Inhibitors of beta-secretase

Inhibitors of beta-secretase

Inhibitors of beta-secretase

Verfahren zur Herstellung von Isocyanaten und Isothiocyanaten

INHIBITORS OF BETA-SECRETASE

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the ß- secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of ß-amyloid aggregates.

INHIBITORS OF BETA-SECRETASE

Inhibitors of beta-secretase

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the - secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of -amyloid aggregates.

STABILIZED SULFORAPHANE

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

СПОСОБ ПОЛУЧЕНИЯ АДАМАНТИЛСОДЕРЖАЩИХ ИЗОТИОЦИАНАТОВ

FIELD: chemistry. SUBSTANCE: invention relates to chemistry of adamantane derivatives, specifically to a method of producing adamantyl-containing isothiocyanates, which are intermediate products for synthesis of biologically active substances. Proposed method of producing adamantyl-containing isothiocyanates involves reaction of adamantane derivative with an isothiocyanate derivative while boiling in a solvent medium followed by extraction and recrystallisation of reaction product from alcohol. Method is characterised by that adamantane derivative used is adamantyl-containing amine, selected from a series of 1-aminoadamantane, 1-(adamantan-1-yl)-ethane-1-amine or 1-amino-3,5-dimethyladamantane, and isothiocyanate derivative is phenylisothiocyanate. Reaction is carried out in a toluene medium for 3 hours in molar ratio adamantyl-containing amine : phenylisothiocyanate : toluene = 1.2:1:25. Product is separated by distilling solvent. EFFECT: method enables to obtain desired isothiocyanates with high output using a simpler method. 1 cl, 3 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 599 993 C1 (51) МПК C07C 331/18 (2006.01) C07C 331/26 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ (21)(22) Заявка: ИЗОБРЕТЕНИЯ К ПАТЕНТУ 2015133687/04, 11.08.2015 (24) Дата начала отсчета срока действия патента: 11.08.2015 (45) Опубликовано: 20.10.2016 Бюл. № 29 2 5 9 9 9 9 3 R U (54) СПОСОБ ПОЛУЧЕНИЯ АДАМАНТИЛСОДЕРЖАЩИХ ИЗОТИОЦИАНАТОВ (57) Реферат: Изобретение относится к химии производных производного адамантана используют адамантана, а именно к способу получения адамантилсодержащий амин, выбранный из ряда адамантилсодержащих изотиоцианатов, которые 1-аминоадамантан, 1-(адамантан-1-ил)-этан-1являются полупродуктами для синтеза амин или 1-амино-3,5-диметиладамантан, а в биологически активных веществ. Предлагаемый качестве изотиоцианатного производного способ получения адамантилсодержащих фенилизотиоцианат. Реакцию ведут в среде изотиоцианатов заключается во ...

STABILIZED SULFORAPHANE

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

Chemical Compounds

STABILIZED SULFORAPHANE

НОВЫЙ СПОСОБ ПОЛУЧЕНИЯ 1-АДАМАНТИЛИЗОТИОЦИАНАТА

FIELD: chemistry. SUBSTANCE: invention relates to a method of obtaining a 1-adamantyl isothiocyanate by heating in boiling 1-adamantyl isothiocyanate with phenyl isothiocyanate in dimethylformamide during 1 hour with the subsequent crystallisation product of reaction during cooling. EFFECT: new way to produce 1-adamantyl isothiocyanate without the use of hazardous reagents, characterised by simplicity of synthesis, short reaction time and high yield of the desired product. 1 ex

PHENYLIMINO-THIADIAZABICYCLOALKANE DERIVATIVES, PROCESSES AND INTERMEDIATES FOR THEIR PREPARATION AND THEIR USE AS HERBICIDES

Compounds of formula (I): wherein R is C1-C6alkyl, C1-C6haloalkyl, C3C6alkenyl, C3-C6alkynyl, C1-C4alkoxy or C3-C6cycloalkyl; R1 is halogen; R2 and R3 are each independently of the other C1-C4alkyl; R4 is halogen or a group of the formula -X-R5, -X-A-R6 or (a); R5 is hydrogen, C1-C6alkyl, C1-C8haloalkyl, C1-C4alkoxy-C1-C4alkyl, C1-C10alkylthio-C1-C4alkyl, C1-C4alkylamino-C1-C4alkyl, di-C1-C4alkylamino-C1-C4alkyl, cyano-C1-C8-alkyl, C3-C8alkenyl, C3C8haloalkenyl, C3-C8alkynyl, C3-C6cycloalkyl, oxetanyl, C3-C7-halocycloalkyl, C3-C7cycloalkyl-C1-C4alkyl, phenyl-C1-C3alkyl that is unsubstituted or substituted in the phenyl ring by 1, 2 or 3 identical or different substituents selected from halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy and C1-C4haloalkoxy, or R5 is an alkali metal, alkaline earth metal or ammonium ion, or is the group -N=C(CH3)2, -CH2-O-N=C(CH3)2 or -CH2CH2-O-N=C(CH3)2; X is oxygen or sulfur; A is C1-C4 alkylene; R6 is a 5- or 6membered heterocyclic ring that contains from ...

Phenylimino-thiadiazabicycloalkane derivatives, processes and intermediates for their preparation and their use as herbicides

Compounds of formula (I): wherein R is C1-C6alkyl, C1-C6haloalkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C4alkoxy or C3-C6cycloalkyl; R1 is halogen; R2 and R3 are each independently of the other C1-C4alkyl; R4 is halogen or a group of the formula -X-R5, -X-A-R6 or (a); R5 is hydrogen, C1-C6alkyl, C1-C8haloalkyl, C1-C4alkoxy-C1-C4alkyl, C1-C10alkylthio-C1-C4alkyl, C1-C4alkylamino-C1-C4alkyl, di-C1-C4alkylamino-C1-C4alkyl, cyano-C1-C8-alkyl, C3-C8alkenyl, C3-C8haloalkenyl, C3-C8alkynyl, C3-C6cycloalkyl, oxetanyl, C3-C7-halocycloalkyl, C3-C7cycloalkyl-C1-C4alkyl, phenyl-C1-C3alkyl that is unsubstituted or substituted in the phenyl ring by 1, 2 or 3 identical or different substituents selected from halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy and C1-C4haloalkoxy, or R5 is an alkali metal, alkaline earth metal or ammonium ion, or is the group -N=C(CH3)2, -CH2-O-N=C(CH3)2 or -CH2CH2-O-N=C(CH3)2; X is oxygen or sulfur; A is C1-C4 alkylene; R6 is a 5- or 6-membered heterocyclic ring that contains from 1 to 3 hetero atoms selected from the group oxygen, nitrogen and sulfur and that is bonded via the carbon or nitrogen atom to the alkylene chain A, it being possible for the heterocyclic ring in turn also to be benzene-fused and mono- or di-substituted by halogen, C1-C4alkyl, C1-C3haloalkyl, C1-C3alkoxy, C1-C3haloalkoxy, di-C1-C3alkylamino, hydroxy or by an oxy function; R7 is hydrogen, C1-C6alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4alkoxy-C1-C4alkyl, C3-C6alkenyl, C3-C6alkynyl, C3-C8cycloalkyl, hydroxy-C1-C4alkyl or cyano-C1-C4alkyl; R8 is hydrogen, C1-C6alkyl, C1-C4haloalkyl, C1-C4alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, C3-C6alkenyl, phenyl or phenyl-C1-C3alkyl, the phenyl ring being unsubstituted or mono-, di- or tri-substituted by halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or by C1-C4haloalkoxy; or R7 and R8, together with the nitrogen atom to which they are bonded, form a pyrrolidino, piperidino, morpholino, thiomorpholino or piperazino ring that is unsubstituted or ...

CHEMOPROTECTIVE ISOTHIOCYANATES

Sulforaphane has been isolated and identified as a major and very potent phase II enzyme inducer in broccoli (Brassica oleracea italica). Sulforaphane is a monofunctional inducer, inducing phase II enzymes selectively without the induction of aryl hydrocarbon receptor-dependent cytochromes P-450 (phase I enzymes). Analogues differing in the oxidation state of sulfur and the number of methylene groups were synthesized, and their inducer potencies were measured. Sulforaphane is the most potent of these analogues. Other analogues having different substituent groups in place of the methylsulfinyl group of sulforaphane were also synthesized and assessed. Of these, the most potent are 6-isothiocyanato-2-hexanone and exo-2-acethyl-6-isothiocyanatonorbornane.

Stabilized sulforaphane

New cyclohexane derivatives, useful as components of liquid crystal media for liquid crystal displays and electro-optical displays

New cyclohexane derivatives containing 1,4-cyclohexylene and/or 1,3-dioxan-2,5-diyl units substituted at positions 1 and/or 4 or 2 and/or 5 respectively with axial isothiocyanate, azide, nitro or isothiocyanatocarbonyl groups New cyclohexane derivatives of formula (I) are claimed: R<1> = H, 1-12 C alkyl (optionally monosubstituted with halogen and/or with 1 or more nonadjacent CH2 groups replaced by O, S, -CO-, cyclo-butane-1,3-diyl, -COO-, -OCO-, -OCOO- or -CH=CH-); Y = H, 1-10C alkyl or alkoxy (optionally monosubstituted with halogen), 2-10 C alkenyl or alkenyloxy, CN, F, OCHF2, OCF3, OCHFCF3, OCH2CF3 or OCF2CF3; X<1>, X<2> = H, NCS, -CONCS, NO2 or -N3 in the axial position (at least one of these groups is not H); Q = -CH2- or -O-; B = carbon or silicon; A<1>, A<2> = trans-1,4-cyclohexylene (optionally substituted with F or CN and/or with 1 or more nonadjacent CH2 replaced by O and/or S), cyclobutane-1,3-diyl or a group of formula (II); Z<1>, Z<2> = -COO- or -OCO-; Z<3> (sic) = -CH2O- ...

THE-SECRETASE INHIBITORS

Acilguanidinas espirocíclicas. Su uso como inhibidores de la actividad de la enzima b-secretasa (BACE1). Composiciones farmacéuticas que las comprenden. Métodos para usarlas como agentes terapéuticos en el tratamiento de los trastornos neurodegenerativos, de los trastornos caracterizados por un deterioro cognitivo, de las alteraciones cognitivas, de la demencia y de las enfermedades que se caracterizan por la producción de agregados b-amiloides. Reivindicación 1: Un compuesto caracterizado porque está representado por cualquiera de las fórmulas estructurales del Grupo (1), o una sal farmacéuticamente aceptable de éste.

LIQUID CRYSTAL ISOTHIOCYANATE DERIVATIVES

Isothiocyanate derivatives can be used as components of liquid crystal phases.

Stabilized sulforaphane

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

Phenylimino-thiadiazabicycloalkane derivatives, processes and intermediates for their preparation and their use as herbicides

N-Acylethanolamine Hydrolyzing Acid Amidase (NAAA) Inhibitors And Their Use Thereof

A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. Compounds of Formula I are inhibitors of N-acylethanolamine hydrolyzing acid amidase (NAAA). The present technology is directed to compounds, compositions, and methods to inhibit N-acylethanolamine hydrolyzing acid amidase and to treat N-acylethanolamine hydrolyzing acid amidase mediated conditions in a subject. 2. The compound of claim 1 , wherein M is C or CR claim 1 , and D is pyridyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , or pyrimidinyl claim 1 , with the proviso that where Z is CN claim 1 , M is C or CR and a N of the pyridyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , or pyrimidinyl is attached to M.3. The compound of claim 1 , wherein:{'sub': 2', '3, 'Z is NCS, CN, CHCN, CH(CH)CN, or C(cyclopropane)CN;'}{'sub': 2', 'n, 'W is (CH)where n is 0 or 1;'}{'sub': 2', '2', '2, 'D is CH, CHCH, or pyridyl, with the proviso that where D is pyridyl, M is C or CR, and Z is —CN and M is attached to a N atom of the pyridyl group;'}{'sub': 2', 'n', '2', 'n', '3', '2', 'n', '2', 'n', '2', 'n', '2', 'n', '3, 'Y is (CH), O(CH), NR(CH), (CH)O, (CH)NH, or (CH)NCH;'}{'sub': 3', '2', '3', '2', 'n, 'V is O, NCH, SO, CONCH, or (CH)wherein n is 0 or 1;'}{'sub': 2', 'n′, 'B is (CH), phenyl, or a 5 or 6-member heterocyclyl; and'}A is phenyl or a 5 or 6-member heterocyclyl.4. The compound of claim 1 , wherein:{'sub': 2', '1-5', '2', '1-5, 'sup': 1', '2', '1', '2, 'Z is NCS, —(CH)NCS, CN, —(CH)CN, or —CRRCN, wherein Rand Rare H or form cyclopropyl;'}M is N or C;{'sub': 2', 'n, 'W is (CH), and n is 0, 1, or 2;'}D is a cycloalkyl, aryl, heterocyclyl, or heteroaryl;{'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'n', '1', '4, 'sup': 3', '3', '3, 'Y is O, (CH), O(CH), (CH)O, NR(CH), (CH)NR, where n is 0, 1, or 2, and Ris H or C-Calkyl;'}{'sub': 2', 'n, 'X is (CH), wherein n is 0, 1, or 2;'}{'sub': 2', 'n′, 'B is (CH)wherein n′ is 2, 3, or ...

FLUESSIGKRISTALLINE SENFOELE

INHIBITORS OF BETA-SECRETASE

STABILIZED SULFORAPHANE

LIQUID CRYSTAL ISOTHIOCYANATE DERIVATIVES

Isothiocyanate derivatives can be used as components of liquid crystal phases.

Verfahren zur Herstellung von Isocyanatosenfoelen

FLUESSIGKRISTALLINE ISOTHIOCYANATE-DERIVATE.

STABILIZED SULFORAPHANE

Sülforafanın stabilize edilmesine yönelik bir yöntem sağlanır. Yöntem, sülforafan veya bunun bir analogunun ve bir siklodekstrinin sülforafan veya bunun bir analogu ve siklodekstrin arasında bir kompleks oluşturmak üzere temas ettirilmesini içerir. A method of stabilizing the sulforaphane is provided. The method comprises contacting sulforafan or an analog thereof and a cyclodextrin to form a complex between sulforafan or an analog thereof and cyclodextrin.

ISOTHIOCYANATES AND GLUCOSINOLATE COMPOUNDS AND ANTI-TUMOR COMPOSITIOS CONTAINING SAME

The present invention provides glucosinolate and isothiocyante compounds and related methods for synthesizing these compounds and analogs. In certain embodiments, these glucosinolate and isothiocyanate compounds are useful and chemopreventive and or chemotherapeutic agents.

STABILIZED SULFORAPHANE

Chemical compounds

A compound of formula I: where the substitutents have the meanings assigned to them in claim 1, compositions comprising a compound of formula (I) and the use of such compounds and/or compositions controlling insects, acarines, nematodes or molluscs.

STABILIZED SULFORAPHANE

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

CHEMICAL COMPOUNDS

A compound of formula (I) where the substituents have the meanings assigned to them in claim 1, compositions comprising a compound of formula (I) and the use of such compounds and/or compositions controlling insects, acarines, nematodes or molluscs.

Stabilized sulforaphane

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

METODO PARA COMBATIR Y CONTROLAR LOS INSECTOS, ACAROS O MOLUSCOS EL CUAL COMPRENDE APLICAR UNA CANTIDAD EFECTIVA DE INSECTICIDA DE UN COMPUESTO DERIVADO DE TIOUREA; COMPUESTO DERIVADO DE TIOUREA; PROCESO PARA ELABORAR DICHO COMPUESTO; Y COMPOSICION I

ISOTHIOCYANATES AND GLUCOSINOLATE COMPOUNDS AND ANTI-TUMOR COMPOSITIOS CONTAINING SAME

The present invention provides glucosinolate and isothiocyante compounds and related methods for synthesizing these compounds and analogs. In certain embodiments, these glucosinolate and isothiocyanate compounds are useful and chemopreventive and or chemotherapeutic agents.

Liquid-crystalline mustard oils

Mustard oils of the formula I R--(A1 --Z1)n --A2 --Z2 --A3 --NCS in which A1, A2, A3, R, Z1, Z2 and n have the meaning specified in claim 1 can be used as components of liquid-crystalline phases.

INHIBITORS OF BETA-SECRETASE

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the beta-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of beta-amyloid aggregates.

Isothiocyanate synthesized by three components and preparation method of isothiocyanate

本发明公开了一种异硫氰酸酯及其制备方法，通过以伯胺、二氟溴乙酸钠和硫单质作为反应物进行反应；在铜催化剂作用下进行反应，铜催化剂为氯化亚铜、溴化亚铜、碘化亚铜、氯化铜和三氟甲磺酸铜中的任意一种；还加入了碱，碱为碳酸氢钠、碳酸钾、碳酸铯、磷酸钾、DABCO和叔丁醇钠中的任意一种；整个反应是在溶剂中进行，溶剂为乙腈或二甲基亚砜，反应温度为80‑120℃，反应时间为10‑14小时；本发明方法可以直接合成目标产物，无需分离中间产物，只需在常压下搅拌加热反应既可获得目标物，产率最高可达到87％；且反应过程中废弃溶液较少，具有保护环境和保障操作人员健康的优点；此外，可以制备一系列异硫氰酸酯衍生物，该方法具有较强的底物普适性。

LIQUID CRYSTAL ISOTHIOCYANATE DERIVATIVES

Stabilized sulforaphane

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

Stabilized Sulforaphane

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

Inhibitors of beta-secretase

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the -secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of -amyloid aggregates.

Tertiary amine-thiourea difunctional chiral catalyst as well as preparation method and application thereof

本发明公开了一种叔胺‑硫脲类双功能手性催化剂及其制备方法与应用。其结构式如式I所示。以（ 1S ， 2S ）‑环己二胺为原料，经酰化、 N ‑甲基化、肼解制备（ 1S ， 2S ）‑ N,N ‑二甲基环己二胺，再与硫光气反应制备（ 1S ， 2S ）‑ N，N ‑二甲氨基环己基异硫氰酸酯，最后与四氨基金刚烷反应制备式I。本发明的叔胺‑硫脲类双功能手性催化剂具有高效、环境友好的特征。

Chemoprotective isothiocyanates

Sulforaphane has been isolated and identified as a major and very potent phase II enzyme inducer in broccoli (Brassica oleracea italica). Sulforaphane is a monofunctional inducer, inducing phase II enzymes selectively without the induction of aryl hydrocarbon receptor-dependent cytochromes P-450 (phase I enzymes). Analogues differing in the oxidation state of sulfur and the number of methylene groups were synthesized, and their inducer potencies were measured. Sulforaphane is the most potent of these analogues. Other analogues having different substituent groups in place of the methylsulfinyl group of sulforaphane were also synthesized and assessed. Of these, the most potent are 6-isothiocyanato-2-hexanone and exo-2-acetyl-6-isothiocyanatonorbornane.

CHEMICAL COMPOUNDS

H2S-BASED THERAPEUTIC AGENTS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

The present invention concerns the field of neurodegenerative diseases, and in particular relates to compounds, pharmaceutical compositions and their uses in the protection of neuronal cells from inflammation and from oxidative stress in the early stage of Parkinson's Disease as well as in Alzheimer's Disease.

INHIBITORS OF BETA-SECRETASE

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β- secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

Liquid-crystalline mustard oils

Mustard oils of the formula I R--(A.sup.1 --Z.sup.1).sub.n --A.sup.2 --Z.sup.2 --A.sup.3 --NCS in which A 1 , A 2 , A 3 , R, Z 1 , Z 2 and n have the meaning specified in claim 1 can be used as components of liquid-crystalline phases.

Insecticidal hydroxyethyl thlourea derivatives

The present invention relates to novel derivatives of substituted hydroxyethyl thiourea derivatives, to processes for their preparation and to their use for controlling animal pests, especially arthropods, in particular insects.

PHENYLIMINO-THIADIAZABICYCLOALKANE DERIVATIVES, PROCESSES AND INTERMEDIATES FOR THEIR PREPARATION AND THEIR USE AS HERBICIDES

Compounds of formula (I): wherein R is C1-C6alkyl, C1-C6haloalkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C4alkoxy or C3-C6cycloalkyl; R1 is halogen; R2 and R3 are each independently of the other C1-C4alkyl; R4 is halogen or a group of the formula -X-R5, -X-A-R6 or (a); R5 is hydrogen, C1-C6alkyl, C1-C8haloalkyl, C1-C4alkoxy-C1-C4alkyl, C1-C10alkylthio-C1-C4alkyl, C1-C4alkylamino-C1-C4alkyl, di-C1-C4alkylamino-C1-C4alkyl, cyano-C1-C8-alkyl, C3-C8alkenyl, C3-C8haloalkenyl, C3-C8alkynyl, C3-C6cycloalkyl, oxetanyl, C3-C7-halocycloalkyl, C3-C7cycloalkyl-C1-C4alkyl, phenyl-C1-C3alkyl that is unsubstituted or substituted in the phenyl ring by 1, 2 or 3 identical or different substituents selected from halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy and C1-C4haloalkoxy, or R5 is an alkali metal, alkaline earth metal or ammonium ion, or is the group -N=C(CH3)2, -CH2-O-N=C(CH3)2 or -CH2CH2-O-N=C(CH3)2; X is oxygen or sulfur; A is C1-C4 alkylene; R6 is a 5- or 6-membered heterocyclic ring that contains ...

Chemoprotective isothiocyanates

Sulforaphane has been isolated and identified as a major and very potent phase II enzyme inducer in broccoli (Brassica oleracea italica). Sulforaphane is a monofunctional inducer, inducing phase II enzymes selectively without the induction of aryl hydrocarbon receptor-dependent cytochromes P-450 (phase I enzymes). Analogues differing in the oxidation state of sulfur and the number of methylene groups were synthesized, and their inducer potencies were measured. Sulforaphane is the most potent of these analogues. Other analogues having different substituent groups in place of the methylsulfinyl group of sulforaphane were also synthesized and assessed. Of these, the most potent are 6-isothiocyanato-2-hexanone and exo-2-acetyl-6-isothiocyanatonorbornane.

Stabilized Sulforaphane

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

DERIVATIVES OF TIOUREA, PROCESSES OF PREPARATION, COMPOSITIONS AND METHODS TO FIGHT PLAGUES.

Composiciones que los comprenden, y el uso de dichos compuestos y dichas composiciones para el control de insectos, acáridos, nematodos o moluscos. Reivindicacion 1: Un método para combatir y controlar insectos, acáridos, nematodos o moluscos, que comprende la aplicacion a una plaga, al lugar de una plaga, o a una planta sensible al ataque de una plaga, de una cantidad eficaz como insecticida, acaricida, nematicida o molusquicidamente eficaz de un compuesto de la formula (1), donde R73 es hidrogeno, G-, formilo, G-C(O)-, G-C(S)-, G-O-C(O)-, G-O-C(S)-, R78R79N-C(O)-, R78R79N-C(S)-, donde R78 y R79 son independientemente H o G-; o R78 y R79 junto con el átomo N al cual están unidos forman un grupo N=CRaRb, donde Ra y Rb son H, alquilo C1-6 o fenilo; o R78 y R79 junto con el átomo N al cual están unidos forman un anillo de cinco, seis o siete miembros que puede contener uno o dos heteroátomos adicionales seleccionados de O, N o S, y que puede estar opcionalmente sustituido con uno a cuatro ...

Stabilized Sulforaphane

A method of stabilizing sulforaphane is provided. The method includes contacting sulforaphane, or an analog thereof, and a cyclodextrin to form a complex between the sulforaphane, or analog thereof, and the cyclodextrin.

Novel method for preparing isothiocyanate

本发明涉及一种制备异硫氰酸酯的新方法，包括以下步骤：将有机伯胺和苯异硫氰酸酯加入到高沸点溶剂中，在氮气保护的条件下进行搅拌，反应温度保持100℃～150℃或加热回流、常压条件下反应1‑9h，反应完成后，待反应液冷却，通过真空旋转蒸发除去溶剂，浓缩物经硅胶柱色谱提纯得异硫氰酸酯。本发明优点在于：1)本发明所使用的原料有机伯胺和苯异硫氰酸酯均是常见的化工原料，特别是苯异硫氰酸酯价廉易得；2)本发明反应条件较为温和，安全性高，温度一般在100℃～150℃，常压下反应；3)本发明工艺过程及后处理简单，易于操作，成本低，产品纯度高，工业化应用前景好。

CHEMICAL COMPOUNDS

A compound of formula I where the substituents have the meanings assigned to them in claim 1, compositions comprising a compound of formula (I) and the use of such compounds and/or compositions controlling insects, acarines, nematodes or molluscs.

N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and use thereof

Disclosed herein are compounds represented by Structural Formula I: or a pharmaceutically acceptable salt thereof. Values for the variables in Structural Formula I are described herein. The compounds can be used to modulate (e.g., inhibit) N-acylethanolamine hydrolyzing acid amidase (NAAA) and thereby treat a variety of diseases, disorders and conditions mediated by NAAA, such as a gastrointestinal motility disorder, irritable bowel syndrome, an inflammatory bowel disorder, neuroinflammation, nicotine addiction, cancer, opioid dependence, analgesia, chemotherapy-induced neuropathic pain and pain. Also disclosed herein are compositions and methods including compounds of Structural Formula I, or a pharmaceutically acceptable salt thereof.

BICYCLO[2.2.1.]HEPT-5(6)-YL COMPOUNDS

N-Acylethanolamine Hydrolyzing Acid Amidase (NAAA) Inhibitors And Use Thereof

... or a pharmaceutically acceptable salt thereof. Values for the variables in Structural Formula I are described herein. The compounds can be used to modulate (e.g., inhibit) N-acylethanolamine hydrolyzing acid amidase (NAAA) and thereby treat a variety of diseases, disorders and conditions mediated by NAAA, such as a gastrointestinal motility disorder, irritable bowel syndrome, an inflammatory bowel disorder, neuroinflammation, nicotine addiction, cancer, opioid dependence, analgesia, chemotherapy-induced neuropathic pain and pain. Also disclosed herein are compositions and methods including compounds of Structural Formula I, or a pharmaceutically acceptable salt thereof.

Chemoprotective isothiocyanates

Sulforaphane has been isolated and identified as a major and very potent phase II enzyme inducer in broccoli (Brassica oleracea italica). Sulforaphane is a monofunctional inducer, inducing phase II enzymes selectively without the induction of aryl hydrocarbon receptor-dependent cytochromes P-450 (phase I enzymes). Analogues differing in the oxidation state of sulfur and the number of methylene groups were synthesized, and their inducer potencies were measured. Sulforaphane is the most potent of these analogues. Other analogues having different substituent groups in place of the methylsulfinyl group of sulforaphane were also synthesized and assessed. Of these, the most potent are 6-isothiocyanato-2-hexanone and exo-2-acetyl-6-isothiocyanatonorbornane.

Inhibitors of beta-secretase

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the -secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of -amyloid aggregates.

inibidores de beta-secretase

Addition rearrangement products of thiocyanic acid and cyclopentadiene-olefinic adducts

N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof

A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. Compounds of Formula I are inhibitors of N-acylethanolamine hydrolyzing acid amidase (NAAA). The present technology is directed to compounds, compositions, and methods to inhibit N-acylethanolamine hydrolyzing acid amidase and to treat N-acylethanolamine hydrolyzing acid amidase mediated conditions in a subject.

N-Acylethanolamine Hydrolyzing Acid Amidase (NAAA) Inhibitors And Use Thereof

Disclosed herein are compounds represented by Structural Formula I: or a pharmaceutically acceptable salt thereof. Values for the variables in Structural Formula I are described herein. The compounds can be used to modulate (e.g., inhibit) N-acylethanolamine hydrolyzing acid amidase (NAAA) and thereby treat a variety of diseases, disorders and conditions mediated by NAAA, such as a gastrointestinal motility disorder, irritable bowel syndrome, an inflammatory bowel disorder, neuroinflammation, nicotine addiction, cancer, opioid dependence, analgesia, chemotherapy-induced neuropathic pain and pain. Also disclosed herein are compositions and methods including compounds of Structural Formula I, or a pharmaceutically acceptable salt thereof.

N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof

A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: Compounds of Formula I are inhibitors of N-acylethanolamine hydrolyzing acid amidase (NAAA).

N-Acylethanolamine Hydrolyzing Acid Amidase (NAAA) Inhibitors And Their Use Thereof

A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: 2. The compound of claim 1 , wherein M is C or CR claim 1 , and D is pyridyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , or pyrimidinyl claim 1 , with the proviso that where Z is CN claim 1 , M is C or CR and a N of the pyridyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , or pyrimidinyl is attached to M.3. The compound of claim 1 , wherein:{'sub': 2', '3, 'Z is NCS, CN, CHCN, CH(CH)CN, or C(cyclopropane)CN;'}{'sub': 2', 'n, 'W is (CH)where n is 0 or 1;'}{'sub': 2', '2', '2, 'D is CH, CHCH, or pyridyl, with the proviso that where D is pyridyl, M is C or CR, and Z is —CN and M is attached to a N atom of the pyridyl group;'}{'sub': 2', 'n', '2', 'n', '3', '2', 'n', '2', 'n', '2', 'n', '2', 'n', '3, 'Y is (CH), O(CH), NR(CH), (CH)O, (CH)NH, or (CH)NCH;'}{'sub': 3', '2', '3', '2', 'n, 'V is O, NCH, SO, CONCH, or (CH)wherein n is 0 or 1;'}{'sub': 2', 'n′, 'B is (CH), phenyl, or a 5 or 6-member heterocyclyl; and'}A is phenyl or a 5 or 6-member heterocyclyl;4. The compound of claim 1 , wherein:{'sub': 2', '1-5', '2', '1-5, 'sup': 1', '2', '1', '2, 'Z is NCS, —(CH)NCS, CN, —(CH)CN, or —CRRCN, wherein Rand Rare H or form cyclopropyl;'}M is N or C;{'sub': 2', 'n, 'W is (CH), and n is 0, 1, or 2;'}D is a cycloalkyl, aryl, heterocyclyl, or heteroaryl;{'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'n', '1', '4, 'sup': 3', '3', '3, 'Y is O, (CH), O(CH), (CH)O, NR(CH), (CH)NR, where n is 0, 1, or 2, and Ris H or C-Calkyl;'}{'sub': 2', 'n, 'X is (CH), wherein n is 0, 1, or 2;'}{'sub': 2', 'n′, 'B is (CH)wherein n′ is 2, 3, or 4, cycloalkyl, heterocyclyl, aryl, heteroaryl;'}{'sup': 5', '6', '7', '8', '6', '7', '8, 'sub': 2', '2', 'n', '1', '4', '1', '4, 'V is O, NR, SO, SO, CO, CONR, CRR, or (CH), wherein Ris H or C-Calkyl; and Rand Rare each independently H, C-Calkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, or together with the C ...

Chemoprotective isothiocyanates

Sulforaphane has been isolated and identified as a major and very potent phase II enzyme inducer in broccoli (Brassica oleracea italica). Sulforaphane is a monofunctional inducer, inducing phase II enzymes selectively without the induction of aryl hydrocarbon receptor-dependent cytochromes P-450 (phase I enzymes). Analogues differing in the oxidation state of sulfur and the number of methylene groups were synthesized, and their inducer potencies were measured. Sulforaphane is the most potent of these analogues. Other analogues having different substituent groups in place of the methylsulfinyl group of sulforaphane were also synthesized and assessed. Of these, the most potent are 6-isothiocyanato-2-hexanone and exo-2-acetyl-6-isothiocyanatonorbornane.

Method for preparing isothiocyanate by base catalysis

本发明公开了一种碱催化制备异硫氰酸酯的方法，该方法在碱催化作用下实现伯胺向异硫氰酸酯的一步转化，包括在‑20～40℃下，将伯胺溶于甲醇中得到伯胺溶液，向伯胺溶液中依次加入碱催化剂、二硫化碳和氧化剂搅拌反应，然后减压蒸馏，经萃取和柱色谱纯化后即得；所述的伯胺、碱催化剂、二硫化碳和氧化剂的摩尔比为1:(0.05～0.2)：(2.5～10):(1.2～4.5)；所述的伯胺的结构通式为：R‑NH 2 ，异硫氰酸酯的结构通式为：R‑N＝C＝S，其中，所述的R基团为烷基、芳基、苄基或烯丙基。本发明中的伯胺在碱催化剂和氧化剂的作用下与二硫化碳反应可直接生成异硫氰酸酯，避免了硫光气和过量碱的使用，整个反应原子经济性高、操作简单更加适用于功能有机中间体以及活性生物分子的制备。

Inhibitors of beta-secretase

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β- secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

Stabilized Sulforaphane

Inhibitors of beta-secretase

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β- secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

Σταθεροποιημενη σουλφοραφανη

Παρέχεται μία μέθοδος σταθεροποίησης της σουλφοραφάνης. Η μέθοδος περιλαμβάνει την επαφή σουλφοραφάνης ή ενός αναλόγου αυτής και μιας κυκλοδεξτρίνης ώστε να σχηματιστεί ένα σύμπλοκο μεταξύ της σουλφοραφάνης ή αναλόγου αυτής και της κυκλοδεξτρίνης.

一种异硫氰酸类化合物、制备方法及其防治植物病害的应用

本发明涉及植物气孔调节抑菌技术领域，具体的，涉及一种异硫氰酸类化合物、制备方法及其防治植物病害的应用，其分子式如下所示： 其中，R独立地选自取代或未取代的C2～C6的链烷基、取代或未取代的C3～C6的环烷基、取代或未取代的C3～C6的杂环烷基或取代或未取代的C6～C18的芳基；n代表NCS基团的个数，n为1～6的整数；L独立地选自H或C1～C6亚烷基本发明通过具体实例中的数据证实了本发明的异硫氰酸类化合物可作为良好的植物气孔关闭诱导物质，且具有良好的抑菌活性。

一种异硫氰酸类化合物、制备方法及其防治植物病害的应用

本发明涉及植物气孔调节抑菌技术领域，具体的，涉及一种异硫氰酸类化合物、制备方法及其防治植物病害的应用，其分子式如下所示： 其中，R独立地选自取代或未取代的C2～C6的链烷基、取代或未取代的C3～C6的环烷基、取代或未取代的C3～C6的杂环烷基或取代或未取代的C6～C18的芳基；n代表NCS基团的个数，n为1～6的整数；L独立地选自C1～C6亚烷基。本发明通过具体实例中的数据证实了本发明的异硫氰酸类化合物可作为良好的植物气孔关闭诱导物质，且具有良好的抑菌活性。

一种叔胺-硫脲类双功能手性催化剂及其制备方法与应用

本发明公开了一种叔胺‑硫脲类双功能手性催化剂及其制备方法与应用。其结构式如式I所示。以（ 1S ， 2S ）‑环己二胺为原料，经酰化、 N ‑甲基化、肼解制备（ 1S ， 2S ）‑ N,N ‑二甲基环己二胺，再与硫光气反应制备（ 1S ， 2S ）‑ N，N ‑二甲氨基环己基异硫氰酸酯，最后与四氨基金刚烷反应制备式I。本发明的叔胺‑硫脲类双功能手性催化剂具有高效、环境友好的特征。

A method of new black mustard oils

液晶カラシ油化合物

(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-acylethanolamine hydrolyzing acid amidase (naaa) inhibitors and use thereof

Disclosed herein are compounds represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. Values for the variables in Structural Formula I are described herein. The compounds can be used to modulate ( e.g , inhibit) N - acylethanolamine hydrolyzing acid amidase (NAAA) and thereby treat a variety of diseases, disorders and conditions mediated by NAAA, such as a gastrointestinal motility disorder, irritable bowel syndrome, an inflammatory bowel disorder, neuroinflammation, nicotine addiction, cancer, opioid dependence, analgesia, chemotherapy-induced neuropathic pain and pain. Also disclosed herein are compositions and methods including compounds of Structural Formula I, or a pharmaceutically acceptable salt thereof

H2s-based therapeutic agents for the treatment of neurodegenerative diseases

The present invention concerns the field of neurodegenerative diseases, and in particular relates to compounds, pharmaceutical compositions and their uses in the protection of neuronal cells from inflammation and from oxidative stress in the early stage of Parkinson's Disease as well as in Alzheimer's Disease.

一种异硫氰酸类化合物、制备方法及其防治植物病害的应用

本发明涉及植物气孔调节抑菌技术领域，具体的，涉及一种异硫氰酸类化合物、制备方法及其防治植物病害的应用，其分子式如下所示： 其中，R独立地选自取代或未取代的C2～C6的链烷基、取代或未取代的C3～C6的环烷基、取代或未取代的C3～C6的杂环烷基或取代或未取代的C6～C18的芳基；n代表NCS基团的个数，n为1～6的整数；L独立地选自H或C1～C6亚烷基本发明通过具体实例中的数据证实了本发明的异硫氰酸类化合物可作为良好的植物气孔关闭诱导物质，且具有良好的抑菌活性。

一种碱催化制备异硫氰酸酯的方法

本发明公开了一种碱催化制备异硫氰酸酯的方法，该方法在碱催化作用下实现伯胺向异硫氰酸酯的一步转化，包括在‑20～40℃下，将伯胺溶于甲醇中得到伯胺溶液，向伯胺溶液中依次加入碱催化剂、二硫化碳和氧化剂搅拌反应，然后减压蒸馏，经萃取和柱色谱纯化后即得；所述的伯胺、碱催化剂、二硫化碳和氧化剂的摩尔比为1:(0.05～0.2)：(2.5～10):(1.2～4.5)；所述的伯胺的结构通式为：R‑NH 2 ，异硫氰酸酯的结构通式为：R‑N＝C＝S，其中，所述的R基团为烷基、芳基、苄基或烯丙基。本发明中的伯胺在碱催化剂和氧化剂的作用下与二硫化碳反应可直接生成异硫氰酸酯，避免了硫光气和过量碱的使用，整个反应原子经济性高、操作简单更加适用于功能有机中间体以及活性生物分子的制备。

一种制备异硫氰酸酯的新方法

本发明涉及一种制备异硫氰酸酯的新方法，包括以下步骤：将有机伯胺和苯异硫氰酸酯加入到高沸点溶剂中，在氮气保护的条件下进行搅拌，反应温度保持100℃～150℃或加热回流、常压条件下反应1‑9h，反应完成后，待反应液冷却，通过真空旋转蒸发除去溶剂，浓缩物经硅胶柱色谱提纯得异硫氰酸酯。本发明优点在于：1)本发明所使用的原料有机伯胺和苯异硫氰酸酯均是常见的化工原料，特别是苯异硫氰酸酯价廉易得；2)本发明反应条件较为温和，安全性高，温度一般在100℃～150℃，常压下反应；3)本发明工艺过程及后处理简单，易于操作，成本低，产品纯度高，工业化应用前景好。

一种三组分合成的异硫氰酸酯及其制备方法

本发明公开了一种异硫氰酸酯及其制备方法，通过以伯胺、二氟溴乙酸钠和硫单质作为反应物进行反应；在铜催化剂作用下进行反应，铜催化剂为氯化亚铜、溴化亚铜、碘化亚铜、氯化铜和三氟甲磺酸铜中的任意一种；还加入了碱，碱为碳酸氢钠、碳酸钾、碳酸铯、磷酸钾、DABCO和叔丁醇钠中的任意一种；整个反应是在溶剂中进行，溶剂为乙腈或二甲基亚砜，反应温度为80‑120℃，反应时间为10‑14小时；本发明方法可以直接合成目标产物，无需分离中间产物，只需在常压下搅拌加热反应既可获得目标物，产率最高可达到87％；且反应过程中废弃溶液较少，具有保护环境和保障操作人员健康的优点；此外，可以制备一系列异硫氰酸酯衍生物，该方法具有较强的底物普适性。

一种叔胺-硫脲类双功能手性催化剂及其制备方法与应用

本发明公开了一种叔胺‑硫脲类双功能手性催化剂及其制备方法与应用。其结构式如式I所示。以（ 1S ， 2S ）‑环己二胺为原料，经酰化、 N ‑甲基化、肼解制备（ 1S ， 2S ）‑ N,N ‑二甲基环己二胺，再与硫光气反应制备（ 1S ， 2S ）‑ N，N ‑二甲氨基环己基异硫氰酸酯，最后与四氨基金刚烷反应制备式I。本发明的叔胺‑硫脲类双功能手性催化剂具有高效、环境友好的特征。