СПОСОБ ПОЛУЧЕНИЯ ЦИКЛОАЛКИЛКАРБОКСАМИДО-ИНДОЛЬНЫХ СОЕДИНЕНИЙ

Настоящее изобретение относится к способу получения ()-1-(2,2-дифторбензо[d][1,3]диоксол-5-ил)-N-(1-(2,3-дигидроксипропил)-6-фтор-2-(1-гидрокси-2-метилпропан-2-ил)-1-индол-5-ил)циклопропанкарбоксамида (соединение I), полезного для лечения заболеваний, опосредованных CFTR, таких как кистозный фиброз, а также к способам получения промежуточных соединений. 5 н. и 57 з.п. ф-лы, 2 табл.

ИНДОЛИН-СУЛЬФОНАМИДНЫЕ СОЕДИНЕНИЯ

FIELD: chemistry. SUBSTANCE: invention relates to novel indoline-sulphonamides of formula (I): , where R 1 denotes H, halogen; R 2 denotes I I, Ar, Ar-C(O)-, Ar-CH 2 -, Ar-SO 2 -, Ar-O-C(O)-, , R"-C(O)-, where Ar is unsubstituted phenyl or phenyl which is substituted with one substitute selected from a group comprising halogen, NO 2 , CN, alkoxy, CH 3 OC(O)-, or denotes a six-member heteroaryl with one N atom as a heteroatom, or is its N-oxide derivative, or denotes a five-member heteroaryl with one S or O atom as a heteroatom; R' and R" independently denote C 1 -C 10 alkyl; R 3 denotes C 1 -C 10 alkyl. EFFECT: compounds can inhibit tubulin polymerisation which enables their use in cancer treatment. 16 cl, 25 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 402 530 (13) C2 (51) МПК C07D 209/08 (2006.01) A61K 31/404 (2006.01) A61P 35/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21), (22) Заявка: 2007132670/04, 30.08.2007 (24) Дата начала отсчета срока действия патента: 30.08.2007 (73) Патентообладатель(и): Тайпей Медикал Юнивёрсити (TW), Нейшнл Хелс Резерч Инститьютс (TW) (43) Дата публикации заявки: 10.03.2009 2 4 0 2 5 3 0 (45) Опубликовано: 27.10.2010 Бюл. № 30 (56) Список документов, цитированных в отчете о поиске: RU 2127259 C1, 10.03.1999. J. of Medicinal Chemistry, v.49, n.23, 2006, p.6656-6659. 2 4 0 2 5 3 0 R U (54) ИНДОЛИН-СУЛЬФОНАМИДНЫЕ СОЕДИНЕНИЯ SO2-, Ar-O-C(O)-, , где Ar является незамещенным фенилом или фенилом, замещенным одним заместителем, выбранным из группы, включающей галоген, NO2, CN, алкокси, CH3OC(O)-, или означает шестичленный гетероарил с одним атомом N в качестве гетероатома, или является его Nоксидным производным, или означает пятичленный гетероарил с одним атомом S или О в качестве гетероатома; R' и R'' независимо означают C1-С1 0алкил; R 3 означает C1-С1 0 алкил. Соединения обладают способностью ингибировать полимеризацию тубулина, что позволяет ...

ПРОИЗВОДНЫЕ ИНДОЛИН-2-ОНА И ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ ДЛЯ ИХ ПОЛУЧЕНИЯ

Производные индолина общей формулы 1, где R1 - галоген, низший алкил, низший алкокси, ОН, NO2, алкоксикарбонил, СООН, R2 - Н, замещенный или незамещенный низший алкил, замещенный или незамещенный низший алкенил, замещенный или незамещенный арил; R3 - замещенный или незамещенный низший алкил, замещенный или незамещенный циклоалкил, замещенный или незамещенный арил; R4 - замещенный или незамещенный низший алкил, замещенный или незамещенный арил, OR5, -NR6R7, где R5, R6, R7 могут быть одинаковыми или различными и каждый представляет Н, замещенный или незамещенный низший алкил, замещенный или незамещенный циклоалкил, замещенный или незамещенный арил, замещенный или незамещенный пиридил, пиримидил, индолил, индолинил или низшая алкоксигруппа, или R6 и R7 взятые вместе образуют -(CH2)m- или -(CH2)lNR8- (CH2)h (где h, l, m каждый, равны 1-8, R8 - Н, низший алкил), Х и Y могут быть одинаковыми или различными и каждый представляет -СН2-, -NH-, -O-; n = 0-4. Соединения проявляют избирательный антагонизм ...

Способ получения производных аминопиррола или его солей

Способ получения производных пиразоло (1,5-с) хиназолина или солей

Compounds are provided having the structure <IMAGE> wherein R1 and R2 may be the same or different and R1 is hydrogen, alkyl of 1-3 carbons, phenyl optionally substituted by R4 or <IMAGE> R2 is <IMAGE> hydrogen, lower alkyl or phenyl optionally substituted by R4 with the proviso that at lest one of R1 and R2 is <IMAGE> R3 is hydrogen, lower alkyl, benzyl or phenyl optionally substituted by R4; and R4 and R5 are the same or different and represent hydrogen, lower alkyl, lower alkoxy, alkanoyloxy, benzyloxy, hydroxy, halogen (C1, Br and F), nitro, and trifluoromethyl; R6 is hydrogen, lower alkyl, alkanoyl, aroyl, aralkanoyl, aralkyl or phenyl; and R7, R8, m and n are as defined hereinafter.

INDOL DERIVATIVE ALS INHIBITOREN DER LÖSLICHEN ADENYLATZYKLASE

SULFOBENZOYL HYDRAZONES

... 1,210,539. Sulphobenzoylhydrazones. ROUSSEL UCLAF. 22 Dec., 1967 [26 Dec., 1966; 23 March, 1967], No. 58466/67. Headings C2A, C2C and C2U. The invention comprises compounds of the Formula I in which the sulpho group is in the 3- or 4-position of the benzene ring wherein Y represents hydrogen when the group = C-Z represents the residue of an aldehyde of the formula O=CHZ or =C(Y)Z represents the residue of a ketone or quinone of the formula O=C(Y)Z, and salts thereof with bases e.g. tetracycline and their preparation by reacting a corresponding hydrazide of the Formula II or a salt thereof with an aldehyde, ketone or quinone in the presence of a metal, ammonia or organic base salt of a carboxylic acid. Examples of compounds of the formula O=C(Y)Z are 3#-hydroxy- 17-oxo-androst-5-ene, isatin; N- propyl-, N-benzyl- and 5-nitro-isatin, 3#- hydroxy - 20 - oxo - pregn - 5 - ene and 5- nitrofurfuraldehyde. Therapeutic compositions in forms suitable for oral, parenteral, rectal or topical administration ...

ª‡-aliphatic carboxylic acid derivatives

Novel compounds of formula wherein A is an aroyl or heteroaroyl radical, each of R1 and R2 is H, alkyl, acyl, cycloalkyl, alkenyl, aryl or aralkyl, R3 is H or a C1- 6 alkyl radical, R4 is H, halogen, C1- 5 alkyl, C1- 5 alkoxy or CF3, R5 is H, halogen, C1- 5 alkyl, NO2, C1- 5 alkoxy, amino, mono- or di-(C1- 5 alkyl) amino, haloalkyl, C2- 6 alkanoylamino, C2- 6 alkanoyl, bis-(hydroxy-C1- 5 alkyl) amino, 1-pyrrolidino, 4-methyl-1-piperazinyl, 4-morpholino, cyano, amino-C1- 5 alkyl, di-(C1- 5 alkyl) amino-C1- 5 alkyl, CF3, OH, di-(C1- 5 alkyl) sulphamoyl, benzylthio, benzyloxy, (C1- 5 alkyl) benzyloxy, (C1- 5 alkoxy) benzyloxy, C2- 5 alkenyl, C2- 5 alkenyloxy, 1-azacyclopropyl, cyclopropylmethyloxy or cyclobutylmethyloxy, M is OH, amino, substituted amino (including heterocyclic amino), C1- 5 alkoxy, C2- 5 alkenyloxy, C2- 5 alkynyloxy, aryloxy, C3- 6 cycloalkoxy, C3- 6 cycloalkenyloxy or C3- 6 cycloalkynyloxy or a substituted derivative thereof or OZ where Z is a cation ...

Methylbenzene sulphonamides

A "physical form" of N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl]- 3-methoxybenzoyl]-2-methylbenzenesulphonamide (Compound A) free of other forms and having defined ir spectral peaks is obtained by heating a physical form of the monohydrate of Compound A under reduced pressure. A physical form of the monohydrate with defined ir peaks and XRD pattern is claimed as novel. The physical form of Compound A may also be prepared by spray drying a solution, e.g. aqueous acetone, containing mixed "physical forms" of the sulphonamide. Solutions of the physical forms in acetone are also claimed. Pharmaceutical compositions containing physical forms of compound A e.g. with activity against asthma are also disclosed.

Indole compounds as anti-inflammatory/analgesic agents..

The invention provides a compound of the following formula: and pharmaceutically acceptable salts thereof, where l is oxygen or sulphur; y is a direct bond or c1-4 alkylidene; q is c1-6 alkyl, c3-7 cycloalkyl, phenyl, naphthyl, heteroaryl or the like; r1 is hydrogen, c1-6 alkyl or the like; r2 is hydrogen, c1-4 alkyl c(o)r5 wherein r5 is c1-22 alkyl or c2-22 alkenyl, halosubstituted c1-8 alkyl, halosubstituted c2-8alkenyl, -y-c3-7cycloalkyl, -y-c3-7cycloalkenyl, phenyl, naphthyl, heteroaryl or the like; x is halo, c1-4 alkyl, hydroxy, c1-4 alkoxy or the like; and n is 0, 1,2 or 3 with the proviso that a group of formula -y-q is not methyl or ethyl when x is hydrogen; l is oxygen; r1 is hydrogen; and r2 is acetyl. This invention also provides a pharmaceutical composition useful for the treatment of medical condition in which prostaglandis are implicated as pathogens.

Pharmaceutical composition comprising a particular pysical form of a heterocyclic amide derivative.

The invention provides a pharmaceutical physical form of n-(4=(5-(cyclopentyloxy carbonyl)amino-1-methylindol-3-yl-methyl)-3-methoxybenzoyl)-2-methyl benzenesulphonamide and polyvinypyrrolidone. It also provides methods for preparing this physical form, and another physical form of n-(4-(5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl)-3-methoxybenzoyl)-2-methylbenzesulphonamide useful in the prepatation of the first mentioned physical form. The compositions are useful in the treatment of diseases in which leukotrienes are implicated, for example asthma ...

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHARMACEUTICAL AGENTS

Antivral drugs for treatment of arenavirus infection

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Antivral drugs for treatment of arenavirus infection

Heterocyclic compounds nitrogenized digests, proceeded them to separate and pharmaceutical composition while containing.

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHARMACEUTICAL AGENTS

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Antivral drugs for treatment of arenavirus infection

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PHOSPHONATE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

PROCEDURE FOR the PRODUCTION OF 7-BENZOYLINDOLIN-2-ONEN

INDOL OF DERIVATIVES AS INHIBITORS THE SOLUBLE ADENYLATZYKLASE

CB1-MODULATORVERBINDUNGEN

DIARYLHARNSTOFFDERIVATE AND THEIR USE AS CHLORIDE CHANNEL BLOCKERS

3 ', 6-SUBSTITUIERTE INDIRUBINE AND YOUR BIOLOGICAL APPLICATIONS

3 ', 6-SUBSTITUIERTE INDIRUBINE AND YOUR BIOLOGICAL APPLICATION

PROCEDURE FOR THE PRODUCTION OF CHINAZOLINONDERIVATEN

PROCEDURE FOR THE PRODUCTION OF NEW AMINOPYRROLDERIVATE AND THEIR SALTS

PROCEDURE FOR the PRODUCTION OF 2-AMINO-3BENZOYLPHENYLESSIGS [UREN, YOUR METAL SALTS OR LOW ALKYL STAR

DRUG.

INDOL SULFONAMIDE AS ANTI-TUMOR MEANS

INDOL CONNECTIONS AS COX-2 INHIBITORS

PROCEDURE FOR THE PRODUCTION OF NEW AMINOPYRROLDERIVATE AND THEIR SALTS

NEW ENZYMATIC SUBSTRATES TO THE PROOF OF PSEUDOMONAS AERUGINOSA

INDOLIN-2-ON-DERIVATE

CYCLOHEXANDIHARNSTOFF DERIVATIVES AND PROCEDURES FOR THEIR PRODUCTION

GROWTH-HORMONE-SETTING FREE OXINDOLDERIVATE

Thrombopoietin activity modulating compounds and methods

Non-nucleoside reverse transcriptase inhibitors

1-sulfonylindole derivatives, their preparation and their use as 5-HT6 ligands

Substituted benzyl amine compounds

Indoline-sulfonamides compounds

Process for Pd-catalysed C-N coupling in specific solvent systems

Arylosulfonamides for the treatment of CNS diseases

Arylsulphonamide derivatives of formula (I) and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of disorders of the central nervous system.

Intermediates and processes for the preparation of 4- (acetylamino) ) -3- [ (4-chloro-phenyl) thio] -2-methyl-1H-indole-1-acetic acid

The invention relates to compounds of formula (X), and salts thereof, and their use as intermediates in improved manufacturing processes for the synthesis of pharmaceutical compound of formula (I): X is =0, =N-0H or =N-OC(O)Me; Y is hydrogen, PhS- or ...

New phenylpiperazines

Chondrongenesis promotors and indolin-2-one derivatives

NOVEL FENAMIC ACID HYDROXAMATE DERIVATIVES HAVING CYCLOOXYGENASE AND 5-LIPOXYGENASE INHIBITION

New heterocycloalkylbenzocyclobutane and heteroarylbenzocyclobutane compounds, a process for their preparation and pharmaceutical compositions containing them

N-acetylserotonin derivatives and uses thereof

PHARMACEUTICAL AGENTS

The invention provides a pharmaceutical composition comprising a particular physical form of N-[4-[5-(cyclopentyloxy- carbonyl)amino-1-methylindol-3-yl-methyl]-3-methoxybenzoyl]-2-methyl- benzenesulphonamide and polyvinylpyrrolidone. It also provides methods for preparing this physical form, and another physical form of N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl]- -3-methoxybenzoyl]-2-methylbenzenesulphonamide useful in the preparation of the first mentioned physical form. The compositions are useful in the treatment of diseases in which leukotrienes are implicated, for example asthma.

POLYSUBSTITUTED AS-TRIAZINO(5,6-B)INDOLES

COMPOUNDS ACTING AS MELANOCORTIN RECEPTOR LIGANDS

The present invention provides novel compounds and use of compounds of general formula (I) as ligands to the melanocortin receptors and/or for treatment of disorders in the melanocortin system: Wherein X and Y are independently chosen from O, N, S and (CH2)n, where n is 0, 1, 2, 3, 4 or 5, or a combination of these and may contain carbon-carbon multiple bonds and branched chains as well as alicyclic and heterocyclic groups; Q is H or OH; R1 and R2 can be either the same or different and are chosen from hydrogen or the residue of an aromatic group as listed in Scheme 1 and the pharmacologically active salts thereof.

PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING ACUTE MYELOID LEUKEMIA OR METASTATIC BREAST CANCER

The present invention relates to a pharmaceutical composition comprising an indirubin derivative as an effective ingredient for prevention or treatment of acute myeloid leukemia or metastatic breast cancer. When used, the composition of the present invention can effectively inhibit the activity of FLT3 kinase and can be usefully applied to the prevention or treatment of acute myeloid leukemia or metastatic breast cancer.

COMPOUNDS AND METHODS OF TREATING INFECTIONS

SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME

The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts, solvates and prodrugs thereof: Formula (I) wherein Q is selected from O, S and Se; J is S or Se; W1 and W2, when present, are independently selected from N and C; R1 and R2 are independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12alkenyl, C2-C12alkynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, cycloalkenyl, amino, amido, alkylthio, acyl, arylalkyl and acylamido, all of which may be optionally substituted; and wherein at least one of W1 and W2 is present and is a nitrogen atom and when R1 and R2 are cyclic then the respective W1 or W2 may form part of the ring structure. The present invention also relates to pharmaceutical compositions including such compounds, to methods of treatment using such compounds, in particular in relation to NLRP3 inflammasome mediated disorders, and to associated diagnostic uses.

A PHYSICAL FORM OF N-[4-[5-(CYCLOPENTYLOXYCARBONY)AMINO-1-METHYLINDOL-3YL-METHY1]-3-METHOXYBENZOY1]-2-METHLBENZENESULPHONAMIDE, PROCESSES FOR ITS PREPARATION AND COMPOSITIONS CONTAINING IT

2-OXOINDOLINE DERIVATIVE

OXINDOLE DERIVATIVES

There is provided compounds of the formula (I) wherein R6, V, W, X, Y and n are as described. The compounds exhibit activity as anticancer agents. ...

INHIBITORS OF FATTY ACID AMIDE HYDROLASE

COMPOUNDS AND METHODS OF TREATING INFECTIONS

The invention provides compounds of Formula (I), and methods of treating or preventing a bacterial infection in a subject using a compound of Formula (I). The invention also provides the use of a compound of Formula (I) in the manufacture of a medicament for the treatment of a bacterial infection in a subject. The invention further provides a medical device when used in a method of treating or preventing a bacterial infection in a subject and to a medical device comprising the composition of the invention.

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R12 or R13 on the A group is an amide substituent (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

AMINO COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R12 or R13 on the A group is an amino substituent (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

SUBSTITUTED INDOLE COMPOUNDS AS ANTI-INFLAMMATORY AND ANALGESIC AGENTS

This invention provides a compound of the following formula: (I) or the pharmaceutically acceptable salts thereof wherein R1 is H or C1-4 alkyl; R2 is C(=L')R3 or SO2R4; Y is a direct bond or C1-4 alkylene; L and L' are independently oxygen or sulfur; Q is selected from the following: C1-6 alkyl, halo- substituted C1-4 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted phenyl or naphthyl, optionally substituted 5 or 6-membered monocyclic aromatic group; R3 is -OR6, -NR7R8, N(OR1)R7 or a group of formula: Z is a direct bond, O, S or NR5; R4 is C1-6 alkyl, halo-substituted C1-4 alkyl, optionally substituted phenyl or naphthyl; R5 is C1-4 alkyl or halo-substituted C1-4 alkyl; R6 is C1-4 alkyl, C3-7 cycloalkyl, C1-4 alkyl-C3-7 cycloalkyl, halo-substituted C1 -4 alkyl, optionally substituted C1-4 alkyl-phenyl or phenyl; R7 and R8 are each selected from the following: H, optionally substituted C1-6 alkyl, optionally substituted C3- 7 cycloalkyl, optionally substituted ...

Procédé de préparation de dérivés solubles dans l'eau d'adrénochrome

Verfahren zur Herstellung von farbigen Kondensationsprodukten

Verfahren zur Herstellung von o-Amino-benzonitrilen

4-Aryl-2-(1H)-quinazolinones prepn - by hydrolysis or thermolysis of 2-(acylureido)-benzophenones

Title cpds. of formula: (where R1-R3 = H, hal, CF3, NO2, 1-4C alkyl, or 1-4C alkoxy, and R4 = H, 1-4C (polyhalo)alkyl, or cycloalkylalkyl) are prepd. by thermolysis or acid/base hydrolysis of (II) (where R5 = H, 1-4C alkyl, Ph, 1-4C alkoxy, PhCH2O, NH2, CO2H, CONH2 or lower alkoxycarbonyl). (II) are prepd. (a) from 2-carboxyazido 3-aryl-indoles by reaction with alkanol or alkanecarboxylic acid followed by oxidn. e.g. with O3, H2O2 peracid or KMnO4, or (b) from a 3-aryl-1,2-dicarboxyamido indale by (i) oxidn. as above, and (ii) reaction with H2O2, NH3 or alkanol.

Procédé de préparation de nouvelles hydrazones

Verfahren zur Herstellung von neuen Isatin-thiosemicarbazonen

Verfahren zur Herstellung von Farbstoffen

Verfahren zur Herstellung von N-o-Cyanophenyl-N',N'-dialkylformamidiniumsalzen

Verfahren zur Herstellung virostatisch wirksamer substituierter Isatin-isothiosemicarbazone

Procédé de préparation de composés amino-3-aryloxindoles substitués en la position 3

1-3-methyl-piperidino-methyl-isatin-3-thiosemicarbazone

Cpd. of formula I (Go-1428) and its salts. Antiviral agents. 8.8 g. II in 150 ml. THF was treated with 3.96 g. III and 3.6 ml. 37% aqs. formaldehyde. Mixture refluxed for 3 hrs., solvent evaporated and residue stirred with 2 ml. ethanol, cooled, filtered and recryst. from absolute ethanol to give I, m.p. 172 deg.C.

Verfahren zur Herstellung neuer Isatin-B-Thiosemicarbazone

Verfahren zum Färben oder Bedrucken von hydrophoben Textilmaterialien

Procédé de préparation de sels d'alcaloïdes ou d'antibiotiques de méta- ou para-sulfobenzoyl-hydrazones

7H-Indolo[2,3-c]isoquinolines and process for their preparation

... 7H-Indolo[2,3-c]isoquinolines of the general formula in which R1, R2, R3 and R4 have the meaning given in Patent Claim 1, and their salts with acids are claimed. The compounds in which R2 does not denote hydrogen are prepared by reaction of a compound of the general formula in which R1, R3 and R4 have the meaning given in Claim 1, with a reactive ester of an alcohol of the general formula R8-OH in which R8 has the meaning given in Claim 5. The compounds obtained are optionally converted into a salt by reaction with an inorganic or organic acid. The compounds are useful pharmaceutical substances which can be employed for the control of malignant neoplasms. The parent substance of the abovementioned general formula, in which R2 denotes a hydrogen atom, is prepared by heating the corresponding 2-isocyanato-3-phenylindole.

7 A-ACYLINDOLES IN AND THEIR USE FOR THE PREPARATION OF 7 A-ACYLINDOLINE AND 2 A-ONS.

(1 (2-BENZOXAZOLYL, 2-BENZTHIAZOLYL AND 2-INDOLYL) - HYDRAZINO) - ALKANE NITRILE DERIVATIVES.

New biologically active compound n-[3-(4-nitrophenylamino)-indole-2-ilmethylene]aminoguanidine hydrochloride with anti-inflammatory activity

The present invention relates to chemical-pharmaceutical industry and medicine. The present invention relates to N-[ 3 -( 4 -nitrophenylamino)-indole- 2 -ilmethylene]aminoguanidine hydrochloride of formula ( 2 ) having anti-inflammatory and chondroprotective activity. The compound does not exhibit adverse effects.

Novel methods for the preparation of p2x7r antagonists

Disclosed are novel methods for the synthesis of N-substituted indol-3-yl-alkylamide compounds which act as P2X7R antagonists, said methods involving the rearrangement of an oxime intermediate.

Antiviral Drugs for Treatment of Arenavirus Infection

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, and Pichinde), Filoviridae (Ebola and Marburg viruses), Flaviviridae (yellow fever, Omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever). 167-. (canceled)68. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a pharmaceutically effective amount of a compound or a pharmaceutically-acceptable salt thereof , selected from the group consisting of2-Phenyl-cyclopropanecarboxylic acid [1-(4-amino-phenyl)-eth-(E)-ylidene]-hydrazide;Cyclopropanecarboxylic acid (4-[1-[(2-phenyl-cyclopropanecarbonyl)-hydrazono]-ethyl]-phenyl)-amide;2-Phenyl-cyclopropanecarboxylic acid [1-(2,4-dimethoxy-phenyl)-eth-(E)-ylidene]-hydrazide;2-Phenyl-cyclopropanecarboxylic acid [1-p-tolyl-eth-(E)-ylidene]-hydrazide;2-Phenyl-cyclopropanecarboxylic acid [1-biphenyl-4-yl-eth-(E)-ylidene]-hydrazide;2-Phenyl-cyclopropanecarboxylic acid [1-(3,4-dimethoxy-phenyl)-eth-(E)-ylidene]-hydrazide;Furan-2-carboxylic acid (4-[1-[(2-phenyl-cyclopropanecarbonyl)-hydrazono]-ethyl]-phenyl)-amide;2,4-Dichloro-N-(4-[1-[(2-Phenyl-cyclopropanecarbonyl)-hydrazono]-ethyl]-phenyl)-benzamide;2-Phenyl-cyclopropanecarboxylic acid [1-(2-hydroxy-phenyl)-eth-(E)-ylidene]-hydrazide;Thiophene-2-carboxylic acid (4-[1-[(2-phenyl-cyclopropanecarbonyl)-hydrazono]-ethyl]-phenyl)-amide;2-Phenyl-cyclopropanecarboxylic acid [1-(4-dimethylamino-phenyl)-eth-(E)-ylidene]-hydrazide;2-Phenyl-cyclopropanecarboxylic acid [1-(4-methoxy- ...

Hydrazone modulators of cannabinoid receptors

Hydrazone compounds which modulate cannabinoid receptors are presented. Pharmaceutical compositions containing these compounds, methods of using these compounds as modulators of cannabinoid receptors and processes for synthesizing these compounds are also described herein.

INDIRUBIN DERIVATIVES AND USES THEREOF IN TREATING CHRONIC MYELOGENOUS LEUKEMIA

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). One aspect of the invention relates to a method of treating CML using at least one indirubin derivative compound or a pharmaceutical composition thereof. Indirubin derivatives (IRDs) potently inhibited Signal Transducer and Activator of Transcription 5 (Stat5) protein in CML cells. Compound IRD 810 inhibits Bcr-Abl/Stat5 or Src/Stat5 signaling in human KCL-22 CML and imatinib-resistant human KCL-22 CML cells expressing the T315I mutant Bcr-Abl. Previous studies indicate that SFKs cooperate with Bcr-Abl to activate downstream Stat5 signaling. Activation of Stat5 was strongly blocked by IRD 810 in CML cells. IRDs disclosed herein have been identified as potent inhibitors of Bcr-Abl/Stat5 or SFK/Stat5 signaling pathway. IRDs disclosed herein are new therapeutics for wild type or T315I mutant Bcr-Abl-positive CML patients, and may also treat other solid tumors, including prostate cancer and lymphoma. 2. A pharmaceutical composition comprising a therapeutically effective amount of at least one IRD according to .3. The pharmaceutical composition according to claim 2 , further comprising a pharmaceutically acceptable carrier.4. A method of treating a cancer in a subject comprising administering to the subject a pharmaceutical composition according to .5. The method according to claim 4 , wherein the cancer is CML.6. The method according to claim 5 , wherein the CML is a CML resist to one or more drugs selected from the group consisting of imatinib claim 5 , dasatinib and nilotinib.7. The method according to claim 6 , wherein the at least one IRD is selected from the group consisting of IRDs 681 claim 6 , 682 claim 6 , 684 claim 6 , 790 claim 6 , 791 claim 6 , 800 claim 6 , 801 claim 6 , 804˜807 claim 6 , and 810.8. The method according to claim 4 , wherein the cancer treated is prostate cancer claim 4 , and the at least one ...

Ether compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R 12 or R 13 on the A group is an ether (R 32 ) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

Compounds for Treatment of Complement Mediated Disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 7. The pharmaceutical composition of claim 6 , wherein Xis CRand Xis CR.8. The pharmaceutical composition of claim 7 , wherein Ris C-Calkyl.9. The pharmaceutical composition of claim 8 , wherein Ris hydrogen.10. The pharmaceutical composition of claim 8 , wherein C-Calkyl is methyl.11. The pharmaceutical composition of claim 10 , wherein Ris hydrogen.12. The pharmaceutical composition of claim 7 , wherein Rand Rare both hydrogen.17. The pharmaceutical composition of claim 1 , wherein the composition is suitable for delivery to a human.18. The pharmaceutical composition of claim 1 , wherein the composition is suitable for systemic delivery.19. The pharmaceutical composition of claim 1 , wherein the composition is suitable for topical delivery.20. The pharmaceutical composition of claim 1 , wherein the composition is suitable for ocular delivery.21. The pharmaceutical composition of claim 1 , wherein the composition is suitable for intravitreal delivery. This application is a continuation of U.S. application Ser. No. 14/631,828, filed Feb. 25, 2015, which claims the benefit of provisional U.S. Application No. 61/944,189 filed Feb. 25, 2014, provisional U.S. Application No. 62/022,916 filed Jul. 10, 2014, and provisional U.S. Application 62/046,783 filed Sep. 5, 2014. The entirety of each of ...

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 2. The process of claim 1 , wherein Rand R are independently chosen from hydrogen claim 1 , halogen claim 1 , and C-Calkyl.3. The process of claim 1 , wherein Ris hydrogen.5. The process of claim 1 , wherein Ris hydrogen.6. The process of claim 1 , wherein B is —(C-Calkyl)(aryl) or —(C-Calkyl)(heteroaryl); each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.7. The process of claim 1 , wherein B is —(C-Calkyl)(heteroaryl) which is unsubstituted or substituted with one or more substituents independently chosen from Rand R.8. The process of claim 1 , wherein Ris selected from halogen and C-Calkyl.14. The process of claim 13 , wherein Rand R are independently chosen from hydrogen claim 13 , halogen claim 13 , and C-Calkyl.15. The process of claim 14 , wherein Ris C-Calkanoyl.16. The process of claim 15 , wherein B is —(C-Calkyl)(heteroaryl); each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R.17. The process of claim 16 , wherein Ris hydrogen.18. The process of claim 17 , wherein Ris selected from halogen and C-Calkyl. This application is a continuation of U.S ...

Smyd2 inhibitors

The present disclosure generally relates to compounds having cellular anti-proliferative activities, and more particularly relates to compounds which inhibit the activity of human SMYD2, a SET and MYND domain-containing protein lysine methyltransferase.

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 12. The pharmaceutical composition of claim 1 , wherein B is —(C-Calkyl)(aryl) or —(C-Calkyl)(heteroaryl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.13. The pharmaceutical composition of claim 12 , wherein B is —(CH)(aryl) substituted with two substituents independently chosen from Rand R.14. The pharmaceutical composition of claim 13 , wherein Ris halogen.15. The pharmaceutical composition of claim 14 , wherein there are two Rsubstituents and one is chlorine and the other is fluorine.18. The pharmaceutical composition of claim 12 , wherein B is aryl or heteroaryl each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R.19. The pharmaceutical composition of claim 18 , wherein B is aryl.20. The pharmaceutical composition of claim 18 , wherein B is heteroaryl.21. The pharmaceutical composition of claim 20 , wherein heteroaryl is 2-pyridine.22. The pharmaceutical composition of claim 21 , wherein 2-pyridine is substituted with one substituent independent chosen from R.23. The pharmaceutical composition of claim 22 , wherein Ris halogen.31. The ...

Compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

Benzamides and nicotinamides as syk modulators

The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.

Inhibitor of indoleamine-2,3-dioxygenase (ido)

The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating a disease associated with IDO, for example, cancer or an infectious disease (e.g., viral or bacterial infectious diseases). Also, provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

METHOD OF USING AN INDOLINONE MOLECULE AND DERIVATIVES FOR INHIBITING LIVER FIBROSIS AND HEPATITIS

This invention relates to methods of reversing and inhibiting liver fibrosis and hepatitis using a small indolinone molecule Hesperadin and related compounds. Methods of identifying such agents and using them to inhibit the expression of collagens and ECM proteins including MMPs and TIMPs in purified hepatic stellate cells are provided. In vivo data of Hesperadin in inhibiting induced collagen production are presented. This method of specifically targeting drugs to hepatic stellate cells in vivo, provides a novel therapy for liver diseases. 2. The method according to claim 1 , wherein X is carbon claim 1 , n is 0 claim 1 , Ris NSO—CH claim 1 , and the compound is a member selected from the group consisting of:(Z)-N-(2-oxo-3-(phenyl(4-(piperidin-1-ylmethyl)phenylamino)methylene)indolin-5-yl)ethanesulfonamide (Hesperadin)(Z)-N-(2-oxo-3-(phenyl(phenylamino)methylene)indolin-5-yl)ethanesulfonamide(Z)-N-(2-oxo-3-(phenyl(p-tolylamino)methylene)indolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-methoxyphenylamino)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-(dimethylamino)phenylamino)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-fluorophenylamino)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-chlorophenylamino)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-bromophenylamino)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-nitrophenylamino)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-(morpholinomethyl)phenylamino)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-(diphenylmethylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(2-oxo-3-(phenyl(p-tolyl)methylene)indolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-methoxyphenyl)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-(dimethylamino)phenyl)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4-fluorophenyl)(phenyl)methylene)-2-oxoindolin-5-yl)ethanesulfonamide(Z)-N-(3-((4- ...

SUBSTITUTED FUSED BI- OR TRI- HETEROCYCLIC COMPOUNDS AS EHMT2 INHIBITORS

The present disclosure relates to substituted fused bi- or tri-heterocyclic compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., sickle cell anemia) via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, by administering a substituted fused bi- or tri-heterocyclic compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes. 2. The compound of claim 1 , wherein when n is 2 claim 1 , Xis CRR claim 1 , Xis N claim 1 , Xis C claim 1 , Ris NH claim 1 , and at least one Ris OR claim 1 , then one of (1)-(4) below applies:{'sup': 1', '11', '1', '1', '1', '1', '5', '6', '5', '6', '5', '6', '5', '5', '5', '5', '6', '5', '6', '5', 'S1', 'S1', 'S1', '6', '5', '5', '5', '6, 'sub': 1', '6', '1', '6', '3', '12', '1', '6', '2', '2', '2', '1', '6, '(1) at least one of Rand Ris -Q-T, in which Qis a C-Calkylene linker optionally substituted with one or more of halo, cyano, hydroxyl, or C-Calkoxyl, and Tis cyano, NRR, C(O)NRR, —OC(O)NRR, C(O)OR, —OC(O)R, C(O)R, —NRC(O)R, —NRC(O)OR, OR, or R, in which Ris C-Ccycloalkyl, phenyl, 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N, O, and S, or a 5- or 6-membered heteroaryl and Ris optionally substituted with one or more of halo, C-Calkyl, hydroxyl, oxo, —C(O)R, —SOR, —SON(R), —NRC(O)R, amino, mono- or di-alkylamino, or C-Calkoxyl; or'}{'sup': 1', '11', '1', '1', '1', '1', '5', '6', '5', '6', '5', '6', '5', '5', '5', '5', '6', '5', '6', '5', 'S1', 'S1', 'S1', '6', '5', '5', '5', '6, 'sub': 2', '6', '2', '6', '1', '6', '3', '12', '1', '6', '2', '2', '2', '1', '6, '(2) at least one of Rand Ris -Q-T, in which Qis a C-Calkenylene or C-Calkynylene linker optionally substituted with one or more of halo, cyano, hydroxyl, or C-Calkoxyl, and Tis H, halo, cyano, NRR ...

COMPOUNDS AND METHODS FOR INHIBITING FASCIN

Provided are compounds, compositions and methods for inhibiting fascin activity or treating a condition or disorder mediated by fascin activity in a subject in need thereof. 134-. (canceled)36. The compound of claim 35 , wherein Ris phenyl optionally substituted with 1 to 3 R.37. The compound of claim 35 , wherein Lis selected from the group consisting of —C(O)NH— and —NHC(O)—.38. The compound of claim 35 , wherein Ris the 5- to 10-membered heteroaryl.39. The compound of claim 35 , wherein m is 1 or 2.40. The compound of claim 35 , wherein Ris optionally substituted with 1 to 4 R claim 35 , and Ris selected from the group consisting of furan claim 35 , benzofuran claim 35 , pyridine claim 35 , pyridazine claim 35 , pyrimidine claim 35 , pyrazine claim 35 , thiophene claim 35 , thiazole claim 35 , isothiazole claim 35 , oxazole claim 35 , isoxazole claim 35 , oxadiazole claim 35 , imidazole claim 35 , pyrrole claim 35 , and pyrazole.41. The compound of claim 35 , wherein Ris not optional and is selected from the group consisting of lower alkyl claim 35 , halo claim 35 , lower haloalkyl claim 35 , —OH claim 35 , —OR claim 35 , cyano and phenyl optionally substituted methyl claim 35 , and wherein Ris lower alkyl or lower haloalkyl.42. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.44. The compound of claim 35 , wherein Ais N.45. The compound of claim 35 , wherein Ais N. This application is a continuation U.S. patent application Ser. No. 15/851,141, filed on Dec. 21, 2017, which is a continuation of U.S. patent application Ser. No. 15/437,229, filed on Feb. 20, 2017, now U.S. Pat. No. 9,850,243, issued on Dec. 26, 2017, which is a divisional of U.S. patent application Ser. No. 14/626,791, filed on Feb. 19, 2015, now U.S. Pat. No. 9,573,946, issued on Feb. 21, 2017, which claims the benefit of U.S. Provisional Application No. 61/942,554, filed on Feb. 20, 2014, the complete disclosures of which is hereby incorporated by ...

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an ether (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 7. The compound of claim 6 , wherein Ris hydrogen claim 6 , and wherein B is —(C-Calkyl)(heteroaryl) or —(C-Calkyl)(biphenyl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 6 , and 0 or 1 substituents chosen from Rand R.8. The compound of claim 7 , wherein B is substituted with 0 substituents chosen from Rand R.9. The compound of claim 8 , wherein B is substituted with 0 substituents chosen from R.10. The compound of claim 9 , wherein B is aryl claim 9 , heteroaryl claim 9 , or biphenyl.11. The compound of claim 10 , wherein Ris halogen.16. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier.17. The pharmaceutical composition of claim 16 , wherein the composition is suitable for systemic delivery.18. The pharmaceutical composition of claim 16 , wherein the composition is suitable for topical delivery.19. The pharmaceutical composition of claim 16 , wherein the composition is suitable for ocular delivery.20. The pharmaceutical composition of claim 16 , wherein the composition is suitable for intravitreal delivery. This application is a continuation of U.S. patent ...

5-BROMO-INDIRUBINS

Disclosed herein are compositions and methods for treating cancer, FLT3-AML, and CML. 1. (canceled)2. The method of claim 43 , wherein Ris hydrogen or unsubstituted alkyl.35-. (canceled)6. The method of claim 43 , wherein Ris hydrogen claim 43 , oxo claim 43 , halogen claim 43 , —CF claim 43 , —CN claim 43 , —OH claim 43 , —NH claim 43 , —COH claim 43 , —CHCOOH claim 43 , —CONH claim 43 , —NO claim 43 , or unsubstituted alkyl.79.-. (canceled)10. The method of claim 43 , wherein Ris halogen claim 43 , —OH claim 43 , —NH claim 43 , —COOH claim 43 , —CONH claim 43 , or unsubstituted alkyl.1124.-. (canceled)2629.-. (canceled)30. The method of claim 25 , wherein Ris halogen claim 25 , —CF claim 25 , —CCl claim 25 , —CBr claim 25 , —CI claim 25 , —OCF claim 25 , —OCCl claim 25 , —OCBr claim 25 , —OCI claim 25 , —CN claim 25 , —OH claim 25 , —NH claim 25 , —COOH claim 25 , —C(O)OR claim 25 , —CONH claim 25 , —NO claim 25 , —SH claim 25 , —NHNH claim 25 , —NRR claim 25 , —OR claim 25 , —SR claim 25 , substituted or unsubstituted alkyl claim 25 , substituted or unsubstituted heteroalkyl claim 25 , substituted or unsubstituted cycloalkyl claim 25 , substituted or unsubstituted heterocycloalkyl claim 25 , substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.31. (canceled)32. The method of claim 25 , wherein Rand Rare independently substituted or unsubstituted alkyl claim 25 , substituted or unsubstituted heteroalkyl claim 25 , substituted or unsubstituted cycloalkyl claim 25 , substituted or unsubstituted heterocycloalkyl claim 25 , substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.3342.-. (canceled)4445.-. (canceled)46. The method of or claim 25 , wherein said FLT3-kinase is a FLT3-mutant kinase.47. The method of claim 46 , wherein said FLT3-mutant kinase is a FLT3-TKD mutant kinase.48. The method of claim 47 , wherein said FLT3-TKD mutant kinase comprises a mutation at an amino acid residue position corresponding to D835 ...

CONDUCTING REACTIONS IN LEIDENFROST-LEVITATED DROPLETS

The invention generally relates to conducting reactions in Leidenfrost-levitated droplets. 1. A method for forming and collecting a reaction product , the method comprising conducting a reaction within a Leidenfrost-levitated droplet while maintaining a substantially constant volume of the Leidenfrost-levitated droplet , thereby forming a reaction product within the Leidenfrost-levitated droplet; andcollecting the reaction product in the Leidenfrost-levitated droplet without evaporating the Leidenfrost-levitated droplet.2. The method according to claim 1 , further comprising analyzing the reaction product.3. The method according to claim 2 , wherein analyzing is by a mass spectrometry technique.4. The method according to claim 1 , wherein maintaining the substantially constant volume comprises introducing droplets of pure solvent or the reaction mixture to the Leidenfrost-levitated droplet.5. The method according to claim 4 , wherein a rate at which the droplets of the pure solvent or reaction mixture are introduced to the Leidenfrost-levitated droplet is dependent on an evaporation rate of the Leidenfrost-levitated droplet.6. The method according to claim 1 , wherein the method further comprises conducting multiple reactions in multiple separate Leidenfrost-levitated droplets.7. The method according to claim 6 , wherein the multiple separate Leidenfrost-levitated droplets are merged with each other.8. The method according to claim 6 , wherein the multiple reactions are the same.9. The method according to claim 6 , wherein the multiple reactions are different.10. The method according to claim 1 , wherein the method is conducted without the use of surfactants.11. (canceled)12. A method for forming and collecting a reaction product claim 1 , the method comprising:introducing a first liquid droplet onto a heated surface that is at a temperate that is at or above a Leidenfrost point of the first liquid such that the first liquid droplet levitates on the heated surface, ...

Quinoxaline Compounds and Derivatives

The present invention provides oxazine compounds, method of using and method of making oxazine compounds and its pharmaceutical use. 4. The composition of claim 3 , wherein A is an N and B claim 3 , B′ and A′ are C; or wherein A is an O and B claim 3 , B′ and A′ are C. This patent application is a Divisional application and claims priority based on U.S. patent application Ser. No. 13/428,616, which is a non-provisional patent application of U.S. provisional patent application 61/467,323 filed on Mar. 24, 2011 and entitled “Quinoxaline Compounds and Derivatives”, and U.S. provisional patent application 61/467,335 filed on Mar. 24, 2011 and entitled “Aromatic Neuroprotecting Compounds and Derivatives Thereof” the content of each of which is hereby incorporated by reference in its entirety.Not Applicable.Not Applicable.Not Applicable.The present invention relates in general to the field of pharmaceutical compositions and synthesis, and more particularly, to novel compositions and methods for preparing the compound and its pharmaceutical use.U.S. Patent Application Publication No. 2009/0286797, entitled, Novel Quinoxaline Derivatives and Their Medical Use discloses novel quinoxaline derivatives having medical utility, to use of the quinoxaline derivatives of the invention for the manufacture of a medicament, to pharmaceutical compositions comprising the quinoxaline derivatives of the invention, and to methods of treating a disorder, disease or a condition of a subject, which disorder, disease or condition is responsive to positive modulation of AMPA receptor mediated synaptic responses.U.S. Pat. No. 3,759,912, entitled, Quinoxalines discloses a Quinoxaline useful as broad spectrum antimicrobials in human and veterinary medicine; novel intermediates useful in their preparation; processes for their production from the appropriate quinoxaline, N-monoxide quinoxaline, quinoxaline carboxylic acid or furazan oxide are disclosed.The present invention provides a compound of ...

5-bromo-indirubins

Disclosed herein inter alia are compositions and methods for treating cancer using 5-Br-indirubin derivatives.

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 6. The compound of claim 1 , wherein B is (C-Calkyl)(aryl) or (C-Calkyl)(heteroaryl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.7. The compound of claim 6 , wherein Ris halogen.8. The compound of claim 6 , wherein B is 2-pyridine.12. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.13. A method for the treatment of a disorder mediated by complement factor D claim 1 , comprising administering an effective amount to a host in need thereof of a compound of or a pharmaceutically acceptable salt thereof claim 1 , optionally in a pharmaceutically acceptable carrier.14. The method of claim 13 , wherein the host is a human.15. The method of claim 14 , wherein the disorder is age-related macular degeneration (AMD) or retinal degeneration.16. The method of claim 14 , wherein the disorder is an ophthalmic disease.17. The method of claim 14 , wherein the disorder is paroxysmal nocturnal hemoglobinuria (PNH).18. The method of claim 14 , wherein the disorder is multiple sclerosis claim 14 , arthritis claim 14 , a respiratory ...

ALKYNE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein Ror Ron the A group is an alkyne (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 2. The compound of claim 1 , wherein the compound is a hydrochloride salt. This application is a continuation of U.S. application Ser. No. 14/631,090, filed Feb. 25, 2015, which claims the benefit of provisional U.S. Application No. 61/944,189, filed Feb. 25, 2014, provisional U.S. Application No. 62/022,916, filed Jul. 10, 2014, and provisional U.S. Application 62/046,783, filed Sep. 5, 2014. The entirety of each of these applications is hereby incorporated by reference for all purposes.The complement system is a part of the innate immune system which does not adapt to changes over the course of the host's life, but is recruited and used by the adaptive immune system. For example, it assists, or complements, the ability of antibodies and phagocytic cells to clear pathogens. This sophisticated regulatory pathway allows rapid reaction to pathogenic organisms while protecting host cells from destruction. Over thirty proteins and protein fragments make up the complement system. These proteins act through opsonization (enhancing phaogytosis of antigens), chemotaxis (attracting macrophages and neutrophils), cell lysis (rupturing membranes of foreign cells) and agglutination (clustering and binding of pathogens together).The complement system has three ...

METHODS USING HDAC11 INHIBITORS

The present invention provides methods and uses of inhibitors of histone deacetylase 11 (HDAC11) in the treatment of diseases and/or disorders, such as, for example, cell proliferative diseases. 3. The compound according to claim 2 , wherein L is selected from a bond claim 2 , —CH— claim 2 , —(CH)— claim 2 , —(CH)— claim 2 , —C(O)— claim 2 , —S(O)— claim 2 , —C(O)NR— claim 2 , or —C(O)CH—.4. The compound according to claim 2 , wherein L is selected from —CH— or —C(O)—.5. The compound according to claim 2 , wherein R is hydrogen or an optionally substituted group selected from C-Calkyl claim 2 , aryl claim 2 , C-Ccycloalkyl claim 2 , heterocyclyl claim 2 , or heteroaryl containing 1-5 heteroatoms selected from the group consisting of N claim 2 , S claim 2 , P claim 2 , or O.6. The compound according to claim 2 , wherein R is hydrogen or an optionally substituted group selected from phenyl claim 2 , C-Calkyl claim 2 , cyclopropyl claim 2 , cyclobutyl claim 2 , cyclopentyl claim 2 , cyclohexyl claim 2 , pyridyl claim 2 , or morpholinyl.7. The compound according to claim 2 , wherein R is phenyl optionally substituted with one or more independent occurrences of halogen claim 2 , CF claim 2 , —SOCH claim 2 , phenyl claim 2 , C-Calkyl claim 2 , C-Calkoxy claim 2 , pyridyl claim 2 , —OCFor —OCHphenyl.8. The compound according to claim 4 , wherein R is hydrogen or an optionally substituted group selected from phenyl claim 4 , C-Calkyl claim 4 , cyclopropyl claim 4 , cyclobutyl claim 4 , cyclopentyl claim 4 , cyclohexyl claim 4 , pyridyl claim 4 , or morpholinyl.9. The compound according to claim 4 , wherein R is phenyl optionally substituted with one or more independent occurrences of halogen claim 4 , CF claim 4 , —SOCH claim 4 , phenyl claim 4 , C-Calkyl claim 4 , C-Calkoxy claim 4 , pyridyl claim 4 , —OCFor —OCHphenyl.11. The compound according to claim 2 , wherein L is selected from a bond claim 2 , —CH— claim 2 , —(CH)— claim 2 , —(CH)— claim 2 , —C(O)— claim 2 , —S(O)— ...

COMPOUNDS AND METHODS OF TREATING INFECTIONS

The invention provides compounds of Formula I, and methods of treating or preventing a bacterial infection in a subject using a compound of Formula I. The invention also provides the use of a compound of Formula I in the manufacture of a medicament for the treatment of a bacterial infection in a subject. The invention further provides a medical device when used in a method of treating or preventing a bacterial infection in a subject and to a medical device comprising the composition of the invention. 148.-. (canceled)49. A compound selected from the group consisting of:NCL178 4,6-bis(2-((E)-1-(4-chlorophenyl)ethylidene)hydrazinyl)pyrimidineNCL179 4,6-bis(2-((E)-4-chlorobenzylidene)hydrazinyl)pyrimidin-2-amineNCL180 (2Z,2′Z)-2,2′-(pyrimidine-4,6-diylbis(hydrazin-2-yl-1-ylidene))bis(2-(4-chlorophenyl)ethan-1-ol)NCL 181 4,6-bis(2-((E)-4-chlorobenzylidene)hydrazinyl)pyrimidineNCL183 N4,N6-bis(1-phenylethyl)pyrimidine-4,6-diamineNCL184 N4,N6-bis(1-phenylethyl)pyrimidine-2,4,6-triamineNCL185 4,6-bis(2-((E)-1-(4-chlorophenyl)ethylidene)hydrazinyl)pyrimidinehydrochlorideNCL 187 4,6-bis(2-((E)-4-chlorobenzylidene)hydrazinyl)pyrimidinehydrochlorideNCL189 (2Z,2′Z)-2,2′-(pyrimidine-4,6-diylbis(hydrazin-2-yl-1-ylidene))bis(2-(4-chlorophenyl)ethan-1-ol)hydrochlorideNCL193 4,6-bis(2-((E)-4-bromobenzylidene)hydrazinyl)pyrimidin-2-amineNCL194 N′,N′″-(2-aminopyrimidine-4,6-diyl)di(benzohydrazide)NCL195 4,6-bis(2-((E)-4-methylbenzylidene)hydrazinyl)pyrimidin-2-amineNCL 196 4,4′-((1E,1′E)-((2-aminopyrimidine-4,6-diyl)bis(hydrazin-2-yl-1-ylidene))bis(methanylylidene))diphenolNCL197 3,3′-((1E,1′E)-((2-aminopyrimidine-4,6-diyl)bis(hydrazin-2-yl-1-ylidene))bis(methanylylidene))diphenolNCL198 4,6-bis(2-((E)-4-(tert-butyl)benzylidene)hydrazinyl)pyrimidin-2-aminedihydrochlorideNCL199 4,6-bis(2-((E)-benzylidene)hydrazinyl)pyrimidin-2-amineNCL200 4,6-bis(2-((E)-4-(tert-butyl)benzylidene)hydrazinyl)pyrimidin-2-amineNCL201 4,4′-((1E,1′E)-((2-aminopyrimidine-4,6-diyl)bis(hydrazin-2-yl-1-ylidene)) ...

METHODS USING HDAC11 INHIBITORS

The present invention provides methods and uses of inhibitors of histone deacetylase 11 (HDAC11) in the treatment of diseases and/or disorders, such as, for example, cell proliferative diseases. 3. The compound of claim 2 , wherein X claim 2 , X claim 2 , X claim 2 , and Xare each CR.4. The compound of claim 3 , wherein each Ris independently H claim 3 , halogen claim 3 , —CF claim 3 , —OH claim 3 , —CN claim 3 , —SO(C-Calkyl) claim 3 , phenyl claim 3 , C-Calkyl claim 3 , C-Calkoxy claim 3 , pyridyl claim 3 , —C(O)C-Calkyl claim 3 , —OC-Calkyl claim 3 , —(C-Calkyl)O(C-Calkyl) claim 3 , —OCFor —OCHphenyl.5. The compound of claim 4 , wherein each Ris independently H or halogen.6. The compound of claim 2 , wherein Ris H claim 2 , —(CHR)NRR claim 2 , or —C-Calkyl optionally substituted with one or more substituents selected from —OH claim 2 , halogen claim 2 , —NO claim 2 , oxo claim 2 , —CN claim 2 , —R claim 2 , —O(C-C)alkyl claim 2 , —NH(C-C)alkyl claim 2 , —N(C-Calkyl) claim 2 , —S(O)N(C-Calkyl) claim 2 , —S(O)NHC-Calkyl claim 2 , —C(O)C-Calkyl claim 2 , —C(O)OC-Calkyl claim 2 , —N(C-Calkyl)S(O)C-Calkyl claim 2 , —S(O)R claim 2 , —S(O)N(C-Calkyl) claim 2 , or —N(C-Calkyl)S(O)R.7. The compound of claim 6 , wherein Ris H. This application claims the benefit of U.S. Provisional Application Ser. No. 62/410,766 filed Oct. 20, 2016, 62/410,767 filed Oct. 20, 2016, and 62/410,768 filed Oct. 20, 2016, the contents of all of which are hereby incorporated by reference in their entirety.This application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created, Oct. 19, 2017, is named FOTH039_ST25.txt and is 10.6 KB in size.The present invention relates to inhibitors of histone deacetylase 11 (HDAC11) useful in the treatment of certain diseases and/or disorders, including diseases and disorders associated with cell proliferation (e.g., cancers) and/or diseases and ...

METHODS USING HDAC11 INHIBITORS

The present invention provides methods and uses of inhibitors of histone deacetylase 11 (HDAC11) in the treatment of diseases and/or disorders, such as, for example, cell proliferative diseases. 1. A method of inhibiting or reducing proliferation of cancer cells in a patient in need thereof , comprising administering a HDAC11 inhibitor to the patient.2. The method of claim 1 , wherein at least some of the cancer cells express one or more stem cell markers.3. The method of claim 2 , wherein the stem cell marker is a gene amplification of SOX2 and/or activation of STAT3.4. The method of any one of - claim 2 , wherein the cancer is a lung cancer claim 2 , a hematological cancer claim 2 , a breast cancer claim 2 , a squamous cell carcinoma claim 2 , esophageal cancer claim 2 , gastric cancer claim 2 , breast cancer or adenocarcinoma of the lung.5. The method of any one of - claim 2 , wherein the HDAC11 inhibitor is a siRNA claim 2 , a shRNA claim 2 , an antibody agent claim 2 , or a chemical compound.6. The method of wherein the chemical compound is a small molecule that is at least 10-fold selective for the inhibition of HDAC11 over one or more other histone deacetylase isoforms.7. A method of treating cancer in a patient in need thereof claim 5 , comprising administering to a patient an effective amount of a HDAC11 inhibitor claim 5 , wherein one or more cancer cells in the patient exhibit stem cell-like properties.8. The method of claim 7 , wherein the one or more cancer cells is associated with gene amplification of a marker for a cancer stem cell.9. The method of or claim 7 , wherein the one or more cancer cells is associated with a gene amplification of SOX2.10. The method of any one of - claim 7 , wherein the cancer is esophageal squamous cell carcinoma claim 7 , oral squamous cell carcinoma claim 7 , lung claim 7 , squamous cell carcinoma claim 7 , lung adenocarcinoma claim 7 , non-small cell lung cancer claim 7 , small cell lung cancer or sinonasal cancer.11. ...

Phosphonate compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is a phosphonate (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

CYCLIC VINYLOGOUS AMIDES AS BROMODOMAIN INHIBITORS

Cyclic vinylogous amides of Formula I are disclosed 137-. (canceled)39. The method of claim 38 , wherein the disease or disorder is chronic inflammation.40. The method of wherein the disease or disorder is inflammatory colitis.41. The method of claim 38 , wherein the treatment of a disease or a disorder further comprises administering an additional therapeutic agent.43. The method of claim 38 , wherein the disease or disorder is autoimmune disease.44. The method of claim 38 , wherein the disease or disorder is cancer.45. The method of claim 44 , wherein the cancer is selected from breast cancer claim 44 , triple negative breast cancer claim 44 , prostate cancer claim 44 , acute leukemia claim 44 , chronic leukemia claim 44 , chronic lymphocytic leukemia claim 44 , colon cancer claim 44 , colorectal cancer claim 44 , multiple myeloma claim 44 , glioblastoma claim 44 , lung cancer claim 44 , and liver cancer.46. The method of claim 39 , wherein the disease or disorder is selected from multiple sclerosis claim 39 , inflammatory bowel disease claim 39 , Crohn's disease claim 39 , ulcerative colitis claim 39 , type I diabetes claim 39 , rheumatoid arthritis claim 39 , AIDS claim 39 , and asthma. This application claims priority from U.S. provisional application 61/872,303, filed Aug. 30, 2013, the entire disclosure of which is incorporated herein by reference.This invention was made with U.S. Government support under R01HG004508, R01CA87658 and R33DA029963 awarded by National Institutes of Health. The U.S. Government has certain rights in the invention.The present application relates generally to compositions for treating diseases that arise from inappropriate activity of proteins containing an acetyl-lysine. The compositions comprise a genus of cyclic vinylogous amides that are inhibitors of bromodomain.BRD4 is a member of the bromodomains and extra terminal domain (BET) family of proteins that recognize acetylated chromatin structures through their bromodomains and act ...

Inhibitors of Influenza Viral Entry

Vaccination is the most prevalent prophylactic means for controlling seasonal influenza infections. However, an effective vaccine usually takes at least 6 months to develop for the circulating strains. Therefore, new therapeutic options are needed for acute treatment of influenza infections to control this virus and prevent epidemic/pandemic situations from developing. Described herein are fast-acting, orally active acylated amino-substituted heterocyclyl compounds effective to control this virus. In one aspect, described herein is a method of treating an influenza infection in a subject comprising administering to the subject the compounds described herein.

METHODS USING HDAC11 INHIBITORS

The present invention provides methods and uses of inhibitors of histone deacetylase 11 (HDAC11) in the treatment of diseases and/or disorders, such as, for example, cell proliferative diseases. 149.-. (canceled)50. A method of treating cancer in a patient in need thereof , comprising administering to a patient an effective amount of a HDAC11 inhibitor.51. The method of claim 50 , wherein one or more cancer cells in the patient exhibit stem cell-like properties.52. The method of claim 50 , wherein the cancer is a hematological cancer.53. A method of treating a patient having a myeloproliferative disorder claim 50 , comprising administering to the patient a HDAC11 inhibitor and a second therapeutic agent.54. The method of claim 53 , wherein the second therapeutic agent is a JAK2 inhibitor.55. The method of claim 53 , wherein the myeloproliferative disorder is resistant to a JAK2 inhibitor.56. The method of claim 53 , wherein the second therapeutic agent is a hedgehog pathway inhibitor.57. The method of claim 50 , wherein the patient has received a first line therapy claim 50 , and any cancer cells surviving from the first line therapy are reduced or eliminated after treatment with the HDAC11 inhibitor. This application claims the benefit of U.S. Provisional Application Ser. No. 62/410,766 filed Oct. 20, 2016, 62/410,767 filed Oct. 20, 2016, and 62/410,768 filed Oct. 20, 2016, the contents of all of which are hereby incorporated by reference in their entirety.This application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created, Oct. 19, 2017, is named FOTH039_ST25.txt and is 10.6 KB in size.The present invention relates to inhibitors of histone deacetylase 11 (HDAC11) useful in the treatment of certain diseases and/or disorders, including diseases and disorders associated with cell proliferation (e.g., cancers) and/or diseases and disorders associated with ...

SUBSTITUTED FUSED BI- OR TRI- HETEROCYCLIC COMPOUNDS AS EHMT2 INHIBITORS

The present disclosure relates to substituted fused bi- or tri-heterocyclic compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., sickle cell anemia) via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, by administering a substituted fused bi- or tri-heterocyclic compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes. 24.-. (canceled)5. The compound of claim 1 , wherein at least one of and is a double bond.68.-. (canceled)9. The compound of claim 1 , wherein Xis C.1014.-. (canceled)15. The compound of claim 1 , wherein n is 1 or 2.16. (canceled)18. (canceled)20. The compound of claim 1 , wherein n is 2.2127.-. (canceled)29. The compound of claim 1 , wherein when Ris —NH claim 1 , then Ris not —OCH.3031.-. (canceled)32. The compound of claim 1 , wherein Ris NRRor OR claim 1 , wherein each of Rand Rindependently is H or C-Calkyl optionally substituted with one or more of halo claim 1 , hydroxyl claim 1 , amino claim 1 , mono- or di-alkylamino claim 1 , C-Calkoxyl claim 1 , C-Ccycloalkyl claim 1 , or 4- to 12-membered heterocycloalkyl containing 1-4 heteroatoms selected from N claim 1 , O claim 1 , and S.33. The compound of claim 1 , wherein Ris H claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , or 4- to 12-membered heterocycloalkyl.3436.-. (canceled)39. The compound of claim 1 , wherein at least one of Rand Ris R.4066.-. (canceled)68. (canceled)69. The compound of claim 1 , wherein at least one of Rand R is OR.7077.-. (canceled)78. The compound of claim 1 , wherein Ris H or C-Calkyl optionally substituted with one or more of hydroxyl claim 1 , amino or mono- or di-alkylamino.7986.-. (canceled)8898.-. (canceled)100102.-. (canceled)103. The compound of claim 1 , wherein the compound is selected from ...

5-bromo-indirubins

Disclosed herein inter alia are compositions and methods for treating cancer using 5-Br-indirubin derivatives.

Amino compounds for treatment of complement mediated disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein R12 or R13 on the A group is an amino substituent (R32) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.

3-AMINO-1,5,6,7-TETRAHYDRO-4H-INDOL-4-ONES

Compounds of formula (I) as described hereinprocesses for their production and their use as anti-cancer agents. 5. The compound according to claim 1 , which is selected from the group consisting of:(6RS)-6-(hydroxymethyl)-3-(phenylamino)-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one,tert-butyl [(6RS)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-yl]methylcarbamate,(6RS)-6-[(benzyloxy)methyl]-3-(phenylamino)-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one,tert-butyl [(6RS)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-yl]carbamate,(6RS)-6-amino-3-anilino-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one hydrochloride,N-[(6RS)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-yl]cyclopropanecarboxamide,(6RS)-4-oxo-N-phenyl-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,methyl (6RS)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxylate,4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxylic acid,(6RS)-N-methyl-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,(6RS)-4-oxo-3-(phenylamino)-N-propyl-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,(6RS)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,(6RS)-N-(2-hydroxyethyl)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,methyl (6RS)-2-(3-fluoropyridin-4-yl)-4-oxo-3-(phenylamino)-4,5,6,7-tetrahydro-1H-indol-6-carboxylate,methyl (6RS)-2-(3-methoxypyridin-4-yl)-4-oxo-3-(phenylamino)-4,5,6,7-tetrahydro-1H-indol-6-carboxylate,(6RS)-N-(2-methoxyethyl)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,(6RS)-N-(2-hydroxyethyl)-N-methyl-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,(6RS)-N-ethyl-N-methyl-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide,(6RS)-6-(morpholin-4- ...

ANTIBIOTIC SENSITIVITY-RESTORING AND PHOTOSENSITIVE AGENTS

The present disclosure describes a method to treat conditions, including bacterial infections and cancer, using a photosensitive compound that, upon exposure to white light, can be activated. The photosensitive compound can also interact synergistically with antibiotics used concomitantly to kill drug-resistant bacteria. The photosensitive compounds can also be used to inhibit the proliferation of cancer cells. 152-. (canceled)54. The method of claim 53 , wherein each A claim 53 , A claim 53 , A claim 53 , and Ais independently (CR) claim 53 , and wherein each Ris independently hydrogen.55. The method of claim 53 , wherein Aris substituted phenyl.56. The method of claim 55 , wherein Aris phenyl substituted with halogen.57. The method of claim 53 , wherein Lis alkenylene.58. The method of claim 53 , wherein:{'sup': '2', 'Ris hydrogen;'}{'sup': '2', 'Aris phenyl substituted with halogen; and'}{'sup': 1', '2', '3', '4', '1a', '1a, 'each A, A, A, and Ais (CR), wherein Ris hydrogen.'}62. The method of claim 53 , wherein the subject is human.63. The method of claim 53 , wherein the infection is caused by a microbe.64. The method of claim 63 , wherein the microbe is a bacterium.65. The method of claim 63 , wherein the microbe is Gram-positive bacterium.66. The method of claim 63 , wherein the microbe is Gram-negative bacterium.67. The method of claim 63 , wherein the microbe is a fungus.68. The method of claim 53 , wherein the compound is more effective in the presence of light than in the dark.69. The method of claim 53 , further comprising administering to the subject a therapeutically-effective amount of a second agent.70. The method of claim 69 , wherein the second agent is an antibiotic.71. The method of claim 70 , wherein the method further comprises irradiating the compound and the antibiotic.72. The method of claim 70 , wherein the antibiotic is an aminoglycoside.73. The method of claim 70 , wherein the antibiotic is an ansamycin.74. The method of claim 70 , ...

Compounds and methods for inhibiting fascin

Provided are compounds, compositions and methods for inhibiting fascin activity or treating a condition or disorder mediated by fascin activity in a subject in need thereof.

Acly inhibitors and uses thereof

The present invention provides compounds useful as inhibitors of ATP citrate lyase (ACLY), compositions thereof, and methods of using the same.

5-BROMO-INDIRUBINS

Disclosed herein are compositions and methods for treating cancer, FLT3-AML, and CML. 214. -. (canceled)16. (canceled)17. The method of claim 15 , wherein said cancer is cancer is lung cancer claim 15 , breast cancer claim 15 , ovarian cancer claim 15 , leukemia claim 15 , lymphoma claim 15 , melanoma claim 15 , pancreatic cancer claim 15 , sarcoma claim 15 , bladder cancer claim 15 , bone cancer claim 15 , brain cancer claim 15 , cervical cancer claim 15 , colon cancer claim 15 , esophageal cancer claim 15 , gastric cancer claim 15 , liver cancer claim 15 , head and neck cancer claim 15 , kidney cancer claim 15 , myeloma claim 15 , thyroid cancer claim 15 , or prostate cancer.18. (canceled)19. A method of treating CML expressing an ABL1-kinase claim 1 , said method comprising administering an effective amount of a compound of .20. The method of claim 19 , wherein said ABL1-kinase is a ABL1 mutant-kinase.21. The method of any one of to claim 19 , wherein said ABL1 mutant-kinase is a BCR-ABL1 mutant kinase.2224. -. (canceled)2631. -. (canceled)32. The method of claim 25 , wherein Rand Rare independently substituted or unsubstituted alkyl claim 25 , substituted or unsubstituted heteroalkyl claim 25 , substituted or unsubstituted cycloalkyl claim 25 , substituted or unsubstituted heterocycloalkyl claim 25 , substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.3342. -. (canceled)43. A method of treating acute myeloid leukemia expressing a FLT3-kinase in a subject in need thereof claim 25 , said method comprising administering an effective amount of a compound according to claim 25 , thereby treating said acute myeloid leukemia.4445. -. (canceled)46. The method of claim 43 , wherein said FLT3-kinase is a FLT3-mutant kinase.47. The method of claim 46 , wherein said FLT3-mutant kinase is a FLT3-TKD mutant kinase.48. The method of claim 47 , wherein said FLT3-TKD mutant kinase comprises a mutation at an amino acid residue position corresponding to ...

5-BROMO-INDIRUBINS

Disclosed herein inter alia are compositions and methods for treating cancer using 5-Br-indirubin derivatives. 2. The compound of claim 1 , wherein Rand Rare hydrogen.3. The compound of claim 1 , wherein L is unsubstituted alkylene.4. The compound of claim 1 , wherein L is unsubstituted C-Calkylene.5. The compound of claim 1 , wherein L is unsubstituted C-Calkylene.6. The compound of claim 1 , wherein L is unsubstituted Calkylene.7. The compound of claim 1 , wherein L is a bond.8. The compound of claim 1 , wherein Ris halogen claim 1 , —CX claim 1 , —OCX claim 1 , —CN claim 1 , —OH claim 1 , —NH claim 1 , —COOH claim 1 , —C(O)OR claim 1 , —CONH claim 1 , —NO claim 1 , —SH claim 1 , —NHNH claim 1 , —NRR claim 1 , —OR claim 1 , —SR claim 1 , substituted or unsubstituted alkyl claim 1 , substituted or unsubstituted heteroalkyl claim 1 , substituted or unsubstituted cycloalkyl claim 1 , substituted or unsubstituted heterocycloalkyl claim 1 , substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.9. The compound of any claim 1 , wherein Ris —NRR.10. The compound of claim 9 , wherein Rand Rare independently substituted or unsubstituted alkyl claim 9 , substituted or unsubstituted heteroalkyl claim 9 , substituted or unsubstituted cycloalkyl claim 9 , substituted or unsubstituted heterocycloalkyl claim 9 , substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.11. The compound of claim 10 , wherein Rand Rare independently substituted or unsubstituted alkyl.12. The compound of claim 11 , wherein Rand Rare independently substituted or unsubstituted C-Calkyl.13. The compound of claim 12 , wherein Rand Rare independently substituted or unsubstituted C-Calkyl.14. The compound of claim 13 , wherein Rand Rare independently —OH substituted or unsubstituted C-Calkyl.15. The compound of claim 13 , wherein Rand Rare independently unsubstituted C-Calkyl.16. The compound of claim 1 , wherein Rand Rare joined together to form a substituted or ...

INDIRUBIN DERIVATIVES, AND USES THEREOF

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). Indirubin derivatives (IRDs) potently reduce the viabilities of various cancer cells and affect kinase activities. IRDs disclosed herein provide new therapeutics for cancer and conditions regulated by the kinase activities. 2. The compound according to claim 1 , selected from the group consisting of IRD Nos. 10-11 claim 1 , 13 claim 1 , 128 and 176.3. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to and a pharmaceutically acceptable carrier.4. The pharmaceutical composition comprising a therapeutically effective amount of the compound according to one of as an active ingredient and a pharmaceutically acceptable carrier.5. A method of treating a cancer or tumor in a subject comprising administering to the subject a therapeutically effective amount of a compound selected from the group consisting of IRD Nos. 2 claim 1 , 10 claim 1 , 11 claim 1 , 13 claim 1 , 58 claim 1 , 59 claim 1 , 61 claim 1 , 64-72 claim 1 , 74 claim 1 , 77-88 claim 1 , 90 claim 1 , 129-132 claim 1 , 142-144 claim 1 , 146 claim 1 , and 161.6. The method according to claim 5 , wherein the cancer or tumor is selected from the group consisting of CML claim 5 , prostate cancer claim 5 , melanoma claim 5 , pancreatic cancer claim 5 , ovarian cancer claim 5 , leukemia claim 5 , and lymphoma.7. The method according to claim 6 , wherein the cancer is CML claim 6 , and the indirubin derivative is selected from the group consisting of IRD Nos. 10-11 claim 6 , 13 claim 6 , 59 claim 6 , 61 claim 6 , 68˜71 claim 6 , 79 claim 6 , 80 claim 6 , and 83˜87.8. The method according to claim 6 , wherein the cancer is prostate cancer claim 6 , and the indirubin derivative is selected from the group consisting of IRD Nos. 10-11 claim 6 , 13 claim 6 , 59 claim 6 , 71 claim 6 , 79 claim 6 , 80 claim 6 , 83 claim 6 , 84 ...

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein Ror Ron the A group is an aryl, heteroaryl or heterocycle (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 6. The compound of claim 1 , wherein B is —(C-Calkyl)(aryl) or —(C-Calkyl)(heteroaryl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 1 , and 0 or 1 substituents chosen from Rand R.7. The compound of claim 6 , wherein Ris halogen.8. The compound of claim 6 , wherein B is 2-pyridine.12. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.13. A method for the treatment of a disorder mediated by complement factor D claim 1 , comprising administering an effective amount to a host in need thereof of a compound of or a pharmaceutically acceptable salt thereof claim 1 , optionally in a pharmaceutically acceptable carrier.14. The method of claim 13 , wherein the host is a human.15. The method of claim 14 , wherein the disorder is age-related macular degeneration (AMD).16. The method of claim 14 , wherein the disorder is retinal degeneration.17. The method of claim 14 , wherein the disorder is an ophthalmic disease.18. The method of claim 14 , wherein the disorder is paroxysymal nocturnal hemoglobinuria (PNH).19. The method of claim 14 , wherein the disorder is multiple ...

COMPOUNDS AND METHODS FOR INHIBITING FASCIN

Provided are compounds, compositions and methods for inhibiting fascin activity or treating a condition or disorder mediated by fascin activity in a subject in need thereof. 134-. (canceled)36. The compound of claim 35 , wherein Ris phenyl optionally substituted with 1 to 3 R.37. The compound of claim 35 , wherein Lis selected from the group consisting of —C(O)NH— and —NHC(O)—.38. The compound of claim 35 , wherein Ris the 5- to 10-membered heteroaryl.39. The compound of claim 35 , wherein m is 1 claim 35 , 2 claim 35 , or 3.40. The compound of claim 35 , wherein Ris optionally substituted with 1 to 4 R claim 35 , and Ris selected from the group consisting of furan claim 35 , benzofuran claim 35 , pyridine claim 35 , pyridazine claim 35 , pyrimidine claim 35 , pyrazine claim 35 , thiophene claim 35 , thiazole claim 35 , isothiazole claim 35 , oxazole claim 35 , isoxazole claim 35 , oxadiazole claim 35 , imidazole claim 35 , pyrrole claim 35 , and pyrazole.41. The compound of claim 35 , wherein Ris not optional and is selected from the group consisting of lower alkyl claim 35 , halo claim 35 , lower haloalkyl claim 35 , —OH claim 35 , —OR claim 35 , cyano and phenyl optionally substituted methyl claim 35 , and wherein Ris lower alkyl or lower haloalkyl.42. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier. This application is a continuation of U.S. patent application Ser. No. 15/437,229 filed Feb. 20, 2017, now U.S. Pat. No. 9,850,243, which application is a divisional of U.S. patent application Ser. No. 14/626,791 filed Feb. 19, 2015, now U.S. Pat. No. 9,573,946 granted Feb. 21, 2017, and claims the benefit of U.S. Provisional Patent Application No. 61/942,554, filed Feb. 20, 2014, the complete disclosures of which is hereby incorporated by reference.The present technology relates generally to compounds, compositions and methods for treating or preventing cancer.In recent years, progress has been made in the treatment of ...

Factor D Inhibitors Useful for Treating Inflammatory Disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 22. A pharmaceutical composition comprising a compound of claim 1 , together with a pharmaceutically acceptable carrier.23. A method of treating or preventing a complement D-related disorder comprising administering a therapeutically effective amount of a compound of claim 1 , to a patient in need of such treatment.24. The method of claim 23 , wherein the disorder is paroxysmal nocturnal hemoglobinuria.25. The method of claim 23 , wherein the disorder is age-related macular degeneration.26. The method of claim 23 , wherein the disorder is selected from inflammation of the eye claim 23 , retinal degeneration claim 23 , myasthenia gravis claim 23 , C3 glomerulonephritis claim 23 , abdominal aortic aneurysm claim 23 , or atypical hemolytic uremic syndrome. This application is a continuation of U.S. application Ser. No. 14/630,959, filed Feb. 25, 2015, which claims benefit of provisional U.S. Application No. 61/944,189 filed Feb. 25, 2014, provisional U.S. Application No. 62/022,916 filed Jul. 10, 2014, and provisional U.S. Application 62/046,783 filed Sep. 5, 2014. The entirety of each of these applications is hereby incorporated by reference for all purposes.Complement Factor D is part of the alternative pathway of the complement cascade and plays an early and central role in activating the ...

Benzopyrazole compounds and analogues thereof

Disclosed are compounds of formula I, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of the complement system. Also provided are pharmaceutical compositions comprising a compound of formula I, and methods involving use of the compounds and compositions in the treatment and prevention of diseases and conditions characterized by aberrant complement system activity.

BENZOTHIOPHENE, BENZYLOXYBENZYLIDENE AND INDOLINE DERIVATIVES USEFUL FOR THE TREATMENT OF TUBERCULOSIS

The present invention relates to benzothiophene, benzyloxybenzylidene and indoline-2-one derivatives and the use of said derivatives in the treatment and/or prevention of 2mycobacterium. The inhibitor of virulence of general formula (I) claim 1 , according to claim 1 , wherein R4 is cyclopropane.5mycobacterium. The inhibitor of virulence of general formula (IIA) claim 1 , according to claim 1 , wherein R4 represents —C(═S)—S—CH3.10mycobacterium. The inhibitor of virulence according to any of the preceding claims claim 1 , for use as a medicament.11mycobacteriumtuberculosis.. The inhibitor of virulence according to any of the preceding claims claim 1 , for use in the treatment and/or prevention of12mycobacterium. A pharmaceutical composition comprising the inhibitor of virulence according to any of the preceding claims and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.13mycobacterium. A screening method for identifying inhibitors of virulence claim 1 , said method comprisinga) infecting eukaryotic cells and/or macrophages with wild-type Mtb-Erdman strain at high multiplicities of infection (MOI),b) contacting said infected eukaryotic cells and/or infected macrophages with an inhibitor to be screened,c) quantifying metabolic activity in said eukaryotic cells and/or macrophages,wherein said inhibitor fulfills the following criteria:{'i': 'Mycobacterium tuberculosis', 'i) protects said eukaryotic cells and/or macrophages from (Mtb)-induced cell death during and after the exposure to said inhibitor,'}ii) does not influence Mtb growth, andiii) either inhibits the histidine kinase MprB in Mtb or affects metal ion homeostasis in Mtb.14mycobacterium. The screening method of claim 13 , wherein the influence of inhibitors of virulence on Mtb growth is verified against Mtb in the resazurin reduction microtiter assay (REMA). The present invention relates to benzothiophene, benzyloxybenzylidene and indoline-2-one derivatives and the use of said derivatives ...

ARYLOSULFONAMIDES FOR THE TREATMENT OF CNS DISEASES

Arylsulphonamide derivatives of formula (I) and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of disorders of the central nervous system. 141-. (canceled)43. The compound or salt according to claim 42 , wherein D represents unsubstituted phenyl or phenyl substituted with one or more substituents independently selected from the group consisting of branched C-C-alkyl claim 42 , straight C-C-alkyl in ortho or meta position with respect to sulphonamide group; C-C-alkyloxy claim 42 , halogeno-C-C-alkyl claim 42 , halogeno-C-C-alkyloxy claim 42 , halogen atom claim 42 , —CN claim 42 , —OH claim 42 , and phenyl.44. The compound or salt according to claim 42 , wherein D represents unsubstituted naphthyl or naphthyl substituted with one or more substituents independently selected from the group consisting of C-C-alkyl claim 42 , C-C-alkyloxy claim 42 , halogeno-C-C-alkyl claim 42 , halogen atom claim 42 , —CN claim 42 , —OH claim 42 , and phenyl.45. The compound according to claim 42 , wherein D represents 5-membered aromatic heterocyclic group having 1 to 3 heteroatoms independently selected from the group consisting of N claim 42 , O claim 42 , and S claim 42 , and wherein D is unsubstituted or substituted with one or more substituents independently selected from the group consisting of C-C-alkyl claim 42 , C-C-alkyloxy claim 42 , halogeno-C-C-alkyl claim 42 , halogen atom claim 42 , —CN claim 42 , —OH claim 42 , and phenyl.46. The compounds or salt according to claim 45 , wherein D represents thienyl.47. The compound or salt according to claim 42 , wherein D represents benzene ring fused with 5-membered aromatic heterocyclic ring having 1 to 3 heteroatoms independently selected from the group consisting of N claim 42 , O claim 42 , and S claim 42 , and wherein D is unsubstituted or substituted with one or more substituents independently selected from the group consisting of C-C-alkyl claim 42 , C-C-alkyloxy ...

5-BROMO-INDIRUBINS

Disclosed herein are compositions and methods for treating cancer, FLT3-AML, and CML. 214.-. (canceled)15. A method of treating cancer claim 1 , said method comprising administering to a subject in need thereof an effective amount of a compound of .16. (canceled)17. The method of claim 15 , wherein said cancer is cancer is lung cancer claim 15 , breast cancer claim 15 , ovarian cancer claim 15 , leukemia claim 15 , lymphoma claim 15 , melanoma claim 15 , pancreatic cancer claim 15 , sarcoma claim 15 , bladder cancer claim 15 , bone cancer claim 15 , brain cancer claim 15 , cervical cancer claim 15 , colon cancer claim 15 , esophageal cancer claim 15 , gastric cancer claim 15 , liver cancer claim 15 , head and neck cancer claim 15 , kidney cancer claim 15 , myeloma claim 15 , thyroid cancer claim 15 , or prostate cancer.18. (canceled)19. A method of treating chronic myelogenous leukemia (CML) expressing an ABL1-kinase claim 1 , said method comprising administering an effective amount of a compound of .20. The method of claim 19 , wherein said ABL1-kinase is a ABL1 mutant-kinase.21. The method of claim 20 , wherein said ABL1 mutant-kinase is a BCR-ABL1 mutant kinase.2224.-. (canceled)2629.-. (canceled)30. The method of claim 25 , wherein Ris halogen claim 25 , —CF claim 25 , —CCl claim 25 , —CBr claim 25 , —CI claim 25 , —OCF claim 25 , —OCCl claim 25 , —OCBr claim 25 , —OCI claim 25 , —CN claim 25 , —OH claim 25 , —NH claim 25 , —COOH claim 25 , —C(O)OR claim 25 , —CONH claim 25 , —NO claim 25 , —SH claim 25 , —NHNH claim 25 , —NRR claim 25 , —OR claim 25 , —SR claim 25 , substituted or unsubstituted alkyl claim 25 , substituted or unsubstituted heteroalkyl claim 25 , substituted or unsubstituted cycloalkyl claim 25 , substituted or unsubstituted heterocycloalkyl claim 25 , substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.31. (canceled)32. The method of claim 25 , wherein Rand Rare independently substituted or unsubstituted alkyl claim 25 ...

Organic Electroluminescent Device

An organic electroluminescent device is provided and includes: a pair of electrodes; and at least one organic layer between the pair of electrodes, the at least one organic layer including a light-emitting layer. The at least one organic layer contains an indole compound represented by formula (1): in which Ind 101 represents a substituted or unsubstituted indole ring, L 101 represents a linking group, Ind 101 and L 101 are connected to each other at 2- or 3-position of Ind 101 , and n 101 represents an integer of 2 or more.

Polymerizable compound, composition, polymer, optically anisotropic body, liquid crystal display element, and organic el device

It is an object of the present invention to provide a polymerizable compound having a good liquid crystal property, a good alignment property, sufficient solubility in solvents, high preservation stability in a solution state, and high optical stability; a composition including the polymerizable compound; a polymer produced by polymerizing the polymerizable compound, such as a resin produced using the polymerizable compound; an optically anisotropic body including the polymer; and a liquid crystal display element and an organic EL device that include the optically anisotropic body. As a result of conducting intensive studies in order to achieve the above object, the compound represented by General Formula (I) is developed.

INDIRUBIN DERIVATIVES, AND USES THEREOF

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). Indirubin derivatives (IRDs) potently reduce the viabilities of various cancer cells and affect kinase activities. IRDs disclosed herein provide new therapeutics for cancer and conditions regulated by the kinase activities. 121-. (canceled)23. The method of claim 22 , wherein the cancer or tumor is selected from the group consisting of CML claim 22 , prostate cancer claim 22 , melanoma claim 22 , pancreatic cancer claim 22 , ovarian cancer claim 22 , leukemia claim 22 , and lymphoma.24. The method according to claim 22 , wherein the cancer is prostate cancer claim 22 , and the indirubin derivative is selected from the group consisting of IRD Nos. 10-11 claim 22 , 13 claim 22 , 59 claim 22 , 71 claim 22 , 79 claim 22 , 80 claim 22 , 83 claim 22 , 84 claim 22 , 87 claim 22 , 128 and 176.25. The method according to claim 22 , wherein the cancer is melanoma claim 22 , and the indirubin derivative is selected from the group consisting of IRD Nos. 59 claim 22 , and 176.26. The method according to claim 22 , wherein the cancer is pancreatic cancer claim 22 , and the indirubin derivative is selected from the group consisting of IRD Nos. 9 claim 22 , 11 claim 22 , 13 claim 22 , 59 claim 22 , 61 claim 22 , 68-71 claim 22 , 82-87 claim 22 , 115 claim 22 , and 176.27. The method according to claim 22 , wherein the cancer is ovarian cancer claim 22 , and the indirubin derivative is selected from the group consisting of IRD Nos. 11 claim 22 , 13 claim 22 , 59 claim 22 , 61 claim 22 , 69 claim 22 , 71 claim 22 , 79-82 claim 22 , 84-87 claim 22 , 124 claim 22 , and 176.28. The method according to claim 22 , wherein the cancer is leukemia claim 22 , and the indirubin derivative is selected from the group consisting of IRD Nos. 10-13 claim 22 , 59 claim 22 , 61 claim 22 , 70 claim 22 , 71 claim 22 , 79-80 claim 22 , 83-87 claim 22 , 115 ...

INHIBITORS OF HISTONE METHYLTRANSFERASE G9a

Described herein are compounds, pharmaceutical compositions and methods for treating cancer, inflammation, or autoimmune disease in a subject, or for inhibiting histone methyltransferase G9a.

INDOLINE ANALOGS AND USES THEREOF

Indoline derivative compounds that act as EWS-FLI1 transcription factor inhibitors are provided. Also provided are pharmaceutical compositions of the indoline derivatives, methods of synthesizing the same, methods of treating using same, and assays for identifying the inhibitors of EWS-FLI1 oncoprotein. 113-. (canceled)15. The compound of claim 14 , wherein Ris —OCH.1727-. (canceled)28. The compound of claim 14 , wherein R claim 14 , R claim 14 , R claim 14 , and Rare independently selected from the group consisting of H and Cl.291. The compound of claim claim 14 , wherein Rand Rare Cl and Rand Rare H.301. The compound of claim claim 14 , wherein A is —OH.311. The compound of claim claim 14 , wherein R claim 14 , R claim 14 , and Rare H.321. The compound of claim claim 14 , wherein Ris —OCH.33. A method for treating cancer selected from the group consisting of Ewing's sarcoma claim 14 , prostate cancer claim 14 , glioblastoma claim 14 , acute myeloid leukemia claim 14 , breast cancer claim 14 , head and neck cancer claim 14 , melanoma claim 14 , non-small cell lung cancer claim 14 , ovarian cancer claim 14 , and uterine cancer claim 14 , comprising:{'claim-ref': {'@idref': 'CLM-00014', 'claim 14'}, 'administering an effective amount of the compound of to a subject in need thereof.'}34. A method for killing or inhibiting the growth of a neoplastic cell claim 14 , wherein the neoplastic cell is a cancer cell claim 14 , the cancer being selected from the group consisting of Ewing's sarcoma claim 14 , prostate cancer claim 14 , glioblastoma claim 14 , acute myeloid leukemia claim 14 , breast cancer claim 14 , head & neck cancer claim 14 , melanoma claim 14 , non-small cell lung cancer claim 14 , ovarian cancer claim 14 , and uterine cancer claim 14 , comprising:{'claim-ref': {'@idref': 'CLM-00014', 'claim 14'}, 'contacting the neoplastic cell with an effective amount of the compound of .'}35. A method for inhibiting proliferation of a cell claim 14 , wherein the cell ...

ALKYNE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein Ror Ron the A group is an alkyne (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 2. The compound of claim 1 , wherein Ris chosen from —CHO claim 1 , —CONH claim 1 , and C-Calkanoyl.3. The compound of claim 1 , wherein Ris hydrogen.4. The compound of claim 1 , wherein Ris C-Calkanoyl.6. The compound of claim 1 , wherein B is —(CH)(aryl) substituted with two substituents independently chosen from Rand R.7. The compound of claim 6 , wherein Ris halogen.8. The compound of claim 7 , wherein there are two Rsubstituents and one is chlorine and the other is fluorine.11. A method for the treatment of a disorder mediated by complement factor D claim 1 , comprising administering an effective amount to a host in need thereof of a compound of claim 1 , optionally in a pharmaceutically acceptable carrier.12. The method of claim 11 , wherein the host is a human.13. The method of claim 12 , wherein the disorder is age-related macular degeneration (AMD).14. The method of claim 12 , wherein the disorder is retinal degeneration.15. The method of claim 12 , wherein the disorder is an ophthalmic disease.16. The method of claim 12 , wherein the disorder is paroxysymal nocturnal hemoglobinuria (PNH).17. The method of claim 12 , wherein the disorder is multiple sclerosis.18. The method of claim 12 , wherein the disorder is arthritis.19. The method of ...

ALKYNE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein Ror Ron the A group is an alkyne (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 3. The compound of claim 1 , wherein Ris hydrogen.4. The compound of claim 1 , wherein Ris chosen from —CHO claim 1 , —CONH claim 1 , and C-Calkanoyl.5. The compound of claim 4 , wherein Ris hydrogen.6. The compound of claim 5 , wherein m is 0 or 1.8. The compound of claim 1 , wherein B is —(CH)(aryl) substituted with two substituents independently chosen from Rand R.9. The compound of claim 8 , wherein Ris halogen.10. The compound of claim 9 , wherein there are two Rsubstituents and one is chlorine and the other is fluorine.11. The compound of claim 1 , wherein B is aryl or heteroaryl each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R. This application is a continuation of U.S. application Ser. No. 15/818,559, filed Nov. 20, 2017, which is a continuation of U.S. application Ser. No. 14/631,090, filed Feb. 25, 2015, now U.S. Pat. No. 9,828,396, which claims the benefit of provisional U.S. Application No. 61/944,189, filed Feb. 25, 2014, provisional U.S. Application No. 62/022,916, filed Jul. 10, 2014, and provisional U.S. Application 62/046,783, filed Sep. 5, 2014. The entirety of each of these applications is hereby incorporated by reference for all purposes.The complement system is a ...

ANTIBIOTIC SENSITIVITY-RESTORING AND PHOTOSENSITIVE AGENTS

The present disclosure describes a method to treat conditions, including bacterial infections and cancer, using a photosensitive compound that, upon exposure to white light, can be activated. The photosensitive compound can also interact synergistically with antibiotics used concomitantly to kill drug-resistant bacteria. The photosensitive compounds can also be used to inhibit the proliferation of cancer cells. 1. A method of treating a condition , the method comprising administering to a subject in need thereof a therapeutically-effective amount of a compound that binds a biological structure , thereby decreasing drug resistance in a cell , and a therapeutically-effective amount of a second agent.2. The method of claim 1 , wherein the subject is human.3. The method of claim 1 , wherein the compound that binds the biological structure is more effective in the presence of light than in the dark.4. The method of claim 3 , further comprising irradiating the compound with light having a wavelength of about 200 to about 800 nm.5. The method of claim 1 , wherein the condition is caused by a microbe.6. The method of claim 5 , wherein the microbe is a bacterium.7. The method of claim 5 , wherein the microbe is Gram-positive bacterium.8. The method of claim 5 , wherein the microbe is Gram-negative bacterium.9. The method of claim 5 , wherein the microbe is drug-resistant bacterium.10Staphylococcus aureus.. The method of claim 5 , wherein the microbe is methicillin-resistant11Acinetobacter baumannii.. The method of claim 5 , wherein the microbe is12Escherichia coli.. The method of claim 5 , wherein the microbe is13. The method of claim 1 , wherein the biological structure is an efflux pump.14. The method of claim 1 , wherein the compound lessens an activity of a drug resistance mechanism in the microbe.15. The method of claim 1 , wherein the second agent is an antibiotic.16. The method of claim 15 , wherein the antibiotic is polymyxin B or a pharmaceutically-acceptable salt ...

AMIDE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein Ror Ron the A group is an amide substituent (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 8. The pharmaceutical composition of claim 7 , wherein Ris Rand Ris hydrogen.11. The pharmaceutical composition of claim 7 , wherein Ris hydrogen claim 7 , and wherein B is —(C-Calkyl)(aryl) claim 7 , —(C-Calkyl)(heteroaryl) claim 7 , or —(C-Calkyl)(biphenyl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 7 , and 0 or 1 substituents chosen from Rand R.12. The pharmaceutical composition of claim 11 , wherein B is aryl claim 11 , heteroaryl claim 11 , or biphenyl each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 11 , and 0 or 1 substituents chosen from Rand R.13. The pharmaceutical composition of claim 12 , wherein Ris halogen.14. The pharmaceutical composition of claim 12 , wherein there are two substituents chosen from Rand wherein one is halogen and the other is C-Calkyl.15. The pharmaceutical composition of claim 14 , wherein C-Calkyl is methyl.16. The pharmaceutical composition of claim 1 , wherein B is —(C-Calkyl)(aryl) claim 1 , —(C-Calkyl)(heteroaryl) claim 1 , or —(C-Calkyl)(biphenyl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R ...

CARBAMATE, ESTER, AND KETONE COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein Ror Ron the A group is a carbamate, ester, or ketone substituent (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 8. The pharmaceutical composition of claim 7 , wherein Ris Rand Ris hydrogen.11. The pharmaceutical composition of claim 7 , wherein R′ is hydrogen claim 7 , and wherein B is —(C-Calkyl)(aryl) claim 7 , —(C-Calkyl)(heteroaryl) claim 7 , or —(C-Calkyl)(biphenyl) each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 7 , and 0 or 1 substituents chosen from Rand R.12. The pharmaceutical composition of claim 11 , wherein B is aryl claim 11 , heteroaryl claim 11 , or biphenyl each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R claim 11 , and 0 or 1 substituents chosen from Rand R.13. The pharmaceutical composition of claim 12 , wherein Ris halogen.14. The pharmaceutical composition of claim 12 , wherein there are two substituents chosen from Rand wherein one is halogen and the other is C-Calkyl.15. The pharmaceutical composition of claim 14 , wherein C-Calkyl is methyl.16. The pharmaceutical composition of claim 1 , wherein B is —(C-Calkyl)(aryl) claim 1 , —(C-Calkyl)(heteroaryl) claim 1 , or —(C-Calkyl)(biphenyl) each of which B is unsubstituted or substituted with one or more substituents ...

5-BROMO-INDIRUBINS

Disclosed herein inter alia are compositions and methods for treating cancer using 5-Br-indirubin derivatives. 2. The compound of claim 1 , wherein Rand Rare hydrogen.35.-. (canceled)6. The compound of claim 1 , wherein L is unsubstituted Calkylene or a bond.78.-. (canceled)9. The compound of claim 1 , wherein Ris —NRR.1015.-. (canceled)16. The compound of claim 1 , wherein Rand Rare joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.17. (canceled)18. The compound of claim 1 , wherein Rand Rare joined together to form a substituted or unsubstituted C-Cheterocycloalkyl.1921.-. (canceled)22. The compound of claim 16 , wherein Rand Rare joined together to form a substituted or unsubstituted pyrrolidinyl or substituted or unsubstituted piperazinyl.23. (canceled)24. The compound of comprising a protonated nitrogen cation or a plurality of protonated nitrogen cations.25. (canceled)28. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of .29. The compound of for use in treating cancer in a subject in need thereof.30. The compound of claim 29 , wherein said compound is administered in an effective amount to said subject.31. The compound of claim 29 , wherein said compound is in a pharmaceutical composition comprising a pharmaceutically acceptable excipient.32. The compound of claim 29 , wherein said cancer is lung cancer claim 29 , breast cancer claim 29 , ovarian cancer claim 29 , leukemia claim 29 , lymphoma claim 29 , melanoma claim 29 , pancreatic cancer claim 29 , sarcoma claim 29 , bladder cancer claim 29 , bone cancer claim 29 , brain cancer claim 29 , cervical cancer claim 29 , colon cancer claim 29 , esophageal cancer claim 29 , gastric cancer claim 29 , liver cancer claim 29 , head and neck cancer claim 29 , kidney cancer claim 29 , myeloma claim 29 , thyroid cancer claim 29 , or prostate cancer.33. The compound of claim 29 , wherein said compound is co- ...

Alkyne Compounds for Treatment of Complement Mediated Disorders

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof, wherein Ror Ron the A group is an alkyne (R) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer. 2. The method of claim 1 , wherein the host is a human.4. The method of claim 2 , wherein Ris hydrogen.5. The method of claim 2 , wherein Ris chosen from —CHO claim 2 , —CONH claim 2 , and C-Calkanoyl.6. The method of claim 5 , wherein Ris hydrogen.7. The method of claim 6 , wherein m is 0 or 1.9. The method of claim 2 , wherein B is —(CH)(aryl) substituted with two substituents independently chosen from Rand R.10. The method of claim 9 , wherein Ris halogen.11. The method of claim 10 , wherein there are two Rsubstituents and one is chlorine and the other is fluorine.12. The method of claim 2 , wherein B is aryl or heteroaryl each of which B is unsubstituted or substituted with one or more substituents independently chosen from Rand R.13. The method of claim 2 , wherein the disorder is age-related macular degeneration (AMD).14. The method of claim 2 , wherein the disorder is retinal degeneration.15. The method of claim 2 , wherein the disorder is an ophthalmic disease.16. The method of claim 2 , wherein the disorder is paroxysmal nocturnal hemoglobinuria (PNH).17. The method of claim 2 , wherein the disorder is multiple sclerosis.18. The method of claim 2 , wherein the disorder is arthritis. This application is a continuation of U.S. application ...

Antibiotic Compounds, Pharmaceutical Formulations Thereof And Methods And Uses Therefor

The present invention relates to compounds of formula (I) wherein G 1 to G 8 are as defined herein. The compounds are PK inhibitors and as such represent a new approach to treating pathogenic infections, including multidrug resistant pathogens. Disclosed herein are the compounds of formula (I), pharmaceutical compositions comprising the compounds of formula (I) and their use in the treatment of antimicrobial infection. (Formula (1))

Antibacterial agents: n(alpha)-aroyl-n-aryl-phenylalaninamides

The invention provides compounds having activity as bacterial RNA polymerase inhibitors and antibacterial agents, as well as compositions comprising the compounds and methods for their use. Specifically, phenylalanineamide and tyrosinamide compounds are disclosed that have inhibitory activity toward mycobacterium tuberculosis RNA polymerase. Use of these compounds in the treatment or prevention of M. tuberculosis infections in a mammal, is disclosed.

THERAPEUTIC COMPOUNDS

The invention provides a compound of formula I: 2. The compound of claim 1 , wherein A is a 6-12 membered cycloalkyl that is optionally substituted with one or more groups selected from halo claim 1 , hydroxy claim 1 , nitro claim 1 , cyano claim 1 , NRR claim 1 , Calkyl claim 1 , Calkoxy claim 1 , or Chaloalkyl.3. The compound of claim 1 , wherein A is a 8-11 membered cycloalkyl that is optionally substituted with one or more groups selected from halo claim 1 , hydroxy claim 1 , nitro claim 1 , cyano claim 1 , NRR claim 1 , Calkyl claim 1 , Calkoxy claim 1 , or Chaloalkyl.4. The compound of claim 1 , wherein A is adamantyl.5. The compound of claim 1 , wherein Ris hydrogen.6. The compound of claim 1 , wherein Ris hydrogen.7. The compound of claim 1 , wherein Ris hydrogen.8. The compound of claim 1 , wherein Ris hydrogen.10. A pharmaceutical composition comprising a compound of formula I as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.11. A method to treat cancer in an animal comprising administering a compound of formula I as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to the animal.12. The method of claim 11 , wherein the cancer is selected from the group consisting of skin cancer claim 11 , pancreatic cancer claim 11 , bile duct carcinoma claim 11 , neuroblastoma claim 11 , colon cancer claim 11 , breast cancer claim 11 , myeloma claim 11 , gastric cancer claim 11 , liver cancer claim 11 , glioblastoma claim 11 , ovarian cancer claim 11 , colorectal cancer claim 11 , non-Hodgkin lymphoma claim 11 , lung cancer claim 11 , prostate cancer claim 11 , small-cell lung cancer claim 11 , large cell lung cancer claim 11 , kidney cancer claim 11 , esophageal cancer claim 11 , stomach cancer claim 11 , cervical cancer or lymphoma tumors.13. The method of claim 11 , wherein the cancer is skin cancer.14. The method of claim 11 , wherein the cancer is solar ...

CONDUCTING REACTIONS IN LEIDENFROST-LEVITATED DROPLETS

The invention generally relates to conducting reactions in Leidenfrost-levitated droplets. 1. A method for forming a reaction product , the method comprising conducting a reaction within a Leidenfrost-levitated droplet while maintaining a substantially constant volume of the Leidenfrost-levitated droplet , thereby forming a reaction product within the Leidenfrost-levitated droplet.2. The method according to claim 1 , further comprising analyzing the reaction product.3. The method according to claim 2 , wherein analyzing is by a mass spectrometry technique.4. The method according to claim 1 , wherein maintaining the substantially constant volume comprises introducing droplets of pure solvent or the reaction mixture to the Leidenfrost-levitated droplet.5. The method according to claim 4 , wherein a rate at which the droplets of the pure solvent or reaction mixture are introduced to the Leidenfrost-levitated droplet is dependent on an evaporation rate of the Leidenfrost-levitated droplet.6. The method according to claim 1 , wherein the method further comprises conducting multiple reactions in multiple separate Leidenfrost-levitated droplets.7. The method according to claim 6 , wherein the multiple separate Leidenfrost-levitated droplets are merged with each other.8. The method according to claim 6 , wherein the multiple reactions are the same.9. The method according to claim 6 , wherein the multiple reactions are different.10. The method according to claim 1 , wherein the method is conducted without the use of surfactants.11. The method according to claim 1 , further comprising collecting the reaction product at a surface.12. A method for forming a reaction product claim 1 , the method comprising:introducing a first liquid droplet onto a heated surface that is at a temperate that is at or above a Leidenfrost point of the first liquid such that the first liquid droplet levitates on the heated surface, wherein the first liquid droplet comprises reagents for a reaction; ...

INDOLINE ANALOGS AND USES THEREOF

Indoline derivative compounds that act as EWS-FLI1 transcription factor inhibitors are provided. Also provided are pharmaceutical compositions of the indoline derivatives, methods of synthesizing the same, methods of treating using same, and assays for identifying the inhibitors of EWS-FLI1 oncoprotein. 2. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , and Rare independently selected from the group consisting of H and Cl.3. The compound of claim 1 , wherein Rand Rare Cl and Rand Rare H.4. The compound of claim 1 , wherein A is —OH.5. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , and Rare H.6. The compound of claim 1 , wherein Ris —OCH.9. The compound of claim 8 , wherein Ris —CH.12. The compound of claim 11 , wherein Rand Rare —CH.15. The compound of claim 14 , wherein Ris H.18. The compound of claim 17 , wherein Ris —OCH.24. A method for treating cancer selected from the group consisting of Ewing's sarcoma claim 17 , prostate cancer claim 17 , glioblastoma claim 17 , acute myeloid leukemia claim 17 , breast cancer claim 17 , head and neck cancer claim 17 , melanoma claim 17 , non-small cell lung cancer claim 17 , ovarian cancer claim 17 , and uterine cancer claim 17 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering an effective amount of the compound of to a subject in need thereof'}25. A method for killing or inhibiting the growth of a neoplastic cell claim 17 , wherein the neoplastic cell is a cancer cell claim 17 , the cancer being selected from the group consisting of Ewing's sarcoma claim 17 , prostate cancer claim 17 , glioblastoma claim 17 , acute myeloid leukemia claim 17 , breast cancer claim 17 , head & neck cancer claim 17 , melanoma claim 17 , non-small cell lung cancer claim 17 , ovarian cancer claim 17 , and uterine cancer claim 17 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting the neoplastic cell with an effective amount of the compound of .'}26. A ...

Antibiotic sensitivity-restoring and photosensitive agents

The present disclosure describes a method to treat conditions, including bacterial infections and cancer, using a photosensitive compound that, upon exposure to white light, can be activated. The photosensitive compound can also interact synergistically with antibiotics used concomitantly to kill drug-resistant bacteria. The photosensitive compounds can also be used to inhibit the proliferation of cancer cells.

INDOLINE ANALOGS AND USES THEREOF

Indoline derivative compounds that act as EWS-FLI1 transcription factor inhibitors are provided. Also provided are pharmaceutical compositions of the indoline derivatives, methods of synthesizing the same, methods of treating using same, and assays for identifying the inhibitors of EWS-FLI1 oncoprotein. 3. A method for treating cancer selected from the group consisting of Ewing's sarcoma , prostate cancer , glioblastoma , acute myeloid leukemia , breast cancer , head and neck cancer , melanoma , non-small cell lung cancer , ovarian cancer , and uterine cancer , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering an effective amount of the compound of to a subject in need thereof.'}4. A method for killing or inhibiting the growth of a neoplastic cell , wherein the neoplastic cell is a cancer cell , the cancer being selected from the group consisting of Ewing's sarcoma , prostate cancer , glioblastoma , acute myeloid leukemia , breast cancer , head & neck cancer , melanoma , non-small cell lung cancer , ovarian cancer , and uterine cancer , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting the neoplastic cell with an effective amount of the compound of .'}5. A method for inhibiting proliferation of a cell , wherein the cell overexpresses an ETS gene or comprises an ETS fusion gene , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting the cell with an effective amount of the compound of .'}6. The method of claim 5 , wherein the ETS gene or the ETS fusion gene is selected from the group consisting of FLI1 claim 5 , ERG claim 5 , ETV1 claim 5 , and ETV4. Any and all priority claims identified in the Application Data Sheet, or any correction thereto, are hereby incorporated by reference under 37 CFR 1.57. This application is a divisional of U.S. application Ser. No. 15/680,905, filed Aug. 18, 2017, which is a continuation of U.S. application Ser. No. 15/461,327, filed Mar. 16, 2017, now U.S. Pat. No. 9, ...

COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS

Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement. 6. The compound of claim 2 , wherein:{'sup': 1', '1′', '2', '2′', '3', '3′, 'a) Rand R, or Rand R, or Rand R are linked to form a 3- to 6-membered carbocyclic spiro ring; or'}{'sup': 1', '1′', '2', '2′', '3', '3′, 'b) Rand R, Rand R or Rand R are linked to form a 3- to 6-membered heterocyclic spiro ring; or'}{'sup': 1', '2, 'c) Rand Rare linked to form a 3- to 6-membered carbocyclic or aryl ring; or'}{'sup': 2', '3, 'd) Rand Rare linked to form a 3- to 6-membered carbocyclic ring.'}7. The compound of claim 2 , wherein the Rmoiety has at least one substituent.8. The compound of claim 2 , wherein Ris —C(CH)Rwherein:{'sup': 30', '9', '31', '32, 'Ris optionally substituted —NRC(O)Ror R.'}9. The compound of claim 8 , wherein Ris C-Calkyl claim 8 , C-Chaloalkyl claim 8 , C-Calkenyl claim 8 , C-Calkynyl claim 8 , (C-Ccycloalkyl)C-Calkyl claim 8 , (aryl)C-Calkyl claim 8 , (heterocycle)C-Calkyl and (heteroaryl)C-Calkyl wherein each group can be optionally substituted with one or more substituents independently chosen from hydroxyl claim 8 , nitro claim 8 , cyano claim 8 , amino claim 8 , oxo claim 8 , —B(OH) claim 8 , —Si(CH) claim 8 , —COOH claim 8 , —CONH claim 8 , —P(O)(OH) claim 8 , C-Calkyl claim 8 , C-Calkoxy claim 8 , —C-Calkyl(mono- and di-C-Calkylamino) claim 8 , C-Calkylester claim 8 , C-Calkylamino claim 8 , C-Chydroxylalkyl claim 8 , C-Chaloalkyl claim 8 , and C-Chaloalkoxy.10. The compound of claim 2 , wherein B is selected from a monocyclic carbocyclic or bicyclic carbocyclic moiety which is unsubstituted or substituted with one or more substituents independently chosen from Rand R ...

Pharmaceutical Compound

Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: 13-. (canceled)513-. (canceled)15. (canceled)17. The compound of claim 14 , wherein Ris selected from the group consisting of: H;{'sub': 2', '2', '3', '2', '2', '2', '2', '2', '2, 'a carbonyl group selected from (CO)Me, —(CO)Et, —(CO)Pr, —(CO)iPr, —(CO)nBu, —(CO)iBu, —(CO)tBu, —(CO)Ph, —(CO)CHPh, —(CO)CHOCH, —(CO)CHOH, —(CO)CHNH, —(CO)CHNHMe, —(CO)CHNMe, —(CO)cyclopropyl, and —(CO)isopropyl(1,3)oxy;'}{'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3, 'a sulphonyl group selected from SOMe, —SOEt, —SOPr, —SOiPr, —SOPh, —SO-(2,3 or 4)-F-Ph, —SO-cyclopropyl, and —SOCHCHOCH;'}{'sub': 2', '3', '3', '2, 'a group selected from —(CO)OEt, —(CO)NHEt, —CHCF, -Me, —CF, —CHPh; and'}a heterocyclic group selected from pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, tetrazole-1yl, tetrazole-2-yl, tetrazole-3-yl, tetrazole-4-yl, tetrazole-5-yl, (1,3,4-oxadiazol)-2-yl, (1,3,4-oxadiazol)-5-yl, (1,3-thiazol)-2-yl, (1,3-thiazol)-4-yl, (1,3-thiazol)-5-yl, furan-2-yl, and furan-3-yl).18. The compound of claim 17 , wherein claim 17 , where present claim 17 , Rand Rare independently selected from H;—F; —Cl;-Me;{'sub': '3', '—CF;'}—OMe;—CN;{'sub': '2', '—OCHPh;'}{'sub': 2', '2', '2, '—OCHCHNMe; and'}═O.19. The compound of claim 18 , wherein claim 18 , where present claim 18 , one of Rand Ris H while the other is selected from —H claim 18 , —F claim 18 , —Cl claim 18 , -Me claim 18 , —CF claim 18 , -MeO and —CN.20. The compound of claim 4 , wherein{'sup': '1', 'Ris selected from the group consisting ofa substituted or unsubstituted saturated or unsaturated heterocyclic group selected from pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrimidin-6-yl, tetrazole-1yl, ...

INDOLE (SULFOMYL) N-HYDROXY BENZAMIDE DERIVATIVES AS SELECTIVE HDAC INHIBITORS

Sulfonyl hydroxamic acid compounds have the following general formula: 3. The sulfonyl hydroxamic acid compound as claimed in claim 1 , wherein the sulfonyl hydroxamic acid compounds are represented by:N-hydroxy-4-(N-(1-methyl-3-phenyl-1H-indol-5-yl)sulfamoyl)benzamide(1),4-(N-(3-(4-chlorophenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide(2),4-(N-(3-(4-fluorophenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide(3),4-(N-(3-(3,4-dimethoxyphenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxy benzamide(4),N-hydroxy-4-(N-(1-methyl-3-(naphthalen-1-yl)-1H-indol-5-yl)sulfamoyl)benzamide(5),N-hydroxy-4-(N-(1-methyl-3-(4-nitrophenyl)-1H-indol-5-yl)sulfamoyl)benzamide(6),4-(N-(3-(2,4-difluorophenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide(7),N-hydroxy-4-(N-(3-(2-methoxyphenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)benzamide(8),N-hydroxy-4-(N-(3-(4-methoxyphenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)benzamide (9),N-hydroxy-4-(N-(3-(3-methoxyphenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)benzamide (10),4-(N-(3-(3-chlorophenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide (11),N-hydroxy-4-(N-(1-methyl-3-(naphthalen-2-yl)-1H-indol-5-yl)sulfamoyl)benzamide (12),4-(N-(3-(3-chloro-4-fluorophenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide (13),4-(N-(3-(2-fluorophenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide (14),4-(N-(3-(3-(benzyloxy)phenyl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide(15),4-(N-(3-(benzo[b]thiophen-3-yl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide(16),4-(N-(3-(biphenyl-4-yl)-1-methyl-1H-indol-5-yl)sulfamoyl)-N-hydroxybenzamide(17), andN-hydroxy-4-(N-(1-methyl-3-(3-(trifluoromethyl)phenyl)-1H-indol-5-yl)sulfamoyl) benzamide (18).4. A process for the preparation of a sulfonyl hydroxamic acid compound as claimed in comprising the steps of:a) brominating nitroindole using NBS in a polar non-protonated solvent at −5 to 5° C. for 40-100 minutes;b) protecting indole NH using alkyl halides and hydride base in a ...

Substituted indoles as inhibitors of poly (ADP-ribose) polymerase (PARP)

The present invention relates to a series of substituted indole derivatives of the formula I: wherein R, R 1 , R 2 , R 3 , R 4 , X and Y are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5′-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.

Substituted oxindole derivatives as protein tyrosine kinase and as protein serine/threonine kinase inhibitors

Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C¿1-12? aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R?7¿-sulfonyl, R7-sulfonyl -C¿1-12? aliphatic, R?7¿-aminosulfonyl, R7-aminosulfonyl-C¿1-12? aliphatic, R?7¿-sulfonylamino, R7-sulfonylamino-C¿1-12? aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R?8)¿1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R?4 and R5¿ are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

ISOINDOLINE DERIVATIVES

An isoindoline derivative of formula 3. The isoindoline derivative according to claim 2 , where{'sub': '3', 'Y is phenyl, naphthyl or biphenylyl, which is substituted with COOH, a salt thereof, SOH or a salt thereof.'}4. The isoindoline derivative according to claim 2 , where{'sub': '3', 'Y is phenyl or naphthyl, which is substituted with SOH or a salt thereof.'}5. The isoindoline derivative according to claim 1 , where{'sup': '2', 'X is C—CN or C—COR;'}Y is a radical of formula -A-D (III), where{'sup': 4', '4, 'sub': '2', 'A is —CO—NR— or —SO—NR—;'}{'sub': 1', '6', '1', '6', '1', '6, 'sup': 5', '6', '5', '6, 'D is —(C-C-alkylene)-NRRor —(C-C-alkylene)-NH—NRR, said C-C-alkylene may be interrupted by NH;'}{'sup': '2', 'sub': 1', '4, 'Ris C-C-alkyl;'}{'sup': '4', 'sub': 1', '4, 'Ris H or C-C-alkyl;'}{'sup': 4', '7, 'sub': 1', '4, 'or D and Rtogether with the linking nitrogen form a 5- or 6-membered ring, said 5- or 6-membered ring may be substituted by C-C-alkyl and/or interrupted by NR, O or S;'}{'sup': 5', '6, 'sub': 1', '4, 'Rand Rare independently from one another H or C-C-alkyl;'}{'sup': 5', '6', '8, 'sub': 1', '4, 'or Rand Rtogether with the linking nitrogen form a 5- or 6-membered ring, said 5- or 6-membered ring is interrupted by NRand is optionally substituted by C-C-alkyl;'}{'sup': '7', 'sub': 1', '4, 'Ris H or C-C-alkyl; and'}{'sup': '8', 'sub': 1', '4, 'Ris H, C-C-alkyl or phenyl.'}6. The isoindoline derivative according to claim 1 , which derivative is in a pigmentary form.7. A pigment composition comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) an isoindoline derivative of formula (I), as defined in , and'}(b) an isoindoline pigment.8. The pigment composition according to claim 7 , wherein the isoindoline pigment (b) is selected from Pigment Yellow 139 claim 7 , Pigment Yellow 185 claim 7 , Pigment Orange 64 claim 7 , Pigment Orange 66 claim 7 , Pigment Orange 69 claim 7 , Pigment Red 260 or a combination thereof.9. The pigment ...

Novel indole derivative having carbamoyl group, ureido group and substituted oxy group

Method of producing trifluoroacetates of substituted 6-aminoindoles, having antimicrobial action

FIELD: chemistry.SUBSTANCE: invention relates to a method of producing trifluoroacetates of substituted 6-aminoindoles, in which corresponding substituted 6-aminoindole in a benzene heated to boiling is reacted with trifluoroacetic acid.EFFECT: obtained compounds, such as 2,3,5-trimethyl-1H-indole-6-ammonium trifluoroacetate, 1,2,3,5-tetramethyl-1H-indole-6-ammonium trifluoroacetate, 2,3-dimethyl-5-methoxy-1H-indole-6-ammonium trifluoroacetate, 1,2,3-trimethyl-5-methoxy-1H-indole-6-ammonium trifluoroacetate, can be used as water-soluble synthetic antimicrobial preparations.1 cl, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 721 833 C1 (51) МПК C07D 209/40 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 209/40 (2020.02) (21)(22) Заявка: 2019125299, 09.08.2019 (24) Дата начала отсчета срока действия патента: Дата регистрации: 22.05.2020 (45) Опубликовано: 22.05.2020 Бюл. № 15 2 7 2 1 8 3 3 R U (56) Список документов, цитированных в отчете о поиске: RU 2675806 C1, 25.12.2018. EP 467767 A1, 22.01.1992. Yamashkin, S. A. et al. "Synthesis of pyrroloquinolines from substituted 6aminoindoles and oxaloacetic ester." Chemistry of Heterocyclic Compounds, 2008, 44(7), 793-801. Реферат STN on line 47:63168 Original Reference No. 47:10733i,10734a-b Woolley, D. W. et al, "Antimetabolites of serotonin." (см. прод.) (54) Способ получения трифторацетатов замещенных 6-аминоиндолов, обладающих противомикробным действием (57) Реферат: Изобретение относится к способу получения аммония, трифторацетат 1,2,3,5-тетраметил-1Нтрифторацетатов замещенных 6-аминоиндолов, индол-6-аммония, трифторацетат 2,3-диметил-5в котором соответствующее замещенное 6метокси-1Н-индол-6-аммония, трифторацетат аминоиндола в нагретом до кипения бензоле 1,2,3-триметил-5-метокси-1Н-индол-6-аммония, подвергают взаимодействию с трифторуксусной могут найти применение в качестве кислотой. Полученные соединения, такие как водорастворимых синтетических ...

Novel indole derivative containing carbamoyl group, ureide group and substituted oxy group

FIELD: chemistry. SUBSTANCE: invention relates to novel indole derivatives containing a carbamoyl group, a ureide group and a substituted oxy group or to pharmaceutically acceptable salts, having general formula , where values of R 1 -R 3 , m are given in claim 1. EFFECT: compounds exhibit inhibiting activity on IKKβ, which enables use thereof as a preventive or therapeutic agent for treating several diseases associated with IKKβ. 25 cl, 1 tbl, 9 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 503 661 (13) C2 (51) МПК C07D C07D C07D A61K 209/42 401/12 405/10 31/404 (2006.01) (2006.01) (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2011105161/04, 14.07.2009 (24) Дата начала отсчета срока действия патента: 14.07.2009 (73) Патентообладатель(и): САНТЕН ФАРМАСЬЮТИКАЛ КО., ЛТД. (JP) (43) Дата публикации заявки: 20.08.2012 Бюл. № 23 2 5 0 3 6 6 1 (45) Опубликовано: 10.01.2014 Бюл. № 1 (56) Список документов, цитированных в отчете о поиске: WO 2003/082271 A2, 27.10.2005. US 2003/229047 A1, 29.09.2005. JP 2007-504238, 01.03.2007. JP 2007-517848 A, 05.07.2007. RU 2255087 C2, 27.06.2005. 2 5 0 3 6 6 1 R U (86) Заявка PCT: JP 2009/062698 (14.07.2009) C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 14.02.2011 (87) Публикация заявки РСТ: WO 2010/007972 (21.01.2010) Адрес для переписки: 109012, Москва, ул. Ильинка, 5/2, ООО "Союзпатент" (54) НОВОЕ ПРОИЗВОДНОЕ ИНДОЛА, СОДЕРЖАЩЕЕ КАРБАМОИЛЬНУЮ ГРУППУ, УРЕИДНУЮ ГРУППУ И ЗАМЕЩЕННУЮ ОКСИГРУППУ (57) Реферат: Изобретение относится к новым производным индола, содержащим карбамоильную группу, уреидную группу и замещенную оксигруппу или к их фармацевтически приемлемым солям, общей формулы (I): где значения R 1-R 3, m приведены в пункте 1 формулы. Соединения проявляют ингибирующую активность в отношении IKKβ, что позволяет использовать их в качестве профилактического и/или терапевтического Ñòð.: 1 ru R U Приоритет(ы): (30) Конвенционный приоритет: 14 ...

Silver halide photographic recording material

Solid forms of (r)-1-(2, 2-difluorobenzo[d][1, 3]dioxol-5-yl)-n-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide

FIELD: chemistry.SUBSTANCE: invention relates to a compound of formulaor a salt thereof.EFFECT: technical result is obtaining a novel compound, which is intermediate for producing (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide, which in turn can be used in medicine for treating CFTR-mediated disease.1 cl, 19 dwg, 13 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 711 481 C2 (51) МПК C07D 209/40 (2006.01) C07D 405/12 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 209/40 (2019.08); C07D 405/12 (2019.08) (21)(22) Заявка: 2015153068, 25.03.2011 (24) Дата начала отсчета срока действия патента: Дата регистрации: 17.01.2020 25.03.2010 US 61/317,376; 01.04.2010 US 61/319,953; 07.04.2010 US 61/321,636; 07.04.2010 US 61/321,561 Номер и дата приоритета первоначальной заявки, из которой данная заявка выделена: 2012145295 25.03.2010 (73) Патентообладатель(и): ВЕРТЕКС ФАРМАСЬЮТИКАЛЗ ИНКОРПОРЕЙТЕД (US) (56) Список документов, цитированных в отчете о поиске: US 20090131492 A1, 21.05.2009. WO 2009073757 A1, 11.06.2009. RU 2259998 C2, 10.09.2005. 2 7 1 1 4 8 1 Приоритет(ы): (30) Конвенционный приоритет: R U 25.03.2011 (72) Автор(ы): КЕСХАВАРЗ-СХОКРИ, Али (US), ЧЖАН, Бэйли (US), АЛКАСИО, Тим, Эдвард (US), ЛИ, Элейн, Чунгмин (US), ЧЖАН, Юэган (US), КРАВЕЦ, Мариуш (US) 2 7 1 1 4 8 1 R U (45) Опубликовано: 17.01.2020 Бюл. № 2 Адрес для переписки: 129090, Москва, ул. Большая Спасская, д. 25, строение 3, ООО "Юридическая фирма Городисский и Партнеры" (54) ТВЕРДЫЕ ФОРМЫ (R)-1-(2, 2-ДИФТОРБЕНЗО[d][1, 3]ДИОКСОЛ-5-ИЛ)-N-(1-(2, 3ДИГИДРОКСИПРОПИЛ)-6-ФТОР-2-(1-ГИДРОКСИ-2-МЕТИЛПРОПАН-2-ИЛ)-1H-ИНДОЛ-5ИЛ)ЦИКЛОПРОПАНКАРБОКСАМИДА (57) Реферат: Изобретение относится к соединению получено новое соединение, которое является формулы промежуточным для получения (R)-1-(2,2дифторбензо[d][1,3]диоксол-5-ил)-N-(1-(2,3дигидроксипропил)-6-фтор-2-( ...

不对称铋催化体系及其制备方法和应用

本公开提供了一种不对称铋催化体系及其制备方法和应用，涉及不对称催化技术领域，提供了一种不对称铋催化体系，解决了铋催化体系底物专一性高的问题。该不对称铋催化体系由金属活性中心及手性配体构成，其中所述金属活性中心选自乙酸铋、氢氧化铋、溴化铋或碘化铋的一种或多种，所述手性配体选自手性磷酸。该不对称铋催化体系用于催化多种类型的不对称转化，比如，酮、亚胺的不对称烯丙基化，氧鎓离子的不对称烯丙基化，亚胺与酚类底物的不对称反应等。

Manufacture of 77acylindolinee22one

Ｅｈｍｔ２阻害剤としての置換された融合二環式または三環式複素環化合物

N- [4(5-cyclopentyloxycarbonyl) amino-1-methylindol-3-yl-methyl]-3-methoxybenzoyl]-2-methylbenzenesulfoneamide and the process for the preparation thereof

본 발명은 특정 물리적 형태의 N-[4-[5-(시클로옥시카르보닐)아미노-1-메틸인돌-3-일-메틸]-3-메톡시벤조일]-2-메틸-벤젠설폰아미드에 관한 것이다. 본 발명에서는 또한 상기 물리적 형태, 및 상기 물리적 형태의 제조시 유용한 또다른 물리적 형태의 N-[4-[5-시클로펜틸옥시카르보닐)아미노-1-메틸인돌-3-일-메틸]-3-메톡시벤조일]-2-메틸벤젠설폰아미드의 제조 방법을 제공한다. 상기 화합물은 류코트레인-관련 질병, 예를들면 천식의 치료시 유용하다. The present invention relates to N- [4- [5- (cyclooxycarbonyl) amino-1-methylindol-3-yl-methyl] -3-methoxybenzoyl] -2-methyl-benzenesulfonamide in certain physical forms. It is about. The present invention also relates to the physical form, and another physical form of N- [4- [5-cyclopentyloxycarbonyl) amino-1-methylindol-3-yl-methyl] -3 useful in the preparation of the physical form. -Methoxybenzoyl] -2-methylbenzenesulfonamide. Such compounds are useful in the treatment of leukotlein-related diseases such as asthma.

N-(indolyl)trifluoroacetamides with antimicrobial activity production method

FIELD: chemistry.SUBSTANCE: invention relates to the field of chemistry, namely to the N-(2,3-dimethyl-1H-indole-7-yl)-2,2,2-trifluoroacetamide and N-(1,2,3-trimethyl-1H-indol-7-yl)-2,2,2-trifluoroacetamide production method. Method consists in the corresponding aminoindole interaction with trifluoroacetic acid ethyl ether.EFFECT: invention can be used for the drugs with antimicrobial activity production.2 cl, 2 tbl, 4 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 675 806 C1 (51) МПК C07D 209/40 (2006.01) A61K 31/404 (2006.01) A61P 31/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 209/40 (2018.08); A61K 31/404 (2018.08); A61P 31/00 (2018.08) (21)(22) Заявка: 2018121537, 20.07.2018 (24) Дата начала отсчета срока действия патента: 25.12.2018 Приоритет(ы): (22) Дата подачи заявки: 20.07.2018 (45) Опубликовано: 25.12.2018 Бюл. № 36 Ямашкин, Е.А. Орешкина, М.А. Юровская "Изучение реакции 2,3-диметил-, 1,2,3триметил-6-аминоиндолов с 4,4,4трифторацетоуксусным эфиром", Вестник Московского Университета, Химия 2007, том 48. (54) Способ получения N-(индолил)трифторацетамидов, обладающих противомикробным действием (57) Реферат: Изобретение относится к области химии, а препаратов, обладающих противомикробным именно к способу получения N-(2,3-диметил-1Ндействием. Способ заключается во индол-7-ил)-2,2,2-трифторацетамида и N-(1,2,3взаимодействии соответствующего аминоиндола триметил-1Н-индол-7-ил)-2,2,2с этиловым эфиром трифторуксусной кислоты. 2 трифторацетамида, которые могут найти н.п. ф-лы, 2 табл., 4 пр. применение для получения лекарственных R U 2 6 7 5 8 0 6 (56) Список документов, цитированных в отчете о поиске: WO 2013029338 A1, 07.03.2013. С.А. Стр.: 1 C 1 C 1 Адрес для переписки: 430005, рес. Мордовия, г. Саранск, ул. Большевистская, 68, ФГБОУ ВО "МГУ им. Н.П. Огарёва", начальнику отдела управления интеллектуальной собственностью Сальниковой А.И. 2 6 7 5 8 0 6 (73) Патентообладатель(и): Федеральное ...

Guanidine compounds and use thereof

1H-indol-5-yl-piperazin-1-yl-methanone derivatives

本发明涉及式(I)化合物及其药用盐，其中R 1 至R 4 如说明书和权利要求书中定义。所述化合物可用于治疗和/或预防与H3受体的调节有关的疾病。

Method of producing monochloroacetates of substituted 5-, 6-, 7-aminoindoles, having antimicrobial action

FIELD: chemistry.SUBSTANCE: invention relates to a method of producing monochloroacetates of substituted 5-, 6-, 7-aminoindoles, which involves reacting corresponding substituted 5-, 6-, 7-aminoindoles in benzene heated with boiling with monochloroacetic acid.EFFECT: obtained novel salts, such as 2,3-dimethyl-1H-indole-5-ammonium monochloroacetate, 1,2,3-trimethyl-1H-indole-5-ammonium monochloroacetate, 2,3-dimethyl-5-methoxy-1H-indole-6-ammonium monochloroacetate, 5-methoxy-1,2,3-trimethyl-1H-indole-6-ammonium monochloroacetate, 2,3-dimethyl-1H-indole-7-ammonium monochloroacetate and 1,2,3-trimethyl-1H-indole-5-ammonium monochloroacetate, can be used as water-soluble synthetic antimicrobial preparations.1 cl, 6 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 724 605 C1 (51) МПК C07D 209/40 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 209/40 (2020.02) (21)(22) Заявка: 2019125333, 09.08.2019 (24) Дата начала отсчета срока действия патента: Дата регистрации: 25.06.2020 (45) Опубликовано: 25.06.2020 Бюл. № 18 2 7 2 4 6 0 5 R U (56) Список документов, цитированных в отчете о поиске: RU 2675806 C1, 25.12.2018. EP 497697 A1, 05.08.1992. Yamashkin, S. A. et al. "Synthesis of pyrroloquinolines from substituted 6aminoindoles and oxaloacetic ester." Chemistry of Heterocyclic Compounds, 2008, 44(7), 793-801. Реферат STN on line 47:63168 Original Reference No. 47:10733i,10734a-b Woolley, D. W. et al, "Antimetabolites of serotonin." (см. прод.) (54) Способ получения монохлорацетатов замещенных 5-,6-,7-аминоиндолов, обладающих противомикробным действием (57) Реферат: Изобретение относится к способу получения индол-5-аммония, монохлорацетат 2,3-диметилмонохлорацетатов замещенных 5-,6-,75-метокси-1Н-индол-6-аммония, монохлорацетат аминоиндолов, который включает 5-метокси-1,2,3-триметил-1Н-индол-6-аммония, взаимодействие соответствующих замещенных монохлорацетат 2,3-диметил-1Н-индол-7-аммония 5-,6-,7-аминоиндолов в ...

Derivatives of sulfonylurea or their pharmaceutically acceptable salts, a method of their synthesis and a pharmaceutical composition based on derivatives of sulfonylurea showing antitumor activity

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention relates to derivatives of sulfonylurea of the formula: A-S(O) 2 -NH-C(O)-NH-Ph(R 2 )(R 3 ), where A - 2,3-dihydro-1H-indolyl or IR 1 -indolyl; R 1 is C 1 -C 6 -alkyl; R 2 and R 3 mean independently each of other - H, halogen, C 1 -C 6 - alkyl, trifluoromethyl at condition that only one of substituents R 2 and R 3 can be hydrogen. These derivatives are used in a pharmaceutical composition showing antitumor activity. Compounds are synthesized by interaction of compound Y-Ph(R 2 )(R 3 ) with sulfonyl compound of the formula: A-S(O) 2 -X where Y is NH 2 or NCO; X is NCO, NH 2 or NHCOO-R a where R a is C 1 -C 3 -alkyl at condition that if X means NCO or NHCOO-R a then Y is NH 2 ; if X is NH 2 then Y is NCO. EFFECT: improved method of synthesis, enhanced antitumor effectiveness of compounds. 8 cl, 1 tbl, 7 ex па (19) 13) ВИ "” 2 127 259 ' (51) МПК СЛ С 070 209/24, 209/40, Аб1 К 31/405 РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 95122639/04, 10.03.1994 (71) Заявитель: Эли Лилли энд Компани (1$) (30) Приоритет: 10.03.1993 4$ 08029.095 (72) Изобретатель: Джеральд Барр Гранди (ЦЗ), (46) Дата публикации: 10.03.1999 Кора Сью Гроссман (ЦЗ), Джеймс Джеффри Хауберт (1$), Джеймс Эдвард Рей (4$), Джон (56) Ссылки: 9$ 51168174 А, 1992. 4$ 5169860 А, Элдон Тот (ЦЗ) 1992. Машковский М.Д. Лекарственные <“ средства. - М.: Медицина, 1984, ч.2, с.428, (73) Патентообладатель: Ф) 453, 455. Эли Лилли энд Компани (ЦЗ) (85) Дата перевода заявки РСТ на национальную фазу: 10.10.95 © (86) Заявка РСТ: о) ($ 94102606 < (87) Публикация РСТ: ^—- М\МУО 94/20101 (15.09.94) | м (98) Адрес для переписки: 103735, Москва, ул.Ильинка, 5/2 Союзпатент = Сс' (54) ПРОИЗВОДНЫЕ СУЛЬФОНИЛМОЧЕВИНЫ ИЛИ ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ОСНОВЕ ПРОИЗВОДНЫХ СУЛЬФОНИЛМОЧЕВИНЫ, ОБЛАДАЮЩАЯ ПРОТИВООПУХОЛЕВОИЙ АКТИВНОСТЬЮ — (57) ...

Electrophotographic sensitive material

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

N-heteroaryl-N'-phenylurea derivatives, preparation method and use thereof

고콜레스테롤혈증, 동맥경화증 및 이들로 인해 유발된 질병의 예방 치료제로 유용한 하기 일반식(Ⅰ)의 N-헤테로아릴-N'-페닐우레아 유도체. [상기 식중, R 1 및 R 2 은 동일하거나 상이할 수 있으며, 각각은 수소원자 ; 할로겐원자 ; 비치환 C 1 ~C 10 알킬기 ; 치환기로서 C 2 ~C 8 -디알킬아미노를 갖는 치환 C 1 ~C 6 알킬기 ; 치환기로서 고리내 헤테로원자를 가질 수 있는 포화 환상 아미노기를 갖는 치환 C 1 ~C 6 알킬기 ; C 1 ~C 6 알콕시기 ; 또는 니트로기이고, R 1 및 R 2 은 함께 C 3 ~C 6 알킬렌기를 나타낼 수 있으며, R 3 및 R 4 은 동일하거나 상이할 수 있으며, 각각은 수소원자 ; 할로겐원자 ; C 1 ~C 6 알킬기 ; C 1 ~C 6 할로아킬기 ; C 1 ~C 6 알콕시기 ; 또는 C 1 ~C 6 알킬티오기이고, R 5 R 6 및 R 7 은 동일하거나 상이할 수 있으며, 각각은 수소원자 ; 할로겐원자 ; C 1 ~C 6 알킬기 ; C 1 ~C 6 할로알킬기 ; C 3 ~C 7 알케닐기 ; C 1 ~C 6 알콕시기 ; C 1 ~C 6 알킬티오기 ; 또는 C 2 ~C 8 -디알킬아미노기이고, X는 -O-, -S- 또는 -NR-(식중, R은 C 1 ~C 6 알킬기, 페닐술포닐기 또는 톨루엔술포닐기)이다]

Guanidine compounds and use thereof

본 발명은 미토콘드리아의 산화적 인산화 (OXPHOS)를 억제하기 위한 구아니딘 화합물 및 그의 용도에 관한 것이다. 보다 구체적으로, 본 발명은 미토콘드리아의 산화적 인산화를 억제하고 세포 대사를 재프로그래밍함으로써 OXPHOS와 관련된 질환, 특히 암을 예방 또는 치료하기 위한 약학 조성물에 관한 것이다. The present invention relates to guanidine compounds and their use for inhibiting oxidative phosphorylation (OXPHOS) of mitochondria. More specifically, the present invention relates to pharmaceutical compositions for preventing or treating diseases associated with OXPHOS, in particular cancer, by inhibiting oxidative phosphorylation of mitochondria and reprogramming cell metabolism.

Indol(sulfonil)-n-hydroxybenzamide derivatives as selective hdac inhibitors

FIELD: chemistry.SUBSTANCE: invention relates to compounds of sulfonylhydroxamic acid of a general formula I which can be used as selective inhibitors of histone deacetylases (HDAC). In the general formula I, the ring A constitutes phenyl, naphthalenyl and benzothiophenyl; the ring B constitutes phenyl; R1constitutes alkyl; R2, R3constitute hydrogen, alkoxy, halogen, nitro, benzyloxy, phenyl, CF3; R4, R5, R6constitute hydrogen; X=O. The invention also relates to a method of synthesis of the described compounds and use thereof as selective HDAC inhibitors.EFFECT: achieved is synthesis of compound which can be used as selective HDAC inhibitor.15 cl, 3 dwg, 3 tbl, 18 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 748 835 C1 (51) МПК C07D 209/40 (2006.01) C07D 409/04 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07D 209/40 (2020.08); C07D 409/04 (2020.08) (21)(22) Заявка: 2020117075, 06.08.2018 (24) Дата начала отсчета срока действия патента: Дата регистрации: 31.05.2021 27.11.2017 IN 201711042426 (45) Опубликовано: 31.05.2021 Бюл. № 16 (73) Патентообладатель(и): СОВЕТ НАУЧНЫХ И ПРИКЛАДНЫХ ИССЛЕДОВАНИЙ (IN) (85) Дата начала рассмотрения заявки PCT на национальной фазе: 25.05.2020 (56) Список документов, цитированных в отчете о поиске: WO 2006/017214 А2, 16.02.2006. WO 2008/074132 А1, 26.06.2008. RU 2208607 C2, 20.07.2003. (86) Заявка PCT: 2 7 4 8 8 3 5 R U (87) Публикация заявки PCT: WO 2019/102488 (31.05.2019) C 1 C 1 IN 2018/050514 (06.08.2018) 2 7 4 8 8 3 5 Приоритет(ы): (30) Конвенционный приоритет: R U 06.08.2018 (72) Автор(ы): ШРИВАРИ, Чандрасекар (IN), МАИНКАР, Пратхама Сатьендра (IN), РЕДДИ, Чада Раджи (IN), КОТАМРАДЖУ, Шригиридхар (IN), ТОГАПУР, Паван Кумар (IN), МУППИДИ, Суббарао Мохан Венката (IN), ШАРМА, Сомеш (IN), ДЖХА, Ашок Кумар (IN), АРУМУГАМ, Прем Кумар (IN) Адрес для переписки: 129090, Москва, пр-кт Мира, 6, ООО "Патентно-правовая фирма "ЮС" (54) ИНДОЛ(СУЛЬФОНИЛ)-N-ГИДРОКСИБЕНЗАМИДНЫЕ ...

Indolylalkylidenehydrazine-carboximidamide derivatives as 5-hydroxytryptamine-6 ligands

The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of a disorder relating to or affected by the 5-HT6 receptor.

Indolylalkylidenehydrazine-carboximidamide derivatives as 5-hydroxytryptamine-6 ligands

The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of a disorder relating to or affected by the 5-HT6 receptor.

3-amino-1-arylpropylindole and aza-substituted indole

1. Соединение формулы I ! ! или его фармацевтически приемлемая соль, ! где р представляет собой 0, 1 или 2; ! Y представляет собой CRe; ! Аr представляет собой: ! (а) индолил, выбранный из индол-4-ила, индол-5-ила, индол-6-ила и индол-7-ила, каждый из которых возможно замещен; ! (б) индазолил, выбранный из индазол-4-ила, индазол-5-ила, индазол-6-ила и индазол-7-ила, каждый из которых возможно замещен; ! (в) пирроло[2,3-b]пиридил, выбранный из пирроло[2,3-b]пирид-4-ила, пирроло[2,3-b]пирид-5-ила, пирроло[2,3-b]пирид-6-ила и пирроло[2,3-b]пирид-7-ила, каждый из которых возможно замещен; ! (г) бензимидазолил, выбранный из бензимидазол-4-ила, бензимидазол-5-ила, бензимидазол-6-ила и бензимидазол-7-ила, каждый из которых возможно замещен; ! (д) бензофуранил, выбранный из бензофуран-4-ила, бензофуран-5-ила, бензофуран-6-ила и бензофуран-7-ила, каждый из которых возможно замещен; ! (е) бензотиофенил, выбранный из бензотиофен-4-ила, бензотиофен-5-ила, бензотиофен-6-ила и бензотиофен-7-ила, каждый из которых возможно замещен; ! (ж) бензоксазолил, выбранный из бензоксазол-4-ила, бензоксазол-5-ила, бензоксазол-6-ила и бензоксазол-7-ила, каждый из которых возможно замещен; или (з) бензотиазолил, выбранный из бензотиазол-4-ила, бензотиазол-5-ила, бензотиазол-6-ила и бензотиазол-7-ила, каждый из которых возможно замещен; ! (и) бензизоксазолил, выбранный из бензизоксазол-4-ила, бензизоксазол-5-ила, бензизоксазол-6-ила и бензизоксазол-7-ила; ! (к) бензизотиазолил, выбранный из бензизотиазол-4-ила, бензизотиазол-5-ила, бензизотиазол-6-ила и бензизотиазол-7-ила; ! (л) индолинил, выбранный из индолин-4-ила, индолин-5-ила, индолин-6-ила и индолин-7-ила; или ! (м) 1,3-дигидро-индол-2-онил, выбранный из 1,3-дигидро-индол-2-он-4-ила (19) РОССИЙСКАЯ ФЕДЕРАЦИЯ RU (11) 2008 120 138 (13) A (51) МПК C07D 209/14 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21), (22) Заявка: 2008120138/04, 20.11.2006 (71) Заявитель(и): Ф. ...

SOLID FORMS OF (R)-1-(2,2-DIFLUOROBENZO[d][1,3]DIOXOL-5-YL)-N-(2,3-DIHYDROXYPROPYL)-6-FLUORO-2-(1-HYDROXY-2-METHYLPROPAN-2-YL)-1H-INDOL-5-YL)CYCLOPROPANE CARBOXAMIDE

FIELD: chemistry. SUBSTANCE: invention relates to solid forms of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropane carboxamide (compound 1) in a substantially crystalline form (form A), where form A is characterised by one or more peaks at 19.3-19.7 degrees, 21.5-21.9 degrees and 16.9-17.3 degrees in X-ray powder diffraction, obtained using Cu K alpha-radiation, or an amorphous form, which is in the form of a dry sprayed dispersion, pharmaceutical compositions thereof and treatment methods. EFFECT: improved properties. 82 cl, 19 dwg, 13 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 573 830 C2 (51) МПК C07D 405/12 (2006.01) A61K 31/404 (2006.01) A61P 11/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2012145295/04, 25.03.2011 (21)(22) Заявка: (24) Дата начала отсчета срока действия патента: 25.03.2011 Приоритет(ы): (30) Конвенционный приоритет: US US US US 61/317,376; 61/319,953; 61/321,636; 61/321,561 (73) Патентообладатель(и): ВЕРТЕКС ФАРМАСЬЮТИКАЛЗ ИНКОРПОРЕЙТЕД (US) (45) Опубликовано: 27.01.2016 Бюл. № 3 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 25.10.2012 C 2 C 2 (56) Список документов, цитированных в отчете о поиске: US 20090131492 A1 21.05.2009. Caira M.R.,"Crystalline Polymorfphism of Organic Compounds", Topics in Current Chemistry,Springer,Berlin, v.198, 1998. RU 2002123882 A 20.03.2004. (86) Заявка PCT: 2 5 7 3 8 3 0 US 2011/030032 (25.03.2011) R U 2 5 7 3 8 3 0 (43) Дата публикации заявки: 27.04.2014 Бюл. № 12 R U 25.03.2010 01.04.2010 07.04.2010 07.04.2010 (72) Автор(ы): КЕСХАВАРЗ-СХОКРИ Али (US), ЧЖАН Бэйли (US), АЛКАСИО Тим Эдвард (US), ЛИ Элейн Чунгмин (US), ЧЖАН Юэган (US), КРАВЕЦ Мариуш (US) (87) Публикация заявки PCT: WO 2011/119984 (29.09.2011) Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, строение 3, ООО "Юридическая фирма Городисский и Партнеры" (54) ТВЕРДЫЕ ФОРМЫ (R)-1-( ...

Pharmaceutical composition, method for its obtaining, physical form of n-;4-;5-(cyclopentyloxycarbonyl)amino-1-methilindol-3-il-methyl-3- -methoxybenzoil

FIELD: medicine, pharmacology. SUBSTANCE: method deals with pharmaceutical composition that contains N-[4-[5-(cyclopentyloxycarbonyl) amino-1-methylindol-3-il-methyl] -3-methoxybenzoil] -2-methylbenzolsulfonamide, polyvinylpyrrolidone and carrier at a certain weight ratio. The given composition is obtained by mixing and drying its ingredients. Physical form of active substance is characterized by an intake maximum at 1690, 1530, 1490, 1420, 1155, 1060, 862 and 550 cmcm -1 . The given composition is considered to be an antagonist of leukotriens, it is stable and possesses high pharmaceutical activity. EFFECT: higher efficiency. 5 cl, 7 cl, 3 tbl ОтгЭОГгсС ПЧ Го (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ “” 2106 140 ' ОМК А 64 К 31/48, С 070 209/18 13) СЛ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 5010340/14, 11.12.1991 (30) Приоритет: 12.12.1990 СВ 9027014.1 12.07.1991 СВ 9115107.6 (46) Дата публикации: 10.03.1998 (56) Ссылки: ЕР, патент, 199543, С 070 299/18, 29.10.86. (71) Заявитель: Зенека Лимитед (СВ) (72) Изобретатель: Джеймс Джозеф Холохан[ СВ], Иеуан Джон Эдврдсе[ СВ], Роберт Джозеф Тимко[Ц$], Рэнди Джон Брэдвэй[Ц$], Арлин Клемент Ц $] (73) Патентообладатель: Зенека Лимитед (СВ) (54) ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБ ЕЕ ПОЛУЧЕНИЯ, ФИЗИЧЕСКАЯ ФОРМА М-[4-[5-(ЦИКЛОПЕНТИЛОКСИКАРЬОНИЛ)АМИНО-1-МЕТИЛИНДОЛ-3-ИЛ-МЕТИЛ]-3-МЕТОКСИБЕНЗОИЛ]-2-М ЕТИЛЬЕНЗОЛСУЛЬФОНАМИДА, СПОСОБЫ ЕЕ ПОЛУЧЕНИЯ (57) Реферат: Изобретение относится К фармкомпозиции, содержащей М-[4-[5 (циклопентилоксикарбонил)амино 1-метилиндол-3 ил-метил] 3-метоксибензоил] 2-метилбензолсульфонамид, поливинилпирролидон и носитель при определенном весовом соотношении, способу ее получения путем смешивания и высушивания ингредиентов, физической форме действующего средства, характеризующейся максимумами поглощения при 1690, 1530, 1490, 1420, 1155, 1060, 862 и 550 см”! а также к способам ее получения. Композиция является антагонистом лейкотриенов, стабильна и обладает ...

New phenylpiperazines

본 발명은 흥미로운 약리학적 성질을 갖는 페닐피페라진의 신규한 그룹에 관한 것이다. 본 발명은 화학식 I로 표시되는 일군의 신규한 페닐피페라진 유도체 및 이의 염에 관한 것이다. 화학식 I 상기 화학식 I에서, X는 1) 화학식 1의 그룹(여기서, S 1 은 수소 또는 할로겐이고, S 2 및 S 3 은 독립적으로 수소, 알킬(1-6C), 페닐 또는 벤질이며, S 4 는 두개의 수소원자 또는 옥소 그룹을 나타내고, S 5 는 수소 또는 알킬(1-4C)이며, Y는 C, O 또는 S이다)이거나, 2) 화학식 2의 그룹(여기서, S 1 은 상기에 정의된 바와 같고, R은 H, 알킬(1-4C), 알콕시알킬(2-6C), 알케닐(2-4C) 또는 알키닐(2-4C)이다)이거나, 3) 화학식 3의 그룹(여기서, S 1 은 상기에 정의된 바와 같고, Z는 C, O 또는 N이다)이거나, 4) 화학식 4의 그룹(여기서, S 1 은 상기에 정의된 바와 같다)이거나, 5) 화학식 5의 그룹(여기서, S 1 은 상기에 정의된 바와 같고, A는 O 또는 N이며, 이 그룹은 5 또는 8번 위치에서 피페라진 환에 연결된다)이거나, 6) 화학식 6의 그룹(여기서, S 1 은 상기에 정의된 바와 같고, S 6 및 S 7 은 수소원자 또는 옥소 그룹을 나타낸다)이거나, 7) 화학식 7의 그룹(여기서, 점선 중 하나는 이중결합을 나타낼 수 있고, S 1 은 상기에 정의된 바와 같으며, P=T=Q=질소, 또는 P=T=질소이고 Q=C, 또는 P=Q=질소이고 T=C 또는 C-CH 3 , 또는 P=질소이고 T와 Q는 탄소, 또는 P=질소, T는 탄소 및 Q는 황이다)이고, m은 2 내지 6이며, n은 0 내지 2이고, R 5 및 R 6 은 독립적으로 수소 또는 알킬(1-3C); 또는 R 5 +R 6 은 -(CH 2 ) p -(여기서, p는 3 내지 5이다)이며, R 7 은 알킬(1-3C), 알콕시(1-3C), 할로겐 또는 시아노이고; 또는 R 6 +R 7 (인돌 그룹의 7번 위치에 있는 R 7 )은 그룹 -(CH 2 )q-(여기서, q는 2 내지 4이다)를 나타낸다. 화학식 1 화학식 2 화학식 3 화학식 4 화학식 5 화학식 6 화학식 7