Abstract: An approach to designing families of cocrystals with desired (tunable) pH dependent dissolution is developed. The solubility and dissolution rate of a family of cocrystals with the same API and a series of ligands that are weak acids or weak bases has been found to be determined and controlled by the acid or base dissociation constant of the ligand and the pH of the dissolution medium. In various aspects, pH dependent dissolution is imparted to a non-ionizable API or the dissolution of ionizable API's is modulated.

Abstract: The invention relates to a new pyridyl alkene and pyridyl alkine acid amides according to the general formula (I) as well as methods for their production, medicaments containing these compounds as well as their medical use, especially in the treatment of tumors or for immunosuppression.

Abstract: A method for the preparation of 10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide and 10,11-dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide from carbamazepine via a three-step process involving (i) epoxidation of carbamazepine; (ii) ring-opening of the resulting epoxide and (iii) oxidation of the resulting alcohol

Abstract: A high-yielding method and a useful intermediate, 10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (VII) is disclosed. Also disclosed are methods for the racemization of optically pure or optically enriched mixtures of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) and (R)-(?)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II) to racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III).

Abstract: The present invention provides for new crystal forms of oxcarbazepine, more particularly oxcarbazepine Forms B, C, D and E. The present invention further provides processes for preparation of these forms. Form B is prepared by evaporating the solvents from a solution of oxcarbazepine in toluene and dichloromethane. Form B is also obtained by immediately cooling the solution of oxcarbazepine and toluene. Cooling the same solution at a slower rate, but still fairly rapidly, results in oxcarbazepine Form C. Cooling the same solution at even a slower rate results in another Form, oxcarbazepine Form D. Oxcarbazepine Form E, a solvate of chloroform, is obtained by precipitating a solution of oxcarbazepine and chloroform. The present invention also provides processes for converting one of the newly discovered crystal forms of oxcarbazepine into another crystal form, including Form A, which is in the prior art.

Abstract: A process for preparing Oxcarbazepine III comprising: a) reacting oximinostilbene IV ?with chlorosulfonyl isocyanate in an inert organic solvent and isolating compound V b) hydrolyzing compound V to form crude Oxcarbazepine III c) purifying oxcarbazepine.

Abstract: An efficient and high-yielding method for the preparation of optically pure (S)-(+) -10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide and (R)-(?)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide by resolution of racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide using a tartaric acid anhydride.

Abstract: The invention relates to new processes for the preparation of the pharmaceutical oxcarbazepine, as well as novel intermediates prepared by or used for said processes, and the preparation of said intermediates.

Abstract: The present invention provides a method of preparing a 5H-dibenz[b,f]azepine-5-carboxamide of formula (1) wherein R1, R2, R3, and R4 are independently selected from the group consisting of hydrogen, halogen, nitro, cyano, carboxyl, A, —CO(A), —OCO(A), —O(A), —N(A)2, —CON(A)2, and —COO(A), wherein A is selected from the group consisting of C1–C10 alkyl, C3–C10 cycloalkyl, C2–C10 alkenyl, C5–C10 cycloalkenyl, C2–C10 alkynyl, and C6–C20 aryl, wherein the two A groups of —N(A)2 and —CON(A)2 can be the same or different, and wherein R2 and R3 can together form a bond; comprising reacting a 5H-dibenz[b,f]azepine of formula (2) with a) a cyanate salt selected from the group consisting of alkali metal cyanate salts and alkaline-earth metal cyanate salts, and b) a salt of an amino compound having no N—H bonds, wherein the salt has a Ka (25° C.) of at least about 10×10?11.

Abstract: This invention provides caspase inhibitors of formula I: wherein Z is oxygen or sulfur; R1is hydrogen, —CHN2, R, CH2OR, CH2SR, or —CH2Y; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R3 is a group capable of fitting into the S2 subsite of a caspase enzyme; R4 and R5 are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1? secretion.

Abstract: The invention relates to pharmaceutically active compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention and particularly useful for the treatment or prophylaxis of diseases associated with parasitic infection such as pneumocystis pneumonia, toxoplasmosis, cryptosporidiosis, leischmaniasis and malaria.

Abstract: The invention concerns a process for producing 5H-dibenz[b,f]azepine-5-carboxamide (carbamazepine) by reacting iminostilbene with an alkali cyanate in acetic acid or a mixture of acetic acid with water or with alcohol.

Abstract: A high-yielding method and a useful intermediate, 10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (VII) is disclosed. Also disclosed are methods for the racemisation of optically pure or optically enriched mixtures of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) and (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II) to racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III).

Abstract: A method for the preparation of 10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide and 10,11-dihydro-10-oxo-5H-dibenz/b,f/azepine-5-carboxamide from carbamazepine via a three-step process involving (i) epoxidation of carbamazepine; (ii) ring-opening of the resulting epoxide and (iii) oxidation of the resulting alcohol.

Abstract: A process for the preparation of 10-methoxycarbamazepine, an important intermediate in the preparation of 10-oxo-10, 11-dihydro-5H-dibenz(b,f)azepine-5-carboxamide(oxcarbazepine) from 10-methoxy-5H-dibenz(b,f)azepine(10-methoxyiminostilbene), is disclosed, which process comprises reacting 10-methoxyiminostilbene with cyanic acid (HOCN) in the presence of a mild acidic reagent in a solvent. Also disclosed is an improved method for the hydrolysis of 10-methoxycarbamazepine to oxcarbazepine, which method comprises carrying out the hydrolysis in a biphasic system chosen such that the oxcarbazepine is substantially insoluble in both phases, whereas the by-products or impurities are soluble in at least one of the phases. The oxcarbazepine thereby prepared is an anticonvulsant, and has been proposed for use as an anti-epileptical agent in the treatment of AIDS-related neural disorders, and for the treatment of Parkinson's disease and/or Parkinsonian syndromes.

Abstract: The present invention relates to systems and methods for generating polymorphs of compounds. In particular, the present invention provides high throughput systems and methods for generating and identifying new crystalline polymorphs that find use as improved drugs, pigments, explosives, nonlinear optical crystals, solid-state reactive compounds, and other polymorphic materials.

Abstract: The invention relates to new processes for the preparation of the pharmaceutical oxcarbazepine, as well as novel intermediates prepared by or used for said processes, and the preparation of said intermediates.

Abstract: A compound of the formulae (I) or (II): 1

Abstract: The present invention provides compounds of the general formulas: 1

Abstract: The present invention provides a pyrrolidine compound of the formula (I) wherein each symbol is as defined in the specification, an optically active compound thereof and a pharmaceutically acceptable salt thereof. The present invention further provides a pharmaceutical composition containing a compound of the formula (I), an optically active compound thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive. The compound of the present invention has a serotonin 2 receptor antagonistic action along with a platelet aggregation suppressive action, a peripheral circulation improving action and a lacrimation promoting action. Therefore, the compound of the present invention can be a useful medicine showing effect against thrombotic embolism, dry eye and the like.

Abstract: The present invention provides compounds, pharmaceutical compositions and methods that are useful in modulating the farnesoid X receptor (FXR). As FXR is involved in negatively controlling the expression level of cholesterol 7&agr;-hydroxylase (cyp7a), the rate-limiting enzyme involved in the oxidative metabolism of cholesterol into bile acids, the compounds described herein find utility in treating diseases associated with abnormally high or low cholesterol levels. In certain aspects, the FXR modulators (e.g., antagonists) described herein block the negative feed-back downregulation of cyp7a expression produced by certain cholic acids, the endogenous ligands for FXR. Moreover, as FXR forms heterodimers with the retinoid X receptor (RXR) in some cell types, modulation of the level of FXR activity in cells has a wide range of effects on a variety of biological processes which are mediated by RXR or other RXR-interacting proteins such as PPAR&ggr; and PPAR&agr;.

Abstract: A process for preparing carbamazepine from iminostilbene is disclosed. The iminostilbene is reacted with urea in a protonating medium. This process results in improvements over prior art processes involving iminostilbene. Carbamazepine is a known muscle relaxant, anticonvulsant and antidepressant drug.

Abstract: Method of treating or reducing the risk of human disease or condition in which the synthesis or oversynthesis of nitric oxide forms a contributory part wherein a therapeutically effective amount of the compound of formula (I) as defined in the specification is administered to a person suffering from or susceptible to such disease or condition.

Abstract: Guanidine derivatives of formula I ##STR1## wherein R.sup.8 represents hydrogen, halogen, alkyl C1 to 6, nitro, trifluoromethyl, thioalkyl C1 to 6, hydroxy, alkoxy C1 to 6, or a group selected from --NR.sup.4 R.sup.5, --O(CH.sub.2).sub.p Q, --(CH.sub.2).sub.m OQ, --(CH.sub.2).sub.m NR.sup.1 R.sup.2, --O(CH.sub.2).sub.m NR.sup.1 R.sup.2, --NHCO(CH.sub.2).sub.m NH(CH.sub.2).sub.n Q or --(CH.sub.2).sub.p CONR.sup.1 R.sup.2, or R.sup.8 represents the group A--CO--B; R.sup.9 represents hydrogen, halogen, alkyl C1 to 6, nitro or trifluoromethyl;and R.sup.1, R.sup.2, R.sup.4, R.sup.5, n, m, p, Q, A, B, and W are as defined in the specification, are described together with processes for their manufacture and compositions containing them. Compounds of formula I are useful in therapy.

Abstract: Compounds of general formula I are described ##STR1## as is a process for their preparation which consists of reacting a compound of formula II ##STR2## with hydroxylamine or its derivatives of formula IIIH.sub.2 NOR.sup.2 (III)The compounds cited in the present invention have valuable pharmaceutical properties namely in the treatment of some disturbances in the central and peripheral nervous system.

Abstract: Tricyclic compounds of the general Formula I: ##STR1## as defined herein which exhibit antagonist activity at V.sub.1 and/or V.sub.2 receptors and exhibit in vivo vasopressin antagonist activity, methods for using such compounds in treating diseases characterized by excess renal reabsorption of water, and processes for preparing such compounds.

Abstract: This invention has for its object to provide a method of inducing a transition in crystalline state of a crystallizable medicinal substance with great ease and improved efficiency and uniformity on a high production scale. According to the invention, an extruder is used for inducing a transition from one crystalline state (.DELTA.) to another crystalline state in a crystallizable medicinal substance.

Abstract: New compounds of general formula I, including all possible stereoisomers, are described ##STR1## wherein: R is hydrogen, alkyl, aminoalkyl, halogenalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, alkoxy, phenyl or substituted phenyl or pyridyl group.A process for their preparation consists of reaction of compound II ##STR2## with an acylating agent.

Abstract: The present invention relates to novel water-soluble analogs of carbamazepine and compositions containing them. The novel compositions are particularly suited for intravenous administration. The analogs of carbamazepine are useful in the treatment of epilepsy and related disorders.

Abstract: New carbamazepine hapten analogues are described comprising:(A) an active ester group;(B) a carbamazepine nucleus; and(C) a linking chain (i) linking the carboxamide group of the carbamazepine nucleus to the active ester group, said linking chain having about 4 to about 40 atoms consisting of:(1) alkylene groups; and(2) 5 to 7 membered heterocyclic ring groups, each group being joined into the linking group through chemical groups selected from(a) esters,(b) amides,(c) hetero atoms selected from --0--, --S--, and --NR--; wherein R represents hydrogen or C.sub.1 to C.sub.6 alkyl; and(d) carbonyl groups.The carbamazepine-active ester analogues are useful in preparing labeled carbamazepines. The labeled carbamazepines are useful in immunoassay elements and processes for the detection of carbamazepine drugs, for example, in body fluids.

Abstract: This disclosure relates to a method and reagents for determining ligands in biological fluids such as serum, plasma, spinal fluid, amnionic fluid and urine. In particular, this disclosure relates to a fluorescence polarization immunoassay procedure and to a novel class of tracer compounds employed as reagents in such procedures. The procedure disclosed combines the specificity of an immunoassay with the speed and convenience of fluorescence polarization techniques to provide a means for determining the amount of the specific ligand present in a sample.

Abstract: Diacylpiperazines of general structural formula: ##STR1## are: angiotensin II (A-II) antagonists with affinity for both AT.sub.1 and AT.sub.2 receptors useful in the treatment of hypertension, congestive heat failure, cerebrovascular, cognitive, and CNS disorders.

Abstract: A process for producing carbamazepine ##STR1## by (i) optionally purifying a solution of CCDA ##STR2## in an anhydrous, aromatic solvent; (ii) if required distilling off water in the solution; (iii) diluting the water-free solution with an additional amount of the anhydrous, aromatic solvent; (iv) in a reactor aminating the diluted solution at from about 70.degree. C. to about 105.degree. C.

Abstract: New 3-carbalkoxyamino-5-aminoacyl-5H-dibenz[b,f]azepines and their pharmaceutically acceptable acid addition salts, and methods for their synthesis are described. These compounds are useful as antiarrhythmic agents in the treatment of heart disorders. The new compounds are made by reacting a 3-carbalkoxyamino-5-halogenacyl-5H-dibenz[b,f]azepines with an amine to form the desired target product, which can be optionally converted into its pharmaceutically acceptable acid addition salt.

Abstract: The invention is directed to a process for the synthesis of 5-chlorocarbonyl-5H-dibenz[b,f]azepine, which is the precursor for the industrial scale synthesis of 5-carbamoyl-5H-dibenz[b,f]azepine. The latter substance is used as pharmaceutical compound. In the process phosgene is passed into a suspension of iminostilbene in an inert solvent at 20.degree. C.-60.degree. C. until the iminostilbene reacted to form an almost equimolar mixture of 5-chlorocarbonyl-5H-dibenz[b,f]azepine and iminostilbene hydrochloride, and then iminostilbene is released from the iminostilbene hydrochloride by the addition of an aqueous base. The iminostilbene so released is also made available for a complete phosgenation while an acidic reaction environment is maintained. After the iminostilbene reacted completely, the reaction mixture is heated slowly to 20.degree. C.-90.degree. C. with stirring and is detoxified by the hydrochloric acid that is formed.

Abstract: This disclosure relates to a method and reagents for determining ligands in biological fluids such as serum, plasma, spinal fluid, amnionic fluid and urine. In particular, this disclosure relates to a fluorescence polarization immunoassay procedure and to a novel class of tracer compounds employed as reagents in such procedures. The procedure disclosed combines the specificity of an immunoassay with the speed and convenience of fluorescence polarization techniques to provide a means for determining the amount of the specific ligand present in a sample.

Abstract: N,N-(dibenzohexatrienylene)urea medicaments can be manufactured in a smooth one-step reaction by reacting a corresponding N,N-(dibenzohexatrienylene)amine with cyanic acid.

Abstract: Compounds and methods featuring, in one aspect, compositions containing an organic boronic acid and one or more reporter groups.