Abstract: The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

Abstract: The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

Abstract: A new family of therapeutics which provides a controlled-release delivery platform for non-steroidal anti-inflammatory agents on an ester or an ester-carbonate backbone is disclosed herein. These agents are reversible inhibitors of acetylcholinesterase and are thus useful for clinical conditions benefiting from inflammation suppression and cholinergic intervention. These compounds are of the general formula wherein n=0, 1; X?C, Si, and N+ and NSAID=ibuprofen, naproxen, indomethacin and diclofenac. Other embodiments are also disclosed.

Abstract: The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula I.

Abstract: The invention particularly discloses a process for preparing aryl alkyl carboxylic acid salts by preparing aqueous alkali solution, adding aryl alkyl carboxylic acid to said alkali solution at a temperature ranging from 4° to 121° C. for obtaining a clear solution, preferably by heating and/or stirring and concentrating and cooling to obtain aryl alkyl carboxylic acid salt The invention therefore discloses solid oral dosage forms and compositions of aryl alkyl carboxylic acid salts which are free of organic solvent/so. The solid oral dose compositions of aryl alkyl carboxylic acid salts of the invention are prepared in situ from aryl alkyl carboxylic acids and bases to obtain aryl acid alkyl carboxylic acid sails in crystalline/powder form with or without the use of pharmaceutical excipients.

Abstract: Methods and an apparatus for producing stable crystal polymorphs are provided. Inner surfaces of glass vials with a concave bottom topography are coated with nonstick compounds to select for nucleation of stable polymorphs.

Abstract: The present invention provides an improved process for preparation of highly pure trandolapril. The process comprises of the following steps: (i) crystallization of mixture of racemic benzyl trans-(2S, 3aR, 7aS)-octahydro-1H-indole carboxylate p-toluene sulphonic acid salt (IIa.p-TsOH) and benzyl trans-(2R, 3aS, 7aR)-octahydro-1H-indole carboxylate p-toluene sulphonic acid salt (IIb.p-TsOH) through appropriate selection of solvents to enrich the purity to >99% from a mixture containing the other diastereomers (IIc-h.

Abstract: 5-vinyl-indole derivatives are chemical uncouplers useful e.g. for the treatment of obesity.

Abstract: The present application describes amidinoindoles, amidinoazoles, and analogs thereof of formula I: ##STR1## wherein W, W.sup.1, W.sup.2, and W.sup.3 are selected from CH and N, provided that one of W.sup.1 and W.sup.2 is C(C(.dbd.NH)NH.sub.2) and at most two of W, W.sup.1, W.sup.2, and W.sup.3 are N and one of J.sup.a and J.sup.b is substituted by --(CH.sub.2).sub.n --Z--A--B, which are useful as inhibitors of factor Xa or thrombin.

Abstract: A butenoic or propenoic acid derivative having the following formula in which G is an aryl or a heterocyclic ring, R11 and R12 are hydroben or an alkyl, X is sulfur or oxygen, R2 and R3 are hydrogen, an substituent such as an alkyl and J is pyridyl or phenyl having substituents and a heterocyclic ring may be formed between R2, R3 and J is provided here and is useful in the pharmacological field.

Abstract: The present invention provides a process for the preparation of a complex of indomethacin and a divalent metal comprising forming a solution by dissolving indomethacin and a salt of said divalent metal in a tertiary amide or cyclic tertiary amide, adding a C.sub.1-4 alkanol or C.sub.3-6 ketone to the solution to precipitate the complex, and separating the precipitated complex from the solution. The present invention also provides a method for the treatment of inflammation or pain in a mammal requiring such treatment, comprising administering to said mammal an anti-inflammatory or analgesically effective amount of a complex of indomethacin and a divalent metal, the complex having the formula [M].sub.2 [indomethacin].sub.4 [S].sub.n, wherein M is the divalent metal, S is a molecule of a tertiary amide or a cyclic tertiary amide, and n is 2 or 3, or of a pharmaceutical composition comprising said complex together with a pharmaceutically acceptable carrier, diluent and/or excipient.

Abstract: The present invention provides a method for the treatment of inflammation and pain in a mammal requiring such treatment, comprising administering to said mammal an anti-inflammatory and analgesically effective amount of an indomethacin salt of a divalent metal capable of forming a stable complex with indomethacin, or of a pharmaceutical composition comprising said indomethacin salt together with a pharmaceutically acceptable carrier, diluent and/or excipient. The present invention also provides a process for the preparation of an indomethacin salt of a divalent metal capable of forming a stable complex with indomethacin comprising forming a solution by dissolving indomethacin and a salt of said divalent metal in a tertiary amide or cyclic tertiary amide, adding a C.sub.1-4 alkanol or C.sub.3-6 ketone to the solution to precipitate the indomethacin metal salt and separating the indomethacin metal salt precipitate from the solution.

Abstract: The present invention relates to an indoleacetic acid derivative and a salt thereof expressed by the following formula (I): ##STR1## [wherein X denotes a piperidino group, 1-pyrrolidinyl group or 3-hydroxy-1-pyrrolidinyl group; Y denotes ##STR2## (wherein R.sup.1 denotes a hydrogen atom or a lower alkyl group, and 1 denotes 0, 1 2) or ##STR3## (wherein R.sup.2 denotes a hydrogen atom, a lower alkyl group or a hydroxyl group, m denotes 0, 1 or 2, and n denotes 1, 2 or 3)]. The present invention also relates to anti-inflammatory drugs, anti-rheumatic drugs and anti-ulcer drugs containing the above compounds as active ingredients. The compounds possess a strong antiinflammatory action while causing extremely reduced troubles of digestive organs which is a serious defect with conventional non-steroidal anti-inflammatory drugs, and possess an excellent anti-ulcer action as well.

Abstract: This invention relates to novel 3-substituted-2-oxindole derivatives which are inhibitors of prostaglandin H.sub.2 synthase, 5-lipoxygenase and interleukin-1 biosynthesis. The compounds of the invention are useful as inhibitors of prostaglandin H.sub.2 synthase and interleukin-1 biosynthesis, per se, and as analgesic, antiinflammatory and antiarthritic agents in the treatment of chronic inflammatory diseases. This invention also relates to pharmaceutical compositions comprising said 3-substituted-2-oxindole derivatives; to methods of inhibiting prostaglandin H.sub.2 synthase and biosynthesis of interleukin-1; and to treating chronic inflammatory diseases in a mammal with said compounds. Further, this invention relates to certain novel carboxylic acids useful as intermediates in the preparation of the 3-substituted-2-oxindole derivatives of this invention and to a process for the preparation of the 3-substituted-2-oxindole derivatives.

Abstract: (R,R)-2,5-Diazabicyclo[ 2.2.1]heptanes are prepared from a compound of the formula ##STR1## wherein X and R.sub.2 are as defined herein, by heating with tosylchloride in pyridine, reacting the formed compound of the formula ##STR2## with a C.sub.1 -C.sub.6 alkylamine or ammonia, and reducing or hydrolyzing the formed compound of the formula ##STR3## wherein R.sub.1 is hydrogen or C.sub.1 -C.sub.6 alkyl.

Abstract: The invention relates to new 4-hydroxyindole derivatives of general formula: ##STR1## in which R represents a labile protective group and R.sub.1 can represent hydrogen, a C.sub.1 -C.sub.6 alkyl radical, a C.sub.3 -C.sub.6 cycloalkyl radical, a lower alkoxy radical, a lower hydroxyalkyl radical, a lower (lower alkoxy) alkyl radical, a phenyl radical optionally substituted with a halogen atom or a lower alkyl or lower alkoxy radical, a cyano radical, a radical of formula ##STR2## in which R.sub.2 and R.sub.3, which may be identical or different, each represent hydrogen or a lower alkyl radical, R.sub.4 represents a hydroxy group, a lower alkyl or lower alkoxy radical or a radical ##STR3## in which R.sub.2 and R.sub.3 have the same meaning as above, R.sub.5 represents a lower alkyl radical and Alk represents a single bond or a straight- or branched-chain alkylene radical having from 1 to 4 carbon atoms.

Abstract: The compound characterized by the structural Formula I: ##STR1## is therapeutically useful as an anti-hypertensive agent. A process for the preparation of the compound having Formula I and their synthetic intermediates is described. One of the synthetic intermediates is the compound characterized by the structural Formula: ##STR2## which is also therapeutically useful as an anti-hypertensive agent.

Abstract: The new indole derivatives of the formula ##STR1## in which R.sup.1 and R.sup.2 are identical or different and denote hydrogen or lower alkyl,R.sup.3 denotes hydrogen, lower alkyl or halogen andR.sup.4 and R.sup.5 are identical or different and denote hydrogen, lower alkyl or optionally substituted aryl, and R.sup.4 and R.sup.5 can also represent lower alkenyl, andwhereinR.sup.2 and R.sup.5 can be linked by an alkylene bridge of the formula--CH.sub.2 --CH.sub.2 --CH.sub.2).sub.nin whichn represents the number 0 or 1, can be prepared by reacting an ammonium or phosphonium salt of the corresponding indolecarboxylic acid with a haloacetic acid allyl ester. The new compounds can be used to prepare acemetacin. The new indole derivatives possess a pharmacological action.

Abstract: 1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid carboxymethyl ester as known per se is obtainable by a novel and more simple method comprising mild acid hydrolysis of 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetoxyacetic tetrahydropyran-2-yl ester. The final product is a valuable drug having antiinflammatory activity.

Abstract: A process for preparing acemetacin which process comprises removing a protecting group, which is other than tetrahydropyranyl group and is removable under acidic conditions, from an acemetacin ester represented by the formula ##STR1## wherein R means the protecting group, under the acidic conditions.

Abstract: Acemetacin is prepared by reaction of an indometacin with tert.-butyl halogenoacetate and subsequent cleavage with sulphuric acid and/or sulphonic acid.

Abstract: Indoles of the formula I which are unsubstituted in the 2- and 3-positions: ##STR1## wherein Z is hydrogen or a group --COR, and X and Y have the meanings defined in claim 1, can be produced by a novel, simple and economical process which comprises reacting a compound of the formula II ##STR2## at a temperature of between 0.degree. and 120.degree. C., in the presence of a mercury or palladium catalyst, with benzoic acid vinyl ester, or with the vinyl ester of an aliphatic C.sub.1 -C.sub.4 -monocarboxylic acid; and optionally saponifying compounds of the formula I in which Z is --COR. The compounds of the formula I can be used for example for producing indigo dyes, or they can be used as pharmaceutical or agricultural active substances.

Abstract: The invention relates to a process for the preparation of the known 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetoxyacetic acid which comprises reacting an indolecarboxylic acid of Formula (II) or its derivative with an alcohol of Formula (III). The final product is known to have antiinflammatory activity.

Abstract: Convenient intermediates for preparing 3-substituted-2-hydroxypropyl aryl ether .beta.-blockers, a reaction to the intermediates of the following formula and a conversion to obtain the said .beta.-blockers are disclosed. ##STR1## (wherein X is hydrogen or halogen;Y is halogen, hydroxy, lower acyloxy, amino, lower alkylamino, lower aralkylamino, lower acylamino, di-lower alkylamino, lower alkyleneamino, N-lower alkyl-N-lower aralkylamino, di-lower acylamino, N-lower alkyl-N-lower acylamino or N-tri-lower alkylsilylamino;one of P and R combined together with Q represents lower alkylene or alkenylene optionally interrupted by O, N or S and optionally substituted by lower alkyl, lower aralkyl, lower carboxylic acyl, carboxy, protected carboxy; hydroxy, lower alkoxy, lower acyloxy, oxo; amino, lower alkylamino, lower acylamino, nitro, nitroso, lower alkylthio, lower sulfonic acyl or halogen;and the remaining R or P is hydrogen or halogen;and dotted line represents the presence of one or two double bonds).

Abstract: 1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-3-indole acetic acid as known per se is obtainable by means of a novel and more simple method. This method comprises hydrolizing 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indole acetic acid tetrahydropyranyl ester, which ester is a novel compound. The final product obtained is a valuable drug having antiinflammatory activity.

Abstract: The invention relates to a process for preparing 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetoxyacetic acid which comprises reacting an indolecarboxylic acid or its derivatives with a compound of the formula HO--CH.sub.2 --CO--O--R.sup.2 in the presence of an inert organic solvent in a temperature range from -10.degree. C. to 80.degree. C., so that the resulting product is essentially free from the dechlorinated bi-product. The product of the process of the invention is a known anti inflammatory agent.

Abstract: The invention relates to a process for the preparation of the known 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetoxyacetic acid which comprises reacting an indolecarboxylic acid ester of Formula (II) or its derivative with an alcohol of Formula (III). The final product is known to have antiinflammatory activity.

Abstract: A new process for the preparation of the 1-(4-chloro-benzoyl)-5-methoxy-2-methyl-3-indolyl-acetohydroxamic acid, which comprises reacting the reaction product of 1-(4-chloro-benzoyl)-5-methoxy-2-methyl-3-indolyl-acetic acid and an alkyl-halocarbonate, with hydroxylamine.

Abstract: The invention relates to a process for the production of 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetoxyacetic acid (known to be useful as an antiphlogistic agent) which comprises reacting .alpha.-(4-chlorobenzoyl)-4-methoxyphenylhydrazine hydrochloride or sulphonate with laevulinoyloxyacetic acid and cyclizing the resulting hydrazone to obtain a product free from 1-benzoyl-5-methoxy-2-methyl-3-indolylacetoxyacetic acid.