Abstract: Compounds of formula (I) can modulate the activity of autotaxin (ATX).

Abstract: 3,3-diphenyl-N-(1-phenylethyl) propan-1-amine (fendiline): as a new selective ligand of the sigma-1 receptors, with anti-apoptotic (cytoprotective) properties and prototypical anticancer activity. This invention concerns the prototypical profile of selective sigma-1 ligand and the putative therapeutical properties of the compound 3,3-diphenyl-N-(1-phenylethyl) propan-1-amine (DPPA) and its pharmaceutically acceptable salts, with cytoprotective activity, more specifically for neurons against the neurodegenerative diseases (e.g. Alzheimer's disease, Huntington's disease, Parkinson's disease) via their anti-apoptotic properties induced by their selective sigma-1 agonism. Concerning the cancer cells, DPPA exhibited pro-apoptotic properties associated with neuroprotective activity originating a prototypical anticancer profile consisting in synergistical association with the clinically used anticancer drugs with its analgesic and neuroprotective activities antagonizing the neuropathic pain induced by the later.

Abstract: The present invention regards an improved and industrially advantageous process for the preparation of the 2-hydroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl-methanol intermediates, also called “feso chromenyl” and (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol, also called “(R)-feso deacyl”, which are in turn used in the synthesis of fesoterodine and in particular of fesoterodine fumarate. This process utilises reagents which are non-toxic and manageable at industrial level and enables obtaining a new stable and non-hygroscopic crystalline form of the key intermediate “(R)-feso deacyl”, called form B.

Abstract: The disclosure relates to methods for producing amide bonds and reagents related thereto. In some embodiments, the disclosure relates to methods of producing an amide comprising mixing an O-silylated thionoester and an amine under conditions such that an amide is formed. In another embodiment, the disclosure relates to mixing a thiolacid, a silylating agent, and an amine under conditions such that an amide is formed.

Abstract: The present invention relates to the new impurities of Fesoterodine, Fesoterodine symmetric dimer impurity and asymmetric dimer impurity, process for preparing and isolating thereof. The invention also deals with analytical standards and analytical methods used for the control of the production process and final quality of Fesoterodine.

Abstract: The invention provides compounds of the formula: or a pharmaceutically acceptable salt thereof, where m, n, R1, R2, R3 R4, R5, R6, R7 are those defined herein. The invention also provides pharmaceutical compositions comprising a compound of the invention, methods for using compounds and/or pharmaceutical compositions of the invention, and methods for synthesizing compounds of the invention.

Abstract: The invention concerns coated granules including (A) at least one amine-containing pharmacological active principle, preferably as an acid addition salt, the pharmacological active principle being complexed by low cation-exchange resin containing carboxylic acid groups (COO?), and (B) at least 15 wt. %, based on the total weight of the active principle/low cation-exchange resin complex, of at least one hydrophilic adsorbent, the mixture of the components (A) and (B) being coated with a gastrosoluble polymer. The invention also concerns a method for preparing such granules, as well as orodispesible tablets containing such granules.

Abstract: The present invention involves new and original sigma receptors ligands: (Mono-or dialkylaminoalkyl)-?-butyrolactones, their analogues aminotetrahydroturanes, the (1-adamantyl) benzene alkylamines, the N,N Dialkyl ?-[(adamantyl-1)benzyloxy-2] alkylamines and the 3-cyclopentyl adamantyl-amines or alkylamines or-alkyl phenylamines, their enantiomers or diastereoisomers, their pharmaceutically acceptable salts and Quinacrine Me-thylene blue, Asteinizole and their relative analogues with pro-apoptotic and/or anti-apoptotic properties over cellular biochemical mechanisms, with prototypical anti-cancer, antimetastatic and antiviral activities associated with antagonism of the neuropatic pain and, at very low doses, with cytoprotective and cytoregenerative activity against the cytodegenerative diseases.

Abstract: A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

Abstract: A controlled release dosage form of venlafaxine that comprises an immediate release pellet and an extended release pellet.

Abstract: Methods and compositions that can be used to identify and characterize inhibitors of K-ras localization to the plasma membrane and in doing so inhibit the signal transduction of K-ras. Such compositions can be used to treat K-ras mediated disorders, such as cancer.

Abstract: Compounds that have agonist activity at one or more of the SIP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SIP receptors.

Abstract: A process is described for the preparation of intermediates which can be used for preparation of agents for urinary incontinence therapy, specifically to 2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol and its prodrugs.

Abstract: Compounds of formula Ia and Ib wherein A, B, C, R1 and R14 are described herein.

Abstract: The present invention regards an improved and industrially advantageous process for the preparation of the 2-hydroxy-4-phenyl-3,4-dihydro-2H-chromen-6-yl-methanol intermediates, also called “feso chromenyl” and (R)-2-[3-(diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol, also called “(R)-feso deacyl”, which are in turn used in the synthesis of fesoterodine and in particular of fesoterodine fumarate. This process utilises reagents which are non-toxic and manageable at industrial level and enables obtaining a new stable and non-hygroscopic crystalline form of the key intermediate “(R)-feso deacyl”, called form B.

Abstract: Compounds of formula (Ia) and (Ib), wherein A, B, C, R1and R14 are described herein.

Abstract: Disclosed is a composition for transdermal administration containing tolterodine. The composition comprises lidocaine or a pharmaceutically acceptable salt thereof to achieve enhanced skin penetration. The composition enhances the skin penetration of tolterodine. Therefore, a successful commercial application of a tolterodine-containing transdermal preparation based on the composition can be expected.

Abstract: The present invention relates to an acid salt of tolterodine with superior stabililty and useful as a transdermal drug delivery system. More specifically, the present invention relates to a novel acid salt of tolterodine with superior stabililty to the conventional acid salts of tolterodine, which is useful as a pharmaceutical composition for the treatment of overactive bladder and can be formulated into a transdermal drug delivery system.

Abstract: The present application relates to novel methods for the preparation of secondary carbinamine compounds, particularly the preparation of secondary carbinamine compounds of the formula Ia, formula Ib or formula IV from aldehydes of the formula II and boronic acids of the formula III or formula V, in the presence of ammonia or an ammonia equivalent of the formula NH4+X?.

Abstract: The present disclosure relates to a process for the preparation of 2-(3 -diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)phenol or its phenolic monoesters or salts thereof, characterized by the steps of a) reacting a compound of formula (II) with a mixture of a Grignard initiator and Mg in a solvent; b) optionally reducing the temperature of the Grignard reagent to a lower temperature than in step a), and reacting the resulting Grignard reagent with an excess of a carbonate in a solvent, to obtain a compound of formula (III) wherein A is a C1-C6 alkyl, and the further reacting the compound of formula (III) in a known manner to obtain the desired end product.

Abstract: This disclosure relates to process for the preparation of a compound of formula (I) wherein R is hydrogen, a straight or branched C1-C6 alkyl-carbonyl group or a phenylcarbonyl group, or a salt thereof, comprising the following steps: a) adding to a suspension of Mg a compound of formula (II) R1(MgX)n—LiY wherein n is 1 or 2; R1 is an aromatic, aliphatic, carbocyclic or heterocyclic organic group having 1 to 24 carbon atoms; X and Y are independently selected from Cl, Br and I, b) reacting said reaction mixture with a suitable halogenated compound in a solvent to form a Grignard reagent, c) reacting said Grignard reagent with a suitable linear, branched or cyclic carbonate to obtain a compound of formula (IV) wherein A is a linear, branched or cyclic C1-C6 alkyl group, and preferably a methyl group, and then further reacting the compound of formula (IV) in a known manner to obtain a compound of formula (I) and optionally salt formation.

Abstract: Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

Abstract: Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis.

Abstract: Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis. In certain embodiments, the present invention comprises compositions comprising novel substituted ethylene diamine compounds further comprising antitubercular agents such as rifampicin, isoniazid, pyrazinamide and ethambutol.

Abstract: A new process for preparation of 3-(2-hydroxy-5-substituted phenyl)-N,alkyl-3-phenylpropylamines from cinnamyl chloride via N-alkyl-3-phenylprop-2-en-1-amine has been developed.

Abstract: A transdermal composition comprising tolterodine having improved storage stability is disclosed. The transdermal composition comprising tolterodine contains an antioxidant to stabilize tolterodine and can be stored for a long period of time.

Abstract: Fluorinated compounds and methods of making fluorinated compounds are described herein.

Abstract: A method for storing a transdermally/transmucosally absorbable preparation, comprising keeping a transdermally/transmucosally absorbable preparation enclosed in a container in a low oxygen atmosphere, the transdermally/transmucosally absorbable preparation comprising a drug whose molecule has an amino group substituted with a lower alkyl group.

Abstract: The invention provides a process for producing a compound of formula (I), wherein Y is selected from the group consisting of CH3, CH2OH, CH2CH2OH, CH2Br and Br; comprising the steps of: (i) reacting a compound of formula (II), wherein OX represents hydroxy or O?M+, in which M+ is a cation selected from Li+, Na+ and K+, and Y is as defined above; with trans-cinnamaldehyde (III), in the presence of a secondary amine compound; then (ii) treating the product of the preceding step with acid to afford the compound of formula (I). The above process may also be used in the production of tolterodine and fesoterodine, which are useful in the treatment of overactive bladder.

Abstract: The present application describes deuterium-enriched tolterodine, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: The invention relates to a method of obtaining 3,3-diphenylpropylamines (I), wherein R1 is H, alkyl, haloalkyl or alkoxyalkyl, R2 is alkyl, alkoxy, halogen, NO2, CN, CHO, which may be free or protected, CH2OH or COOR6, and R3 and R4 are selected independently from H and alkyl or together with the nitrogen to which they are bound form a ring having 3 to 7 members. The inventive method consists in reacting a propylenephenylamine and a disubstituted aromatic hydrocarbon and, if necessary, separating the desired enantiomer or the mixture of enantiomers, and/or converting the compound (I) into a salt. Compounds (I) are muscarinic receptor antagonists which can be used in the treatment of urinary incontinence and other symptoms of urinary bladder hyperactivity. Said compounds include tolterodine.

Abstract: Provided are: a compound represented by formula (I): (wherein ring A and ring D each represent a cyclic group which may have a substituent(s); E and G each represent a bond or a spacer having 1 to 8 atoms in its main chain; L represents a hydrogen atom or a substituent; X represents amino which may have a substituent(s), or a heterocyclic group which contains at least one nitrogen atom and which may have a substituent(s); n represents 0 to 3, in which when n is 2 or more, a plurality of ring A's may be the same or different from one another); a salt thereof; an N-oxide form thereof; a solvate thereof, a prodrug thereof; and a medicament which includes those. The compound represented by formula (I) is capable of binding S1P receptors (in particular, EDG-1 and/or EDG-6), and useful for preventing and/or treating rejection in transplantation, autoimmune diseases, allergic diseases, etc.

Abstract: Disclosed is a melanin production inhibitor which has an excellent inhibitory activity on the production of melanin and is highly safe. The melanin production inhibitor comprises a compound represented by general formula (1) (excluding clotrimazole), and/or a pharmacologically acceptable salt thereof.

Abstract: Disclosed is a process for the preparation of (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)-phenol isobutyrate (Fesoterodine) or a pharmaceutically acceptable salt thereof having a low content of impurities such as tolterodine and tolterodine isobutyrate.

Abstract: This invention relates to novel derivatives of tolterodine, 5-hydroxymethyl tolterodine, fesoterodine and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by muscarinic receptor antagonists.

Abstract: Provided herein are novel solid state forms of fesoterodine intermediates, (R)-4-benzyloxy-3-(3-diisopropylamino-1-phenylpropyl)-benzoic acid and (R)-[4-benzyloxy-3-(3-diisopropylamino-1-phenylpropyl)-phenyl]-methanol, and processes for their preparation thereof. The solid state intermediates are useful for preparing fesoterodine or a pharmaceutically acceptable salt thereof in high purity.

Abstract: A process for the preparation of (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-(hydroxymethyl)-phenol isobutyrate (Fesoterodine), its (S)-enantiomer, and novel intermediates useful in thei synthesis.

Abstract: Group 4 catalyst compounds containing di-anionic tridentate nitrogen/oxygen based ligands are provided. The catalyst compounds are useful, with or without activators, to polymerize olefins, particularly ?-olefins, or other unsaturated monomers. Systems and processes to oligomerize and/or polymerize one or more unsaturated monomers using the catalyst compound, as well as the oligomers and/or polymers produced therefrom are also provided.

Abstract: Described is a process of preparing a pure solid or crystalline racemic 3,3-diarylpropylamine compound and the compounds formed thereof. The solid and crystalline forms of racemic 3,3-diarylpropylamine compound are especially suitable for producing highly pure 3,3-diarylpropylamine salts such as tolterodine tartrate. Also described are the highly pure solid or crystalline forms of racemic tolterodine, racemic tolterodine salt and tolterodine tartrate.

Abstract: Described is a process of preparing a pure solid or crystalline racemic 3,3-diarylpropylamine compound and the compounds formed thereof. The solid and crystalline forms of racemic 3,3-diarylpropylamine compound are especially suitable for producing highly pure 3,3-diarylpropylamine salts such as tolterodine tartrate. Also described are the highly pure solid or crystalline forms of racemic tolterodine, racemic tolterodine salt and tolterodine tartrate.

Abstract: Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis.

Abstract: The present application relates to novel methods for the preparation of secondary carbinamine compounds, particularly the preparation of secondary carbinamine compounds of the formula Ia, formula Ib or formula IV from aldehydes of the formula II and boronic acids of the formula III or formula V, in the presence of ammonia or an ammonia equivalent of the formula NH4+X?.

Abstract: The invention relates to a method of obtaining 3,3-diphenylpropylamines (I), wherein R1 is H, alkyl, haloalkyl or alkoxyalkyl, R2 is alkyl, alkoxy, halogen, NO2, CN, CHO, which may be free or protected, CH2OH or COOR6, and R3 and R4 are selected independently from H and alkyl or together with the nitrogen to which they are bound form a ring having 3 to 7 members. The inventive method consists in reacting a propylenephenylamine and a disubstituted aromatic hydrocarbon and, if necessary, separating the desired enantiomer or the mixture of enantiomers, and/or converting the compound (I) into a salt. Compounds (I) are muscarinic receptor antagonists which can be used in the treatment of urinary incontinence and other symptoms of urinary bladder hyperactivity. Said compounds include tolterodine.

Abstract: The invention provides improved crosslinkers which permit more efficient determination of protein interactions in biological samples.

Abstract: A new process for preparation of 3-(2-hydroxy-5-substituted phenyl)-N,alkyl-3-phenylpropylamines from cinnamyl chloride via N-alky-3-phenylprop-2-en-1-amine has been developed.

Abstract: The invention provides a composition comprising (S) 2-amino-1-(4-chloro-phenyl)-1-[4-(1H-pyrazol-4-yl)-phenyl]-ethanol, wherein the composition is either substantially free of (R) 2-amino-1-(4-chloro-phenyl)-1-[4-(1H-pyrazol-4-yl)-phenyl]-ethanol or the composition contains a mixture of the (S) and (R) enantiomers in which the (S) enantiomer predominates. Also provided are processes for the preparation of the (S) 2-amino-1-(4-chloro-phenyl)-1-[4-(1H-pyrazol-4-yl)-phenyl]-ethanol, novel process intermediates and methods for making the novel process intermediates.

Abstract: There is provided an organic photoconductive material that can realize an electrophotographic photoreceptor which is not only excellent in charge transporting ability but also excellent in solubility in a solvent and compatibility with a resin and moreover, which is excellent in both electric properties and durability, and the organic photoconductive material that is useful also as a raw material compound for various types of functional materials. An asymmetric bis-hydroxyenamine compound represented by the following structural formula (1aa) is provided. The compound is allowed to be contained in a charge transporting layer or a surface protective layer of an electrophotographic photoreceptor. This leads realization of the electrophotographic photoreceptor which is excellent in electric properties and durability and can stably form an image of high quality being free of an image defect such as a black spot.

Abstract: The present invention provides novel T type calcium channel inhibitors of formula (I), the use thereof in the treatment of a disease or condition in a mammal associated with influx of extracellular calcium via T type calcium channels, wherein R1 is C1-C4 alkyl, hydroxy, or C1-C4 alkoxy; Z is NH, NCH3, O, S, or CH2; Y is NH, O, or CH2 with the proviso that Y and Z are not the same; R2 is H, halo, NH2, C1-C4 alkyl, hydroxy, or C1-C4 alkoxy; m and n are independently selected from integers ranging from 1-5 with the proviso that m+n=an integer ranging from 2-9; and R3 is H, halo, NH2, C1-C4 alkyl, hydroxy, or C1-C4 alkoxy.

Abstract: The present invention provides compositions and methods for synthesizing labeled drugs. The present invention further provides methods for preventing or stopping prescription drug abuse for all agents registered as a Drug Enforcement Agency (DEA) schedule II through schedule V medications. According to the present invention, methods are provided for monitoring patient compliance with prescribed drug treatment. The present invention also provides methods for facilitating a replacement prescription when a patient is left without access to their prescribed drug. Furthermore, the present invention provides a method to improve employee compliance with an employer's drug policies via either a voluntary or compulsory system for enhanced drug testing.

Abstract: Racemic tolterodine free base in crystalline form, tolterodine with improved purity, compositions and uses thereof, and processes of preparing the same.