USE OF (+) MEFLOQUINE FOR THE TREATMENT OF MALARIA

Use of (+)mefloquine for the treatment of malaria

Use of (+)-(11R,2'S)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer in the manufacture of a medicament having reduced side-effect compared to the racemic (±)-(R*,S*)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol for treating or preventing malaria in a subject. A method of treating or preventing malaria with reduced side-effects comprising administration of (+)-(11R,2'S)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer.

VERWENDUNG VON (+)MEFLOQUINE ZUR BEHANDLUNG VON MALARIA

VERWENDUNG VON (+)MEFLOQUINE ZUR BEHANDLUNG VON MALARIA

Use of (+)mefloquine for the treatment of malaria

Use of (+)-(11R,2'S)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer in the manufacture of a medicament having reduced side-effect compared to the racemic (±)-(R*,S*)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol for treating or preventing malaria in a subject. A method of treating or preventing malaria with reduced side-effects comprising administration of (+)-(11R,2'S)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer.

(-)-mefloquine to block puringergic receptors and to treat movement or neurodegenerative disorders

The present invention relates to the use of (±)-R*,S*)-alpha-2-piperidnyl-2,8-bis(trifluoromethyl)-4-quinolinemthanol and in particular (-)-(11S,2'R)-alpha-2-piperidnyl-2,8-bis(trifluoromethyl)-4-quinolinemthanol in the treatment of disorders in which the reduction of purinergic neurotransmission could be beneficial. The invention relates in particular to adenosine receptors, and particularly adenosine A2a receptors and to the treatment of movement disorders such as Parkinson's disease.

Assay system

The invention provides a method of forming a plurality of re-constitutable doses of at least one drug in a plurality of wells, the method including the steps of (i) placing a known amount of said drug in a suitable carrier to form a first composition having a known concentration (ii) placing at least two selected amounts of that first composition into individual wells and (iii) converting the first composition into a transportable form that can later be converted into a second composition having a known concentration and (iv) sealing the wells.

TRICYCLIC HETEROCYCLIC DERIVATIVES AND USES THEREOF

Disclosed are tricyclic heterocyclic compounds having kinase inhibitory activity, pharmaceutical compositions and kits comprising the compounds, and use of the compounds in the treatment of or in medicaments for the treatment of various diseases and conditions. In particular, disclosed are tricyclic heterocyclic compounds of the formula (I) having CSF-1R (c-FMS kinase) inhibitory activity and their use in the treatment of various diseases and conditions, such as those mediated by CSF-1R, including proliferative or neoplastic diseases and conditions, including cancers, and bone, inflammatory, and autoimmune diseases and conditions. 5. The compound of any one of the preceding claims , wherein X is NR , O , S , SO , or SO.6. The compound of any one of the preceding claims , wherein X is NR , O , or S.7. The compound of any one of the preceding claims , wherein X is O or S.9. The compound of any one of the preceding claims wherein:{'sup': 1', '2', '2', '2, 'sub': 2-6', '2-3', '2-3', '1-3', 'a', '1-3', 'b', '2-3', '1-3', 'a', '1-3', 'b', '1-3', 'a', '1-3', 'b', '2-3, 'Lis Calkylene, —Calkylene-J-Calkylene-*, —(Calkylene)-A-(Calkylene)-*, —Calkylene-J-(Calkylene)-A-(Calkylene)-*, or —(Calkylene)-A-(Calkylene)-J-Calkylene-*;'}{'sup': 2', '2, 'sub': 2-6', '2-3', '2-3, 'Lis Calkylene or —Calkylene-J-Calkylene-*;'}{'sup': 3', '2', '2, 'sub': 1-6', '2-6', '2-3', '1-3, 'Lis a bond, Calkylene, —Calkylene-J-*, or Calkylene-J-Calkylene-*;'}{'sup': 10', '2', '2', '2, 'sub': 1-6', '1-3', '2-3', '1-3', 'a', '1-3', 'b', '1-3', '1-3', 'a', '1-3', 'b', '1-3', 'a', '1-3', 'b', '2-3, 'Lis Calkylene, —Calkylene-J-Calkylene-*, —(Calkylene)-A-(Calkylene)-*, —Calkylene-J-(Calkylene)-A-(Calkylene)-*, or —(Calkylene)-A-(Calkylene)-J-Calkylene-*;'}{'sup': 20', '2, 'sub': 1-6', '1-3', '2-3, 'Lis Calkylene or —Calkylene-J-Calkylene-*;'}{'sup': 30', '2', '2, 'sub': 1-6', '1-6', '1-3', '1-3, 'Lis Calkylene, —Calkylene-J-*, or —Calkylene-J-Calkylene-*.'}10. The compound of any one of the preceding ...

Substituted pyrimidines and triazines and their use in cancer therapy

Provided herein are substituted pyrimidine and triazine derivatives, including bicyclic pyrimidine derivatives, their pharmaceutical compositions, their preparation, and their use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs. In one embodiment, the pyrimidine and triazine derivatives are morpholino-pyrimidine, morpholino-triazine, pyridyl-pyrimidine, and pyridyl-triazine derivatives which are selective irreversible inhibitors of the p110α isoform of PI3K.

Substituted pyrimidines and triazines and their use in cancer therapy

Provided herein are substituted pyrimidine and triazine derivatives, including bicyclic pyrimidine derivatives, their pharmaceutical compositions, their preparation, and their use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs. In one embodiment, the pyrimidine and triazine derivatives are morpholino-pyrimidine, morpholino-triazine, pyridyl-pyrimidine, and pyridyl-triazine derivatives which are selective irreversible inhibitors of the p110α isoform of PI3K.

Process for preparing pyridine derivatives

ABSTRACT OF THE DISCLOSURE Fused carbocyclic ring derivatives of pyridine which contain a nitrile or thioamide group on the carbo-cyclic ring e.g. 8-cyano or thiocarboxamido-5,6,7,8-tetrahydroquinolines are prepared by a process in which a sodium, potassium, lithium or magnesium halide derivative of the pyridine compound is treated with a compound RaRbNCN wherein Ra and Rb are the same or different and represent alkyl, cycloalkyl, or aralkyl, or Ra and Rb are joined to form a heterocyclic ring with the nitrogen, and the product is treated with a proton source to obtain the nitrile which is optionally treated with a sulphurising agent to form the thioamide. The nitriles or thioamides may be isolated as their acid addition salts.

NEW PROCEDURES AND INTERMEDIARIES FOR THE PREPARATION OF PIPERAZINE DERIVATIVES.

COMPUESTOS QUE TIENEN LA FORMULA R 5 O-A-NR 4 -R SUP,2} (V), DONDE R{SUP,2} ES UN GRUPO HETEROARILICO ENLAZADO AL RESIDUO DE LA MOLECULA MEDIANTE UN ATOMO DE CARBONO ADYACENTE A UN ATOMO DE NITROGENO Y R{SUP,4} Y R{SUP,5} SON ATOMOS DE HIDROGENO O JUNTOS REPRESENTAN -SO- O -SO{SUB,2}- Y A ES ALQUILENO C{SUB,2}C{SUB,4} OPCIONALMENTE SUSTITUIDO POR UNO O MAS GRUPOS DE ALQUILO BAJO SON NUEVOS INTERMEDIARIOS EN LA PREPARACION DE DERIVADOS DE PIPERAZINA FARMACEUTICAMENTE UTIL COMO COMPUESTOS FINALES. LOS COMPUESTOS QUE TIENEN LA FORMULA GENERAL (V) DONDE R{SUP,4} Y R{SUP,5} SON HIDROGENO PUEDEN SER PREPARADOS MEDIANTE UNA REDISPOSICION DE UN COMPUESTO QUE TIENE LA FORMULA R{SUP,2}-O-ANH{SUB,2} (VI). COMPOUNDS THAT HAVE FORMULA R 5 OA-NR 4 -R SUP, 2} (V), WHERE R {SUP, 2} IS A HETEROARILICO GROUP LINKED TO THE MOLECULA WASTE THROUGH A CARBON ATOM ADJUSTMENT TO A NITROGEN YR ATOM {SUP, 4} YR {SUP, 5} ARE HYDROGEN ATOMS OR TOGETHER REPRESENT -SO- OR -SO {SUB, 2} - IT'S ALREADY RENTED C {SUB, 2} C {SUB, 4} OPTIONALLY REPLACED BY ONE OR MORE LOW RENT GROUPS ARE NEW INTERMEDIARIES IN THE PREPARATION OF PHARMACEUTICALLY USEFUL PIPERAZINE DERIVATIVES AS FINAL COMPOUNDS. THE COMPOUNDS THAT HAVE THE GENERAL FORMULA (V) WHERE R {SUP, 4} YR {SUP, 5} ARE HYDROGEN CAN BE PREPARED BY A REDISPOSITION OF A COMPOUND THAT HAS THE FORM R {SUP, 2} -O-ANH {SUB , 2} (VI).

Hydrocarbon conversion catalyst and process of using thereof

A catalyst and a process for using the catalyst are disclosed generally for the conversion of hydrocarbons. By the use of at least one high temperature calcination under dry conditions, a catalyst with a beneficial combination of lowered surface area and excellent piece crush is created. X-ray diffraction pattern information is used to distinguish the resulting product.

Piperidine derivatives

Process for the preparation of alpha-aryl-gamma-butyrolactones

A process for preparing a lactone of general formula (I), where R is an optionally substituted phenyl group or an optionally substituted mono- or bicyclic heteroaryl radical which process comprises reacting an anion of a malonate of formula (II) with an ethylene compound of formula (III) Y-CH2-CH2OZ, to give a compound of formula (IV) and hydrolysing the compound of formula (IV) to give a lactone of formula (I). The lactones are of use as intermediates for preparing 5-HT1A binding agents.

Azetidinecarboxamide derivatives for treating cns disorders

A compound of formula (1), wherein: R1 is aryl; R2 is H, alkyl or aryl; and R3 is hydrogen or alkyl; pharmaceutically acceptable addition compounds thereof; and the use of the compounds in therapy, particularly for the treatment and prophylaxis of CNS disorders such as anxiety and epilepsy.

Heterocyclic compounds

Pyridine derivatives, which are intermediates in the production of pharmaceutically active compounds, have the formula <IMAGE> wherein R<1> and R<2> each independently represent hydrogen, lower alkyl, lower alkoxy, carboxyloweralkyl, carboxy, hydroxyloweralkyl, halogen, haloloweralkyl, lower alkoxycarbonyl, optionally substituted aryl or optionally substituted aralkyl, n represents an integer from 3 to 6; R<3> represents hydrogen or single or multiple substitution on one or more of the aliphatic carbons by one or more substituents selected from lower alkyl, optionally substituted aryl and optionally substituted aralkyl; R<5> and R<7> each independently represent hydrogen or lower alkyl; p is 0 or 1; P<1> and P<2> each represent an optional organic silyl protecting group on the carbon in the epi position to the nitrogen; and M is Na, K, Li or MgHal in which Hal is a halogen atom.

Process for preparing thiazolobenzimidazoles and intermediates used therein

The invention concerns a process for preparing a thiazolo[3,2-a]benzimidazole of formula I <CHEM> in which formula n is 1 or 2, and R1 is hydrogen, lower alkyl, lower alkoxy, trifluoromethyl or halo, or a salt thereof which comprises dehydrating a compound of formula II, <CHEM> or a salt thereof wherein n and R, are as defined above, and COOR is an acid or ester function in the presence of an acid selected from sulphuric, sulphonic and phosphoric acid or mixtures thereof and if desired or required an inert solvent provided that if water is present then the amount of water is less than about 15% by volume of the acid, the reaction being carried out with heating if necessary.

Process for making m-hydroxyphenyl substituted compounds

m-Hydroxyphenyl substituted compounds of formula ##STR1## where R is an organic radical and R 1 is hydroen or an organic radical are prepared by dehydrohalogenating a compound of formula ##STR2## (where X is chlorine or bromine, and R and R 1 have the above meanings). Preferred novel starting materials of formula (II) are of the formula ##STR3## (where R 1 and X are as above, n is 2,3 or 4, R 2 is hydrogen or lower alkyl and R 3 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl(lower)alkyl or aryl(lower)alkyl).

Preocess for preparing pyridine derivatives

Azetidinecarboxamide derivatives for treating cns disorders

A compound of formula (1), wherein: R1 is aryl; R2 is H, alkyl or aryl; and R3 is hydrogen or alkyl; pharmaceutically acceptable addition compounds thereof; and the use of the compounds in therapy, particularly for the treatment and prophylaxis of CNS disorders such as anxiety and epilepsy.

Patent GR77800B

Processes and intermediates for the preparation of piperazine derivatives

Compounds having the formula R.sup.5 O--A--NR.sup.4 --R.sup.2 (V) where R 2 is a heteroaryl group linked to the remainder of the molecule via a carbon atom adjacent a nitrogen atom and R 4 and R 5 are both hydrogen atoms or together represent --SO-- or --SO 2 -- and A is C 2 -C 4 alkylene optionally substituted by one or more lower alkyl groups are novel intermediates in the preparation of pharmaceutically useful piperazine derivatives as end compounds. The compounds having formula V where R 4 and R 5 are hydrogen may be prepared by a rearrangement of a compound having the formula (VI). R.sup.2 O--A--NH.sub.2 (VI)

Process for preparing hexahydroazepine, piperidine and pyrrolidine derivatives

2-Oxo-hexahydroazepine, -piperidine or pyrrolidines of formula ##STR1## wherein n is 2,3 or 4, R is hydrogen, lower alkyl, aryl(lower)alkyl, loweralkenylmethyl or cycloalkylmethyl, R 1 is hydrogen or lower alkyl and R 2 is hydrogen, lower alkyl or aryl(lower)alkyl are prepared by a novel process involving reaction of an anion of a lactam of formula ##STR2## where R 3 is lower alkyl, aryl(lower)alkyl, trialkyl-, triaryl- or triarylalkyl-silyl with a benzyne of formula ##STR3## where R 4 is lower alkyl, aryl(lower)alkyl or trialkyl-, triaryl- or triarylalkyl-silyl. The products are useful as intermediates for preparing pharmacologically active 2-unsubstituted -hexahydroazepine, -piperidine and pyrrolidine derivatives.

Substituted 1,3-diaminopropanes

ABSTRACT SUBSTITUTED 1,3-DIAMINOPROPANES N'-Acyl-N-alkyl-1,3-diaminopropanes of formula R1CONH(CH2)3NHR2 where R1 is R- or RNH where R is a substituted or unsubstituted hydrocarbon group and R2 is alkyl) are prepared by selectively acylating N-alkyl-1,3-diaminopropanes. In the process a N-alkyl 1,3-aminopropane is reacted with an aldebyde to form a hexahydropyrimidine, the hexahydropyrimidine is acylated and the acylated hexahydropyrimidine is then hydrolysed to give the product.

PROCEDURE FOR THE PREPARATION OF ALFA-ARIL-GAMMA-BUTIROLACTONAS.

UN PROCESO PARA LA PREPARACION DE UNA LACTONA DE FORMULA GENERAL (I), DONDE R ES UN GRUPO FENILO OPCIONALMENTE SUSTITUIDO O UN RADICAL HETEROARILO MONO- O BICICLICO OPCIONALMENTE SUSTITUIDO CUYO PROCESO COMPRENDE LA REACCION DE UN ANION DE UN MALONATO DE FORMULA (II) CON UN COMPUESTO DE ETILENO DE FORMULA (III) Y-CH2-CH2OZ, PARA PROPORCIONAR UN COMPUESTO DE FORMULA (IV) Y LA HIDROLIZACION DEL COMPUESTO DE FORMULA (IV) PARA PROPORCIONAR UNA LACTONA DE FORMULA (I). LAS LACTONAS SON DE USO COMO COMPUESTOS PARA LA PREPARACION DE AGLUTINANTES 5-HT1A. A PROCESS FOR THE PREPARATION OF A LACTONE OF GENERAL FORMULA (I), WHERE R IS AN OPTIONALLY SUBSTITUTED PHENYLIC GROUP OR AN OPTIONALLY SUBSTITUTED MONO- OR BICYCLE RADICAL WHOSE PROCESS INCLUDES THE REACTION OF AN ANION OF A MALONATE OF FORMULA AN ETHYLENE COMPOUND OF FORMULA (III) AND-CH2-CH2OZ, TO PROVIDE A COMPOUND OF FORMULA (IV) AND THE HYDROLYZATION OF THE FORMULA COMPOUND (IV) TO PROVIDE A FORMULA LACTONE (I). LACTONES ARE FOR USE AS COMPOUNDS FOR THE PREPARATION OF BINDERS 5-HT1A.

Preparation of tetrahydroquinolines and related compounds

METHOD FOR PRODUCING ALPHA ARYL GAMMA BUTYROLACTONES

PCT No. PCT/GB93/02427 Sec. 371 Date May 16, 1995 Sec. 102(e) Date May 16, 1995 PCT Filed Nov. 25, 1993 PCT Pub. No. WO94/12487 PCT Pub. Date Jun. 9, 1994This appliciation discloses a process for preparing a lactone of general formula (I), where R is an optionally substituted phenyl group or an optionally substituted mono- or bicyclic heteroaryl radical which process comprises reacting an anion of a malonate of formula (II) with an ethylene compound of formula (III) Y-CH2-CH2OZ, to give a compound of formula (IV) and hydrolysing the compound of formula (IV) to give a lactone of formula (I). The lactones are of use as intermediates for preparing 5-HT1A binding agents. <IMAGE> (I) <IMAGE> (II) <IMAGE> (IV)

DERIVATIVES OF AZETIDINOCARBOXAMIDE FOR THE TREATMENT OF DISORDERS OF THE CENTRAL NERVOUS SYSTEM.

Un compuesto de fórmula (1) en la que R1 es arilo sustituido con grupos sustituyentes seleccionados entre halo y haloalquilo; y R2 es hidrógeno o alquilo. A compound of formula (1) in which R 1 is aryl substituted with substituent groups selected from halo and haloalkyl; and R2 is hydrogen or alkyl.

Preparation of 3-alkoxycycloalk-2-en-1-ones

AZETIDINOCARBOXAMIDE DERIVATIVES FOR THE TREATMENT OF CNS DISTURBACTIONS

Azetidinecarboxamide derivatives for treating cns disorders

A compound of formula (1) wherein R<1 >is aryl; and R<2 >is hydrogen or alkyl; pharmaceutically acceptable addition compounds thereof; and their use in therapy, particularly for the treatment and prophylaxis of CNS disorders such as anxiety and epilepsy.

Azetidinecarboxamide derivatives for treating cns disorders

A compound of formula (1), wherein: R1 is aryl; R2 is H, alkyl or aryl; and R3 is hydrogen or alkyl; pharmaceutically acceptable addition compounds thereof; and the use of the compounds in therapy, particularly for the treatment and prophylaxis of CNS disorders such as anxiety and epilepsy.

Method of making the derivatives of the hexahydroazepine,piperidine or pyrrolidine

2-Oxo-hexahydroazepine, -piperidine and -pyrrolidine derivatives of general formula (I) …<CHEM>… where n is 2, 3 or 4, R is hydrogen, lower alkyl or aryl(lower)alkyl and R<1> is hydrogen or lower alkyl are novel intermediates for their aromatised derivatives of formula (II) …<CHEM>… where n and R<1> are as defined above, R<2> is hydrogen, lower alkyl or aryl(lower)alkyl and R<3> is hydrogen, lower alkyl, aryl(lower)alkyl, lower alkenyl or lower alkynyl. The aromatised derivatives (of which those in which R<1> is hydrogen are novel) can be converted into 3,3-disubstituted-hexahydroazepine, -piperidine and -pyrrolidine derivatives having pharmacological activity, particularly analgesic activity.

Novel processes and intermediates for the preparation of piperazine derivatives

Verwendung von (+)mefloquine zur behandlung von malaria

Verfahren und zwischenprodukte zur herstellung von piperazinderivaten

Use of (+)mefloquine for the treatment of malaria

Use of (+)-(11R,2'S)-α-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer in the manufacture of a medicament having reduced side-effect compared to the racemic (±)-(R*,S*)-α-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol for treating or preventing malaria in a subject. A method of treating or preventing malaria with reduced side-effects comprising administration of (+)-(11R,2'S)-α-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer.

Azetidincarboxamidderivate zur behandlung von zns-erkrankungen

Thieno2,3-a quinolizin-9-yl sulphonamides

Assay system

NZ 603004 Disclosed is an array including a plurality of well strips, each well strip containing a selected drug which targets a cell signalling molecule, each well strip including a plurality of wells containing a either a sequence of dilutions of the selected drug that span the EC50 of the molecular target of the drug, or the selected drug in a form capable of dilution to create a sequence of dilutions of the selected drug that span the EC50 of the molecular target of the drug, each well also including an inert gaseous environment and being sealed to contain the selected drugs in that inert environment. Also disclosed is a method of providing an array of drugs that target cell signalling molecules, the method including the steps of: selecting a plurality of drugs each of which targets a cell signalling molecule; determining a series of dilutions for each of the selected drugs that span the EC50 of the molecular target of the selected drugs; dispensing an amount of each of the selected drugs into a series of wells; transforming the amount of each of the selected drugs in the wells into a transportable form capable of reconstitution; purging the wells with a suitable gas; sealing the wells; and wherein, the amount of each of the selected drugs dispensed in the wells is such that, when the selected drugs are reconstituted, and a fixed amount of the selected drugs is transferred from each well to a series of fixed volumes of the molecular target, the final range of concentrations created spans the EC50 of the molecular target determined in step B.

Pyrrolidines, piperidones and hexahydroazepinones

Use of (+)mefloquine for the treatment of malaria

Use of (+)-(11R,2'S)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer in the manufacture of a medicament having reduced side-effect compared to the racemic (±)-(R*,S*)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol for treating or preventing malaria in a subject. A method of treating or preventing malaria with reduced side-effects comprising administration of (+)-(11R,2'S)-alpha-2-piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol or a pharmaceutically acceptable salt thereof substantially free of its (-)-enantiomer.

M-hydroxypheny1 substituted compounds

Verfahren zur herstellung von pyridinderivaten.

Meta-hydroxyphenyl-substituierte verbindungen.

Preparation of cyclohexanol derivatives and novel thioamide intermediates

Preparation of cyclohexanol derivatives and novel thioamide intermediates

Preparation of cyclohexanol derivatives and novel thioamide intermediates

Azetidincarboxamidderivate zur behandlung von zns-erkrankungen

Azetidinecarboxamide derivatives for treating cns disorders

A compound of formula (1) wherein R<1 >is aryl; and R<2 >is hydrogen or alkyl; pharmaceutically acceptable addition compounds thereof; and their use in therapy, particularly for the treatment and prophylaxis of CNS disorders such as anxiety and epilepsy.

Novel silyl reagents and their preparation

Procedimiento para la preparacion de derivados de hezahidroacepina,piperidina o pirrolidina

Novel silyl derivatives