquinoline derivatives RHONE-POULENC SA 31 July 1973 [1 Aug 1972 28 Dec 1972] 36418/73 Heading C2C The invention comprises compounds of the formula wherein R is H or CH 3 , and acid addition salts thereof. The compound wherein R is H may be obtained by known methods from an acid of the formula or a derivative thereof such as the amide or an acid halide or a C 1 to C 4 alkyl ester thereof. The compound wherein R is CH 3 may be obtained by reducing a compound of the formula by known methods. Examples are given for the production of the compounds. The compounds of Formula I have analgesic properties and may be administered orally, parenterally or rectally in conventional forms. They may also be administered in the form of their acid-addition salts with inorganic or organic acids. 4 - Carbamoyl - 1,4 - ethano - 2,3 - dihydroquinoline is obtained by reacting 4-chloroformyl- 1,4 - ethano - 2,3 - dihydroquinoline hydrochloride with NH 3 . 4 - Chloroformyl - 1,4 - ethano ...

N-(2-Alkenyl)-Azabicyclo-Octanes and Nonanes

... 1,159,646. Therapeutic and moth proofing agents. UPJOHN CO. 13 July, 1967 [28 July, 1966], No. 32355/67. Headings A5B and A5E [Also in Division C2] Compounds effective as mothproofing agents are the fluosilicic acid salts of compounds of the formula where n is 0 or 1 and R is a C 3-5 2-alkenyl group. Therapeutic compositions effective as diuretics, pseudocholinesterase inhibiting agents, bactericides, cholesterol lowering agents, coccidiostats and anorexic agents comprise compounds of the above formula where n and R are as defined above or their acid addition salts with inorganic or organic acids in combination with pharmaceutical carriers, excipients, solvents or vehicles for administration as tablets, powders, capsules or as solutions or suspensions for oral or parenteral administration.

Sythesis of isoquinuclidine

A process for preparing isoquinuclidine in which a lower alkyl ester of p-aminobenzoic acid is first hydrogenated to form a cis and trans mixture of 4- aminocyclohexanecarboxylic acid alkyl ester on which there is first accomplished a reductive benzylation and then a cyclization to an amide which is then reduced to isoquinuclidine.

BENZOIC ACID DERIVATIVES

Chemical compounds

BENZOIC ACID DERIVATIVES

Aryl-Sulphonyl-Semicarbazides

... 1,176,310. Sulphonyl-ureas. FARBENFABRIKEN BAYER A.G. 14 Nov., 1968 [25 Nov., 1967; 2 Jan., 1968; 2 Sept., 1968], No. 54121/68. Heading C2C. Novel compounds (I) (including alkali metal and alkaline earth metal salts thereof) in which R is H or alkyl, R1 and R11 signify hydrogen or halogen or alkyl, aryl, aralkyl or cycloalkyl which may be substituted by halogen, alkyl, alkoxy or CF 3 , or R1 and R11 may be joined together to constitute an alkylene chain, NR111R1111 is a saturated or unsaturated, monocyclic or polycyclic radical which contains one or more hetero atoms, e.g. N, O, S, SO or SO 2 , and which may be substituted by alkyl, alkoxy, hydroxy or oxo, X signifies an oxygen or sulphur atom or a nitrogen atom having attached thereto a hydrogen atom or an alkyl, aryl or aralkyl radical which may be substituted by halogen, alkyl, alkoxy or CF 3 , Y is a direct bond, or a straight chain or branched C 1-8 alkylene radical, and n is 0, ...

THERAPEUTIC AGENTS

1,1-DIARYL-1-OXADIAZOL-ALKYLAMINES

... 1494943 Oxadiazoles G D SEARLE & CO 1 April 1975 [1 April 1974] 13184/75 Heading C2C Novel compounds I in which Alk is C 2-4 alkylene, R is H or C 1-7 alkyl, X is H, halogen or C 1-7 alkyl, Ar is phenyl, pyridyl, halophenyl or C 1-7 alkyphenyl, and NR1R11 is an azabicycloalkane structure containing 6 to 8 carbon atoms and containing at least 5 atoms in each ring of the azabicycloalkane structure, are prepared by (a) reacting in a basic medium with heating, a compound II with a compound of formula (R111CO) 2 O or R111COCl in which R111 is C 1-7 alkyl or carbalkoxy with the proviso that when R111 is carbalkoxy, the product is heated with an aqueous base and then acidified to give the corresponding carboxylic acid which is decarboxylated to give a compound I where R is H, or (b) reacting a compound IV in which Z is Cl or Br, with a compound of formula HNR1R11 in an inert solvent in the presence of an acid acceptor, the ...

Dibenzyl amine derivatives as CEPT inhibitors

Dibenzyl amine derivatives as CEPT inhibitors

Method of preparation of carboxylic acids aza-bicyclo-octane.

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases.

This invention is directed to quinoline/quinoxaline compounds which inhibit platelet-derived growth factor tyrosine kinase and/or tyrosine kinase, to pharmaceutical compositions comprising these compounds, and to the use of these compounds for treating a patient suffering from or subject to disorders/conditions involving cellular differentiation, proliferation, extracellular matrix production or mediator release and/or t cell activation and proliferation ...

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases.

Quinoline and quhoxaline compounds which inhibit platelet-derived growth factor and /or p561ck tyrosine kinases.

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or P561CK tyrosine kinases

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or P561CK tyrosine kinases

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or P561CK tyrosine kinases

NPY antagonists, preparation and use

Dibenzyl amine derivatives as CEPT inhibitors

New derivatives of triazole their method of preparation and the pharmaceutical compositions containing them

Quinoline and quinoxaline compounds which inhibit platelet-derived growt factor and/or p561ck tyrosine kinases

Process of synthesis of acid alpha amino NR alkyls and their esters. Application to the synthesis of carboxyalkyl dipeptides

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p561ck tyrosine kinases

Quinoline and quinoxaline compounds which inhibit platelet-derived growt factor and/or p561 ck tyrosine kinases

Derived from 1 (Omega, Omega, Omega-triarylalkyl) -4 - phényl-4- piperidin methanols, and their method of preparation.

“New derivatives of substituted amino-acids, their method of preparation the pharmaceutical compositions which contain them”.

News diaryl-l, L oxadiazole-L alkylamines and their method of preparation.

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or P561CK tyrosine kinases

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or P561CK tyrosine kinases

Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or P561CK tyrosine kinases

NPY antagonists, preparation and use

NPY antagonists, preparation and use

SUBSTITUTED FURO (2,3-B) PYRIDIN of DERIVATIVES

PROCEDURE FOR the PRODUCTION of NEW 1,1-DIARYL-1-OXADIAZOL-ALKYLAMINE AND THEIR NON--TOXIC SALTS

PROCEDURE FOR THE PRODUCTION OF NEW ONES 1.1.1 - TRI ARYL ALKYL AMINES AND OF THEM SAEUREADDITIONS SALTS

BRIDGED PIPERIDINDERIVATE AS MELANOCORTIN RECEPTOR AGONISTEN

PROCEDURE FOR the PRODUCTION OF 9-HYDROXYELLIPTICIN AND ITS DERIVATIVES.

SPIROCYCLI CONNECTIONS WITH TWO HETEROATOME ABSTENTION FUENFGLIEDRIGEN RINGS.

TRICYCLI CONNECTIONS.

5-HT3-REZEPTOR-ANTAGONISTEN FOR the TREATMENT OF COUGHS AND BRONCHOKONSTRIKTION.

(2-CYAN-2-OXIMINOACETYL) - AMINO ACID DERIVATIVES.

PROCEDURE FOR the PRODUCTION OF NEW ONE 1,1,1-TRIARYLALKYLAMINEN AND THEIR ACID ADDITION SALTS

ARYLOXYHARNSTOFFE, THEIR PRODUCTION AND USE.

FIBRINOGEN RECEPTOR ANTAGONIST

THIADIAZOLE, USABLE FOR THE TREATMENT OF AGECONDITIONED DEMENTIA.

BENZIMIDAZOLIN-2-OXO-1-CARBOXYLSÄURE-DERIVATE, USABLE AS ANTAGONISTS OF 5-HT-REZEPTOREN.

PROCEDURE FOR THE SYNTHESIS OF N-ALKYLATED ONE ALPHAAMINOS|URE AND THEIR ESTERS, USE WITH THE SYNTHESIS OF CARBOXYALKYLDIPEPTIDEN.

FIBRINOGEN RECEPTOR ANTAGONIST

HETERO-CYCLIC CONNECTIONS, YOUR PRODUCTION AND APPLICATION

Procedure for the production of new Benzolsulfonylsemicarbaziden and their salts

PROCEDURE FOR the PRODUCTION of NEW 1,1-DIARYL-1-OXADIAZOL-ALKYLAMINE AND THEIR NON--TOXIC SALTS

PROCEDURE FOR the PRODUCTION OF NEW ONE 1 - (TRI ARYL ALKYL) - 4-PHENYLPIPERIDINDERIVATEN AND THEIR SAEUREADDITIONSSALZEN

5 (2-OXYPHENYL) - PYRROL DERIVATIVES AS DOPAMIN-D3 RECEPTOR ANTAGONIST

AZABICYCLI ETHERS.

NEW DERIVATIVES OF SUBSTITUTING PROCEDURES FOR THEIR PRODUCTION AND PHARMACEUTICAL PREPARATIONS, IT CONTAINING.

VERFAHREN ZUR HERSTELLUNG VON NEUEN 1,1,1-TRIARYLALKYLAMINEN UND DEREN SALZEN

7-SUBSTITUIERTE-8-SUBSTITUIERTE-9-SUBSTITUIERTE AMINO-7-DEMETHYL-6-DEOXY-TETRACYCLINE AS ANTIBIOTIC MEANS

BENZODIAZEPINDERIVATE

CHINOLIN AND CHINOXALIN CONNECTIONS THE OF BLOOD PANEL ABSTAMMMENDEN GROWTH FACTOR AND/OR PDGF AND P56LCK-TYROSIN-KINASE RESTRAINING

Procedure for the production of new benzene sulphonyl urea and their salts

AMINO-SUBSTITUTED BRIDGED AZABICYCLIC QUINOLONE CARBOXYLIC ACIDS AND ESTERS

FIVE-MEMBERED RING SYSTEMS WITH BONDED AZACYCLIC RING SUBSTITUENTS

BRIDGED BICYCLIC SERINE PROTEASE INHIBITORS

N-`4-(2-IMINO-PYRROLIDIN-1-YL)PHENYL

DIHYDROBENZOFURAN CARBOXAMIDES AND PROCESS FOR THEIR PREPARATION

SUBSTITUTED UREA COMPOUNDS AND THEIR PREPARATION AND USE

Benzodiazepine derivatives

Heterocyclic compounds and their use

NOVEL COMPOUNDS

2-AZABICYCLO 2.2.2. OCTANE-3-CARBOXYLIC ACID DERIVATIVES

Heterocyclic compounds and their use

THIADIAZOLES USEFUL IN THE TREATMENT OF SENILE DEMETIA

5-(2-oxyphenyl)-pyrrole derivatives as dopamine d3 receptor antagonists

BRIDGED PIPERIDINE DERIVATIVES AS MELANOCORTIN RECEPTOR AGONISTS

Certain novel bridged piperidine derivatives of formula (I): (see formula I) are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of (MC-4R), such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

1,4-DIHYDRO-1,4-ETHENO-ISOQUINOLIN-3(2H)-ONES

3-[2-(AZABICYCLO)ETHYL]-1,2,3,4-TETRAHYDRO-5H-BENZOPYRANO[3,4-C]PYRIDIN-5-ONES

METHODS OF TREATING CANCER AND RELATED METHODS

Methods of treating cancer using 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1- yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one are provided. In particular, the methods are effective for the treatment of solid tumors or leukemias, including prostate, colorectal, breast, multiple myeloma, pancreatic, small cell carcinoma, acute myelogenous leukemia, chronic myelogenous leukemia, or myelo-proliferative disease. Further provided are methods of measuring the amount of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2- yl]quinolin-2(1H)-one and determining a metabolic profile therefore.

PROCESS FOR PREPARING CARBOXYLIC AZO-BICYCLO-OCTANE ACIDS

THERAPEUTIC COMPOSITION CONTAINING 1,4-DIHYDRO-1,4-ETHENO-ISOQUINOLEIN-3(24)-ONE

BICYCLIC HETEROCYCLES, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS, THEIR USE AND PROCESSES FOR THE PREPARATION THEREOF

The invention relates to bicyclic heterocycles of general formula (I), in which Ra, Rb, Rc, A, B, C, D, E and X are defined as in Claim 1, to tautomers, stereoisomers, mixtures and salts thereof, particularly their physiologically compatible salts with inorganic or organic acids, which have valuable pharmacological properties, particularly an inhibitory action on the signal transduction imparted by tyrosine kinases. The invention also relates to the use of these compounds for treating diseases, particularly tumor diseases and benign prostatic hyperplasia (BPH), diseases of the lungs and of the respiratory passages and to the production thereof.

PYRIDO[3,4-B] INDOLES AND METHODS OF USE

This disclosure relates to new heterocyclic compounds that may be used to modulate a histamine receptor in an individual. Pyrido[4,3-b]indoles are described, as are pharmaceutical compositions comprising the compounds and methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 17-. (canceled)9. (canceled) This application claims priority to U.S. Provisional Patent Application No. 61/245,140, filed Sep. 23, 2009, and U.S. Provisional Patent Application No. 61/245,259, filed Sep. 23, 2009, the disclosures of each of which are hereby incorporated herein by reference in their entireties.Not applicable.Neurotransmitters such as histamine, serotonin, dopamine and norepinephrine mediate a large number of processes in the central nervous system (CNS) as well as outside the CNS. Abnormal neurotransmitter levels are associated with a wide variety of diseases and conditions including, but not limited to, Alzheimer's disease, Parkinson's Disease, autism, Guillain-Barré syndrome, mild cognitive impairment, schizophrenia (such as cognitive impairment associated with schizophrenia (CIAS), positive symptoms, disorganized symptoms, and negative symptoms of schizophrenia), anxiety, multiple sclerosis, stroke, traumatic brain injury, spinal cord injury, diabetic neuropathy, fibromyalgia, bipolar disorders, psychosis, depression, attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), depression and a variety of allergic diseases. Compounds that modulate these neurotransmitters may be useful therapeutics.Histamine receptors belong to the superfamily of G protein-coupled seven transmembrane proteins. G protein-coupled receptors constitute one of the major signal transduction systems in eukaryotic cells. Coding sequences for these receptors, in those regions believed to contribute to the agonist-antagonist binding ...

NORIBOGAINE SALT TABLETS

Stable noribogaine salt ansolvates are useful for preparing pharmaceutical compositions and for alleviating nociceptive pain in a patient. Such ansolvates can be prepared by slurrying solvated forms, preferably MeOH solvated noribogaine hydrochloride in EtOH/water. 1. A stable pharmaceutically acceptable salt of noribogaine ansolvate.2. The stable salt of noribogaine ansolvate of claim 1 , wherein the salt is a hydrochloride salt.3. The salt of claim 2 , which is crystalline.4. The crystalline salt of claim 3 , characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 11.6° claim 3 , 12.1° claim 3 , 13.5° claim 3 , 13.9° claim 3 , 14.9° claim 3 , 15.7° claim 3 , 17.1 claim 3 , 17.9° claim 3 , 18.3° claim 3 , 19.8° claim 3 , 20.8° claim 3 , 21.0° claim 3 , 21.9° claim 3 , 22.8° claim 3 , 23.3° claim 3 , 24.9° claim 3 , 25.9° claim 3 , 26.4 claim 3 , 29.3° claim 3 , and 29.8°2θ (each ±0.2 °2θ).5. The crystalline salt of claim 3 , which shows substantially no thermal transitions under 300° C. in its differential scanning calorimetry thermogram.6. The crystalline salt of claim 3 , which shows substantially no weight loss at a temperature under 300° C. in its thermogravimetric analysis thermogram.7. The crystalline ansolvate salt of claim 3 , which has a density that is at least 3% and up to 20% greater than the density of a solvated crystalline hydrochloride salt of noribogaine.8. The crystalline ansolvate salt of claim 3 , which has a unit cell volume of less than about 1800 cubic angstrom claim 3 , or less than about 1750 cubic angstrom claim 3 , or less than 1700±2% cubic angstrom.9. A crystalline noribogaine hydrochloride solvate polymorph characterized by about 4% weight loss at temperatures under 125° C. in its differential scanning calorimetry thermogram.10. The crystalline solvate polymorph of characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 9.7 claim 9 , 10.2 claim 9 , 12.0 claim 9 , ...

STABLE CRYSTALLINE NORIBOGAINE SALT ANSOLVATES

Stable noribogaine salt ansolvates are useful for preparing pharmaceutical compositions and for alleviating nociceptive pain in a patient. Such ansolvates can be prepared by slurrying solvated forms, preferably MeOH solvated noribogaine hydrochloride in EtOH/water. 1. A stable pharmaceutically acceptable salt of noribogaine ansolvate.2. The stable salt of noribogaine ansolvate of claim 1 , wherein the salt is a hydrochloride salt.3. The salt of claim 2 , which is crystalline.4. The crystalline salt of claim 3 , characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 11.6° claim 3 , 12.1° claim 3 , 13.5° claim 3 , 13.9° claim 3 , 14.9° claim 3 , 15.7° claim 3 , 17.1 claim 3 , 17.9° claim 3 , 18.3° claim 3 , 19.8° claim 3 , 20.8° claim 3 , 21.0° claim 3 , 21.9° claim 3 , 22.8° claim 3 , 23.3° claim 3 , 24.9° claim 3 , 25.9° claim 3 , 26.4 claim 3 , 29.3° claim 3 , and 29.8° 2θ (each ±0.2° 2θ).5. The crystalline salt of claim 3 , which shows substantially no thermal transitions under 300° C. in its differential scanning calorimetry thermogram.6. The crystalline salt of claim 3 , which shows substantially no weight loss at a temperature under 300° C. in its thermogravimetric analysis thermogram.7. The crystalline ansolvate salt of claim 3 , which has a density that is at least 3% and up to 20% greater than the density of a solvated crystalline hydrochloride salt of noribogaine.8. The crystalline ansolvate salt of claim 3 , which has a unit cell volume of less than about 1800 cubic angstrom claim 3 , or less than about 1750 cubic angstrom claim 3 , or less than 1700±2% cubic angstrom.9. A crystalline noribogaine hydrochloride solvate polymorph characterized by about 4% weight loss at temperatures under 125° C. in its differential scanning calorimetry thermogram.10. The crystalline solvate polymorph of characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 9.7 claim 9 , 10.2 claim 9 , 12.0 claim 9 , ...

SMALL MOLECULE INDUCERS OF GDNF AS POTENTIAL NEW THERAPEUTICS FOR NEUROPSYCHIATRIC DISORDERS

This invention provides a compound having the structure 34-. (canceled)8. (canceled)1112-. (canceled)14. (canceled)1822-. (canceled)2426-. (canceled)2832-. (canceled)34. (canceled)36. (canceled)3844-. (canceled)4647-. (canceled)5052-. (canceled)54. (canceled) Throughout this application, certain publications are referenced in parentheses. Full citations for these publications may be found immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention relates.Neurotrophic factors play important roles not only in the development of the nervous system, but also in maintenance of its function and plasticity. GDNF (Glial cell line-Derived Neurotrophic Factor) is essential for growth, development and plasticity of dopamine and motor neurons as well as other brain cell populations (Airaksinen, M. S. et al. 2002). In the brain, GDNF is released by both neurons and glia cells. Although the signaling mechanisms underlying the expression and release of GDNF are not fully mapped, the released GDNF exerts its function on the brain cells and neurocircuitry through a receptor complex, comprised of GFRα1 (GDNF Family Receptor α1) and receptor tyrosine kinase RET (Trupp, M. et al. 1997). On the basis of the trophic and repair effects GDNF has on neural cells, it was considered as a potential therapeutic agent for several neurological disorders. However, GDNF is a protein and thus not readily administered to the brain. Consequently, small molecule inducers of GDNF release are of interest as potential therapeutics, most notably in the context of Parkinson's disease and neuropathic pain. In the latter case, GDNF's effectiveness has been ascribed to the ability of GDNF signaling to reset the function of several sodium channel subunits (modified in response to injury) (Boucher, T. J. et al. 2000).Recently, it has been shown ...

BRIDGED BICYCLIC ARYL AND BRIDGED BICYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS

Bridged bicyclic aryl or heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed. 2. The compound of selected from:{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-thiophen-2-yl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-pyridin-4-yl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(3-carboxypiperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-bicyclo[2.2.1]heptan-2-yl piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-cyclohexyl piperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-(4-methylpiperazin-1-yl)piperidin-1yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-ethyloxycarbonylmethylpiperazin-1-yl)phenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-phenyl-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(3-fluoro-4-(4-carboxymethylpiperazin-1-yl) ...

METHODS AND COMPOSITIONS FOR PREPARING NORIBOGAINE FROM VOACANGINE

Disclosed are methods and compositions for preparing and purifying the non-addictive alkaloid noribogaine. 1. A method for preparing and purifying noribogaine which method comprises:a) converting voacangine to 12-hydroxyibogamine-18-carboxylic acid or the carboxylic acid salt or ester thereof, wherein the indole nitrogen is optionally protected by an amino protecting group;b) optionally isolating the 12-hydroxyibogamine-18-carboxylic acid or the carboxylic acid salt, ester and/or amino protected derivative thereof;c) converting the product of step a) or b) to noribogaine; andd) isolating noribogaine.2. The method of claim 1 , wherein b) and c) are conducted in a one-pot synthesis.3. The method of claim 1 , wherein step b) further comprises the steps of b′) de-esterifying the 12-hydroxyibogamine-18-carboxylic acid methyl ester to provide 12-hydroxyibogamine-18-carboxylic acid claim 1 , and b″) decarboxylating the 12-hydroxyibogamine-18-carboxylic acid to provide the noribogaine.4. A method for preparing and purifying noribogaine which method comprises:a) converting voacangine to 12-hydroxyibogamine-18-carboxylic acid wherein the indole nitrogen is optionally protected by an amino protecting group;b) converting the 12-hydroxyibogamine-18-carboxylic acid to noribogaine; andc) isolating noribogaine.5. A method for preparing and purifying noribogaine which method comprises:a) converting voacangine to 12-hydroxyibogamine-18-carboxylic acid methyl ester wherein the indole nitrogen is optionally protected by an amino protecting group;b) optionally covalently attaching 12-hydroxyibogamine-18-carboxylic acid methyl ester or amino protected derivative thereof to a solid support via the hydroxyl group of 12-hydroxyibogamine-18-carboxylic acid methyl ester or amino protected derivative thereof so as to form a suspension of solid supports having 12-hydroxyibogamine-18-carboxylic acid methyl ester or amino protected derivative thereof bound thereto;c) removing residual voacangine ...

N-SUBSTITUTED NORIBOGAINE PRODRUGS

This invention relates generally to prodrugs of noribogaine. This invention also relates to pharmaceutical compositions comprising the prodrugs of noribogaine as well as method of treating pain, addiction and/or stress using such compounds and/or pharmaceutical compositions. 2. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , C-Calkyl claim 1 , substituted C-Calkyl claim 1 , C-Calkoxy and substituted C-Calkoxy.3. The compound of claim 1 , wherein L is hydrogen or a biocompatible claim 1 , cleavable linking group and Ris C-Calkoxy optionally substituted with YH claim 1 , YR claim 1 , YC(O)R claim 1 , C(O)YR claim 1 , C(O)NH claim 1 , C(O)NHR claim 1 , C(O)NRR claim 1 , NH claim 1 , NHR claim 1 , NRR claim 1 , NHC(O)R claim 1 , or NRC(O)R claim 1 , where Y is O or S claim 1 , Rand Rare independently C-Calkyl.4. The compound of claim 1 , wherein R is hydrogen claim 1 , L is a covalent bond or —C(O)— claim 1 , and Ris alkyl substituted with —NRRwhere Rand Rare independently selected from the group consisting of hydrogen claim 1 , alkyl claim 1 , alkenyl claim 1 , substituted alkenyl claim 1 , alkynyl claim 1 , substituted alkynyl claim 1 , aryl claim 1 , substituted aryl claim 1 , cycloalkyl claim 1 , substituted cycloalkyl claim 1 , heteroaryl claim 1 , substituted heteroaryl claim 1 , heterocyclic claim 1 , and substituted heterocyclic.5. The compound of claim 1 , wherein Ris selected from H claim 1 , CHCHOH claim 1 , CHCHOCH claim 1 , CHCHOCHPh claim 1 , CHCHOC(O)alkyl claim 1 , and CHCHO(CH)O(CH)O(CH)CH claim 1 , wherein p claim 1 , q claim 1 , and r are independently 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3 claim 1 , or a pharmaceutically acceptable salt and/or solvate thereof.6. The compound of claim 1 , wherein Ris H claim 1 , or a pharmaceutically acceptable salt and/or solvate thereof.7. The compound of claim 1 , wherein Ror Ris H claim 1 , or a pharmaceutically acceptable salt and/or solvate thereof.8. The compound ...

SUBSTITUTED NORIBOGAINE

This invention relates noribogaine derivatives, compositions and methods of use thereof.

(1r,4r) 7-oxo-2-azabicyclo[2.2.2]oct-5-ene and derivatives thereof

This invention provides novel (1R,4R) 7-oxo-2-azabicyclo[2.2.2]oct-5-ene and derivatives thereof, preferably in substantially enantiomerically enriched forms, intermediates thereto, and processes of their synthesis.

PRMT5 INHIBITORS

The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)8. A composition for treating cancer comprising a compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , and a pharmaceutically acceptable carrier.9. A method for treating cancer comprising administering to a patient in need thereof a composition of .10. (canceled) PRMT5 (aka JBP1, SKB1, 1BP72, SKB1his and HRMTIL5) is a Type II arginine methyltransferase, and was first identified in a two-hybrid search for proteins interacting with the Janus tyrosine kinase (Jak2) (Pollack et al., 1999). PRMT5 plays a significant role in control and modulation of gene transcription. Inter alia, PRMT5 is known to methylate histone H3 at Arg-8 (a site distinct from that methylated by PRMT4) and histone H4 at Arg-3 (the same site methylated by PRMT1) as part of a complex with human SWI/SNF chromatin remodelling components BRG1 and BRM.PRMT5 is involved in the methylation and functional modulation of the tumor suppressor protein p53. (See Berger, 2008; Durant et al., 2009; Jansson et al., 2008; Scoumanne et al., 2009). Most of the physiological functions of p53 are attributable to its role as a transcriptional activator, responding to agents that damage DNA. p53 status is wild type in approximately half of human cancer cases. These include 94% in cervix, 87% in blood malignancies, 85% in bones and endocrine glands, and 75% of primary breast cancer. Restoration of p53 in cancer cells harbouring wild type p53, by way of inhibiting mechanisms that suppress its function leads to growth arrest and apoptosis, and is regarded as a potentially effective means of tumor suppression.The role of PRMT5 and p53 arginine methylation on cell cycle regulation and DNA damage response have been explored by both Jansson et al. and Scoumanne et al. (Jansson et al., 2008; ...

(1R, 4R) 7-OXO-2-AZABICYCLO [2.2.2] OCT-5-EH AND ITS DERIVATIVES

1. Соединение Формулы (I) или (Ia):или соль указанного соединения, гдеRвыбран из группы, состоящей из водорода, -COR, -COR, -C(R)и защитной группы для амина;Rвыбран из группы, состоящей из C-Cалкила, возможно замещенного 1-3 заместителями, выбранными из C-Cарила, C-Cциклоалкила, C-Cгетероарила, C-Cгетероциклила, галогена, амино, -N, гидрокси, C-Cалкокси, силила, нитро, циано и группы COH или ее сложноэфирной группы, C-Cалкенила, C-Cалкинила, C-Cарила, C-Cгетероарила, C-Cциклоалкила и C-Cгетероциклила,Rи Rнезависимо выбраны из группы, состоящей из водорода, C-Cалкила, возможно замещенного 1-3 заместителями, выбранными из C-Cарила, C-Cциклоалкила, C-Cгетероарила, C-Cгетероциклила, галогена, амино, -N, гидрокси, C-Cалкокси, силила, нитро, циано и группы COH или ее сложноэфирной группы, C-Cалкенила, C-Cалкинила, C-Cарила, C-Cгетероарила, C-Cциклоалкила и C-Cгетероциклила,Rи Rнезависимо представляют собой водород, гидрокси, C-Cалкил, C-Cалкенил и C-Cалкинил, -SRили -OR, причем указанная алкильная, алкенильная или алкинильная группа возможно замещена 1-3 заместителями, выбранными из группы, состоящей из кето, галогена, C-Cалкокси, амино, гидрокси, циано, нитро, -NHCOCH, -Nи группы -COH или ее сложноэфирной группы, при условии что по меньшей мере один из Rи R, предпочтительно R, является заместителем, отличным от водорода, илиRи Rсовместно с атомом углерода, к которому они присоединены, образуют кетоновую (C=O) группу, основание Шиффа (=NR), винилиденовый фрагмент формулы =CRR, или образуют 5-6-членный циклический кеталь или тиокеталь, причем циклический кеталь или тиокеталь имеет формулу:каждый Rнезависимо выбран из группы, состоящей из C-Cалкила, возможно замещенного 1-3 заместителями, выбранными из C-Cарила, C-Cциклоалкила, C-Cгетероарила, C-Cгетероциклила, галогена, амино, -N, гидрокси, C-Cалкокси, силила, нитро, циано и группы COH или е РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 451/04 (13) 2014 124 531 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ ...

Fused polycyclic and bridged compounds useful as calcium channel blockers

Novel fused polycyclic and bridged compounds are disclosed which are useful as calcium entry blockers.

Quinoline tachykinin receptor antagonists

本发明涉及某些喹啉化合物，其用作神经激肽－1(NK－1)受体拮抗剂，和速激肽及特别是P物质抑制剂。本发明还涉及含有这些化合物作为活性成分的药物制剂以及这些化合物和其制剂在治疗某些疾病，包括呕吐、尿失禁、抑郁及焦虑中的应用。

Methods and compositions for producing noribogaine from voacangine

Изобретение относится к способу получения норибогаина. Способ включает: a) преобразование воакангина в сложный эфир 12-гидроксиибогамин-18-карбоновой кислоты, где индольный азот необязательно защищен аминозащитной группой; b) необязательное выделение сложного эфира 12-гидроксиибогамин-18-карбоновой кислоты и/или его аминозащищенного производного; c) преобразование сложного эфира 12-гидроксиибогамин-18-карбоновой кислоты и/или его аминозащищенного производного, полученных на стадии а) или b), в норибогаин; и d) выделение полученного норибогаина. Также предложены варианты способа и соединения, содержащие соли. Заявленный способ получения норибогаина из воакангина позволяет эффективно и надежно минимизировать примеси ибогаина. 6 н. и 7 з.п. ф-лы, 3 пр. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 592 698 C2 (51) МПК C07D 487/18 (2006.01) C07D 487/04 (2006.01) A61K 31/55 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2013139382/04, 23.01.2012 (24) Дата начала отсчета срока действия патента: 23.01.2012 Приоритет(ы): (30) Конвенционный приоритет: (72) Автор(ы): МЭШ Дебора К. (US), МОРИАРТИ Роберт М. (US), ГЛЕСС Ричард Д. (US) 26.01.2011 US 61/436,511; 17.03.2011 US 61/453,884; 21.03.2011 US 61/454,904 R U (73) Патентообладатель(и): ДЕМЕРКС, ИНК. (US) (43) Дата публикации заявки: 10.03.2015 Бюл. № 7 (56) Список документов, цитированных в отчете о поиске: US 6211360 B1, 03.04.2001. US 4737586 A, 12.04.1988. US 20100311722 A1, 09.12.2010. US 20030153552 A, 14.08.2003. US 2813873 A1, 19.11.1957 . (86) Заявка PCT: C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 26.08.2013 US 2012/022255 (23.01.2012) (87) Публикация заявки PCT: 2 5 9 2 6 9 8 WO 2012/103028 (02.08.2012) R U 2 5 9 2 6 9 8 (45) Опубликовано: 27.07.2016 Бюл. № 21 Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, строение 3, ООО "Юридическая фирма Городисский и Партнеры" (54) СПОСОБЫ И КОМПОЗИЦИИ ДЛЯ ПОЛУЧЕНИЯ НОРИБОГАИНА ...

Methods and compositions for preparing noribogaine from voacangine

The method of obtaining 1,4-dihydro1,4-etheno-isoquinoline-3 (2n) -ones

PROCESS FOR THE PREPARATION OF ISOQUINUCLIDINE

SELON L'INVENTION, ON HYDROGENE UN ESTER ALKYLIQUE INFERIEUR DE L'ACIDE P-AMINOBENZOIQUE CE QUI DONNE UN MELANGE CISTRANS D'ESTERS ALKYLIQUES DE L'ACIDE 4-AMINOCYCLOHEXANE-CARBOXYLIQUE QU'ON SOUMET D'ABORD A BENZYLATION REDUCTIVE PUIS A CYCLISATION EN N-BENZYL-2-AZABICYCLOOCTANE-3-ONE QU'ON REDUIT EN N-BENZYL-2-AZABICYCLOOCTANE DANS LEQUEL ON ELIMINE LE GROUPE BENZYLE. ACCORDING TO THE INVENTION, A LOWER ALKYL ESTER OF P-AMINOBENZOIC ACID IS HYDROGATED, WHICH GIVES A CISTRANS MIXTURE OF ALKYL ESTERS OF 4-AMINOCYCLOHEXANE-CARBOXYLIC ACID WHICH IS FIRST SUBJECTED TO CYCLIZATION THEN REDUCED AYLATION. IN N-BENZYL-2-AZABICYCLOOCTANE-3-ONE WHICH IS REDUCED TO N-BENZYL-2-AZABICYCLOOCTANE IN WHICH THE BENZYL GROUP IS ELIMINATED.

Process for the preparation of isoquinolines

Process for the preparation of isoquinolines

Arylsulfonyl ureas and their preparation

Pharmaceutical compositions for prevention and treatment of central nervous system disorders

Patients susceptible to or suffering from central nervous system disorders (e.g., neurodegenerative diseases including presenile dementia, senile dementia of the Alzheimer's type, and Parkinsonism including Parkinsons's disease, and other CNS disorders including attention deficit disorder, schizophrenia and Tourette's syndrome) are treated by administering an effective amount of 2-azabicyclo [2.2.1] hept-5-ene and 2-azabicyclo [2.2.2] oct-5-ene compounds. Exemplary compounds are (+/-)-3-exo and (+/-)-3-endo forms of 2-methyl-3-(3-pyridyl)-2-azabicyclo[2.2.1]hept-5-ene, (+/-)-3-exo and (+/-)-3-endo forms of 2-methyl-3-(3-pyridyl)-2-azabicyclo[2.2.1]hept-5-ene, (+/-)-3-exo and (+/-)-3-endo forms of 2-benzyl-3-(3-pyridyl)-2-azabicyclo[2.2.1]hept-5-ene, (+/-)-3-exo and (+/-)-3-endo forms of 2-para-anisyl-3-(3-pyridyl)-2-azabicyclo[2.2.1]hept-5-ene, (+/-)-3-exo and (+/-)-3-endo forms of 3-(3-pyridyl)-2-azabicyclo[2.2.2]oct-5-ene, (+/-)-3-exo and (+/-)-3-endo forms of 3-(3-pyridyl)-2-azabicyclo[2.2.2.]oct-5-ene, (+/-)-3-exo and (+/-)-3-endo forms of 2-methyl-3-(3-pyridyl)-2-azabicyclo[2.2.2.]oct-5-ene, the racemic form of 3-(3-pyridyl)-2-azabicyclo[2.2.2]octane, and the racemic form of 2-methyl-3-(3-pyridyl)-2-azabicyclo[2.2.2]octane.

Patent FR5419M

Methods and compositions for preparing noribogaine from voacangine

Disclosed are methods and compositions for preparing and purifying no-addictive alkaloid noribogaine from voancangine. Particular aspects of the disclosure pertain to compounds of Scheme I: (See Scheme 1)

Process for the synthesis of gonadotropin releasing hormone antagonists

The present invention relates to a process for preparing a compound of gonadotropin releasing hormone antagonists having a Formula I,in an efficient way, which involves preparation of key intermediates: 2-arylindole core; a chiral aziridine, in particular chiral nosyl aziridine; and an amine salt. The key process involves the coupling reaction of 2-arylindole and nosyl aziridine under boron trifluoride catalysis, which provides the final compound with unprecedented regioselectivity and enantioselectivity.

Method for preparing noribogaine from voacangine and purification thereof

Therapeutic compositions

A PHARMACEUTICAL COMPOSITION COMPRISING A PHARMACEUTICAL EXCIPIENT AND A THERAPEUTICALLY EFFECTIVE AMOUNT OF A 1,4-DIHYDRO-1,4-THENO-ISOQUINOLIN-3(2H)-ONE HAVING THE FORMULA WHEREIN R1, R2, R3, R4 AND R5 ARE EACH A MEMBER SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL, HYDROXYALKYL, AMINOALKYL, ALKYLAMINOALKYL, DIALKYLAMINOALKYL, SAID ALKYL HAVING 1 TO 4 CARBON ATOMS, ALKENYL HAVING 2 TO 4 CARBON ATOMS, ARYL AND ARALKYL; AND R6 IS A MEMBER SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, HALOGEN, ALKYL AND ALKOXY HAVING 1 TO 4 CARBON ATOMS AND TRIFLUOROMETHYL. ISOQUINOLINE 1-R3,2-R1,3-(O=),4-R2,9-R5,10-R4,R6-1,2,3,4-TETRAHYDRO-

STABILIZATION OF PLASTICS

PROCEDURE FOR THE PREPARATION OF NEW ACID DERIVATIVES 2-AZA-BICYCLE (2.2.2) OCTAN-3-CARBOXYLLIC

(1R, 4R) 7- oxo -2- azabicyclo [2.2.2] octyl- 5- alkene and its derivative

本发明提供了新颖的(1R,4R)7‑氧代‑2‑氮杂双环[2.2.2]辛‑5‑烯及其衍生物，优选地以基本上对映异构富集的形式，与它们有关的中间体和它们的合成方法。

Quinoline tachykinin receptor antagonists

2,6-Methano-3-benzazocines

6(EQ)-R 4 -1,2,3,4,5,6-Hexahydro-3-R 1 -11(ax)-R 3 -11(eq)-CH 2 Z-2,6-methano-3-benzazocines, useful as analgesic agents and narcotic antagonists, and 1-R 1 -2-Q-4aα-R 3 -5α-R 4 -1,2,3,4,4a,5,10,10a-octahydro-3,5-ethano- (and 3,5-ethano) benzo[g]quinolines, useful as analgesic agents, prepared by heating, with formic acid in an organic solvent or with certain ammonium formates in the absence of a solvent, certain 1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinolines, the latter prepared by acid catalyzed cyclization of a 3-benzyl-2-azabicyclo[2.2.2]-oct-5-ene.

(1r,4r) 7-oxo-2-azabicyclo[2.2.2]oct-5-ene and derivatives thereof

N-cycloalkyl-azabicyclooctanes, their derivatives and their manufacturing process

Patent FR5273M

Hydroxyisoquinuclidine derivatives

Analogue method for the preparation of hypoglycemic arylsulphonyl isemicarbazides.

Patent FR7050M

(1r,4r) 7-oxo-2-azabicyclo[2.2.2]oct-5-ene and derivatives thereof

2-azabicyclo compounds

2-Azabicyclo compounds represented by general formula (1) or pharmaceutically acceptable salts thereof, which are nicotinic acetylcholine agonists and useful as remedies for diseases caused by central nerve degeneration such as Alzheimer's disease and Parkinson's disease and as analgesics. In said formula, R1 represents hydrogen or alkyl; one of R?2 and R3¿ represents optionally substituted, nitrogen-containing heteroaryl, while another represents hydrogen, alkyl, alkenyl, alkynyl or aralkyl; n is 1, 2 or 3; and one of X?1 and X2¿ represents hydrogen while another represents hydrogen, hydroxy, halogeno, alkoxy, alkenyloxy or alkynyloxy, or X?1 and X2¿ may form together with the solid line a double bond.

Hydroxyisoquinuclidine derivatives

Quinoline tachykinin receptor antagonists

The present invention is directed to certain quinoline compounds which are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.

Patent CS159778B2

Compositions that modulate splicing

遺伝子によってコードされるプレｍＲＮＡなどのｍＲＮＡのスプライシングを調節する小分子スプライシング調節因子化合物、並びにスプライシングを調節し、かつ疾患及び状態を治療するための小分子スプライシング調節因子化合物の使用方法が本明細書に記載される。【選択図】なし

5-Chloro-benzoxazol-2-yl oxy:acetic acid amide derivs. - used as selective herbicides for cotton, soya, beet and cereal crops

5-Chlorobenzoxazol-2-yl oxy acetic acid amide derivs. of formula (I) are new. In (I), R1 is opt. halo substd. 1-5C alkyl, 3-5C alkenyl, 3-5C alkynyl, cyano-(1-4C)alkyl, 1-4C alkoxy-(1-2C)-alkyl, 3-6C cycloalkyl or phenyl-(1-2C)alkyl; and R2 is opt. halo substd. 1-5C alkyl, 3-5C alkenyl, 3-5C alkynyl, cyano-(1-4C)-alkyl, 1-4C alkoxy-(1-2C)alkyl, 3-6C cycloalkyl, phenyl-(1-2C)-alkyl, or Ph, opt. substd. with Me, F, Cl, Br, CF3, MeO and/or NO2; or R1 and R2 together with the N atom to which they are attached form opt. Me or Et substd. pyrrolidyl, piperidyl, 2-methyl-, 3-methyl-, or 4-methyl-piperidyl, 2,4,6-trimethylpiperidyl, opt. Me-substd. morpholinyl, perhydroazepinyl, indolinyl 2-methylindolinyl, opt. Me or Et substd. perhydroindolyl, opt. Me and/or Et substd. 1,2,3,4-tetrahydroquinolyl, opt. Me and/or Et substd. perhydroquinolyl, or is the gp. (II) or (III). (I) are herbicides, effective against both mono- and dicotyledons. (I) have good selectivity and can be used esp. in cotton, soya bean, beet and cereal (e.g. wheat and rice) crops.

1, 4-ethanoisoquinolines

NYA 2-AZA-BICYCLO / 2,2,2 / OCTAN-3-CARBONSYRADERIVAT, FOERFARANDE FOER DERAS FRAMSTAELLNING, DESSA INNEHAOLLANDE AEMNEN OCH DERAS ANVAENDNING, SAMT AZA-BICYKLO / 2,2,2 / OKTAN-3-KARBONS FOERFARANDEN FOER DERAS FRAMSTAELLNING

Process for preparing 5-hydroxy-or 6-hydroxy-isoquinuclidines

Patent JPH029588B2

New Substituted Azabicyclooctanes

Patent FR2256167A1

Production of diphenyll alkanone derivatives

2- (5- (AMINOCYCLIC) -ETHYL-10, 11-DIHYDRO-5H-DIBENZO (A, D) CYCLOHEPTENYL-5) -5-ALKYL-1,3,4-OXADIAZOLES, THEIR PREPARATION AND THEIR USE AS AN ANTI- DIARRHEA

5-(1-1-diphenyl-3-(5-or 6-hydroxy-2-azabicyclo(2.2.2) oct-2-yl) proxpyl) -2-alkyl-1, 3, 4-oxadiazoles and related compounds

Patent FR2256167B1

1,2,4-benzothiadiazine derivatives,their preparation and use

Verfahren zur herstellung einer pharmazeutisch aktiven verbindung (granisetron)

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Verfahren zur herstellung einer pharmazeutisch aktiven verbindung (granisetron)

一种采用微通道模块化反应装置制备异奎宁环化合物的方法

本发明公开了一种采用微通道模块化反应装置制备异奎宁环化合物的方法，将芳香醛的乙醇溶液和芳香胺的乙醇溶液，通过两个恒流泵分别注入到第一微通道模块化反应装置中，在常压和85-125℃下进行反应，停留时间3-7min；环己烯酮和磷钨酸的混合乙醇溶液通过恒流泵与第一微通道模块化反应装置的出料分别注入第二微通道模块化反应装置中，在常压和100-140℃下进行反应，停留时间为10-25min，将产物导入分离器，静置分层，取上层液体，即得。本发明所提供的异奎宁环化合物的制备方法为连续过程，制备工艺简单易操作控制，安全性高，缩短工艺流程，降低生产成本，降低副产物含量，产品质量稳定，转化率高。

Process for preparing a pharmaceutically active compound (granisetron)

The invention relates to a process for preparing granisetron, or a pharmaceutically acceptable salt thereof, which comprises: a) cyclisation of a compound of formula (I) in an inert solvent and at a temperature between 0-100° C., in the presence of a strong acid, in order to yield the compound of formula (II); b) methylation of the compound of formula (II), with an alkylating agent, in the presence of a base, in an inert solvent and at a temperature between 0° C.-160° C., and with optional formation of a pharmaceutically acceptable salt. The process of the invention yields a granisetron of high purity, preventing impurities due to demethylation, by carrying out the methylation after rather than before cyclisation and with a higher yield.

1,2,4-benzothiadiazine derivatives, their preparation and use

1,2,4-Benzothiadiazine derivatives represented by formulawherein D, R1, R2, R3, R4, R5, R12, R13, R14, R15 are defined in the description, composition thereof and methods for preparing the compounds are described.The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

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Compositions for modulating splicing

Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

1,4-ethano-2,3-dihydroquinoline derivatives

Sett att framstella 5-(1,1-difenyl-3-(5 eller 6-hydroxi-2-azabicyklo-(2,2,2)okt-2-yl)propyl)-2-alkyl-1,3,4-oxadiazoler och dermed beslektade foreningar

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Procedimiento para preparar oxadiazoles.

Procedimiento para preparar oxadiazoles, de fórmula general *** En la que R es alquilo con 1 a 6 átomos de carbono; R¿es hidrógeno o alcanoilo con 2 a 7 átomos de carbono; y ^^^^Or¿ está unido a la posición 5 ó 6 según la configuración endo o exo caracterizado porque comprende hacer reaccionar un tetrazol de fórmula: ***

Verfahren zur herstellung von 5-(1,1-diphenyl-3-(5- oder 6-hydroxy-2-azabicyclo(2,2,2)-oct-2-yl)propyl)-2-alkyl-1,3,4-oxadiazolen und deren 0-alkanoylderivaten.

Composiciones para modular el corte y empalme.

En la presente descripción se describen compuestos moduladores del corte y empalme de molécula pequeña que modulan el corte y empalme del ARNm, tal como pre-ARNm, codificado por genes, y métodos de uso de los compuestos moduladores del corte y empalme de molécula pequeña para modular el corte y empalme y tratar enfermedades y afecciones.

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2- eckige klammer auf 5-(cycl.-amino) aethyl-10,11-dihydro-5h-dibenzo eckige klammer auf a,d eckige klammer zu cyclohepten-5-yl eckige klammer zu -5-alkyl- 1,3,4-oxadiazole und analoga sowie diese enthaltende pharmazeutische zubereitungen

Procedimiento para la obtencion de amidas del acido 1-benzotriazoliloxi-acetico, de efecto herbicida.

1,2,4-benzotiadiazinderivater, deres fremstilling og anvendelse

1,2,4-benzotiadiazinderivater som har formel (I) b 12 hvor D, R1, R2, R3, R4, R5, R12, R13, R14 og R15 er definert i beskrivelsen, pre- parater derav og fremgangsmåter for fremstilling av forbindelsene er be- skrevet. Forbindelsene kan anvendes ved behandlingen av sykdommer i sentralner- vesystemet, det kardiovaskulære system, det pulmonale system, det gastrointes- tinale system og det endokrinologiske system.

Derivados 1,2,4- benzotiadiazina, su preparacion y usos.

SE DESCRIBEN DERIVADOS DE 1,2,4 - BENZOTIADIAZINAS REPRESENTADOS POR LA FORMULA (I) EN LA QUE D, R 1 , R 2 , R SUP,3 , R 4 , R 5 , R 12 , R 13 , R 14 , R15 REPRESENTAN LO DEFINIDO EN LA DESCRIPCION, COMPOSICIO NES DE LOS MISMOS Y METODOS PARA LA PREPARACION DE LOS COMPUESTOS. LOS COMPUESTOS SON UTILES EN EL TRATAMIENTO DE ENFERMEDADES DEL SISTEMA NERVIOSO CENTRAL, DEL SISTEMA CARDIOVASCULAR, DEL SISTEMA PULMONAR, DEL SISTEMA GASTROINTESTINAL Y DEL SISTEMA ENDOCRINO.

1,2,4-benzothiadiazin-derivate, ihre herstellung und verwendung

1,2,4-benzothiadiazinové deriváty, jejich příprava a použití

1,2,4-benzothiadiazin-derivate, ihre herstellung und verwendung

1,2,4－苯并噻二嗪衍生物、其制备方法及其应用

由式I表示的1，2，4-苯并噻二嗪衍生物，其中D、R 1 、R 2 、R 3 、R 4 、R 5 、R 12 、R 13 、R 14 和R 15 如说明书定义、其组合物及其制备所述组合物的方法。该组合物用于治疗中枢神经系统、心血管系统、肺系统、胃肠系统和内分泌系统疾病。

1,2,4-Benzotiadiazin-származékok,valamint ezeket tartalmazó gyógyászati készítmények

A találmány tárgyát képezik az új, (I) általánős képletű 1,2,4-benzőltiadiazin-származékők vagy ezek gyógyászatilag megfelelő savvalvagy bázissal képzett sói, vagy őptikai izőmerjei, vagy az őptikaiizőmerek elegyei, ideértve a racém elegyeket vagy taűtőmer alakőkatis. A találmány tárgyáhőz tartőznak e vegyületeket tartalmazó gyó-gyászati készítmények és a vegyület előállítására szőlgáló eljárás is.Az (I) általánős képletű vegyületek káliűmcsatőrna-nyitó hatástfejtenek ki, és így eredményesen alkalmazhatók a közpőnti idegrendszermegbetegéseinek, a szív- és érrendszer, a tüdő, a győmőr- ésbélrendszer, valamint az endőkrinőlógiai rendszer betegségeinekkezelésére. Az (I) általánős képletben a szűbsztitűensek jelentésetöbbek között a következő: R1 és R5 jelentése többek között egymástól függetlenül hidrőgénatőm,hidrőxil-, 1-6 szénatőmős alkőxi, 3-6 szénatőmős ciklőalkilcső-pőrtvagy 1-6 szénatőmős alkil-, 2-6 szénatőmős alkenil- vagy 2-6szénatőmős alkinilcsőpőrt, és R4 jelentése hidrőgénatőm, vagy R4 és R5 együttes jelentése az (I) általánős képlet 2-es és 3-ashelyzetében lévő atőmők közötti kettőskötés egyik kötése és R1jelentése a fentiekben megadőtt, vagy R4 és R1 együttes jelentése az (I) általánős képlet 3-as és 4-eshelyzetében lévő atőmők közötti kettős kötés egyik kötése és R5jelentése a fentiekben megadőttakkal azőnős, D jelentése -S(=O)2 vagy -S(=O)-, R2 jelentése többek között hidrőgénatőm, hidrőxil-, 1-6 szénatőmősalkőxi-, 3-6 szénatőmős ciklőalkilcsőpőrt, hidrőxil-, vagy 1-6szénatőmős alkil-, 2-6 szénatőmős alkenil- vagy 2-6 szénatőmősalkinilcsőpőrt, R3 jelentése többek között R8, -OR8, C(=X1OR8, biciklűsős alkil-,aril-, heterőaril-, aril-alkil- vagy heterőarilcsőpőrt, ahől aképletben R8 jelentése többek között hidrőgénatőm, 3-6 szénatőmősciklőalkil- vagy (3-6 szénatőmős ciklőalkil)-(1-6 szénatőmős alkil)-csőpőrt, egy vagy több heterőatőmőt tartalmazó 3-6-tagú telítettgyűrűrendszer, vagy egyenes vagy elágazó láncú 1-18 szénatőmősalkilcsőpőrt, X1 jelentése őxig ...

Process for preparing a pharmaceutically active compound (granisetron)

The invention relates to a process for preparing granisetron, or a pharmaceutically acceptable salt thereof, which comprises: a) cyclisation of a compound of formula (I) in an inert solvent and at a temperature between 0-100°C, in the presence of a strong acid, in order to yield the compound of formula (II); b) methylation of the compound of formula (II), with an alkylating agent, in the presence of a base, in an inert solvent and at a temperature between 0°C-160°C, and with optional formation of a pharmaceutically acceptable salt.The process of the invention yields a granisetron of high purity, preventing impurities due to demethylation, by carrying out the methylation after rather than before cyclisation and with a higher yield.

Process for preparing a pharmaceutically active compound (granisetron)

Process for preparing a pharmaceutically active compound (granisetron)

The invention relates to a process for preparing granisetron, or a pharmaceutically acceptable salt thereof, which comprises: a) cyclisation of a compound of formula (I) in an inert solvent and at a temperature between 0-100° C., in the presence of a strong acid, in order to yield the compound of formula (II); b) methylation of the compound of formula (II), with an alkylating agent, in the presence of a base, in an inert solvent and at a temperature between 0° C.-160° C., and with optional formation of a pharmaceutically acceptable salt. The process of the invention yields a granisetron of high purity, preventing impurities due to demethylation, by carrying out the methylation after rather than before cyclisation and with a higher yield.

Processo de preparacao de um composto activo sob o ponto de vista farmaceutico (granisetron)

Process for prepating a pharmaceutically active compound (granisetron)

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邻氨基苯磺酸协同茂锆Lewis酸高效催化制备氮杂双环化合物的方法

本发明公开了一种邻氨基苯磺酸协同茂锆Lewis酸高效催化制备氮杂双环化合物的方法，该方法以2‑环己烯‑1‑酮、芳醛、芳胺为原料，以乙醇为溶剂，以二氯二茂锆为催化剂，二氯二茂锆在加入Bronsted酸——邻氨基苯磺酸的条件下，可以高效高产率的制备一系列氮杂双环化合物。本发明催化剂用量少，价廉，无毒，对空气稳定，反应条件温和，原子经济性高，反应结束后只需将产物经过简单的分离、重结晶，即可得到氮杂双环化合物，为氮杂双环化合物的制备开辟了新的低成本且绿色高效的途径，具有广阔的应用前景。

Werkwijze voor het bereiden van bicyclisch ge- rde verbindingen als stabilisatiemiddelen ultraviolet licht; werkwijze voor het sta- eren van organische materialen met deze sta- atiemiddelen, alsmede de gevormde gestabi- rde organische materialen.

Verfahren zur herstellung von neuen 1,4-athano-2,3-dihydrochinolinderivaten und deren salzen

Azabicyclic esters of omega-%4-biphenylyl<alkanoic acids

Verfahren zur herstellung neuer azabicyklischer ester von omega-(4-biphenylyl)-alkancarbonsauren und ihren salzen

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Azabicyclic esters of omega-(4-biphenylyl)alkanoic acids

Azabicyklische ester von omega-(4biphenylyl)-alkancarbonsaeuren

Esters azabicycliques d'acides omega-(4-biphenylyl)-alcandiques

Verfahren zur herstellung neuer azabicyklischer ester von omega-(4-biphenylyl)-alkancarbonsauren und ihren salzen