Process

New pyridine-2-ethers or pyridine-2-thioethers having a nitrogen-containing cycloaliphatic ring

There are disclosed pyridine-2-ethers and pyridine-2-thioethers having a nitrogen-containing cycloaliphatic ring corresponding to the formula I the pyridine-N-oxides and/or amine oxides thereof and the pharmaceutically acceptable salts thereof. The compounds show analgesic activity.

Keg valve

... 1,103,775. Hose connections. POLYTOP CORPORATION. 1 Oct., 1965 [2 Oct., 1964], No. 41869/65. Heading F2G. A beer-dispensing valve 10 includes a nut 80 having lugs 84 which engage with lugs 82 on a nut 66, the latter being formed with lugs which co-operate with cam lugs 22 provided on the beer keg 12; on the nut 66 are locking fingers with dogs 76 which snap-over ribs 23 on the keg nozzle 18 to prevent loosening of the nut 66 and a lock ring 78 prevents spreading of the fingers. Rotation of the nut 80 causes the probe 94 to open the spring-loaded valve 42, a gaseous fluid under pressure passing from the inlet 90 through the passages 108 and 36 and the valve 56 to the interior of the keg whereby beer is forced through the dip tube 54, the valves 42, 106 to the outlet 100. The handle 114 includes a blow-out plug 118 which is ruptured should the gas pressure become excessive.

ANTIMUSCARINIC BRONCHODILATORS

BENZOIC ACID DERIVATIVES

Matrix metalloproteinase inhibitors

ANTIARRHYTHMIC QUINUCLIDINE CARBOXYLIC ACID XLIDIDE

New thiadiazoles and oxadiazoles and their use as phosphodiesterase-7- inhibitors

Polymorphs of crystalline (2-benzhydryl-1-azabicycloÄ2-2-2-Üoct-3-yl)-(5-isopropyl-2-methoxybenzyl)-amine citrate as NK-1 receptor antagonists.

Quatenary ammonium compounds as tachykinin antagonists

New cyclohexyl and quinuclidinyl carbamate derivatives having beta 2 adrenergic agonist and M3 muscarinic antagonsit activity

QUINUCLIDINE THERAPEUTIC AGENTS

Triazine compounds as P13 kinase and MTOR inhibitors.

Muscarinic acetylcholine receptor antagonists

Triazine compounds as P13 kinase and MTOR inhibitors.

Polymorpds of a crystalline azabicyclo (2,2,2) octan-3-amine citrate and their pharmaceutical compositions

Quaternary ammonium compounds as tachykinin antagonists.

The present invention provides a compound of the formula: wherein R is phenyl, C3-C7 cycloalkyl or heteroaryl, each of which being optionally benzo- or C3-C7 cycloalkyl-fused and optionally substituted, including in the benzo- or C3-C7 cycloalkyl-fused portion, by from 1 to 3 substituents each independently selected from C,-C4 alkyl, fluoro(C1-C4)alkyl, C,-C4 alkoxy, fluoro(C,-C4)alkoxy, phenoxy, C2-C4 alkanoyl, halo, C,-C4 alkoxycarbonyl, C3-C7 cycloalkyl, -S(O)m(CrC4 alkyl), cyano, -NR2R3, -S(O)mNR2R3, -NR4(C,-C4 alkanoyl) and -CONR2R3, or R is 2,3-dihydrobenzo[b]furanyl or chromanyl; R1 is H or C,-C6 alkyl; X is unbranched C2-C4 alkylene; Y is phenyl, naphthyl, benzyl, pyridyl, thienyl or C3-C7 cycloalkyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C,-C4 alkyl, fluoro(CrC4)alkyl, C,-C4 alkoxy, fluoro(C,-C4)alkoxy, halo and cyano; Ar is phenyl, naphthyl, benzyl, thienyl, benzo[b]thienyl or indolyl, each of which being optionally ...

Azabicyclic carbamoyloxy mutilin derivatives for antibacterial use.

Compounds of formula (3), and pharmaceutically acceptable salts and derivatives thereof: in which: R.1 is vinyl or ethyl; and R2 is a group R3, R4CH2~, or R5R6C=CH-; wherein each of R3 and R4 is an azabicyclic ring system or R5 and R^ together with the carbon atom to which they are attached form an azabicyclic ring system, are useful in the prevention and treatment of microbial infections.

Quinolinone derivatives as tyrosine kinase inhibitors.

Organic compounds having the formulas I and II are provided where the variables have the values described herein. Pharmaceutical formulations include the organic compounds or pharrnaceulically acceptable sails thereof and a pharmaceutically acceptable carrier and may be prepared by mixing the organic compounds or pharmaceutically acceptable salts of the organic compounds with a carrier and water. A method of treating a patient includes administering a pharmaceutical formulation according to the invention to a patient in need thereof.

2-aminopyridines containing fused ring substituents.

The present invention relates to 2-aminopyridine derivatives of the formula wherein g,r1 snd r2 are defined as in the specification, that exhibit activity as nitric oxide synthase (nos)inhibitors, to pharmaceutical compsotiions containing tham and to their use in the treatment and prevention of central nervous system and other disorders.

Polymorphs of crysstalline (2-benzhydryyl-1-azabicyclo ¬2,2,2¾oct-3-yl)-(5-isopropyl-2-meth oxybenzyl) ammoniumchloride as nk-1 receptor atagonists

Quinuclidine therapeutic agents

A series of ...

Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease.

The invention provides, compounds of Formula (I) wherein Azabicyclo is formulas (II-VII). W is formulas( VIII-X). These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof.. The compounds of formula I are useful in pharmaccuticals in which a7 is known to be involved.

Indole derivatives useful in the treatment of osteoporosis.

A compound of formula (i)or a salt thereof, or a solvate thereof, wherein either (i)ra represents a group r5 which is hydrogen alkyl or optionally substituted aryl and rb represents a moiety of formula (a), wherein x represents a hydroxy or an alkoxy group wherein the alkyl group may be substituted or unsubstituted or x represents a group nrsrt wherein rs and rt each independently represent hydrogen, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted arylalkyl, an optionally substituted heterocyclic group or an optionally substituted heterocyclylalkyl group, or rs and rt together may form a heterocyclic group; re represents an alkyl or a substituted or unsubsituted aryl group; and r2, r3 and r4 each independently represent hydrogen, alkyl, aryl or sustituted aryl or (ii)ra represents a moiety of the above defined formula (a)and rb represents the above defined r5; r6 and r7 each independently represents hydrogen, hydroxy, amino, ...

Azole derivatives and fused bicyclic azole derivatives as therapeutic agents

This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

Carbonate derivatives for the treatment of cough

The invention relates to use of certain quinuclidine carbonate derivatives as cough suppressants, particularly for treating patients with upper respiratory tract infections or asthma.

Muscarinic acetylcholine receptor antagonists

Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.

Therapeutic isoxazole compounds

The invention provides a compound of formula I: wherein A 1 , A 2 , A 3 , R 1 , X, Y, and B have any of the values described herein, as well as salts of such compounds, compositions comprising such compounds, and therapeutic methods that comprise the administration of such compounds. The compounds are inhibitors of monoamine oxidase B (MAO-B) enzyme function and are useful for improving cognitive function and for treating psychiatric disorders in animals.

3,4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinase and glycogen synthase kinase-3 modulators

The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof, and combinations thereof with other anti-cancer agents, for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3.

Diazonium-free method to make an indazole intermediate in the synthesis of bicyclic 5-(trifluormethoxy)-1h-3-indazolecarboxylic acid amides

The present invention provides novel methods for preparing 5-(trifluoromethoxy)-1H-3-indazolecarboxylic acid (3), which is a useful precursor for the preparation of bicyclic-5-trifluoromethoxy-1H-indazole-3-carboxylic acid amides of Formula (1). Compounds of Formula (1) are active as agonists and partial agonists of the nicotinic α-7 receptor and are being studied for their use in the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain, such as for the treatment of Alzheimer's disease and schizophrenia, as well as other psychiatric and neurological disorders. The present methods are useful for preparing compound (3) on scale up levels.

Processes for preparing substituted pyrimidines

The present invention provides a facile process for the preparation of tri- and tetra-substituted pyrimidines. The process is useful for preparing inhibitors of protein kinases, especially Aurora kinase. These inhibitors are useful for treating or lessening the severity of Aurora-mediated diseases or conditions.

NOVEL PALONOSETRON SALTS AND PROCESSES FOR PREPARATION AND PURIFICATION THEREOF

Provided are novel salts of 2-(1-azabicyclo-[2.2.2]oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one, methods of using such salts, and processes for producing such salts. 1. (canceled)2. A method of preparing pure palonosetron or a salt thereof , the method comprising:(a) dissolving or partially dissolving impure palonosetron in an organic solvent;(b) optionally cooling the solution or partial solution of step (a) to a temperature below 20° C.;(c) admixing an acid and the solution of step (a) or step (b) to form crystals of a pure palonosetron salt, which is different from the HCl salt, and(d) optionally converting the pure palonosetron salt into the free base, wherein the impure palonosetron has a purity of up to 99.1% and an isomer ratio of up to 97:3 (3S),(3aS) isomer:(3S),(3aR) isomer, and the pure palonosetron or salt thereof has a purity of at least 99.5% and a (3S),(3aS):(3S),(3aR) isomer ratio of 99:1 or greater.3. The method of claim 2 , further comprising isolating the crystals.4. The method of claim 2 , wherein the organic solvent is selected from the group consisting of methanol claim 2 , ethanol claim 2 , n-propanol claim 2 , isopropanol claim 2 , and mixtures thereof.5. The method of claim 4 , wherein the organic solvent is ethanol.6. The method of claim 2 , wherein the acid of step (c) is selected from oxalic acid claim 2 , benzoic acid claim 2 , maleic acid claim 2 , malonic acid claim 2 , fumaric acid claim 2 , tartaric acid claim 2 , succinic acid claim 2 , citric acid claim 2 , methanesulfonic acid claim 2 , hydrobromic acid claim 2 , phosphoric acid claim 2 , and mixtures thereof.721-. (canceled) This patent application claims the benefit of U.S. Provisional Patent Application No. 60/932,139, filed May 29, 2007, which is incorporated herein by reference.The present invention relates to organic chemistry and more particularly to processes for preparation and purification of palonosetron and salts thereof.Palonosetron, 2-(1-azabicyclo-[ ...

OXAZOLE TYROSINE KINASE INHIBITORS

The invention provides a compound which is an amide of the formula (1), or a salt, solvate, N-oxide or tautomer thereof; wherein: a is 0 or 1; b is 0 or 1: provided that the sum of a and b is 0 or 1; T is O or NH Aris a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S, and being optionally substituted en by one or more substituents R; ArJs a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R; and Rand Rare as defined in the claims. The compounds are inhibitors of kinases and in particular FLT3, FLT4 and Aurora kinases. 176-. (canceled)85. A compound according to wherein Aris selected from substituted monocyclic 5- and 6-membered aryl and heteroaryl rings containing up to 2 heteroatoms selected from O claim 77 , N and S claim 77 , each of the aryl and heteroaryl rings being optionally substituted by one or more substituents R.86. A compound according to wherein Aris selected from optionally substituted phenyl claim 85 , thiophene claim 85 , furan claim 85 , pyridine and pyrazole rings.87. A compound according to wherein Aris phenyl optionally substituted by one or more substituent groups R.88. A compound according to wherein the aryl or heteroaryl group Aris substituted by 0 claim 77 , 1 or 2 substituents R.89. A compound according to wherein Ris selected from halogen; cyano; or a group R—R;{'sup': aa', 'cc', 'cc', 'cc', 'cc', 'cc', 'cc', 'cc, 'sub': 2', '2', '2, 'Ris a bond, O, CO, OC(O), C(O)O, NRC(O), C(O)NR, NR, OC(O)O, NRC(O)O, OC(O)NR, NRC(O)NR, S, SO, SO, SONR″ or NR″SOwherein'}{'sup': 'bb', 'claim-text': hydrogen; or', {'sup': '3a', 'a 3 to 8-membered non-aromatic carbocyclic or heterocyclic ring containing up to 2 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R; or'}, {'sup': '3a', 'a 5- or 6-membered ...

Synthesis of mse-framework type molecular sieves

A method of synthesizing a crystalline molecular sieve having an MSE framework type comprises crystallizing a reaction mixture comprising a source of water, a source of an oxide of a tetravalent element, Y, selected from at least one of silicon, tin, titanium, vanadium, and germanium, optionally a source of a trivalent element, X, a source of an alkali or alkaline earth metal, M, and a source of organic dications, Q, such as 3-hydroxy-1-(4-(1-methylpiperidin-1-ium-1 yl)butyl)quinuclidin-1-ium, 3-hydroxy-1-(5-(1-methylpiperidin-1-ium-1-yl)pentyl)quinuclidin-1-ium, 1,1′-(butane-1,4-diyl)bis(1-methylpiperidin-1-ium), 1,1′-(pentane-1,5-diyl)bis(1-methylpiperidin-1-ium), 1,1′-(hexane-1,6-diyl)bis(1-methylpiperidin-1-ium), and 1,1′-((3as,6as)-octahydropentalene-2,5-diyl)bis(1-methylpiperidin-1-ium).

NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE

The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X). 2. The process according to claim 1 , wherein the process of step-(i) is carried out in the presence of a base in a solvent.3. The process according to claim 2 , wherein the base used in step-(i) is selected from inorganic base such as sodium hydride claim 2 , potassium hydride claim 2 , sodium hydroxide claim 2 , potassium hydroxide claim 2 , lithium hydroxide claim 2 , sodium carbonate claim 2 , potassium carbonate and the organic base such as an amine claim 2 , for example diethylamine claim 2 , triethylamine claim 2 , diisopropylethylamine claim 2 , tert-butylamine claim 2 , pyridine.4. The process according to claim 2 , wherein the solvent used in step-(i) is selected from acetonitrile claim 2 , cyclic or acyclic alkanes such as hexane claim 2 , heptane claim 2 , methylcyclohexane claim 2 , aromatic solvents such as toluene claim 2 , halogenated solvents such as dichloromethane (MDC) claim 2 , dichloroethane claim 2 , chloroform claim 2 , esters such as ethyl acetate claim 2 , butyl acetate claim 2 , isopropyl acetate or ethers such as diethyl ether claim 2 , tetrahydrofuran or tert-butyl methyl ether and/or mixtures thereof.5. The process according to claim 1 , wherein the solvent used in step-(ii) is selected from methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , ethyl acetate or mixtures there of.6. The process according to claim 1 , wherein the process is carried out in a single step without isolating diastereomeric mixture of Solifenacin.8. The process according to claim 7 , ...

HETEROARYL CARBOXAMIDES

The invention relates to novel heteroaryl carboxamides, a process for their preparation, and pharmaceutical compositions containing them. These materials are useful for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning and/or memory. 5) A compound having the IUPAC name:N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenazinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-7-quinolinecarboxamide hydrochloride;N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-propyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-propyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-6-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-7-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-7-quinolinecarboxamide;or a salt thereof. This application is a Continuation application of U.S. application Ser. No. 10/496,404 filed on May 13, 2004, which is a 371 of PCT/EP02/12375 filed Nov. 6, 2002, which claims priority to German Patent Application No. 101 56 719.7 filed Nov. 19, 2001, the contents of each of which are incorporated herein by reference.The invention relates to novel heteroaryl carboxamides, processes for their preparation, and their use for producing medicaments for the treatment and/or prophylaxis of diseases and for ...

QUINUCLIDINE ESTERS OF 1-AZAHETEROCYCLYLACETIC ACID AS ANTIMUSCARINIC AGENTS, PROCESS FOR THEIR PREPARATION AND MEDICINAL COMPOSITIONS THEREOF

Compounds of formula (I): 2. A compound according to wherein:{'sub': 3', '3', '4, 'A is O, S, N(R), or C(R)R,'}{'sub': 1', '6', '1', '10', '1', '10, 'R1 is aryl, aryl(C-C)alkyl, or heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, (C-C)alkyl, (C-C)alkoxyl, aryloxy, and heteroaryl.'}3. A compound according to claim 1 , wherein:{'sub': 3', '4, 'A is C(R)R,'}m and n are both 2,{'sub': 1', '10', '1', '10, 'R1 is aryl or heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, (C-C)alkyl, (C-C)alkoxyl, aryloxy, and heteroaryl;'} {'br': None, 'sub': 2', '2, 'i': p', 'q, '(CH)-P—(CH)-W\u2003\u2003(Y)'}, 'R3 is a group of formula (Y)whereinp is 0, 1, or 3,P is CO,Q is 0,{'sub': 1', '10', '1', '10', '1', '10', '1', '10, 'W is s (C-C)alkyl, aryl, or heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, (C-C)alkyl, (C-C)alkoxyl, OH, and (C-C)alkanoyl.'}4. A compound according to claim 1 , wherein:W is phenyl, benzothioxolyl, thiophenyl, or thiazolyl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, OH, methyl, and acetyl.5. A compound according to claim 1 , wherein:{'sup': '−', 'X is chloride, bromide, iodide, trifluoroacetate, formate, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate, or p-toluenesulfonate.'}8. A pharmaceutical composition claim 1 , comprising a compound according to and one or more pharmaceutically acceptable carriers or excipients.9. A pharmaceutical composition according to claim 8 , which is in a form selected from the group of a powder for inhalation claim 8 , propellant-driven pressurised metered dose inhaler claim 8 , and propellant-free nebulised ...

PYRIDAZINONES AS GPR119 AGONISTS

The present invention relates to pyridazinone derivatives of general formula I, wherein the groups A, G and Rare as defined in the application, the tautomers thereof, stereoisomers thereof, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity. 8. The physiologically acceptable salts of the compounds of formula I according to .9. A medicament comprising a compound of formula I according to or a physiologically acceptable salt and an inert carriers or diluents.10. A method of treating or preventing a metabolic disease in a patient in need thereof comprising administering to the patient a compound according to .11. The compound according to claim 1 , excluding each of the compounds:5-methyl-6-[2-(3-thienyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-furyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-thienyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(3-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-pyrazinyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(4-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(1-acetyl-piperidino)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(4-methyl-5-oxazolyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(5-pyrimidinyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-amino-5-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,6-[2-(2-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,6-[2-(2-furyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(4-thiomorpholino)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(1-piperidino)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(1-oxido-4-thiomorpholino)-benzoxazol-6-yl]-4,5-dihydro ...

Crystalline Form of (R)-7-Chloro-N-(Quinuclidin-3-yl)benzo[B]thiophene-2-Carboxamide Hydrochloride Monohydrate

Crystalline Forms I and II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate and compositions, methods of manufacture and therapeutic uses thereof are described. 1. A crystalline Form I of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate , characterized by an x-ray powder diffraction pattern having peaks expressed as 2⊖ at one or both of 17.48 and 20.58±0.20 degrees when measured against an internal silicon standard.2. The crystalline Form I of claim 1 , characterized by an x-ray powder diffraction pattern further having at least one peak expressed as 2⊖ at 4.50 claim 1 , 9.04 claim 1 , 14.60 claim 1 , 15.14 claim 1 , 15.80 claim 1 , 16.60 claim 1 , 18.16 claim 1 , 18.44 claim 1 , 19.48 claim 1 , 21.74 claim 1 , and 25.46±0.20 degrees when measured against an internal silicon standard.3. The crystalline Form I of claim 2 , characterized by an x-ray powder diffraction pattern further having at least two peaks expressed as 2⊖ at 4.50 claim 2 , 9.04 claim 2 , 14.60 claim 2 , 15.14 claim 2 , 15.80 claim 2 , 16.60 claim 2 , 18.16 claim 2 , 18.44 claim 2 , 19.48 claim 2 , 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard.4. The crystalline Form I of claim 2 , characterized by an x-ray powder diffraction pattern further having at least four peaks expressed as 2⊖ at 4.50 claim 2 , 9.04 claim 2 , 14.60 claim 2 , 15.14 claim 2 , 15.80 claim 2 , 16.60 claim 2 , 18.16 claim 2 , 18.44 claim 2 , 19.48 claim 2 , 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard.5. The crystalline Form I of claim 2 , characterized by an x-ray powder diffraction pattern further having at least six peaks expressed as 2⊖ at 4.50 claim 2 , 9.04 claim 2 , 14.60 claim 2 , 15.14 claim 2 , 15.80 claim 2 , 16.60 claim 2 , 18.16 claim 2 , 18.44 claim 2 , 19.48 claim 2 , 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard.6. The ...

PYRIDAZINONE DERIVATIVES

Compounds of the formula (I), in which R, R, R, R, R have the meanings indicated in Claim , are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours. 16. A pharmaceutical composition claim 1 , comprising at least one compound of formula I according to or a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof claim 1 , and one or more pharmaceutically acceptable excipients and/or adjuvants.1725-. (canceled)26. A pharmaceutical composition according to claim 16 , further comprising at least one further pharmaceutically active ingredient.27. A kit claim 16 , comprising separate packs of{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) a compound of formula I according to or a pharmaceutically acceptable solvate, salt, tautomer or stereoisomer thereof,'}and(b) a further pharmaceutically active ingredient.28. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof.29. A compound according to claim 14 , or a pharmaceutically acceptable salt thereof. The invention had the object of finding novel compounds having valuable properties, in particular those which can be used for the preparation of medicaments.The present invention relates to compounds and to the use of compounds in which the inhibition, regulation and/or modulation of signal transduction by kinases, in particular tyrosine kinases and/or serine/threonine kinases, plays a role, furthermore to pharmaceutical compositions which comprise these compounds, and to the use of the compounds for the treatment of kinase-induced diseases.In particular, the present invention relates to compounds and to the use of compounds in which the inhibition, regulation and/or modulation of signal transduction by Met kinase plays a role.One of the principal mechanisms by which cellular regulation is effected is through the transduction of extracellular signals across the membrane that in turn modulate ...

PYRIDAZINONE DERIVATIVES

Compounds of the formula (I), in which R, R, R, R, R, have the meanings indicated in Claim , are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours. 2. A method according to claim 1 , wherein in the compound of formula I or in a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof{'sup': 2', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '+', '−', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'sub': 2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'p', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n', '2, 'Rdenotes an unsaturated, saturated or aromatic 6-membered heterocycle having 1 to 4 N and/or O atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, [C(R)]OR, N═CRN(R), CN, COOR, [C(R)]N(R), [C(R)]Het, O[C(R)]OR, O[C(R)]N(R), O[C(R)]C≡C[C(R)]N(R), O[C(R)]NO(R), O[C(R)]Het, NR[C(R)]N(R), NR[C(R)]Het, [C(R)]NHCO[C(R)]N(R), [C(R)]NHCO[C(R)]Het, CONR[C(R)]N(R), CONR[C(R)]NRCOOA, CONR[C(R)]OR, CONR[C(R)]Het, COHet, CH═CH—COOR, CH═CH—N(R)and/or ═O.'}3. A method according to claim 1 , wherein in the compound of formula I or in a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof{'sub': m', '2', '2', '1', '2', '2', 'n', '2', 'n', '2', '2', 'n, 'sup': 3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'Ar denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by A, Hal, CN, S(O)A, NRCOA, CON(R), O[C(R)]N(R), [C(R)]OR, CONR[C(R)]N(R)and/or CONR[C(R)]Het.'}4. A method according to claim 1 , wherein in the compound of formula I or in a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof ...

Alkaloid aminoester derivatives and medicinal composition thereof

Alkaloid aminoester compounds which act as muscarinic receptor antagonists are useful for the prevention and/or treatment of a broncho-obstructive or inflammatory diseases.

SOLIFENACIN SALTS

The invention concerns fumarate salts of solifenacin, as well as pharmaceutical compositions comprising fumarate salts of solifenacin. The invention furthermore concerns a process for preparing solifenacin and salts thereof. The fumarate salt provides improved properties over the known solifenacin salts, especially in terms of its stability. The novel process for its preparation is furthermore improved over known processes for preparing solifenacin in that it provides a higher yield and recovers a greater amount of starting material. 1. A fumarate salt of solifenacin.216-. (canceled)17. The fumarate salt according to claim 1 , wherein said fumarate salt is a hydrogenfumarate (1:1) salt.18. The fumarate salt according to claim 1 , wherein said fumarate salt is substantially crystalline.19. A pharmaceutical composition comprising the fumarate salt according to and one or more pharmaceutically acceptable carriers claim 1 , wherein said pharmaceutical composition is a solid formulation.20. The pharmaceutical composition according to claim 19 , wherein said pharmaceutical composition is formulated for oral administration.21. The pharmaceutical composition according to claim 19 , wherein said pharmaceutical composition is in the form of a tablet claim 19 , a capsule claim 19 , a gelcap claim 19 , a granule claim 19 , a sachet or a pill.22. The pharmaceutical composition according to claim 21 , wherein said pharmaceutical composition is in the form of a tablet.23. A process for preparing solifenacin or a pharmaceutically acceptable salt thereof comprising:a) reacting a solifenacin base with a fumaric acid to form a fumarate salt thereof; andb) optionally transforming the fumarate salt obtained in step a) to solifenacin base and/or a different pharmaceutically acceptable salt of solifenacin.24. The process according to claim 23 , wherein step a) is preceded by the steps:a′) reacting 1(S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline with a C1-6 alkyl chloroformate to form a ...

QUINOLINE DERIVATIVES AND MELK INHIBITORS CONTAINING THE SAME

The present invention directs a compound represented by formula (I). 2. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein Ris a hydrogen atom or a halogen and Ris a hydrogen atom.3. The compound or a pharmaceutically acceptable salt thereof of claim 2 , wherein Ris R[Rrepresents a cyano claim 2 , a C-Calkylsulfinyl claim 2 , a C-Calkylsulfonyl claim 2 , or —CO—R(wherein claim 2 , Rrepresents a C-Calkyl claim 2 , or a C-Ccycloalkyl)] claim 2 ,{'sup': 2', '2A', '2A', '6A', '7A', '6A', '7A', '10A', '10A', '6A', '7A, 'sub': 2', 'n', '3', '10', '1', '6, 'Ris R{Rrepresents an optionally substituted aryl which may have a substituent group selected from Substituent Group C, an optionally substituted aromatic heterocyclic group which may have a substituent group selected from Substituent Group H, or —NRR[wherein, Rrepresents a hydrogen atom, and Rrepresents —(CH)—R(wherein, n represents an integer of 0 to 6, and Rrepresents an optionally substituted C-Ccycloalkyl which may have a substituent group selected from Substituent Group D, an optionally substituted aryl which may have a substituent group selected from Substituent Group E, an aliphatic heterocyclic group which may be substituted with a C-Calkyl, an aromatic heterocyclic group which may have a substituent group selected from Substituent Group I), or Rand Rform with an adjacent nitrogen atom an optionally substituted heterocyclic group which may have a substituent group selected from Substituent Group F]},'}{'sup': 3', '3A', '3A, 'Ris R(Rrepresents an optionally substituted aryl which may have a substituent group selected from Substituent Group G, or an optionally substituted aromatic heterocyclic group which may have a substituent group selected from Substituent Group H), and'}{'sup': '4', 'Ris a hydrogen atom or a halogen, and'} [{'sub': 1', '6', '1', '6, 'Substituent Group C: a halogen, a hydroxy, a C-Calkoxy, and a di(C-Calkyl) amino;'}, {'sub': 1', '6', '1', '6', '1', '6', '1', '6', ' ...

Compositions and Methods for Treatment of Neurodegenerative Disease

Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed. 2. (canceled)3. The compound of claim 1 , wherein X is S(O).4. The compound of claim 1 , wherein Ris H or methyl.5. The compound of claim 1 , wherein Ris methyl or ethyl.6. The compound of claim 1 , wherein Ris methyl or ethyl.7. The compound of claim 1 , wherein the compound is a compound of formula (I) and n is one or two and each Ris methyl.8. The compound of claim 1 , wherein the compound is a compound of formula (I) and n is at least 3 claim 1 , and two occurrences of Rare gem-dimethyl groups and one occurrence of Ris oxo.9. The compound of claim 1 , wherein X is C(O) and Ris —N(RR).10. The compound of claim 9 , wherein Rand Rare each independently unsubstituted C-Calkyl.11. The compound of claim 9 , wherein Rand Rare taken together with the nitrogen atom to which they are attached to form a 4-10-membered heterocyclic ring.12. The compound of claim 1 , wherein the compound is a compound of formula (I) and Ris H and Ris —(CH)N(ethyl).14. A method of treating or preventing a neurodegenerative disease or disorder claim 1 , the method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to the subject claim 1 , thereby treating or preventing the neurodegenerative disease or disorder.15. The method of claim 14 , wherein the neurodegenerative disease or disorder is glaucoma.16. The method of claim 15 , wherein the neurodegenerative disease or disorder is glaucoma that is not neovascular glaucoma.17. The method of claim 14 , wherein the step of administering the compound includes administering the compound in a pharmaceutically acceptable composition.18. The method of claim 14 , wherein the subject is a mammal.19. The method of claim 14 , wherein the subject is a human.20. The method of claim 14 , further comprising the step of monitoring ...

INDAZOLES, BENZOTHIAZOLES, BENZOISOTHIAZOLES, BENZISOXAZOLES, AND PREPARATION AND USE THEREOF

The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nACh receptors), activation of nACh receptors, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (e.g., indazoles and benzothiazoles), which act as ligands for the α7 nACh receptor subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof. 147-. (canceled)49. A method according to claim 48 , wherein said patient is suffering from schizophrenia claim 48 , anxiety claim 48 , mania claim 48 , depression claim 48 , manic depression claim 48 , Tourette's syndrome claim 48 , Parkinson's disease claim 48 , Huntington's disease claim 48 , Alzheimer's disease claim 48 , Lewy Body Dementia claim 48 , Amyotrophic Lateral Sclerosis claim 48 , memory impairment claim 48 , memory loss claim 48 , cognition deficit claim 48 , attention deficit claim 48 , and/or Attention Deficit Hyperactivity Disorder.52. (canceled)53. (canceled)54. (canceled)55. (canceled)56. (canceled)57. (canceled)60. A method according to claim 59 , wherein said memory impairment is due to decreased nicotinic acetylcholine receptor activity.61. (canceled)62. (canceled)63. (canceled)64. (canceled)65. (canceled)66. (canceled)68. A method according to claim 67 , wherein said inflammatory disease is rheumatoid arthritis claim 67 , diabetes or sepsis.69. A method according to claim 48 , wherein said patient is a human.70. The method according to claim 48 , wherein R′ is H or CH.71. The method according to claim 48 , wherein Ris alkynyl having 2 to 6 carbon atoms claim 48 , fluorinated hydroxyalkyl having 1 to 4 carbon atoms claim 48 , or Ar-alkynyl.72. The method according to claim 48 , wherein said compound is of formula I.73. The method according to claim 72 , wherein Ris NH claim 72 , CF claim 72 , OCH claim 72 , ...

PRODUCTION PROCESS OF OPTICALLY ACTIVE 3-QUINUCLIDINOL DERIVATIVE

A process is provided for efficiently producing an optically active 3-quinuclidinol derivative of high optical purity using a readily available ruthenium compound as an asymmetric reduction catalyst. This process is a process for producing an optically active 3-quinuclidinol derivative represented by the following formula (III) comprising asymmetrically hydrogenating a 3-quinuclidinone derivative represented by the following formula (I) in the presence of a ruthenium compound (II) represented by formula (II): Ru(X)(Y)(P)[RRC*(NRR)-A-RRC*(NRR)] (in the formulas, R represents a hydrogen atom or C7 to C18 aralkyl group and the like, X and Y represent hydrogen atoms or halogen atoms and the like, Px represents a phosphine ligand, n represents 1 or 2, R1 to R8 represent hydrogen atoms or C1 to C20 alkyl groups and the like, * represents an optically active carbon atom and A represents an ethylene group and the like). 15-. (canceled) The present invention relates to a process for producing optically active 3-quinuclidinol derivatives that are useful as production raw materials of physiologically active substances, and particularly pharmaceuticals.The present application claims priority on Japanese Patent Application No. 2007-230973, filed on Sep. 6, 2007, and Japanese Patent Application No. 2008-032311, filed on Feb. 13, 2008, the contents of which are incorporated herein by reference.Many alkaloids, and particularly those compounds having an azabicyclo ring structure, are useful as physiologically active substances. In particular, optically active 3-quinuclidinol derivatives are important compounds as production raw materials of pharmaceuticals.A conventionally known process for industrial production of optically active 3-quinuclidinol consists of direct asymmetric hydrogenation of 3-quinuclidinone using inexpensive hydrogen gas for the hydrogen source in the presence of an asymmetric hydrogenation catalyst (Patent Documents 1 to 4).In this production process, an ...

COMPOUNDS USEFUL AS INHIBITORS OF CHOLINE KINASE

The present invention relates to compounds useful as inhibitors of choline kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. 2. The compound of claim 1 , wherein Ris H.3. The compound according to any one of or claim 1 , wherein Ris R.4. The compound of claim 3 , wherein Ris phenyl claim 3 , a 5-6 membered monocyclic heteroaryl claim 3 , or an −8-12 membered bicyclic heteroaryl.5. The compound of claim 4 , wherein Ris phenyl claim 4 , benzothiazolyl claim 4 , pyridinyl claim 4 , indolyl claim 4 , or imidazolyl.7. The compound of claim 5 , wherein Ris phenyl or benzothiazolyl9. The compound of claim 7 , wherein Ris benzothiazolyl.11. The compound of claim 7 , wherein Ris phenyl.13. The compound according to claim 1 , wherein Jis —ORor R.14. The compound of claim 13 , wherein —Ris H.15. The compound of claim 13 , wherein —Ris R.16. The compound of claim 15 , wherein Ris —Caliphatic claim 15 , wherein up to four methylene groups may be replaced with C═O claim 15 , nitrogen claim 15 , sulfur claim 15 , or oxygen.17. The compound of claim 16 , wherein Ris substituted with at least one occurrence of W.18. The compound of claim 17 , wherein W is a −4-8 membered monocyclic heterocyclyl.19. The compound of claim 18 , wherein W is independently piperazinyl claim 18 , morpholinyl claim 18 , piperidinyl claim 18 , or pyrrolidinyl.21. The compound of claim 15 , wherein Ris independently a 5-6 membered monocyclic heteroaryl or −4-8 membered monocyclic heterocyclyl.22. The compound of claim 21 , wherein Ris a −4-8 membered monocyclic heterocyclyl.23. The compound of claim 22 , wherein Ris a pyranyl.25. The compound of claim 21 , wherein Ris a 5-6 membered monocyclic heteroaryl.26. The compound of claim 25 , wherein Ris an imidazolyl.28. The compound ...

COMPOUNDS USEFUL AS INHIBITORS OF CHOLINE KINASE

The present invention relates to compounds useful as inhibitors of choline kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. 2. The compound of claim 1 , wherein n is 0.3. The compound according to any one of or claim 1 , wherein Qis independently selected from phenyl claim 1 , thiazolyl claim 1 , or pyridinyl.53. The compound according to any one of - claims 1 , wherein Qis phenyl.65. The compound according to any one of - claims 1 , wherein Jis NRR.7. The compound of claim 6 , wherein Ris Calkyl and Ris Calkyl.8. The compound according to any one of claim 6 , wherein Rand R claim 6 , taken together with the nitrogen to which they are bound claim 6 , form a 5 membered heterocyclic ring.9. The compound of claim 8 , wherein Jis pyrrolidinyl.106. The compound according to any one of - claims 1 , wherein Rand R claims 1 , taken together with the nitrogen to which they are bound claims 1 , form a 6 membered heterocyclic ring.11. The compound of claim 10 , wherein Jis piperidinyl.12. The compound according to any one of or claim 10 , wherein Jis ethyl or tert-butyl.1312. The compound according to any one of - claims 1 , wherein Qis absent.1412. The compound according to any one of - claims 1 , wherein Qis fused to Q.15. The compound of claim 14 , wherein Qis benzo.16. The compound of claim 15 , wherein Qis fused to Q1 to form naphthalene.17. The compound of claim 16 , wherein Jis Calkyl18. The compound of claim 17 , wherein Jis methyl.19. The compound of claim 14 , wherein Qis a 5 or 6 membered non-aromatic ring having 1-2 heteroatoms selected from nitrogen or oxygen.20. The compound of claim 19 , wherein Qis independently selected from pyrrolidinyl claim 19 , morpholinyl claim 19 , piperazinyl claim 19 , or dioxolyl.22. The compound of ...

PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES

A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof. 17-. (canceled)9. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein B is NH.10. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is thiazolyl claim 8 , benzothiazolyl claim 8 , pyridyl claim 8 , isoxazolyl claim 8 , isoquinolinyl claim 8 , quinolyl claim 8 , benzothiadiazolyl claim 8 , thiadiazolyl claim 8 , pyrazolyl or pyrazinyl claim 8 , which is optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.11. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is thiazolyl or benzothiazolyl optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.12. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is C-Cheteroaryl substituted by at least one selected from the group consisting of chloro claim 8 , methyl claim 8 , ethyl claim 8 , propyl claim 8 , iso-propyl claim 8 , tert-butyl claim 8 , cyclopentyl claim 8 , phenyl claim 8 , chlorophenyl claim 8 , benzyl claim 8 , cyclohexyl and methoxy.13. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is selected from thiazolyl claim 8 , methylthiazolyl claim 8 , ethylthiazolyl claim 8 , propylthiazolyl claim 8 , iso- ...

VINYL QUINUCLIDINE USEFUL AS A SYNTHESIS INTERMEDIATE IN THE PREPARATION OF (R)-MEQUITAZINE

The present invention relates to the use of the vinyl quinuclidine enantiomer (R) of the following formula 2 as a synthesis intermediate in the preparation of (R)-mequitazine. 1. (canceled)4. The method according to claim 3 , wherein step (a) is carried out by ozonolysis.5. The method according to claim 3 , wherein step (a) is carried out from an acid addition salt of the (R) enantiomer of the vinyl quinuclidine of formula 2 as defined in .6. The method according to claim 3 , wherein step (b) is carried out in the presence of a hydride.7. The method according to claim 6 , wherein the hydride is NaBH.8. The method according to claim 3 , wherein R3 represents a mesylate (OMs).9. The method according to claim 8 , wherein step (c) is carried out in the presence of mesyl chloride (MsCl) and a base.10. The method according to claim 9 , wherein the base is pyridine.11. The method according to claim 3 , wherein step (d) is carried out in the presence of a base.12. The method according to claim 11 , wherein the base is potassium tert-butoxylate. The present invention relates to the optically pure vinyl quinuclidine of the following formula 2 as a synthesis intermediate in the preparation of the (R) enantiomer, dextrorotary, of the mequitazine of the following formula 1a:Mequitazine 1 is an active ingredient developed by the Pierre Fabre laboratories and commercialised in the racemic version thereof (mixture of 2 enantiomers 1a and 1b, Scheme 1) under the name of Primalan®. This medicine is used as an anti-histaminic for the treatment for example of urticaria, hay fever or certain allergies. Its preparation in the racemic form and in the levorotary form thereof 1b has been described in the patents FR 2 522 660 and EP 0 089 860. The drawback of the protocol for synthesising mequitazine in an optically active form (1a or 1b) is that it involves a step of resolution of the racemic, via the formation of a complex with tartaric acid. This resolution involves the loss of 50% at ...

NOVEL QUINUCLIDINE DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME

Provided is a pharmaceutical composition comprising: (i) 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo-[2.2.2]octane or an enantiomer, mixture of enantiomers, or a racemate thereof, wherein an anion X with a single negative charge is associated with the positive charge of the nitrogen atom; and (ii) a phosphodiesterase IV inhibitor and methods of using the same. 135-. (canceled)36. A pharmaceutical composition comprising:{'sup': '−', '(i) 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo-[2.2.2]octane or an enantiomer, mixture of enantiomers, or a racemate thereof, wherein an anion X with a single negative charge is associated with the positive charge of the nitrogen atom; and'}(ii) a phosphodiesterase IV inhibitor.37. The composition of further comprising a pharmaceutically acceptable carrier or diluent.38. The composition of wherein the anion X is chloride claim 36 , bromide claim 36 , iodide claim 36 , sulfate claim 36 , nitrate claim 36 , phosphate claim 36 , acetate claim 36 , maleate claim 36 , fumarate claim 36 , citrate claim 36 , oxalate claim 36 , succinate claim 36 , tartrate claim 36 , malate claim 36 , mandelate claim 36 , methanesulfonate claim 36 , p-toluenesulfonate claim 36 , or trifluoroacetate.39. The composition of which is suitable for inhalation.40. The composition of wherein the composition is a liquid inhalant claim 36 , powder inhalant claim 36 , or inhalation aerosol.41. The composition of further comprising a steroid.42. The composition of further comprising a βagonist.43. The composition of further comprising a βagonist.44. The composition of wherein the pharmaceutically acceptable carrier or diluent is lactose.45. A method for treating chronic obstructive pulmonary disease claim 36 , chronic bronchitis claim 36 , bronchial hyperreactivity claim 36 , asthma claim 36 , or rhinitis which method comprises administering to a human or animal patient in need of such treatment an effective ...

Azolyl Urea Compounds and Methods of Use Thereof

Provided herein are azolyl urea compounds for treatment of CSF-1R kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions. 3. The compound of claim 1 , wherein A is optionally substituted isoxazolyl or optionally substituted pyrazolyl claim 1 , wherein substituents when present are selected from one claim 1 , two or three Rgroups claim 1 , each independently selected from hydrogen claim 1 , halo claim 1 , alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , alkoxy claim 1 , hydroxyl claim 1 , haloalkoxy claim 1 , cycloalkyl claim 1 , cycloalkylalkyl claim 1 , hydroxyalkyl claim 1 , haloalkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , heterocyclyl claim 1 , heterocyclylalkyl claim 1 , heteroaryl claim 1 , and heteroarylalkyl claim 1 , where the alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , alkoxy claim 1 , haloalkoxy claim 1 , cycloalkyl claim 1 , cycloalkylalkyl claim 1 , hydroxyalkyl claim 1 , haloalkyl claim 1 , aryl claim 1 , heterocyclyl claim 1 , and heteroaryl groups are optionally substituted with 1 to 5 groups selected from halo claim 1 , hydroxy claim 1 , alkoxy claim 1 , cycloalkyl claim 1 , cyano claim 1 , and —RN(R)(R) claim 1 , where Ris independently alkylene or a direct bond claim 1 , R claim 1 , and Rare each independently hydrogen or alkyl.9. The compound of claim 1 , where Ris hydrogen claim 1 , alkyl or alkoxy.10. The compound of claim 1 , where Ris hydrogen claim 1 , cycloalkyl claim 1 , heterocyclyl or heterocyclylalkyl claim 1 , where the cycloalkyl claim 1 , heterocyclyl and heterocyclylalkyl are optionally substituted with one or two alkyl groups.13. The compound of claim 1 , wherein each Qis independently selected from —CH claim 1 , —CH—CH claim 1 , —CHCF claim 1 , —CH—(CH) claim 1 , —C(O)O(CH) claim 1 , —(CH)S(O)CH claim 1 , —CHC(O)N(CH) claim 1 , —C(CH) claim 1 , cyclopropyl and oxetanyl.15. The compound of claim 1 , wherein the compound is ...

5-HT3 RECEPTOR MODULATORS, METHODS OF MAKING, AND USE THEREOF

Novel 5-HTreceptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention. 2. The compound according to in the (S) configuration.3. The compound according to in the (R) configuration.4. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to and a pharmaceutically acceptable carrier.5. A method of treating irritable bowel syndrome comprising:selecting a patient with irritable bowel syndrome; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the patient a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof.'}6. The method according to further comprising:{'sub': 3', '4, 'administering to the patient a therapeutically effective amount of a second serotonin 5-HTreceptor modulator or a serotonin 5-HTreceptor modulator.'}7. The method according to claim 6 , wherein the second serotonin 5HTreceptor modulator or serotonin 5HTreceptor modulator is selected from the group consisting of Alosetron claim 6 , renzapride claim 6 , cilansetron claim 6 , Tegaserod claim 6 , Prucalopride claim 6 , ondansetron claim 6 , somatostatin analogs claim 6 , muscarinic receptor antagonists claim 6 , laxatives claim 6 , antispasmodics claim 6 , antidepressants claim 6 , antidiarrheal agents claim 6 , prokinetic agents claim 6 , peripheral opiate narcotic antagonists claim 6 , and combinations thereof.8. A method of treating emesis comprising:selecting a patient with emesis; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the patient a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof.'}9. The method according to further comprising:administering to the patient a ...

Tertiary amines, medicaments containing said amines, use thereof and processes for the preparation thereof

The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.

PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES

A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof. 17-. (canceled)9. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein B is NH.10. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is phenyl or naphthyl optionally substituted by at least one selected from the group consisting of halo claim 8 , amino claim 8 , phenyl claim 8 , C-Calkyl claim 8 , C-Calkynyl claim 8 , C-Ccycloalkyl claim 8 , C-Calkoxy claim 8 , C-Caralkoxy claim 8 , C-Caryloxy claim 8 , C-Calkylthio claim 8 , C-Caralkylthio claim 8 , C-Carylthio claim 8 , C-Calkylsulfonyl and C-Cheteroaryl.11. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is phenyl optionally substituted by at least one selected from the group consisting of halo claim 8 , amino claim 8 , phenyl claim 8 , C-Calkyl claim 8 , C-Calkynyl claim 8 , C-Ccycloalkyl claim 8 , C-Calkoxy claim 8 , C-Caralkoxy claim 8 , C-Caryloxy claim 8 , C-Calkylthio claim 8 , C-Caralkylthio claim 8 , C-Carylthio claim 8 , C-Calkylsulfonyl and C-Cheteroaryl.12. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein the compound is a compound of Formula I and A is phenyl optionally substituted by at least one selected from the group consisting of halo claim 8 , amino claim 8 , phenyl claim 8 , C-Calkyl claim 8 , C-Calkynyl claim 8 , C-Ccycloalkyl claim 8 , C-Calkoxy claim 8 , C-Caralkoxy claim 8 , C-Caryloxy claim 8 , C-Calkylthio claim 8 , C-Caralkylthio claim 8 , C-Carylthio claim 8 , C-Calkylsulfonyl and C-Cheteroaryl.13. The compound of or a pharmaceutically ...

Amides of acetic and propionic acids

The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory.

2-Phenoxy- and 2-Phenylsulfonamide Derivatives with CCR3 Antagonistic Activity for the Treatment of Inflammatory or Immunological Disorders

Provided herein are 2-phenoxy- and 2-phenylsulfonamide derivatives with CCR3 antagonistic activity. These compounds are useful for the treatment of diseases associated with CCR3 activity, including but not limited to, atopic dermatitis, allergic rhinitis, rheumatoid arthritis, Grave's disease, HIV infection, Alzheimer's disease, atherosclerosis and other inflammatory and/or immunological disorders. 117.-. (canceled)22. The method of claim 18 , wherein the compound claim 18 , its tautomeric or stereoisomeric form claim 18 , or a physiologically acceptable salt thereof claim 18 , is selected from the group consisting of:(R)—N-(1-Aza-bicyclo[2.2.2]oct-3-yl)-5-cyano-2-(3,5-dichloro-phenoxy)-benzenesulfonamide;(S)—N-(1-Aza-bicyclo[2.2.2]oct-3-yl)-5-cyano-2-(3,5-dichloro-phenoxy)-benzenesulfonamide;N-(1-aza-bicyclo[2.2.2]oct-3-yl)-2-(3,5-dichloro-phenylsulfanyl)-5-nitro-benzenesulfonamide; and(R)-5-cyano-2-(3,5-dichlorophenoxy)-N-(2-(2,5-dioxopyrrolidin-1-yl)ethyl)-N-(1-aza-bicyclo[2.2.2]oct-3-yl)benzenesulfonamide.23. The method of claim 18 , wherein the compound claim 18 , its tautomeric or stereoisomeric form claim 18 , or a physiologically acceptable salt thereof is formulated with one or more pharmaceutically acceptable excipients.24. The method of claim 23 , wherein the excipient is an inert substance selected from the group consisting of a carrier claim 23 , a diluent claim 23 , a flavoring agent claim 23 , a sweetener claim 23 , a lubricant claim 23 , a solubilizer claim 23 , a suspending agent claim 23 , a binder claim 23 , a tablet disintegrating agent and an encapsulating agent. The present invention relates to a benzenesulfonamide derivative, which is useful as an active ingredient of pharmaceutical preparations. The benzenesulfonamide derivatives of the present invention have CCR3 (CC type chemokine receptor 3) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with CCR3 activity, in particular for the treatment of ...

5-ht3 receptor antagonists

The present invention provides 5-HT3 receptor antagonists of Formula (I): which are useful for the treatment of diseases treatable by inhibition of 5-HT3 receptor such as emesis, pain, drug addiction, neurodegenerative and psychiatric disorders, and GI disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

(2S,3R)-N-(2-((3-PYRIDINYL)METHYL)-1-AZABICYCLO[2.2.2]OCT-3-YL)BENZYOFURN-2-CARBOXAMIDE, NOVEL SALT FORMS, AND METHODS OF USE THEREOF

The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central and autonomic nervous systems. 1. A method for treating one or more of mild cognitive impairment , age-associated memory impairment , pre-senile dementia , early onset Alzheimer's disease , senile dementia , dementia of the Alzheimer's type , or Alzheimer's disease comprising administering a compound (2S ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide or a pharmaceutically acceptable salt thereof , substantially free of (2S ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , and pharmaceutically acceptable salts thereof.2. The method of claim 1 , wherein the treatment is for Alzheimer's disease.3. The method of claim 1 , wherein the treatment is for early onset Alzheimer's disease. The present invention is a continuation of U.S. patent application Ser. No. 13/116,080, filed May 26, 2011, which is a continuation of U.S. patent application Ser. No. 12/184,312, filed Aug. 1, 2008, now U.S. Pat. No. 7,981,906 issued Jul. 19, 2011, which claims benefit to U.S. Provisional Application Nos. 60/971,654, filed Sep. 12, 2007, 60/953,610, filed Aug. 2, 2007, 60/953,613, filed Aug. 2, 2007, and 60/953,614 filed Aug. 2, 2007, each of which is incorporated herein by reference in its entirety.The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating ...

1,4-disubstituted 1,2,3-triazoles, methods for preparing same, and diagnostic and therapeutic uses thereof

A compound having the following general formula (I): wherein: X is a nitrogen atom and Y is a carbon atom; or X is a carbon atom and Y is a nitrogen atom; the Ar group is an aryl or heteroaryl group; and the RN and RN′ groups, together with the carbon atoms to which they are bound, form a monocyclic or bicyclic azacycloalkane group. The pharmaceutically acceptable salts thereof, the hydrates or polymorphic crystalline structures thereof, and to the racemates, diastereoisomers, or enantiomers thereof are also described.

COMPOUNDS CONTAINING AN ALICYCLIE STRUCTURE AND ANTI-TUMOR APPLICATION

This invention relates with anti-tumor activities of new compounds containing an adamantyl group or analogs thereof. The invention also relates with the medication applications of anti-tumor and other diseases by this kind of compounds with the combination of S, P, T structures containing adamantyl group and the formation of stereoisomer, tautomers, prodrug, pharmaceutically acceptable salts, complex salts or solvates to their anticancer application and anticancer agents, which have the following general formula: 2. The compound according to the S formula of claim 1 , wherein:{'sub': 1', '2', '3', '4', '2', '1-10, 'The dotted lines are optionally substituted single bonds, optionally substituted double bond or a optionally substituted heterocyclic group containing carbon, oxygen, sulfur or nitrogen element; said X, X, X, Xare, independently at each occurrence, C═O, C═S, C═NH, C═Rb—Ra, CHOH, CHORb, CHRb or substituent, where Rb contains, independently at each occurrence, one or combination of C, N or P element; Ra is H, H, optionally substituted straight-alkyl, optionally substituted branched-alkyl, Coptionally substituted saturated alkyl, optionally substituted 1-4 double bond, optionally substituted 1-4 triple bond, optionally substituted unsaturated alkyl, optionally substituted saturated or unsaturated alicyclic, optionally substituted arylcyclic, optionally substituted aryl or optionally substituted heterocyclic, optionally substituted arylheterocyclic, fused heterocyclic group where contains hydroxyl, halogen, oxygen, nitrogen, sulfur, phosphorus element or selenium element;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8, 'said A, A, A, A, A, A, Aor Ais, independently at each occurrence, optionally substituted independently cyclic, alkyl, aryl, alicyclic, heterocyclic, aliphatic, aromatic heterocyclic, heterocyclic, glycosyl, multi-hydroxyl, amino acid, phosphate, acyloxyl, phosphoric, sulfonyloxyl, alkoxy, aryloxyl, heterocyclic oxyl, aryl cyclic, aliphatic ...

Substituted indole compounds having nos inhibitory activity

The present invention features inhibitors of nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing conditions such as, for example, stroke, reperfusion injury, neurodegeneration, head trauma, CABG, migraine headache with and without aura, migraine with allodynia, central post-stroke pain (CPSP), neuropathic pain, morphine/opioid induced tolerance and hyperalgesia.

STABLE CRYSTALLINE SALT OF (R)-3-FLUOROPHENYL-3,4,5-TRIFLUOROBENZYLCARBAMIC ACID 1-AZABICYCLO [2.2.2]OCT-3-YL ESTER

The present invention refers to a stable crystalline salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo [2.2.2]oct-3-yl ester and its use as medicament, in particular for the treatment of urinary incontinence or other diseases involving genitourinary disorders 2. The method of claim 1 , wherein the D-tartrate salt of compound I is a substantially anhydrous crystalline salt.3. The method of claim 1 , wherein the disease involving genitourinary disorders is urinary incontinence.4. The method of claim 1 , wherein the disease involving genitourinary disorders is overactive bladder.6. The method of claim 5 , wherein the D-tartrate salt of compound I is a substantially anhydrous crystalline salt.7. A method of claim 5 , wherein the disease or condition involving genitourinary disorders is urinary incontinence.8. A method of claim 5 , wherein the disease or condition involving genitourinary disorders is overactive bladder. The present invention relates to a stable crystalline salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo [2.2.2]oct-3-yl ester and to pharmaceutical formulations of this salt, in particular for medical use including treatment of urinary incontinence urge or other diseases involving genitourinary disorders.WO0200652 discloses compound I ((R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo [2.2.2]oct-3-yl ester) which has the following formula (I)Compound I is also disclosed in WO2004000840. On the other hand, compound I is exemplified as hydrochloride salt in WO2003053966 as an intermediate in the synthesis of other compounds. However, this acid addition salt known from the prior art had the disadvantage that its physicochemical stability was poor. Upon storage or formulation of said known salt, progressive decomposition and concomitantly an increase in the amount and number of impurities was observed. Obviously, this problem is further aggravated under demanding environmental conditions such ...

3-(HETEROARYL-OXY)-2-ALKYL-1-AZA-BICYCLOALKYL DERIVATIVES AS ALPHA. 7-NACHR LIGANDS FOR THE TREATMENT OF CNS DISEASES

The present invention relates to 1-aza-bicycloalkyl derivatives of formula (I) wherein the substituents are as defined in the specification, to processes for their production, their use as pharmaceuticals in the prevention and treatment of psychotic and neurodegenerative disorders. The claimed compounds act as nicotinic acetylcholine receptors (NACHR) ligands. 115-. (canceled)171. A method for treating or preventing a disease or condition in which α7 nAChR activation plays a role or is implicated , in a subject in need of such treatment , which comprises administering to such subject a therapeutically effective amount of a compound of claim in free base or pharmaceutically acceptable acid addition salt form.20. A method according to claim 17 , wherein the compound of formula I is selected from the group consisting of(2SR,3RS)-3-[5-(1H-Indol-5-yl)-pyridin-2-yloxy-]2-methyl-1-aza-bicyclo[2.2.2]octane;(+)-3-[5-(1H-Indol-5-yl)-pyridin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(−)-3-[5-(1H-Indol-5-yl)-pyridin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2SR,3RS)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2S,3R)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2R,3S)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2SR,3RS)-3-[5-(1H-Indol-5-yl)-pyrimidin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;{'b': '3-', '(2S,3R)--[5-(1H-Indol-5-yl)-pyrimidin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;'}{'b': '3-', '(2R,3S)--[5-(1H-Indol-5-yl)-pyrimidin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane; and'}(2SR,3RS)-3-[6-(1H-Indol-5-yl)-pyridin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane.21. A method according to claim 17 , wherein the compound of formula I is (2SR claim 17 ,3RS)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane.22. A method according to claim 17 , wherein the compound of formula I is(2S,3R)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza- ...

TETRAHYDROISOQUINOLIN-1-ONE DERIVATIVE OR SALT THEREOF

To provide a pharmaceutical, in particular a compound which can be used as a therapeutic agent for irritable bowel syndrome (IBS). It was found that a tetrahydroisoquinolin-1-one derivative having an amide group at the 4-position or a pharmaceutically acceptable salt thereof has an excellent bombesin 2 (BB2) receptor antagonistic action. It is also found that the tetrahydroisoquinolin-1-one derivative is highly effective on bowel movement disorders. From the above, the tetrahydroisoquinolin-1-one derivative of the present invention is useful as a therapeutic agent for diseases associated with a BB2 receptor, in particular IBS. 1. (canceled)4. The method as described in claim 3 , wherein Ris —H.5. The method as described in claim 4 , wherein Ris phenyl which may be substituted with halogen claim 4 , lower alkyl claim 4 , or —OR.6. The method as described in or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris —N(R)-lower alkylene-(aryl or heteroaryl claim 5 , which may each be substituted) claim 5 , or —N(R)—O-lower alkylene-(aryl or heteroaryl claim 5 , which may each be substituted).7. The method as described in claim 6 , wherein Ris (lower alkylene)-OH or substituted cycloalkyl {wherein said lower alkylene may be substituted with a member selected from the group consisting of —OH and phenyl (which may be substituted with halogen claim 6 , lower alkyl claim 6 , or —OR claim 6 , and said substituted cycloalkyl is substituted with a member selected from the group consisting of —OR claim 6 , —N(R) claim 6 , —N(R)C(O)R claim 6 , —N(R)-lower alkylene-OR claim 6 , —N(R)S(O)-lower alkyl and heterocyclic group}.8. The method according to claim 3 , wherein the compound is (4-{[({[(3R claim 3 ,4R)-3-(2 claim 3 ,4-dichlorophenyl)-2-{(1S claim 3 ,2S)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1 claim 3 ,2 claim 3 ,3 claim 3 ,4-tetrahydroisoquinolin-4-yl]carbonyl}amino)oxy]methyl}phenyl)acetic acid claim 3 , or a pharmaceutically acceptable salt thereof.10. The ...

Pyrimidine derivatives as protein kinase inhibitors

The present invention relates to a compound of formula (VII)I, or pharmaceutically acceptable salt or ester thereof, wherein: X is NR 7 ; Y is O or N—(CH 2 ) n R 19 ; n is 1, 2 or 3; m is 1 or 2; R 1 and R 2 are each independently H, alkyl or cycloalkyl; R 4 and R 4′ are each independently H or alkyl; or R 4 and R 4′ together form a spiro cycloalkyl group; R 19 is H, alkyl, aryl or a cycloalkyl group; R 6 is OR 8 or halogen; and R 7 and R 8 are each independently H or alkyl. Further aspects relate to pharmaceutical compositions comprising said compounds and use therefore in the treatment of proliferative disorders and the like.

MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS

Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided. 2. The compound according to wherein X is a pharmaceutically acceptable anion selected from the group consisting of chloride claim 1 , bromide claim 1 , iodide claim 1 , hydroxide claim 1 , sulfate claim 1 , nitrate claim 1 , phosphate claim 1 , acetate claim 1 , trifluoroacetate claim 1 , fumarate claim 1 , citrate claim 1 , tartrate claim 1 , oxalate claim 1 , succinate claim 1 , mandelate claim 1 , methanesulfonate claim 1 , and p-toluenesulfonate.3. The compound according to wherein M is O.4. The compound according to wherein n is 2.5. The compound according to wherein l is 2.6. The compound according to wherein V is CH.7. The compound according to wherein V is O.8. The compound according to wherein M is CH.9. The compound according to wherein l is 1.10. The compound according to wherein l is 2.15. The compound according to which is:4-[hydroxy(diphenyl)methyl]-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1-azoniabicyclo[2.2.2]octane bromide.16. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier thereof.17. A pharmaceutical composition comprising a compound according to claim 15 , and a pharmaceutically acceptable carrier thereof.18. A pharmaceutical composition according to in a form suitable for administration by oral or nasal inhalation.19. A pharmaceutical composition according to wherein the form is suitable for administration by inhalation via a medicament dispenser selected from a reservoir dry powder inhaler claim 18 , a multi-dose dry powder inhaler claim 18 , or a metered dose inhaler.20. A pharmaceutical composition according to which is a dry powder composition. This invention relates to novel quinuclidines derivatives, pharmaceutical compositions, and use thereof in treating muscarinic acetylcholine receptor mediated diseases of the respiratory tract.Acetylcholine released from cholinergic neurons in the ...

Partially Saturated Tricyclic Compounds and Methods of Making and Using Same

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 2. The tricyclic compound of claim 1 , wherein X′ is selected from the group consisting of: —O—* claim 1 , —N(R)—* claim 1 , —C(RR)—C(RR)—* claim 1 , —C(R)═C(R)—* claim 1 , —O—C(RR)—* claim 1 , —N(R)—C(RR)—* claim 1 , —O—C(O)—* claim 1 , —N(R)—C(O)—* claim 1 , —N═C(R)—* and —O—C(RR)—C(RR)—*;{'sup': '+', 'wherein the and * indicate the attachment points of X′ as indicated in Formula I.'}3. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —NH—* claim 1 , —O—CH—* claim 1 , —NH—CH—* claim 1 , —N═CH—* and —CH═CH—*;{'sup': '+', 'wherein the and * indicate the attachment points of X′ as indicated in Formula I.'}4. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —O—* claim 1 , —N(R)—* claim 1 , —C(RR)—C(RR)—* claim 1 , —O—C(RR)—* claim 1 , —N(R)—C(RR)—* claim 1 , —O—C(O)—* claim 1 , —N(R)—C(O)—* claim 1 , and —O—C(RR)—C(RR)—*; wherein the and * indicate the attachment points of Xas indicated in Formula II.5. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —O—CH—* and —NH—CH—*; wherein the and * indicate the attachment points of Xas indicated in Formula II.6. The tricyclic compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , Rand Rare independently selected for each occurrence from the group consisting of hydrogen and methyl.7. The tricyclic compound of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , Rand Rare hydrogen.8. The tricyclic compound of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare independently selected for each occurrence from the group consisting of hydrogen claim 1 , fluorine claim 1 , cyano and Calkyl.9. The tricyclic compound of claim 7 , ...

IMIDAZOPYRIDINE COMPOUNDS

[Problem] 2. The compound or a salt thereof according to claim 1 , wherein{'sup': '1', 'Ais cyclohexyl, or phenyl optionally substituted with one or more F atoms,'}{'sup': '1', 'Ris H,'}{'sup': 2', '0, 'Ris R,'}{'sup': '3', 'Ris H,'}{'sup': '5', 'Ris H,'}{'sup': 4', '2', '3, 'Ris —Y-Aor A,'}{'sub': '1-10', 'sup': '2', 'Y is Calkylene optionally substituted with at least one group selected from Group G,'}{'sup': '2', 'sub': '2', 'Group Gis —COH and —OH,'}{'sup': '2', 'sub': '2', 'Ais H, cycloalkyl, pyridyl, or phenyl optionally substituted with a group selected from the group consisting of lower alkyl and —COH,'}{'sup': 3', '1', '1, 'Ais cycloalkyl selected from the group consisting of cyclopentyl, indanyl, dihydrocyclopentathienyl, dihydrocyclopentafuranyl, and dihydrocyclopentapyrrolyl, the above cycloalkyl is optionally substituted with at least one group selected from Group G, or piperidyl or pyrrolidinyl each optionally substituted with at least one group selected from Group G, and'}{'sup': 1', '0', '0', '0, 'sub': 2', '2', '2', '2', '2', '3', '3, 'Group Gis R, halogen, —COH, —OH, —COR, —CN, —NO, phenyl, —SO—NH, —SOH, and —SOR.'}4. The compound or a salt thereof according to claim 3 , wherein Ais 2 claim 3 ,6-difluorophenyl claim 3 , Ris methyl claim 3 , Ris a group represented by the formula (A) or the formula (B) claim 3 , X is —HC═CH— claim 3 , n is 1 claim 3 , Ris F claim 3 , and Ris —COH.6. The compound or a salt thereof according to claim 3 , wherein Ris methyl and Ris a group represented by the formula (C) or (D).7. The compound or a salt thereof according to claim 3 , wherein Ais cyclohexyl or 2 claim 3 ,6-difluorophenyl claim 3 , Ris methyl claim 3 , Ris A claim 3 , Ais a group represented by the formula (A) or the formula (B) claim 3 , X is —HC═CH— claim 3 , n is 1 claim 3 , Ris each H claim 3 , Ris H claim 3 , and Ris —COH.8. The compound or a salt thereof according to claim 3 , wherein Ris methyl and Ris a group represented by the formula (E).9. The ...

PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES

A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof. 17-. (canceled)9. The method of claim 8 , wherein B is NH.10. The method of claim 8 , wherein A is thiazolyl claim 8 , benzothiazolyl claim 8 , pyridyl claim 8 , isoxazolyl claim 8 , isoquinolinyl claim 8 , quinolyl claim 8 , benzothiadiazolyl claim 8 , thiadiazolyl claim 8 , pyrazolyl or pyrazinyl claim 8 , which is optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.11. The method of claim 8 , wherein A is thiazolyl or benzothiazolyl optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.12. The method of claim 8 , wherein A is C-Cheteroaryl substituted by at least one selected from the group consisting of chloro claim 8 , methyl claim 8 , ethyl claim 8 , propyl claim 8 , iso-propyl claim 8 , tert-butyl claim 8 , cyclopentyl claim 8 , phenyl claim 8 , chlorophenyl claim 8 , benzyl claim 8 , cyclohexyl and methoxy.13. The method of claim 8 , wherein A is selected from thiazolyl claim 8 , methylthiazolyl claim 8 , ethylthiazolyl claim 8 , propylthiazolyl claim 8 , iso-propylthiazolyl claim 8 , tert-butylthiazolyl claim 8 , cyclopentylthiazolyl claim 8 , cyclohexylthiazolyl claim 8 , phenylthiazolyl claim 8 , chlorophenylthiazolyl claim 8 , benzylthiazolyl claim 8 , chlorothiazolyl and dimethylthiazolyl.14. The method of claim 13 , wherein B is NH.15. The method of claim 8 , wherein the compound is selected from the group consisting of:N-(1-azabicyclo[ ...

TETRAHYDROISOQUINOLIN-1-ONE DERIVATIVE OR SALT THEREOF

To provide a pharmaceutical, in particular a compound which can be used as a therapeutic agent for irritable bowel syndrome (IBS). It was found that a tetrahydroisoquinolin-1-one derivative having an amide group at the 4-position or a pharmaceutically acceptable salt thereof has an excellent bombesin 2 (BB2) receptor antagonistic action. It is also found that the tetrahydroisoquinolin-1-one derivative is highly effective on bowel movement disorders. From the above, the tetrahydroisoquinolin-1-one derivative of the present invention is useful as a therapeutic agent for diseases associated with a BB2 receptor, in particular IBS. 17-. (canceled)9. The pharmaceutical composition of claim 8 , wherein Ris —N(R)-lower alkylene-(aryl or heteroaryl claim 8 , which may each be substituted) claim 8 , or —N(R)—O-lower alkylene-(aryl or heteroaryl claim 8 , which may each be substituted).10. The pharmaceutical composition of claim 9 , wherein Ris phenyl which may be substituted with halogen claim 9 , lower alkyl claim 9 , or —OR.11. The pharmaceutical composition of claim 9 , wherein Ris —H.12. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is a solid composition.13. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is a liquid composition.14. The pharmaceutical composition of claim 13 , wherein the liquid composition is for parenteral administration.15. The pharmaceutical composition of claim 13 , wherein the liquid composition is for oral administration.17. The compound of claim 16 , wherein Ris —N(R)-lower alkylene-(aryl or heteroaryl claim 16 , which may each be substituted) claim 16 , or —N(R)—O-lower alkylene-(aryl or heteroaryl claim 16 , which may each be substituted).18. The compound of claim 17 , wherein Ris (lower alkylene)-OH or substituted cycloalkyl claim 17 , wherein said lower alkylene may be substituted with a member selected from the group consisting of —OH and phenyl (which may be substituted ...

MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS

Methods of using Muscarinic Acetylcholine Receptor Antagonists are provided. 3. A compound according to selected from the group of:1-(2-{[(3-fluorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-bromophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-chlorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[bis(4-fluorophenyl)(hydroxy)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;4-{hydroxy[bis(3-methylphenyl)]methyl}-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-fluorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylcarbonyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(3-fluorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-{hydroxy[bis(4-methylphenyl)]methyl}-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-{3-[(methylsulfonyl)amino]propyl}-1-azoniabicyclo[2.2.2]octane bromide;4-[bis(3-fluorophenyl)(hydroxy)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(3-chlorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(di-2-thienyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-cyanophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(4-bromophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[bis(4-fluorophenyl)(hydroxy)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(4-fluorophenyl)oxy]propyl}-4-[ ...

CLASS OF BIFUNCTIONAL COMPOUNDS WITH QUANTERNARY AMMONIUM SALT STRUCTURE

The invention provides a class of compounds represented by formula (I), having bifunctional active quaternary ammonium salt structure of a β-adrenoreceptor agonist and an M receptor antagonist, a pharmaceutically acceptable salt, solvate, and optical isomer thereof. A pharmaceutical composition comprising such a compound with quaternary ammonium salt structure, a method for preparing such a compound with quaternary ammonium salt structure and an intermediate thereof, and uses thereof in treating pulmonary disorders are also provided. The compounds of the invention have high selectivity to the M receptor subtype, and have less adverse reaction and lower toxic and side effects in the treatment of pulmonary diseases such as COPD and asthma. 2. The compound according to claim 1 , or the pharmaceutically acceptable salt claim 1 , solvate claim 1 , optical isomer thereof claim 1 , wherein L is an unsubstituted phenyl claim 1 , pyridyl claim 1 , furyl or thienyl.3. The compound according to claim 1 , or the pharmaceutically acceptable salt claim 1 , solvate claim 1 , optical isomer thereof claim 1 , wherein W is unsubstituted (3-7C)cycloalkyl.4. The compound according to claim 3 , or the pharmaceutically acceptable salt claim 3 , solvate claim 3 , optical isomer thereof claim 3 , wherein W is cyclobutyl claim 3 , cyclopentyl or cyclohexyl.5. The compound according to claim 1 , or the pharmaceutically acceptable salt claim 1 , solvate claim 1 , optical isomer thereof claim 1 , wherein Rand Rare each independently selected from (1-1° C.)alkylene claim 1 , -(1-4C)alkyleneoxy claim 1 , alkyleneamido; and Ais independently selected from (6-10° C.)arylene claim 1 , wherein the arylene may be unsubstituted or substituted with 1-2 substituents independently selected from halogen claim 1 , (1-6C)alkyl claim 1 , (1-6C)alkoxy claim 1 , carboxy claim 1 , nitro claim 1 , cyano claim 1 , amido claim 1 , and ester group.6. The compound according to claim 1 , or the pharmaceutically ...

PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 144.-. (canceled)46. The tricyclic compound of claim 45 , wherein Ris selected from hydrogen or methyl.47. The tricyclic compound of claim 45 , wherein Ris selected from hydrogen or fluorine.48. The tricyclic compound of claim 45 , wherein Ris Calkenyl substituted by RRN—.49. The tricyclic compound of claim 45 , wherein Ris (Z)-3-(N claim 45 ,N-diethylamino)prop-1-enyl. This application is a continuation of U.S. patent application Ser. No. 15/014,524, filed Feb. 3, 2016; which is a continuation of U.S. patent application Ser. No. 14/116,023, filed Nov. 6, 2013; which is a national stage filing under U.S.C. §371 of PCT/US2012/036789, filed May 7, 2012; which claims priority to U.S. Provisional Patent Application 61/559,856, filed Nov. 15, 2011; and U.S. Provisional Patent Application 61/483,257, filed May 6, 2011; all of which are incorporated by reference in their entirety.Over 1.1 billion people worldwide are reported to be overweight. Obesity is estimated to affect over 90 million people in the United States alone. Twenty-five percent of the population in the United States over the age of twenty is considered clinically obese. While being overweight or obese presents problems (for example restriction of mobility, discomfort in tight spaces such as theater or airplane seats, social difficulties, etc.), these conditions, in particular clinical obesity, affect other aspects of health, i.e., diseases and other adverse health conditions associated with, exacerbated by, or precipitated by being overweight or obese. The estimated mortality from obesity-related conditions in the United States is over 300,000 annually (O'Brien et al. Amer J Surgery (2002) 184:4S-8S; and Hill et al. (1998) Science, ...

COT MODULATORS AND METHODS OF USE THEREOF

The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof. 2. The compound of claim 1 , wherein Ris hydrogen claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein m is 0 claim 1 , or a pharmaceutically acceptable salt thereof.7. The compound according to claim 1 , wherein Ris hydrogen claim 1 , halo claim 1 , —CN claim 1 , —S(O)—R claim 1 , —S(O)R claim 1 , —SON(R)(R) claim 1 , —C(O)R claim 1 , —C(O)N(R)(R) claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccycloalkyl claim 1 , aryl claim 1 , heterocyclyl claim 1 , or heteroaryl;{'sub': 1-9', '2-6', '2-6', '3-15, 'sup': '5', 'wherein each Calkyl, Calkenyl, Calkynyl, Ccycloalkyl, aryl, heterocyclyl, and heteroaryl may be optionally substituted with one to four Z, or a pharmaceutically acceptable salt thereof.'}8. The compound according to claim 1 , wherein Ris hydrogen claim 1 , halo claim 1 , —CN claim 1 , —C(O)R claim 1 , —S(O)R claim 1 , or heteroaryl claim 1 , or a pharmaceutically acceptable salt thereof.9. The compound according to claim 1 , wherein Ris hydrogen claim 1 , or a pharmaceutically acceptable salt thereof.10. The compound according to claim 1 , wherein Ris Calkyl claim 1 , Ccycloalkyl claim 1 , heterocyclyl claim 1 , aryl claim 1 , or heteroaryl; and said Calkyl claim 1 , Ccycloalkyl claim 1 , heterocyclyl claim 1 , aryl claim 1 , or heteroaryl may be optionally substituted with one to four substituents independently selected the group consisting of halo claim 1 , —CN claim 1 , —O—R claim 1 , —C(O)—R claim 1 , —C(O)O—R claim 1 , Calkyl claim 1 , and aryl claim 1 , or a pharmaceutically acceptable salt thereof.11. The compound according to claim 1 , wherein Ris Calkyl claim 1 , optionally substituted with one to four substituents independently selected the group consisting of halo claim 1 , —CN claim 1 , —O—R claim 1 , —C(O)O—R claim 1 , Calkyl claim 1 , and aryl claim 1 , or a ...

QUINUCLIDINES FOR MODULATING ALPHA 7 ACTIVITY

Provided are substituted quinuclidine compounds, pharmaceutical compositions comprising such compounds, and methods of modulating α7 nicotinic acetylcholine receptors and treating neurological disorders using such compounds. 2. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris C-Calkyl or C-Ccycloalkyl claim 1 , wherein the C-Calkyl or C-Ccycloalkyl is unsubstituted or substituted with 1 to 5 halo substituents.3. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris unsubstituted C-Calkyl.4. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —CH.5. The compound of claim 1 , or a salt thereof claim 1 , wherein R is C-Calkoxy claim 1 , which is unsubstituted or substituted with 1 to 5 halo substituents.6. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —OCH.7. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris bromo.8. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris hydrogen.9. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris C-Calkyl or C-Ccycloalkyl.10. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —CH.11. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris halo.12. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris fluoro or chloro.13. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris cyano.14. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —OR claim 1 , and Ris hydrogen or unsubstituted C-Calkyl.15. The compound of claim 14 , or a salt thereof claim 14 , wherein Ris —CH.16. The compound of claim 1 , or a salt thereof claim 1 , wherein R is —OR claim 1 , and Ris C-Calkyl substituted with C-Calkoxy.17. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris hydrogen.18. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris C-Calkyl or C-Ccycloalkyl.19. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —CH.20. The compound of claim 1 , or ...

CRYSTALLINE FORM OF (R)-7-CHLORO-N-(QUINUCLIDIN-3-YL)BENZO[B]THIOPHENE-2-CARBOXAMIDE HYDROCHLORIDE MONOHYDRATE

Crystalline Forms I and II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate and compositions, methods of manufacture and therapeutic uses thereof are described. 1. A crystalline Form II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate , characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at:i) one or both of 21.16 and 21.38±0.20 degrees when measured against an internal silicon standard; andii) at least four peaks selected from a group of peaks consisting of: 4.48, 9.00, 13.58, 15.62, 16.48, 19.02, 19.44, 22.46, and 25.00±0.20 degrees when measured against an internal silicon standard.2. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern claim 1 , wherein at least six peaks are selected from the group of peaks.3. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern claim 1 , wherein at least eight peaks are selected from the group of peaks.4. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern claim 1 , wherein all of the peaks are selected from the group of peaks.5. A pharmaceutical composition comprising the crystalline Form II of .6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Alzheimer's disease.7. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Schizophrenia.8. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Alzheimer's disease.9. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Schizophrenia.10. A pharmaceutical composition ...

SALTS OF AZA-BICYCLIC DI-ARYL ETHERS AND METHODS TO MAKE THEM OR THEIR PRECURSORS

The present invention relates to salts of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane, to methods for making them or their precursors, to pharmaceutical compositions comprising them, and to their use as medicaments. 1. A salt of (R)-3-(6-(4-methylphenyI)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane wherein said salt is the fumarate , maleate , chloride , phosphate , succinate , or malonate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane.2. The salt according to claim 1 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form.3. The salt according to claim 2 , wherein the salt is characterized by an XRPD pattern substantially the same as the XRPD pattern shown in .4. The salt according to claim 1 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form claim 1 , wherein the mean particle size of the crystals is at least 15 μm.5. The salt according to claim 2 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form claim 2 , and wherein the salt is in substantially pure form.6. The salt according to claim 2 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form claim 2 , and wherein the salt has a purity greater than 90 weight %.7. A method for the prevention claim 1 , treatment claim 1 , and/or delay of progression of a disease or condition claim 1 , in which nAChR α7 activation plays a role or is implicated claim 1 , in a subject in need of such treatment claim 1 , which comprises administering to such subject a therapeutically effective amount of a salt as defined in .8. A method for the prevention claim 1 , treatment claim 1 , and/or delay of progression of psychiatric or neurodegenerative ...

PYRIDAZINONE DERIVATIVES

Compounds of the formula (I), in which R, R, R, R, Rhave the meanings indicated in Claim , are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours. 127-. (canceled)29. A pharmaceutical composition according to claim 28 , which comprises a compound of formula I or a pharmaceutically acceptable solvate claim 28 , salt claim 28 , tautomer or stereoisomer thereof in an amount of 1 mg to 700 mg per unit dosage.30. A pharmaceutical composition according to claim 28 , which is in the form of a single dosage unit.31. A pharmaceutical composition according to claim 28 , which comprises a compound of formula I or a pharmaceutically acceptable salt thereof.32. A pharmaceutical composition according to claim 28 , wherein in the compound of formula I{'sup': 2', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '+', '−', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'sub': 2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'p', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n-', '2', '2', 'n', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n, 'claim-text': {'sup': '3', 'sub': '2', 'CH═CH—N(R)and/or ═O.'}, 'Rdenotes pyrimidinyl, which is monosubstituted by Hal, A, [C(R)]OR, N═CRN(R), CN, COOR, [C(R)]N(R), [C(R)]Het, O[C(R)]OR, O[C(R)]N(R), O[C(R)]C≡C[C(R)]N(R), O[C(R)]NO(R), O[C(R)]Het, NR[C(R)]N(R), NR[C(R)]Het, [C(R)]NHCO[C(R)]N(R), [C(R)]NHCO[C(R)]Het, CONR[C(R)]N(R), CONR[C(R)]NRCOOA, CONR[C(R)]OR, CONR[C(R)]Het, COHet, CH═CH—COOR,'}33. A pharmaceutical composition according to claim 28 , wherein in the compound of formula I{'sub': m', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n, 'sup': 3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'Ar denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by ...

NOVEL BENZYLAMINO SUBSTITUTED PYRIDOPYRIMIDINONES AND DERIVATIVES AS SOS1 INHIBITORS

The present invention encompasses compounds of formula (1) 2. A compound or salt according to claim 1 , wherein{'sup': 1', 'a1, 'Ris R;'}{'sup': a1', 'b1', 'c1, 'sub': 1-6', '1-6', '3-10', '4-10', '6-10', '1-6', '1-6', '3-10', '4-10', '6-10, 'Ris selected from the group consisting of Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl, wherein the Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl are all optionally substituted by one or more, identical or different Rand/or R;'}{'sup': b1', 'c1', 'c1', 'c1', 'c1', 'c1', 'c1', 'c1, 'each Ris independently selected from the group consisting of —OR, —NRR, halogen, —CN, —C(O)R, —C(O)ORand —C(O)NRR;'}{'sup': c1', 'd1', 'e1, 'sub': 1-6', '1-6', '3-10', '4-10', '6-10', '1-6', '1-6', '3-10', '4-10', '6-10, 'each Ris independently selected from the group consisting of hydrogen, Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl, wherein the Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl are all optionally substituted by one or more, identical or different Rand/or R;'}{'sup': d1', 'e1', 'e', 'e1', 'e1', 'e1', 'e1', 'e1, 'each Ris independently selected from the group consisting of —OR, —NRR, halogen, —CN, —C(O)R, —C(O)ORand —C(O)NRR;'}{'sup': 'e1', 'sub': 1-6', '1-6', '3-10', '4-10', '6-10, 'each Ris independently selected from the group consisting of hydrogen, Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl.'}3. A compound or salt according to claim 2 , wherein{'sup': 1', 'a1, 'Ris R;'}{'sup': a1', 'b1', 'c1, 'sub': 1-6', '1-6', '3-10', '4-10', '1-6', '1-6', '3-10', '4-10, 'Ris selected from the group consisting of Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl and 5-10 membered heteroaryl, ...

AMIDES OF ACETIC AND PROPIONIC ACIDS

The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory. 110-. (canceled)11: A method of improving perception , concentration , learning or memory , after a cognitive impairment in a patient in need thereof , comprising administering to the patient a compound selected from the group consisting of:2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-bromo-1-benzothien-2-yl)acetamide hydrochloride;2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(6-bromo-1-benzothien-2-yl)acetamide hydrochloride;2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-quinolinyl)acetamide hydrochloride;2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(2-naphthyl)acetamide hydrochloride; and2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(8-nitro-2-naphthyl)acetamide hydrochloride.12: The method of claim 11 , wherein the cognitive impairment is mild cognitive impairment or Alzheimer's disease.13: The method of claim 11 , wherein the cognitive impairment is schizophrenia or schizophrenia with dementia.14: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-bromo-1-benzothien-2-yl)acetamide hydrochloride.15: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(6-bromo-1-benzothien-2-yl)acetamide hydrochloride.16: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-quinolinyl)acetamide hydrochloride.17: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(2-naphthyl)acetamide hydrochloride.18: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(8-nitro-2-naphthyl)acetamide hydrochloride.20: The method of claim 19 , wherein the cognitive impairment is mild cognitive impairment or Alzheimer's disease.21: The method of claim 19 , wherein the cognitive impairment is schizophrenia or schizophrenia with ...

Methods of Treating an Overweight or Obese Subject

The disclosure herein generally relates to methods of treating an overweight or obese condition, and overweight- or obesity-related conditions. In one embodiment, the disclosure provides a method of treating an overweight or obese condition involving administering to the subject in need thereof, an amount of a pharmaceutical composition including a MetAP-2 inhibitory compound, or a salt, ester, or prodrug thereof, effective to result in weight loss in the subject. 3. The method of claim 1 , wherein the subject has a Body Mass Index measurement selected from the group consisting of: at least about 25 kg/m claim 1 , at least about 30 kg/m claim 1 , and at least about 40 kg/m.412.-. (canceled)14. (canceled) This application is a continuation of U.S. Ser. No. 14/802,473, filed Jul. 17, 2015, which is a continuation of U.S. Ser. No. 14/616,002, filed Feb. 6, 2015, which is a continuation of U.S. Ser. No. 13/133,062, filed Sep. 22, 2011, (now abandoned) which is a national phase filing under 35 U.S.C. §371 of PCT/US2009/066809, filed Dec. 4, 2009, which claims priority to U.S. provisional applications U.S. Ser. No. 61/119,875 filed Dec. 4, 2008, U.S. Ser. No. 61/119,881 filed Dec. 4, 2008, U.S. Ser. No. 61/119,884 filed Dec. 4, 2008, U.S. Ser. No. 61/119,886 filed Dec. 4, 2008, U.S. Ser. No. 61/275,688 filed Aug. 3, 2009, and U.S. Ser. No. 61/260,194 filed Nov. 11, 2009, each application of which is hereby incorporated by reference in its entirety.Obesity is a complex medical disorder of appetite regulation and metabolism resulting in excessive accumulation of adipose tissue mass. Typically defined as a body mass index (BMI) of 30 kg/mor more, obesity is a world-wide public health concern that is associated with cardiovascular disease, diabetes, certain cancers, respiratory complications, osteoarthritis, gallbladder disease, decreased life expectancy, and work disability. The primary goals of obesity therapy are to reduce excess body weight, improve or prevent obesity- ...

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

Biologically active glutarimide derivatives of the following formula: 1. A compound having the following formula:or a pharmaceutically acceptable salt thereof. This application is a continuation of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published as WO 2014/168522 A1), filed Apr. 10, 2014, which claims priority to Application RU 2013116826, filed Apr. 12, 2013. Benefit of the filing date of each of these prior applications is hereby claimed. Each of these prior applications is hereby incorporated by reference in its entirety.The invention relates to novel biologically active compounds, in particular to glutarimide derivatives or pharmaceutically acceptable salt thereof, to use thereof as agents for the prevention and treatment of upper respiratory tract diseases, and to methods for preparing said compounds.Upper respiratory tract chronic diseases are the most common diseases in children and adults throughout the world. The upper respiratory tract chronic diseases include, in particular, rhinosinusitis.Rhinosinusitis is an inflammation of the mucous tunic of the nose and paranasal sinuses (PNS) and is the most actual problem in the otorhinoryngology (Fokkens W. J., Lund V. J., Mullol J. et al., European Position Paper on Rhinosinusitis and Nasal Polyps. Rhinology 2007; 45; 20:1-139). A cause of rhinosinusitis almost always is mucous congestion, blockage of natural ostia of the PNS, and a disturbance in their ventilation when the mechanism of mucociliary clearance suffers since said mechanism is an important primary innate mechanism protecting the respiratory tract from damaging action of inhaled pollutions, allergens and causal organisms.Acute rhinosinusitis is a frequent complication of an acute respiratory viral infection (ARVI).Today, the rhinosinusitis therapy starts with administration of corticosteroids since they have ...

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

A medicament or pharmaceutical composition for the treatment of a respiratory tract disease, which is a compound having the following formula: 2. The medicament of claim 1 , wherein the respiratory tract disease is rhinosinusitis.3. The medicament of claim 1 , wherein the respiratory tract disease is caused by an RNA-comprising virus.4. The medicament of claim 3 , wherein the virus is selected from the group consisting of rhinovirus claim 3 , Coxsackie virus claim 3 , respiratory syncytial virus claim 3 , and influenza virus.5. The medicament of claim 1 , wherein the disease is exacerbations of bronchitis and mucoviscidosis claim 1 , which are caused by rhinovirus claim 1 , influenza virus and/or respiratory syncytial virus.7. The pharmaceutical composition of claim 6 , wherein the respiratory tract disease is rhinosinusitis.8. The pharmaceutical composition of claim 6 , wherein the respiratory tract disease is caused by an RNA-comprising virus.9. The pharmaceutical composition of claim 8 , wherein the virus is selected from the group consisting of rhinovirus claim 8 , Coxsackie virus claim 8 , respiratory syncytial virus claim 8 , and influenza.10. The pharmaceutical composition of claim 6 , wherein the disease is exacerbations of bronchitis and mucoviscidosis claim 6 , which are caused by rhinovirus claim 6 , influenza virus and/or respiratory syncytial virus.12. The method of claim 11 , wherein the respiratory tract disease is rhinosinusitis.13. The method of claim 11 , wherein the respiratory tract disease is caused by an RNA-comprising virus.14. The method of claim 13 , wherein the virus is selected from the group consisting of rhinovirus claim 13 , Coxsackie virus claim 13 , respiratory syncytial virus claim 13 , and influenza virus. This application is a continuation of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published ...

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

A medicament or pharmaceutical composition for the treatment of exacerbations of asthma and chronic obstructive pulmonary disease, which is a compound having the following formula: This application is a continuation of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published as WO 2014/168522 A1), filed Apr. 10, 2014, which claims priority to Application RU 2013116826, filed Apr. 12, 2013. Benefit of the filing date of each of these prior applications is hereby claimed. Each of these prior applications is hereby incorporated by reference in its entirety.The invention relates to novel biologically active compounds, in particular to glutarimide derivatives or pharmaceutically acceptable salt thereof, to use thereof as agents for the prevention and treatment of upper respiratory tract diseases, and to methods for preparing said compounds.Upper respiratory tract chronic diseases are the most common diseases in children and adults throughout the world. The upper respiratory tract chronic diseases include, in particular, rhinosinusitis.Rhinosinusitis is an inflammation of the mucous tunic of the nose and paranasal sinuses (PNS) and is the most actual problem in the otorhinoryngology (Fokkens W. J., Lund V. J., Mullol J. et al., European Position Paper on Rhinosinusitis and Nasal Polyps. Rhinology 2007; 45; 20:1-139). A cause of rhinosinusitis almost always is mucous congestion, blockage of natural ostia of the PNS, and a disturbance in their ventilation when the mechanism of mucociliary clearance suffers since said mechanism is an important primary innate mechanism protecting the respiratory tract from damaging action of inhaled pollutions, allergens and causal organisms.Acute rhinosinusitis is a frequent complication of an acute respiratory viral infection (ARVI).Today, the rhinosinusitis therapy starts with administration of ...

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

A method for preparing a compound of formula I: 2. The method of claim 1 , wherein the dehydrating agent is glutaric anhydride claim 1 , and the method is performed under heating in an organic solvent.3. The method of wherein the organic solvent is dimethylformamide4. The method of claim 1 , wherein the dehydrating agent is propionic anhydride claim 1 , and the method is performed under heating in an organic solvent.5. The method of wherein the organic solvent is toluene6. The process of claim 4 , wherein the method is performed with addition of sodium acetate.7. The method of claim 1 , wherein the dehydrating agent is acetic anhydride claim 1 , and the method is performed under heating in an organic solvent.8. The method of wherein the organic solvent is dioxane.9. The process of claim 7 , wherein the method is performed with addition of sodium acetate.10. The method of claim 1 , wherein the dehydrating agent is acetic acid chloroanhydride claim 1 , and the method is performed under heating in an organic solvent.11. The method of wherein the organic solvent is acetic acid12. The method of claim 10 , wherein the dehydrating agent and the solvent are acetic acid anhydride claim 10 , and the method is performed at 90-100° C.13. The method of claim 1 , wherein the dehydrating agent is carbonyldiimidazole. This application is a divisional of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published as WO 2014/168522 A1), filed Apr. 10, 2014, which claims priority to Application RU 2013116826, filed Apr. 12, 2013. Benefit of the filing date of each of these prior applications is hereby claimed. Each of these prior applications is hereby incorporated by reference in its entirety.The invention relates to novel biologically active compounds, in particular to glutarimide derivatives or pharmaceutically acceptable salt thereof, to use thereof ...

Aminoester derivatives

Compounds of formula (I) are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of diseases of the respiratory tract characterized by airway obstruction.

Amides of acetic and propionic acids

The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory.

METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease. 1232-. (canceled)234. The compound of claim 233 , wherein Ris hydrogen.235. The compound of claim 233 , wherein Ris straight chain alkyl.236. The compound of claim 233 , wherein Ris t-butyl.237. The compound of claim 233 , wherein Ris carbocyclic.238. The compound of claim 233 , wherein Ris C-Cbicycloalkyl.239. The compound of claim 233 , wherein said bicyclic fused ring group is indolyl.240. The compound of claim 233 , wherein Lis CHCHor absent.251. A method of treating or preventing an amyloid-related disease in a subject comprising administering to a subject in need thereof a compound of in an amount effective to treat or prevent an amyloid related disease.252. The method according to claim 251 , wherein said amyloid-related disease is Alzheimer's disease claim 251 , cerebral amyloid angiopathy claim 251 , inclusion body myositis claim 251 , macular degeneration claim 251 , MCI claim 251 , or Down's syndrome.253. The method according to claim 251 , wherein amyloid fibril formation or deposition claim 251 , neurodegeneration claim 251 , microglial inflammatory response claim 251 , or cellular toxicity is reduced or inhibited upon administration of said compound.254. The method according to claim 251 , wherein said amyloid-related disease is diabetes claim 251 , AA amyloidosis claim 251 , AL amyloidosis claim 251 , or hemodialysis related amyloidosis (βM).255. The method of claim 251 , wherein said subject has Alzheimer's disease claim 251 , Mild Cognitive Impairment claim 251 , or cerebral amyloid angiopathy claim 251 , and stabilization of cognitive function claim 251 , prevention of a further decrease in cognitive function claim 251 , or prevention claim 251 , slowing claim 251 , or stopping of disease progression occurs in said patient upon administration.256. A method for inhibiting amyloid deposition in a subject comprising administering ...

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

A compound having the following formula: 2. A medicament for the treatment of a respiratory tract disease claim 1 , which is a compound or a pharmaceutically acceptable salt thereof of .3. The medicament of claim 2 , wherein the respiratory tract disease is rhinosinusitis.4. The medicament of claim 2 , wherein the respiratory tract disease is caused by an RNA-comprising virus.5. The medicament of claim 4 , wherein the virus is selected from the group consisting of rhinovirus claim 4 , Coxsackie virus claim 4 , and influenza virus.6. The medicament of claim 2 , wherein the disease is exacerbations of asthma claim 2 , chronic obstructive pulmonary disease claim 2 , bronchitis and mucoviscidosis claim 2 , which are caused by rhinovirus claim 2 , influenza virus and/or respiratory syncytial virus.7. A pharmaceutical composition for the treatment of a respiratory tract disease claim 1 , comprising an effective amount of a compound or a pharmaceutically acceptable salt thereof of claim 1 , and a pharmaceutically acceptable carrier.8. The pharmaceutical composition of claim 7 , wherein the respiratory tract disease is rhinosinusitis.9. The pharmaceutical composition of claim 7 , wherein the respiratory tract disease is caused by an RNA-comprising virus.10. The pharmaceutical composition of claim 9 , wherein the virus is selected from the group consisting of rhinovirus claim 9 , Coxsackie virus claim 9 , and influenza.11. The pharmaceutical composition of claim 7 , wherein the disease is exacerbations of asthma claim 7 , chronic obstructive pulmonary disease claim 7 , bronchitis and mucoviscidosis claim 7 , which are caused by rhinovirus claim 7 , influenza virus and/or respiratory syncytial virus.12. A method of treating a respiratory tract disease claim 1 , comprising administering to a patient an effective amount of a compound or a pharmaceutically acceptable salt thereof of .13. The method of claim 12 , wherein the respiratory tract disease is rhinosinusitis.14. The ...

QUATERNARY AMMONIUM SALTS AS INHIBITORS OF TRIMETHYLAMINE PRODUCTION

Provided are compounds that can inhibit pathogenic, bacterial metabolite production and conjugates of the same. Also provided are pharmaceutical compositions comprising the same and methods of using the same. 5. The compound of claim 4 , wherein Ris Calkyl substituted with —O-(acylated sugar) and is optionally further substituted with oxo.6. The compound of or claim 4 , wherein Ris methyl.7. The compound of any one of claim 4 , claim 4 , and claim 4 , wherein Ris Calkyl.8. The compound of any one of - claim 4 , wherein Ris propargyl.9. The compound of claim 4 , wherein{'sup': '1', 'sub': '2-6', 'Ris Calkyl substituted with —O-(acylated sugar) and is optionally further substituted with oxo;'}{'sup': '2', 'Ris methyl;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl; and'}{'sup': '4', 'Ris propargyl.'}10. The compound of claim 4 , wherein{'sup': '1', 'sub': '2-6', 'Ris Calkyl substituted with isosorbide and is optionally further substituted with oxo and/or methene;'}{'sup': '2', 'Ris methyl;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl; and'}{'sup': '4', 'Ris propargyl.'}13. The compound of claim 4 , wherein{'sup': '1', 'sub': 3-4', '1-2, 'Ris Ccycloalkyl Calkyl;'}{'sup': '2', 'sub': '2-6', 'Ris Calkyl optionally substituted with one or two hydroxyl, oxo, and —O-(acylated sugar);'}{'sup': 1', '2', 's', 's, 'sub': 2', 'n, 'or Rand R, together with the nitrogen atom to which both are attached, combine to form a 4- or 5-membered heterocyclic ring optionally substituted with ethynyl or —(CH)—ORor an acylated sugar, wherein n is 0 or 1, Ris hydrogen or an acylated sugar;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl optionally substituted with a halogen or hydroxyl; and'}{'sup': '4', 'sub': '1-6', 'Ris Calkyl or propargyl.'}14. The compound of claim 13 , wherein Ris Ccycloalkyl Calkyl.15. The compound of or claim 13 , wherein Ris Calkyl optionally substituted with one or two hydroxyl groups.16. The compound of claim 13 , wherein Rand R claim 13 , together with the nitrogen atom to which both ...

Substituted Pyrazolo [1,5-A] Pyrimidine Compounds as TRK Kinase Inhibitors

Compounds of Formula I: 2. The method of claim 1 , wherein:{'sup': '1', 'Ris H or -(1-6C alkyl);'}{'sup': 2', '1', '1', '2', '2', '1, 'sub': 2', '2', '2', '2', '2, 'Ris H, -(1-6C)alkyl, -(1-6C)fluoroalkyl, -(1-6C)hydroxyalkyl, -(2-6C)dihydroxyalkyl, -(1-6C alkyl)CN, -(1-6C alkyl)SONH, -(1-6C alkyl)NHSO(1-3C alkyl), -(1-6C alkyl)NH, -(1-6C alkyl)NH(1-4C alkyl), -(1-6C alkyl)N(1-4C alkyl), -(1-6C alkyl)hetCyc, -(1-6C alkyl)hetAr, hetAr, hetCyc, —O(1-6C alkyl), —O(3-6C cycloalkyl), Cyc, or a bridged 7-membered cycloalkyl ring,'}{'sup': 1', '2, 'sub': 2', '2, 'or NRRforms a 4-6 membered azacyclic ring optionally substituted with one or more substituents independently selected from -(1-6C)alkyl, —OH, —COH and -(1-3C alkyl)COH;'}{'sup': 1', '1, 'hetCycis a 5-6 membered heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O, wherein hetCycis optionally substituted with oxo;'}{'sup': 2', '2, 'sub': 2', '2', '2, 'hetCycis a 6 membered carbon-linked heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O, wherein hetCycis optionally substituted with F, SONH, or SO(1-3C alkyl);'}{'sup': '1', 'hetAris a 5-membered heteroaryl ring having 1-2 ring heteroatoms independently selected from N and O and optionally substituted with -(1-4C)alkyl;'}{'sup': '2', 'hetAris a 5-6 membered heteroaryl ring having 1-2 ring nitrogen atoms and optionally substituted with one or more substituents independently selected from -(1-4C)alkyl;'}{'sup': '1', 'sub': '2', 'Cycis 3-6 membered cycloalkyl ring which is optionally substituted with one or more substituents independently selected from -(1-4C alkyl), —OH, —OMe, —COH and -(1-4C alkyl)OH;'}{'sub': 3', '2, 'sup': '3', 'Y is (i) phenyl optionally substituted with one or more substituents independently selected from halogen, -(1-4C)alkoxy, —CF—CHF, —O(1-4C alkyl)hetCycand —O(1-4C alkyl)O(1-3C alkyl), or (ii) a 5-6 membered heteroaryl ring having a ring heteroatom selected from N and S, wherein said ...

DIAZABICYCLO[3.3.1]NONANES, METHODS OF SYNTHESIS, AND USES THEREOF

The present invention relates to compounds that bind to and modulate the activity of neuronal nicotinic acetylcholine receptors, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central nervous system (CNS). 2. (canceled)3. A method for treatment of central nervous system disorders and dysfunctions claim 1 , comprising administering to a mammal in need of such treatment claim 1 , a therapeutically effective amount of the compound according to .4. The method of claim 3 , wherein the disorder is selected from the group consisting of age-associated memory impairment claim 3 , mild cognitive impairment claim 3 , pre-senile dementia claim 3 , early onset Alzheimer's disease claim 3 , senile dementia claim 3 , dementia of the Alzheimer's type claim 3 , Lewy body dementia claim 3 , vascular dementia claim 3 , Alzheimer's disease claim 3 , stroke claim 3 , AIDS dementia complex claim 3 , attention deficit disorder claim 3 , attention deficit hyperactivity disorder claim 3 , dyslexia claim 3 , schizophrenia claim 3 , schizophreniform disorder claim 3 , schizoaffective disorder claim 3 , cognitive deficits in schizophrenia claim 3 , and cognitive dysfunction in schizophrenia.5. The method of claim 4 , wherein the disorder is selected from the group consisting of mild to moderate dementia of the Alzheimer's type claim 4 , attention deficit disorder claim 4 , attention deficit hyperactivity disorder claim 4 , mild cognitive impairment claim 4 , age-associated memory impairment claim 4 , cognitive deficits in schizophrenia claim 4 , and cognitive dysfunction in schizophrenia.6. A pharmaceutical composition comprising a compound according to claim 1 , and one or more pharmaceutically acceptable carrier.7. (canceled)8. A method of treating inflammation claim 1 , the inflammatory ...

METHOD OF PREPARING GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer. 122.-. (canceled)24. (canceled) The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.Glucosylceramide synthase (GCS) is a pivotal enzyme which catalyzes the initial glycosylation step in the biosynthesis of glucosylceramide-base glycosphingolipids (GSLs) namely via the pivotal transfer of glucose from UDP-glucose (UDP-Glc) to ceramide to form glucosylceramide. GCS is a transmembrane, type III integral protein localized in the cis/medial Golgi. Glycosphingolipids (GSLs) are believed to be integral for the dynamics of many cell membrane events, including cellular interactions, signaling and trafficking. Synthesis of GSL structures has been shown (see, Yamashita et al., Proc. Natl. Acad. Sci. USA 1999, 96(16), 9142-9147) to be essential for embryonic development and for the differentiation of some tissues. Ceramide plays a central role in sphingolipid metabolism and downregulation of GCS activity has been shown to have marked effects on the sphingolipid pattern with diminished expression of glycosphingolipids. Sphingolipids (SLs) have a biomodulatory role in physiological as well as pathological cardiovascular conditions. In particular, sphingolipids and their regulating enzymes appear to play a role in adaptive responses to chronic hypoxia in the neonatal rat heart (see, El Alwanit et al., Prostaglandins & Other Lipid Mediators 2005, 78(1-4), 249-263).GCS inhibitors have been proposed for the treatment of a variety of diseases (see for example, WO2005068426). Such treatments include ...

METHOD OF PREPARING GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer. 4. A method according to , or , wherein n is 1; t is 0; y is 1 and z is 1.5. A method according to claim 4 , wherein Xis CRR.6. A method according to claim 5 , wherein Rand Rare each methyl.7. A method according to claim 6 , wherein Ais (C-C)heteroaryl.8. A method according to claim 7 , wherein Ais thiophene claim 7 , thiazole claim 7 , isothiazole claim 7 , furane claim 7 , oxazole claim 7 , isoxazole claim 7 , pyrrole claim 7 , imidazole claim 7 , pyrazole claim 7 , triazole claim 7 , pyridine claim 7 , pymiridine claim 7 , pyridazine claim 7 , indole claim 7 , benzotiazole claim 7 , benzoisoxazole claim 7 , benzopyrazole claim 7 , benzoimidazole claim 7 , benzofuran claim 7 , benzooxazole or benzoisoxazole.9. A method according to claim 8 , wherein Ais thiazole.10. A method according to claim 9 , wherein Ris H.11. A method according to claim 10 , wherein Xis a direct bond.12. A method according to claim 11 , wherein Ais (C-C)aryl.13. A method according to claim 12 , wherein Ais phenyl.14. A method according to claim 13 , wherein the phenyl group is substituted by halo.15. A method according to claim 14 , wherein the halo group is fluoro.16. A method according to claim 15 , wherein Ris hydrogen. The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.Glucosylceramide synthase (GCS) is a pivotal enzyme which catalyzes the initial glycosylation step in the biosynthesis of glucosylceramide-base glycosphingolipids (GSLs) namely via the pivotal transfer of glucose from UDP-glucose (UDP-Glc) to ...

HETEROARYL CARBOXAMIDES

The invention relates to novel heteroaryl carboxamides, processes for their preparation, and their use for producing medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning and/or memory. 19-. (canceled)10: A method of treating a cognitive impairment in a patient in need thereof , comprising administering to the patient a compound selected from the group consisting of:N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenazinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-7-quinolinecarboxamide hydrochloride;N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl]-2-propyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-propyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-6-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-7-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-6-quinolinecarboxamide; andN-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-7-quinolinecarboxamide;or a salt thereof.11: The method of claim 10 , wherein the cognitive impairment is Alzheimer's disease.12: The method of claim 10 , wherein the cognitive impairment is schizophrenia.13: The method of claim 10 , wherein the method improves perception claim 10 , concentration claim 10 , learning claim 10 , or memory.14: A method of treating a cognitive impairment in a patient in need thereof claim 10 , ...

(2S,3R)-N-2-3-PYRIDINYLMETHYL-1-AZABICYCLO 2.2.2 OCT-3-YL BENZOFURAN-2-CARBOXAMIDE, NOVEL SALT FORMS, AND METHODS OF USE THEREOF

The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central and autonomic nervous systems. 1. A method for treating a neurodegenerative disorder comprising administering a compound (2S ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide or a pharmaceutically acceptable salt thereof , substantially free of (2S ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , and pharmaceutically acceptable salts thereof.2. The method of claim 1 , wherein the treatment is for dementia.3. The method of claim 1 , wherein the treatment is for ataxia. The present invention is a continuation of U.S. patent application Ser. No. 13/947,157 filed Jul. 22, 2013, which is a continuation of U.S. patent application Ser. No. 13/116,080, filed May 26, 2011, now U.S. Pat. No. 8,541,446, issued Sep. 24, 2013, which is a continuation of U.S. patent application Ser. No. 12/184,312, filed Aug. 1, 2008, now U.S. Pat. No. 7,981,906 issued Jul. 19, 2011, which claims benefit to U.S. Provisional Application Nos. 60/971,654, filed Sep. 12, 2007, 60/953,610, filed Aug. 2, 2007, 60/953,613, filed Aug. 2, 2007, and 60/953,614 filed Aug. 2, 2007, each of which is incorporated herein by reference in its entirety.The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated ...

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 1188-. (canceled)190. The process of claim 189 , wherein the suitable conditions to form an amine comprise reacting the compound of formula 27 under Buchwald-Hartwig amination conditions.192. The process of claim 191 , wherein suitable halogen exchange conditions comprise reacting the compound of formula 18 with potassium fluoride in the presence of an aprotic solvent and a phase transfer catalyst.193. The process of claim 192 , wherein the aprotic solvent is independently selected from DMSO claim 192 , DMF claim 192 , and sulfolane.194. The process of claim 192 , wherein the phase transfer catalyst is MeNCl.195. The process of claim 191 , wherein suitable displacement conditions comprise reacting the compound of formula 32 with a compound of formula 22 in the presence of a base.196. The process of claim 195 , wherein the base is an aliphatic amine.197. The process of claim 196 , wherein the aliphatic amine is DIPEA.199. The process of claim 198 , wherein suitable halogenation conditions comprise 1) reacting the compound of formula 31 with a base to generate an anion; and 2) reacting the anion with a chlorinating agent.200. The process of claim 199 , wherein the base is LDA.201. The process of claim 199 , wherein the chlorinating agent is 1 claim 199 ,1 claim 199 ,1 claim ...

HETEROCYCLIC COMPOUND AND USE THEREOF

Compounds represented by the formulas 34-. (canceled)7. (canceled)920-. (canceled)21. 1-(2-Fluorophenyl)-5-(4-methoxybutyl)-N-(2-methylpropyl)-N-[(3S ,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-1 ,2 ,3-triazole-4-carboxamide or a salt thereof.2231-. (canceled) The present invention relates to a heterocyclic compound and the like, which has a superior renin inhibitory activity and is useful as an agent for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension, and the like.Hypertension is one of representative lifestyle-related diseases. Hypertension which is left untreated for long time lays a heavy burden on the cardiovascular system and results in arteriosclerosis to progress, thus causing various disorders in important organs, such as cerebral hemorrhage, cerebral infarction, cardiac failure, angina pectoris, myocardial infarction, renal failure and the like. Accordingly, the purpose of treating hypertension lies not only in lowering the blood pressure, but also in improving and/or preventing disorders in important organs including brain, heart and kidney, by controlling the blood pressure. As a method of treating hypertension, there are available fundamental treatments based on improvement in the lifestyle, such as dietetic therapy, exercise therapy and the like, as well as an attempt to control the blood pressure by positive pharmaceutical intervention.The renin-angiotensin (RA) system is a system of biosynthesis of angiotensin II (AII), which is a major vasopressor factor, and takes an important role in the control of the blood pressure and the amount of body fluid. AII exhibits a strong vasoconstrictive effect brought by the intervention of AII receptors on the cellular membrane, thus raising the blood pressure, and also promotes cellular propagation or production of extracellular matrix by directly acting on the AII receptors in the cardiac cells or renal cells. Therefore, drugs inhibiting increase in the ...

NOVEL DISUBSTITUTED 1, 2, 4-TRIAZINE COMPOUND

This invention provides a novel disubstituted 1,2,4-triazine compound or a pharmaceutically acceptable salt thereof, which has an aldosterone synthetase inhibitory activity and is useful for preventing and/or treating various diseases or conditions associated with aldosterone; a method for preparing it; use of it; as well as a pharmaceutical composition comprising it as an active ingredient. A compound of the general formula [I]: 2. The compound according to claim 1 , [{'sup': '1', 'a substituent of (1) a cycloalkyl group which may be substituted, (2) an aryl group which may be partially hydrogenated and may be substituted, and (3) a heteroaryl group which may be partially hydrogenated and may be substituted, represented by ring Ain the above formula (A-1) is 1-3 groups selected independently from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkoxy group, and an alkylenedioxy group which may be substituted with 1-2 halogen atoms,'}, 'an aryl moiety in the aryl group which may be partially hydrogenated and may be substituted is 6- to 10-membered monocyclic or bicyclic aryl,', 'a heteroaryl moiety in the heteroaryl group which may be partially hydrogenated and may be substituted is 5- to 10-membered monocyclic or bicyclic heteroaryl which contains 1-2 heteroatoms selected independently from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom;', {'sup': '2', 'ring Ain the above formula (A-2) is a 6- to 10-membered monocyclic or bicyclic aryl group which may be substituted with (a) a cycloalkyl group, or (b) a halogen atom,'}, {'sup': '1', 'Qis a single bond, an oxygen atom, or —NH—;'}, {'sup': 'B', 'Ris'}, '(a) a monocyclic cycloalkyl group,', '(b) an isoindolinyl group,', '(c) a group represented by the above formula (B-1):', {'sup': '1', 'wherein ring Aris a 6- to 10-membered monocyclic or bicyclic aryl group,'}, '(d) a group represented by the above formula (B-2):', {'sup': ...

Oxaspiro[2.5]Octane Derivatives and Analogs

The invention provides oxaspiro[2.5]octane derivatives and analogs, methods for preparation thereof, intermediates thereto, pharmaceutical compositions, and uses thereof in the treatment of various disorders and conditions, such as overweight and obesity. 4. The compound of claim 1 , wherein Ris Cstraight saturated alkyl.5. The compound of claim 1 , wherein Ris selected from the group consisting of Cstraight saturated alkyl or Cstraight saturated alkyl.6. The compound of claim 1 , wherein Ris Calkylene substituted on the terminal end by —C(O)OH claim 1 , —C(O)—O-Me claim 1 , or C(O)-Et.8. A pharmaceutically acceptable composition comprising a compound of and a pharmaceutically acceptable excipient.9. A method of treating and/or controlling obesity claim 1 , comprising administering to a patient in need thereof an effective amount of the compound of .10. The method of claim 9 , wherein the patient is a human.11. The method of claim 10 , wherein the patient has a body mass index greater than or equal to about 25 kg/mbefore the administration.12. The method of claim 1 , wherein after administration claim 1 , thioredoxin 1 is not significantly present in the testes of male patient.14. The compound of claim 13 , wherein Z is C. This application is a continuation of U.S. patent application Ser. No. 14/003,906, filed Oct. 29, 2014, which is a national stage filing under U.S.C. §371 of PCT/US2012/028068, filed Mar. 7, 2012, which claims priority to U.S. Provisional Patent Application No. 61/450,301 filed Mar. 8, 2011, all of which are hereby incorporated by reference in their entirety.Over 1.1 billion people worldwide are reported to be overweight. Obesity is estimated to affect over 90 million people in the United States alone. Twenty-five percent of the population in the United States over the age of twenty is considered clinically obese. While being overweight or obese presents problems (for example restriction of mobility, discomfort in tight spaces such as theater or ...

Geminal Substituted Aminobenzisoxazole Compounds as Agonists of Alpha7-Nicotinic Acetylcholine Receptors

The present invention relates to novel geminal substituted aminobenzisoxazole compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom. 2. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , or halogen radical.35-. (canceled)6. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , or halogen radical.713-. (canceled)14. The compound of claim 1 , wherein Rindependently represents —F claim 1 , —Cl claim 1 , —Br claim 1 , —CN claim 1 , —CH claim 1 , —CHCH claim 1 , cyclopropyl radical claim 1 , —CHF claim 1 , —CHF claim 1 , —CF claim 1 , —CHCF claim 1 , —OCH claim 1 , —OCHCH claim 1 , —OCH(CH) claim 1 , —O-cyclopropyl claim 1 , or —OCF.15. (canceled)16. The compound of claim 1 , wherein Rindependently represents —F claim 1 , —Cl claim 1 , —CH claim 1 , or —OCH.1718-. (canceled)19. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , —F claim 1 , —Cl claim 1 , —CN claim 1 , —CH claim 1 , —CH(CH) claim 1 , cyclopropyl radical claim 1 , cyclobutyl radical claim 1 , —CHF claim 1 , —CHF claim 1 , —CF claim 1 , —CHCF claim 1 , —OCH claim 1 , —OCHCH claim 1 , —OCH(CH) claim 1 , —O-cyclopropyl claim 1 , —OCF claim 1 , or —OCHCF.20. (canceled)21. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , —F claim 1 , —Cl claim 1 , —CH claim 1 , or —OCH.22. The compound of claim 1 , wherein Rand Rindependently represent —H or -D.2326-. (canceled)27. The compound of claim 1 , wherein ...

GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer. 2271-. (canceled)273. A method for treating a disease or disorder mediated by glucosylceramide synthase (GCS) or a disease or disorder in which GCS is implicated in a subject in need of such treatment claim 1 , the method comprising the step of administering to the subject an effective amount of a compound according to .275. The method according to claim 274 , wherein Rand Rare each methyl.276. The method according to claim 274 , wherein Ris H.277. The method according to claim 274 , Xis a direct bond278. The method according to claim 274 , Xis a CRR.279. The method according to claim 278 , wherein Rand Rare each methyl.280. The method according to claim 274 , wherein Ais (C-C)aryl.281. The method according to claim 274 , wherein Ais (C-C)heteroaryl.282. The method according to claim 281 , wherein Ais pyridine.283. The method according to claim 274 , wherein Ais (C-C)heterocycloalkyl.284. The method according to claim 283 , wherein Ais pyrrolidinyl claim 283 , tetrahydrofuranyl claim 283 , dihydrofuranyl claim 283 , tetrahydropyranyl claim 283 , pyranyl claim 283 , thiopyranyl claim 283 , aziridinyl claim 283 , azetidinyl claim 283 , oxiranyl claim 283 , methylenedioxyl claim 283 , chromenyl claim 283 , barbituryl claim 283 , isoxazolidinyl claim 283 , 1 claim 283 ,3-oxazolidin-3-yl claim 283 , isothiazolidinyl claim 283 , 1 claim 283 ,3-thiazolidin-3-yl claim 283 , 1 claim 283 ,2-pyrazolidin-2-yl claim 283 , 1 claim 283 ,3-pyrazolidin-1-yl claim 283 , piperidinyl claim 283 , thiomorpholinyl claim 283 , 1 claim 283 ,2-tetrahydrothiazin-2-yl claim 283 , 1 claim 283 ,3-tetrahydrothiazin-3-yl claim 283 , tetrahydrothiadiazinyl claim 283 , morpholinyl claim 283 , 1 claim 283 ,2-tetrahydrodiazin-2-yl claim 283 , 1 claim 283 ...

QUINUCLIDINE DERIVATIVE

Provided is a novel therapeutic agent for chronic obstructive pulmonary disease. 2: The quinuclidine derivative according to claim 1 , wherein:m is an integer of 2 to 5;l is a number of 0 or 1; andn is a number of 0 or 1.3: The quinuclidine derivative according to claim 1 , wherein n is 0.4: The quinuclidine derivative according to claim 1 , wherein:m is 3; andl is 0.5: The quinuclidine derivative according to claim 1 , wherein the quinuclidine derivative is an (R) isomer.6: A medicament claim 1 , comprising the quinuclidine derivative according to as an active ingredient.7: The medicament according to claim 6 , wherein the medicament is a therapeutic agent for chronic obstructive pulmonary disease.8: A pharmaceutical composition claim 1 , comprising the quinuclidine derivative according to claim 1 , and a pharmaceutically acceptable carrier.911-. (canceled)12: A method for treating chronic obstructive pulmonary disease claim 1 , the method comprising administering an effective amount of the quinuclidine derivative according to . The present invention relates to a quinuclidine derivative, and to a medicament containing the quinuclidine derivative.Chronic obstructive pulmonary disease (COPD) is a generic term for diseases that have been conventionally called chronic bronchitis or emphysema. COPD is a chronic disease of the lungs, which is caused by long-term inhalation exposure of harmful substances mainly containing tobacco smoke, and is said to be a lifestyle-related disease that occurs in middle-aged or older people against the background of smoking habit.In the drug therapy for COPD, a bronchodilator (an anticholinergic drug, a β-agonist, or a theophylline drug) is mainly used, and an inhaled anticholinergic drug or an inhaled β-agonist that mainly dilates the bronchi for a long time is used. In addition, an inhaled corticosteroid is used in severe cases.In recent years, as a drug effective for the treatment of COPD, for example, a quinuclidine derivative as a ...

RESIST COMPOSITION AND PATTERNING PROCESS

A resist composition comprising a base polymer and a quencher in the form of an amine compound having an iodized aromatic ring bonded to the nitrogen atom via a divalent hydrocarbon group offers a high sensitivity and minimal LWR or improved CDU, independent of whether it is of positive or negative tone. 1. A resist composition comprising a base polymer and a quencher , the quencher being an amine compound having an iodine-substituted aromatic ring bonded to the nitrogen atom via a C-Cdivalent hydrocarbon group which may contain at least one moiety selected from ester bond and ether bond.3. The resist composition of claim 1 , further comprising an acid generator capable of generating a sulfonic acid claim 1 , imide acid or methide acid.4. The resist composition of claim 1 , further comprising an organic solvent.6. The resist composition of which is a chemically amplified positive resist composition.7. The resist composition of wherein the base polymer is free of an acid labile group.8. The resist composition of which is a chemically amplified negative resist composition.10. The resist composition of claim 1 , further comprising a surfactant.11. The resist composition of claim 1 , further comprising a quencher other than the amine compound.12. A process for forming a pattern comprising the steps of applying the resist composition of onto a substrate claim 1 , baking to form a resist film claim 1 , exposing the resist film to high-energy radiation claim 1 , and developing the exposed resist film in a developer.13. The process of wherein the high-energy radiation is ArF excimer laser radiation of wavelength 193 nm or KrF excimer laser radiation of wavelength 248 nm.14. The process of wherein the high-energy radiation is EB or EUV of wavelength 3 to 15 nm. This non-provisional application claims priority under 35 U.S.C. § 119(a) on Patent Application No. 2018-150050 filed in Japan on Aug. 9, 2018, the entire contents of which are hereby incorporated by reference.This ...

QUINUCLIDINE-3-ONE DERIVATIVES AND THEIR USE IN CANCER TREATMENT

The invention relates to certain substituted quinuclidine-3-one compounds for use in the treatment of hyperproliferative disease, such as cancer, and diseases associated with inflammation. More particularly, the present invention relates to certain substituted 3-quinuclidinones, pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the same, and to methods for using such compounds. In this manner, these compounds are of use for treating hyperproliferative diseases and inflammatory diseases. 3. A compound according to claim 2 , wherein{'sup': '1a', 'sub': ['1', '6', '1', '6', '1', '6'], '#text': 'Ris selected from the group consisting of H, C-Calkyl and C-Chaloalkyl, said alkyl and haloalkyl being optionally substituted with one or more C-Calkoxy; and'}{'sup': '2a', 'sub': ['1', '6'], '#text': 'Ris C-Chaloalkyl;'}or an enantiomer, mixture of enantiomers, pharmaceutically acceptable salt, hydrate, solvate or combination thereof.4. A compound according to or claim 2 , wherein{'sup': '1a', 'sub': ['1', '6', '1', '6'], '#text': 'Ris selected from the group consisting of H and C-Calkyl, said alkyl being optionally substituted with one or more C-Calkoxy; and'}{'sup': '2a', 'sub': ['1', '6'], '#text': 'Ris C-Chaloalkyl;'}or an enantiomer, mixture of enantiomers, pharmaceutically acceptable salt, hydrate, solvate or combination thereof.5. A compound according to any one of - claim 2 , wherein{'sup': '1a', '#text': 'Ris selected from the group consisting of H and ethyl; and'}{'sup': '2a', '#text': 'Ris selected from the group consisting of trihalomethyl and dihalomethyl;'}or an enantiomer, mixture of enantiomers, pharmaceutically acceptable salt, hydrate, solvate or combination thereof.6. A compound according to claim 2 , wherein Ris H claim 2 , or an enantiomer claim 2 , mixture of enantiomers claim 2 , pharmaceutically acceptable salt claim 2 , hydrate claim 2 , solvate or combination thereof.7. A compound according to claim 2 , wherein Ris ethyl ...

GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer. 1248-. (canceled)250. The method of claim 249 , wherein the disease or disorder is cancer a metabolic disorder claim 249 , or a neuropathic disease.251253-. (canceled)254. The method of claim 250 , wherein the neuropathic disease is Parkinson's disease.255295-. (canceled)296. The method of claim 249 , wherein n is 1 claim 249 , t is 0 claim 249 , y is 1 claim 249 , and z is 1.297. The method of claim 249 , wherein m is 1 claim 249 , E is O claim 249 , Xis O claim 249 , and Xis NH.298. The method of claim 249 , wherein Ais (C-C)heteroaryl.299. The method of claim 298 , wherein Ais thiophene claim 298 , thiazole claim 298 , isothiazole claim 298 , furane claim 298 , oxazole claim 298 , isoxazole claim 298 , pyrrole claim 298 , imidazole claim 298 , pyrazole claim 298 , triazole claim 298 , pyridine claim 298 , pymiridine claim 298 , pyridazine claim 298 , indole claim 298 , benzothiazole claim 298 , benzopyrazole claim 298 , benzoimidazole claim 298 , benzofuran claim 298 , benzooxazole or benzoisoxazole.300. The method of claim 249 , wherein Ais (C-C)aryl.301. The method of claim 249 , wherein the compound is administered at a dosage of from 0.5 mg/kg to 300 mg/kg by intraperitoneal claim 249 , oral or equivalent administration from one to five times daily.302. The method of claim 249 , wherein the compound is administered at a dose of from about 10 mg/day to about 500 mg/day.303. The method of claim 249 , wherein the compound is administered in an oral dose of from about 1 mg/kg/day to about 100 mg/kg/day.305. The compound of claim 304 , wherein n is 1 claim 304 , t is 0 claim 304 , y is 1 claim 304 , and z is 1.306. The compound of claim 304 , wherein Xis a direct bond.307. The compound of claim 304 , ...

AZABICYCLIC CARBAMATES AND THEIR USE AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS

The invention relates to novel benzothiophene-, benzofuran-, and indole ureas and to the use thereof for producing medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning, and/or memory. 12. A medicament comprising at least one compound as claimed in and at least one pharmaceutically acceptable claim 1 , essentially nontoxic carrier or excipient.13. A method for improving perception claim 1 , concentration claim 1 , learning and/or memory comprising administering to a human or animal an effective amount of a compound of .14. A method for the treatment and/or prophylaxis of impairments of perception claim 1 , concentration claim 1 , learning and/or memory comprising administering to a human or animal an effective amount of a compound of .15. A method for the treatment and/or prophylaxis of impairments of perception claim 12 , concentration claim 12 , learning and/or memory comprising administering to a human or animal an effective amount of a medicament of . The invention relates to novel benzothiophene-, benzofuran- and indoleureas, processes for their preparation, and their use for producing medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning and/or memory.Nicotinic acetylcholine receptors (nAChR) form a large family of ion channels which are activated by the messenger acetylcholine which is produced in the body (Galzi et al., 1995, 34, 563-582). A functional nAChR consists of five subunits which may be different (certain combinations of α1-9 and (β1-4,γ,δ,ε subUnits) or identical (α 7-9). This leads˜to the formation of a diversity of subtypes which differ in the distribution in the muscles, the nervous system and other organs (McGehee et al, 1995, 57, 521-546). Activation of nAChR leads to influx of cations into the cell and to stimulation of nerve cells or muscle cells. Selective activation of individual nAChR subtypes restricts this ...

TARGETED NITROXIDE AGENTS

A compound having a structure of: 18-. (canceled)13. The compound of claim 9 , further comprising a detector label moiety coupled to the compound.14. The compound of claim 14 , wherein the detector label moiety comprises a fluorophore covalently bonded to the compound.15. The compound of claim 9 , wherein the compound is in the form of a nitroxide claim 9 , a hydroxylamine claim 9 , or a nitroxonium ion.16. The compound of claim 9 , wherein the compound is in the form of a pharmaceutically acceptable salt or ester thereof.17. A pharmaceutical composition comprising a compound of claim 9 , and at least one pharmaceutically acceptable additive.19. The method of claim 18 , wherein the compound is administered after the subject has been exposed to radiation.20. The method of claim 18 , wherein the compound is administered to the subject prior to the subject's exposure to radiation.21. The method of claim 18 , wherein the radiation is ionizing radiation.23. The method of claim 18 , wherein the compound is preferentially delivered to the mitochondria. This is a divisional application of U.S. application Ser. No. 14/000,173, filed Aug. 16, 2013, which is the U.S. National Stage of International Application No. PCT/US2012/025586, filed Feb. 17, 2012, which was published in English under PCT Article 21(2), which in turn claims the benefit of U.S. Provisional Application No. 61/444,492, filed Feb. 18, 2011, U.S. Provisional Application No. 61/454,003, filed Mar. 18, 2011, and U.S. Provisional Application No. 61/474,915, Apr. 13, 2011, all of which are incorporated herein by reference in their entireties.This invention was made with government support under grant number AI068021 and grant number GM067082 awarded by the National Institutes of Health, Department of Health and Human Services. The government has certain rights in the invention.Provided herein are novel compounds and compositions of matter comprising a nitroxide group-containing cargo (or “nitroxide containing ...

TREPROSTINIL DERIVATIVE COMPOUNDS AND METHODS OF USING SAME

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used. 181-. (canceled)83. The compound of claim 82 , wherein Ris Pand Ris H.84. The compound of claim 82 , wherein Ris H and Ris P.85. The compound of claim 82 , wherein Ris Pand Ris P.88. The compound of claim 82 , wherein each of Rto Ris H.89. The compound of claim 82 , wherein at least one of Rto Ris deuterium.90. The compound of claim 82 , wherein Z is —OH claim 82 , —OR claim 82 , —N(R)Ror P.91. The compound of claim 82 , wherein Z is P.92. The compound of claim 82 , wherein Z is —OH.93. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.94. The pharmaceutical composition of claim 93 , which is formulated for transdermal delivery claim 93 , optionally via a patch.95. A method of treating pulmonary hypertension claim 82 , comprising administering to a subject in need of treatment a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.96. The method of claim 95 , wherein the pulmonary hypertension is pulmonary arterial hypertension.97. The method of claim 95 , wherein the compound is administered orally claim 95 , topically or parenterally.98. The method of claim 97 , wherein the compound is administered transdermally claim 97 , optionally via a patch.99. The method of claim 95 , further comprising administering an additional therapeutic agent.100. The method of claim 99 , wherein the additional therapeutic agent is selected from the group consisting of vasoactive agents claim 99 , diuretics claim 99 , anticoagulants and cardiac glycosides. This application is ...

Small Molecule Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors and Methods of Treatment

Provided are compounds of formulas (I), (II), (III), and (IV), which effectively inhibit protein arginine methyltransferase 5 (PRMT5). Also provided are methods of using the compounds, including a method of treating cancer, a method of inhibiting the activity of PRMT5 in a cell, and a method of treating a disease associated with increased activity of PRMT5. 3. The compound of claim 2 , wherein Rishalo,heterocycloalkyl selected from the group consisting of isoxazolyl, thiazolinyl, imidazolidinyl, piperazinyl, homopiperazinyl, pyrrolyl, pyrrolinyl, pyrazolyl, pyranyl, piperidyl, oxazolyl, and morpholinyl, orheteroaryl selected from the group consisting of pyridinyl, pyridazinyl, pyrimidyl, pyrazinyl, benzimidazolyl, triazinyl, imidazolyl, (1,2,3)-triazolyl, (1,2,4)-triazolyl, pyrazinyl, tetrazolyl, furyl, pyrrolyl, thienyl, isothiazolyl, thiazolyl, isoxazolyl, and oxadiazolyl.4. The compound of or claim 2 , wherein Ris halo claim 2 , C-Chaloalkoxy claim 2 , C-Chaloalkyl claim 2 , haloaryl claim 2 , or haloaryloxy.5. The compound of any one of - claim 2 , wherein Ris C-Calkyl claim 2 , halo claim 2 , or C-Chaloalkyl.6. The compound of any one of - claim 2 , wherein Ris H.7. The compound of any one of - claim 2 , wherein X is a bond claim 2 , —(CH)NR— claim 2 , or —NR(CH)—.8. The compound of any one of - claim 2 , wherein m is 1.9. The compound of any one of - claim 2 , wherein o is 1 or 2.12. The compound of claim 11 , wherein Rishydrogen,halo,heterocycloalkyl selected from the group consisting of isoxazolyl, thiazolinyl, imidazolidinyl, piperazinyl, homopiperazinyl, pyrrolyl, pyrrolinyl, pyrazolyl, pyranyl, piperidyl, oxazolyl, and morpholinyl, orheteroaryl selected from the group consisting of pyridinyl, pyridazinyl, pyrimidyl, pyrazinyl, benzimidazolyl, triazinyl, imidazolyl, (1,2,3)-triazolyl, (1,2,4)-triazolyl, pyrazinyl, tetrazolyl, furyl, pyrrolyl, thienyl, isothiazolyl, thiazolyl, isoxazolyl, and oxadiazolyl.13. The compound of or claim 11 , wherein Ris —NR(CH) ...

GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer. 2246-. (canceled)247. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , selected from the group consisting of:1-azabicyclo[2.2.2]oct-3-yl [2-(2,4′-difluorobiphenyl-4-yl)propan-2-yl]carbamate;1-azabicyclo[2.2.2]oct-3-yl {2-[4-(1,3-benzothiazol-6-yl)phenyl]propan-2-yl}carbamate;1-azabicyclo[3.2.2]non-4-yl {1-[5-(4-fluorophenyl)pyridin-2-yl]cyclopropyl}carbamate;1-azabicyclo[2.2.2]oct-3-yl {1-[3-(4-fluorophenoxy)phenyl]cyclopropyl}carbamate;1-azabicyclo[2.2.2]oct-3-yl {1-[4-(1,3-benzothiazol-5-yl)phenyl]cyclopropyl)}carbamate;1-azabicyclo[2.2.2]oct-3-yl [1-(4′-fluoro-3′-methoxybiphenyl-4yl)cyclopropyl]carbamate;1-azabicyclo[2.2.2]oct-3-yl [3-(4′-fluorobiphenyl-4-yl)oxetan-3-yl]carbamate;1-azabicyclo[2.2.2]oct-3-yl {1-[6-(4-fluorophenoxy)pyridin-2-yl]cyclopropyl}) carbamate;1-azabicyclo[2.2.2]oct-3-yl [3-(4′-fluorobiphenyl-4-yl)pentan-3-yl]carbamate;1-azabicyclo[2.2.2]oct-3-yl {2-[2-(4-fluorophenyl)-2H-indazol-6-yl]propan-2 yl}carbamate;1-azabicyclo[2.2.2]oct-3-yl {2-[2-(1H-pyrrol-1-yl)pyridin-4-yl]propan-2-yl}carbamate;1-(3-ethyl-1-azabicyclo[2.2.2]oct-3-yl)-3-[1-(4′-fluorobiphenyl-4-yl)cyclopropyl]urea;N-(1-azabicyclo[2.2.2]oct-3-yl)-N′-[1-(4′-fluorobiphenyl-4yl)cyclopropyl]ethanediamide;1-azabicyclo[2.2.2]oct-3-yl (1-{4[(4,4difluorocyclohexyl)oxy]phenyl}cyclopropyl) carbamate;1-(4-methyl-1-azabicyclo[3.2.2]non-4-yl)-3-[1-(5-phenylpyridin-2-yl)cyclopropyl]urea;1-[1-(4′-fluorobiphenyl-4-yl)cyclopropyl]-1-methyl-3-(3-methyl-1-azabicyclo[2.2.2]oct-3-yl)urea;1-[1-(4′-fluorobiphenyl-4-yl)cyclopropyl]-1-methyl-3-(3-methyl-1-azabicyclo[2.2.2]oct-3-yl)urea;1-{2-[4′-(2-methoxyethoxy)biphenyl-4-yl]propan-2-yl}-3-(3-methyl-1-azabicyclo[2.2.2]oct-3-yl)urea;2-(1-azabicyclo[3.2.2] ...

SUBSTITUTED INDOLE ETHER COMPOUNDS

Disclosed are compounds of Formula (I) (I) N-oxides, or salts thereof, wherein R, G, A, R, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases. 2. The compound according to claim 1 , N-oxide claim 1 , or a salt thereof claim 1 , wherein:{'sub': x', 'x', '1-2', '2', '2', 'x', 'x', 'x', '0-2', '2', 'x', '2', '2, 'L is a bond, —(CRR)—, —CHC(O)—, —CHC(O)NR(CRR)—, —CHNRC(O)—, or —CHNRC(O)CH—;'}{'sub': 1', '1-4', '1-2', '1-2', '1-2, 'Ris H, Cl, —CN, Calkyl, Cfluoroalkyl, Chydroxyalkyl, or —C(O)O(Calkyl);'}{'sub': 2', '1-4', '1-2', '1-2', '1-3', '1-3', '2', '0-2', '1-4', 'y', 'y', '2', '0-2', 'y', 'y', 'x', '1-4', 'x', '2-4', 'x', '3-6', '2', '1-2', '2', '1-3', '2', '0-1', '3-6', '2', '0-1, 'each Ris independently F, Cl, —CN, —OH, Calkyl, Cfluoroalkyl, Ccyanoalkyl, Chydroxyalkyl, Caminoalkyl, —(CH)O(Calkyl), —NRR, —(CH)C(O)NRR, —C(O)NR(Chydroxyalkyl), —C(O)NR(Calkoxyalkyl), —C(O)NR(Ccycloalkyl), —(CH)S(O)(Calkyl), —(CH)(Ccycloalkyl), morpholinyl, —(CH)(phenyl), or dimethyl pyrazolyl;'}{'sub': 2a', '1-4', '1-2', '1-4', '2', '1-3', '3', '3-6', '2', 'x', 'x', '2', '3-6', '2, 'Ris Calkyl, Cfluoroalkyl, Chydroxyalkyl, —(CH)OCH, Ccycloalkyl, —CHC(O)NRR, —CH(Ccycloalkyl), —CH(phenyl), tetrahydrofuranyl, or phenyl;'}{'sub': 2b', 'x', 'x', '1-6', '1-2', '1-3', '2', '0-2', '1-2', '2', '1-2', 'x', 'x', '2', '1-3', '1-2', 'x', '1-3', 'x', '2', '3-6, 'each Ris independently H, F, Cl, —CN, —NRR, Calkyl, Cfluoroalkyl, Chydroxyalkyl, —(CH)O(Calkyl), —(CH)C(O)NRR, —(CH)(cyclopropyl), —C(O)O(Calkyl), —C(O)NR(Calkyl), —CR═CH, or —CH═CH(Ccycloalkyl);'}{'sub': 5', '1-2', '3, 'each Ris independently F, Cl, —CN, Calkyl, or —OCH;'}{'sub': '6', 'claim-text': [{'sub': x', 'x', '2', '2', 'x', 'x', '2', '2', '2', 'x', 'x', '2', '2', '2', 'x', 'x', '2', '2', 'x', 'x, '(i) —NRR ...

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 1203-. (canceled)205. The method of claim 204 , wherein Ring B is a 3-7 membered fully saturated claim 204 , partially unsaturated claim 204 , or aromatic monocyclic ring having 0-3 heteroatoms selected from the group consisting of oxygen claim 204 , nitrogen claim 204 , and sulfur.208. The method of claim 204 , wherein the cancer has a defect in a base excision repair protein.209. The method of claim 207 , wherein the cancer has a defect in a base excision repair protein.210. The method of claim 208 , wherein the base excision repair protein is selected from UNG claim 208 , SMUG1 claim 208 , MBD4 claim 208 , TDG claim 208 , OGG1 claim 208 , MYH claim 208 , NTH1 claim 208 , MPG claim 208 , NEIL1 claim 208 , NEIL2 claim 208 , NEIL3 (DNA glycosylases); APE1 claim 208 , APEX2 (AP endonucleases); LIG1 claim 208 , LIG3 (DNA ligases I and III); XRCC1 (LIG3 accessory); PNK claim 208 , PNKP (polynucleotide kinase and phosphatase); PARP1 claim 208 , PARP2 (Poly(ADP-Ribose) Polymerases); PolB claim 208 , PolG (polymerases); FEN1 (endonuclease) or Aprataxin.211. The method of claim 209 , wherein the base excision repair protein is selected from UNG claim 209 , SMUG1 claim 209 , MBD4 claim 209 , TDG claim 209 , OGG1 claim 209 , MYH claim 209 , NTH1 claim 209 , MPG claim 209 , NEIL1 ...

5HT3 RECEPTOR ANTAGONISTS

The present invention provides compounds of the formula: 2. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris selected from the group consisting of furanyl claim 1 , pyrrolyl claim 1 , imidazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , oxadiazolyl claim 1 , thiazolyl claim 1 , isothiazolyl claim 1 , thiadiazolyl claim 1 , triazolyl claim 1 , tetrazolyl claim 1 , pyrazinyl claim 1 , pyridazinyl claim 1 , each optionally substituted with one or two substituents independently selected from Calkyl claim 1 , Chaloalkyl claim 1 , Chaloalkoxy claim 1 , Calkoxy claim 1 , hydroxy claim 1 , cyano claim 1 , or halo.3. The compound or pharmaceutically acceptable salt of claim 1 , wherein Z is O.4. The compound or pharmaceutically acceptable salt of claim 1 , wherein Z is NH.5. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris a ring of formula (a) claim 1 , (d) claim 1 , (e) claim 1 , (f) claim 1 , or (g).6. The compound or pharmaceutically acceptable salt of claim 5 , wherein Ris a ring of formula (a) or (d).7. The compound or pharmaceutically acceptable salt of claim 5 , wherein Ris a ring of formula (e) claim 5 , (f) claim 5 , or (g).8. The compound or pharmaceutically acceptable salt of claim 5 , wherein Ris a ring of formula (e).9. The compound or pharmaceutically acceptable salt of claim 1 , wherein each Ris hydrogen.10. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris methyl.11. The compound or pharmaceutically acceptable salt of claim 1 , wherein is where all of X-Xare CRand each Ris hydrogen.12. The compound or pharmaceutically acceptable salt of claim 11 , wherein Xis N.13. The compound or pharmaceutically acceptable salt of claim 11 , wherein Xis CRand Ris hydrogen.14. A compound of selected from:(1R,3R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 5-fluoro-1-(2,2,2-trifluoroethyl)-1H-indole-3-carboxylate;(1R,3R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 5-fluoro-1-((R)-tetrahydrofuran-3- ...

Inhibitors of histone deacetylase useful for the treatment or prevention of hiv infection

The present invention relates to Compounds of Formula I and pharmaceutically acceptable salts or prodrug thereof, wherein R 1 , R 2 , R 3 , R 4 , X and A are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treating or preventing HIV infection in a subject.

NOVEL COMPOUNDS

Compounds of formula (I) described herein are both inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists, and are useful for the prevention and/or treatment of diseases of the respiratory tract characterized by airway obstruction. 6. A compound claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt according to claim 1 , which is a compound selected from the group consisting of[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl](2S)-3-[3-[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]carbamoyl]phenyl]sulfonylthiazolidine-2-carboxylate;[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl](2S)-3-[3-[(N-[(3R)-quinuclidin-3-yl]oxycarbonyl anilino)methyl]benzoyl]thiazolidine-2-carboxylate;[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl](2S)-1-[3-[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]phenyl]sulfonylpyrrolidine-2-carboxylate;[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl](2R)-1-[3-[[1-(3-fluorophenyl)-2-oxo-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]phenyl]sulfonylpyrrolidine-2-carboxylate;[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl](2S)-3-[3-[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]phenyl]sulfonylthiazolidine-2-carboxylate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl) ethyl](2S)-3-[3-[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]carbamoyl]phenyl]sulfonylthiazolidine-2-carboxylate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl](2S)-1-[3-[(2-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoyl]piperidine-2-carboxylate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl](4R)-3-[3-[(2-fluoro-N-[( ...

NOVEL COMPOUNDS

Compounds of formula (I) described herein are inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of diseases of the respiratory tract characterized by airway obstruction. 7. A compound claim 1 , N-oxide claim 1 , deuterated derivative claim 1 , or a pharmaceutically acceptable salt according to which is a compound selected from the group consisting of:(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]3-[(4-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]3-[(2-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]3-[(3-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]3-[(2-methoxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]3-[(3-methoxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]3-[(4-methoxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]4-[(N-[(3R)-quinuclidin-3-yl]oxycarbonylanilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]4-[(2-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]4-[(4-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]4-[(2-methoxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido- ...

NOVEL COMPOUNDS

Compounds of formula (I) defined herein are both inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of a disease of the respiratory tract characterized by airway obstruction. 4. A compound claim 1 , N-oxide claim 1 , deuterated derivative claim 1 , or pharmaceutically acceptable salt according to claim 1 , wherein{'sub': 5', '1', '6', '1', '6, 'Ris (C-C) haloalkyl or (C-C) alkyl,'}{'sub': 4', '3', '7', '1', '6', '3', '7, 'Ris (C-C) cycloalkyl or (C-C) alkyl which is optionally substituted by (C-C) cycloalkyl.'}7. A compound claim 1 , N-oxide claim 1 , deuterated derivative claim 1 , or pharmaceutically acceptable salt according to claim 1 , which is a compound selected from the group consisting of:[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[[1-(2-methoxyphenyl)-2-oxo-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]methyl]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-fluoro-4-[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]benzoate;[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl] 4-[[1-(3-fluorophenyl)-2-oxo-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]-4-[[1-(2-fluorophenyl)-2-oxo-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]-4-[[1-(3-fluorophenyl)-2-oxo-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]benzoate;[(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4- ...

Treatment of Cognitive Disorders with Certain Alpha-7 Nicotinic Acid Receptor Agonists in Combination with Nicotine

A method for improving cognition comprising co-administering to a subject an alpha 7 agonist, or a pharmaceutically acceptable salt thereof and a tobacco-free nicotine dosage is described together with related compositions. 2. The method according to wherein Ris hydrogen claim 1 , Ris hydrogen claim 1 , A is sulfur claim 1 , and Z is halogen claim 1 , formyl claim 1 , carbamoyl claim 1 , cyano claim 1 , trifluoromethyl claim 1 , trifluoromethoxy claim 1 , nitro claim 1 , amino claim 1 , formamido claim 1 , acetamido claim 1 , (C-C)alkyl claim 1 , (C-C)alkyoxy claim 1 , (C-C)alkylthio claim 1 , or (C-C)alkylamino.3. The method according to wherein Z is heteroaryl-carbonylamino claim 1 , arylcarbonylamino claim 1 , (C-C)alkylsulfonylamino claim 1 , di(arylsulfonyl)amino claim 1 , (C-C)cycloalkylcarbonylmethyl or amino(hydroxyimino).4. The method according to wherein Z is halogen claim 1 , cyano claim 1 , trifluoromethyl claim 1 , trifluoromethoxy claim 1 , methyl claim 1 , ethyl claim 1 , methoxy claim 1 , or ethoxy.5. The method according to wherein the compound of formula (I) is (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide.6. The method of wherein the subject has been diagnosed with Alzheimer's disease or pre-Alzheimer's disease.7. The method of wherein the subject has been diagnosed with mild to moderate Alzheimer's disease.8. The method of wherein the subject has been diagnosed with moderate to severe Alzheimer's disease.9. The method of wherein the subject has been diagnosed with schizophrenia or schizoaffective disorder.10. The method of claim 1 , wherein the method improves one or more of: learning claim 1 , delayed memory claim 1 , attention claim 1 , working memory claim 1 , visual learning claim 1 , speed of processing claim 1 , vigilance claim 1 , verbal learning claim 1 , visual motor function claim 1 , social cognition claim 1 , long term memory or executive function.11. The method of wherein the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[ ...

Compounds which have a protective activity with respect to the action of toxins and of viruses with an intracellular mode of action

The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells.

TRICYCLIC SULPHONAMIDE COMPOUNDS AND METHODS OF MAKING AND USING SAME

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 1. A compound selected from the group consisting of: (1aR ,7bS)-5-[2-(2-diethylaminomethylcyclopropyl)-4-fluoro-benzenesulfonylamino]-1 ,1a ,2 ,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid , or enantiomers thereof; (1aR ,7bS)-5-{4-fluoro-2-[2-(pyrrolidin-1-ylmethyl)cyclopropyl]-benzenesulfonylamino}-1 ,1a ,2 ,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR ,7bS)-5-[2-(3-diethylamino-2 ,2-dimethylpropyl)-4-fluorobenzenesulfonylamino]-1 ,1a ,2 ,7b-tetrahydrocyclopro-[c]chromene-4-carboxylic acid; (1aR ,7bS)-5-[4-fluoro-2-((R)-pyrrolidin-3-ylmethyl)benzene-sulfonylamino]-1 ,1a ,2 ,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid; (1aR ,7bS)-5-[4-fluoro-2-((S)-pyrrolidin-3-ylmethyl)benzene-sulfonylamino]-1 ,1a ,2 ,7b-tetrahydrocyclopropa [c]chromene-4-carboxylic acid; (1aR ,7bS)-5-{4-fluoro-2-[(R)-1-(2-hydroxy-2-methylpropyl)-pyrrolidin-3-ylmethyl]benzenesulfonylamino}-1 ,1a ,2 ,7b-tetrahydrocyclopropa [c]chromene-4-carboxylic acid; (1aR ,7bS)-5-[2-(1-azabicyclo[2.2.2]oct-3-ylmethyl)-4-fluoro-benzenesulfonylamino]-1 ,1a ,2 ,7b-tetrahydro cyclopropa-[c]chromene-4-carboxylic acid; (1aR ,7bS)-5-[2-((Z)-1-azabicyclo[2.2.2]oct-3-ylidenemethyl)-4-fluorobenzenesulfonylamino]-1 ,1a ,2 ,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR ,7bS)-5-[2-((E)-1-azabicyclo[2.2.2]oct-3-ylidenemethyl)-4-fluorobenzenesulfonylamino]-1 ,1a ,2 ,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR ,7bS)-5-{2-[(E)-(1-ethylpiperidin-3-ylidene)methyl]-4-fluorobenzenesulfonylamino}-1 ,1a ,2 ,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR ,7bS)-5-{2-[(Z)-(1-ethylpiperidin-3-ylidene)methyl]-4-fluorobenzenesulfonylamino}-1 ,1a ,2 ,7b-tetrahydrocyclopropa-[c]chromene-4- ...

COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY

Compounds of formula (I) described herein act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for the prevention and/or treatment of broncho-obstructive or inflammatory diseases. 6. A pharmaceutical composition claim 1 , comprising a compound or pharmaceutically acceptable salt according to and one or more pharmaceutically acceptable carriers and/or excipients.7. A method for the prevention and/or treatment of a broncho-obstructive or inflammatory disease claim 1 , comprising administering an effective amount of a compound or pharmaceutically acceptable salt according to to a subject in need thereof.8. A method according to claim 7 , wherein said broncho-obstructive or inflammatory disease is asthma claim 7 , chronic bronchitis claim 7 , or chronic obstructive pulmonary disease.9. A combination claim 1 , comprising a compound or pharmaceutically acceptable salt according to and one or more active ingredients selected from the group consisting of a beta2-agonist claim 1 , antimuscarinic agent claim 1 , mitogen-activated protein kinase (P38 MAP kinase) inhibitor claim 1 , nuclear factor kappa-B kinase subunit beta (IKK2) inhibitor claim 1 , human neutrophil elastase (FINE) inhibitor claim 1 , phosphodiesterase 4 (PDE4) inhibitor claim 1 , leukotriene modulator claim 1 , non-steroidal anti-inflammatory agent (NSAID) claim 1 , antitussive agent claim 1 , mucus regulator claim 1 , mucolytic claim 1 , expectorant/mucokinetic modulator claim 1 , peptide mucolytic claim 1 , antibiotic claim 1 , inhibitor of JAK claim 1 , SYK inhibitor claim 1 , inhibitor of PI3Kdelta or PI3Kgamma claim 1 , corticosteroid claim 1 , and M3-antagonist/PDE4-inhibitor (MAPI).10. A pharmaceutical composition according to claim 6 , which is in a form suitable to be administered by inhalation.11. A pharmaceutical composition according to claim 6 , which is an inhalable powder claim 6 , a propellant-containing metering aerosol claim 6 , or a propellant- ...