Abstract: The present invention is directed to compounds useful in the treatment of migraine which have the general formula (II).

Abstract: This invention provides compounds of the Formula I: which are useful as tachykinin receptor antagonists. This invention also provides methods employing these compounds, as well as pharmaceutical formulations comprising these compounds.

Abstract: Disclosed are compounds of the formula or the pharmaceutically acceptable non-toxic salts thereof wherein: W represents substituted or unsubstituted aryl or heteroaryl; T is hydrogen, halogen, hydroxyl, amino or alkyl; X is hydrogen, hydroxy, or lower alkyl; m is 0, 1, or 2; n is 0, 1, or 2; and R3 and R4 represent substituted or unsubstituted organic residues. These compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory.

Abstract: Disclosed are compounds of the formula 1

Abstract: The invention provides a process for the production of a compound of formula I, which comprises reacting a compound of formula II with a compound of formula III, in the presence of a strong base and a palladium(0) catalyst, at an elevated temperature, in a solvent which does not adversely affect the reaction. Compounds of formula I may be further processed to compounds of formula V, which are useful in the treatment of inter alia migraine.

Abstract: Cyclic amino acid derivatives of Formula I are antagonists of VLA-4 and/or &agr;4&bgr;7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of asthma, allergies, inflammation, multiple sclerosis, and other inflammatory and autoimmune disorders.

Abstract: Compounds effective in treating disorders of the serotonin-affected neurological symptoms are provided, such compounds having the following formula: ##STR1## wherein: R.sub.1 and R.sub.5 are each, independently, hydrogen, halogen, lower alkoxy, lower alkyl, cyano, or trifluoromethyl;R.sub.2 and R.sub.4 are each, independently, hydrogen, lower alkyl, phenyl, or substituted phenyl;R.sub.3 is hydrogen or lower alkyl; andX and Y are each, independently, O, NR.sub.6, or CH.sub.2, whereinR.sub.6 is hydrogen, lower alkyl, phenyl, or substituted phenyl; or pharmaceutically acceptable salts thereof.

Abstract: There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.

Abstract: The present invention relates to compounds of Formula I that inhibit matrix metalloproteinases and to a method of inhibiting matrix metalloproteinases using the compounds ##STR1## More particularly, the present invention relates to a method of treating diseases in which matrix metalloproteinases are involved such as multiple sclerosis, atherosclerotic plaque rupture, restenosis, aortic aneurysm, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, osteoporosis, rheumatoid or osteoarthritis, renal disease, left ventricular dilatation, or other autoimmune or inflammatory diseases dependent upon tissue invasion by leukocytes.

Abstract: The invention involves the formation of a prodrug from a fatty acid carrier and a neuroactive drug. The prodrug is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The prodrug passes readily through the blood brain barrier. Once in the central nervous system, the prodrug is hydrolyzed into the fatty acid carrier and the drug to release the drug.In a preferred embodiment, the carrier is 4, 7, 10, 13, 16, 19 docosahexa-enoic acid and the drug is dopamine. Both are normal components of the central nervous system. The covalent bond between the drug and the carrier preferably is an amide bond, which bond may survive the conditions in the stomach. Thus, the prodrug may be ingested and will not be hydrolyzed completely into the carrier molecule and drug molecule in the stomach.

Abstract: Topically applicable dermocosmetic compositions for combating the clinical signs of skin aging and/or for improving the appearance of the skin, the scalp or the hair, comprise an anti-free-radical effective amount of at least one novel melatonin derivative having the structural formula (I): ##STR1## in which R.sub.1 is a lower alkyl radical, R.sub.2 is a hydrogen atom or a lower alkyl radical, and R.sub.3 is a hydrogen atom or a lower acyl radical, with the proviso that the hydroxyl radical is in the 4-, 6- or 7-position on the indole ring system, or a physiologically acceptable salt, solvate or bioprecursor/prodrug thereof, formulated into a topically applicable, cosmetically/dermatologically acceptable vehicle, carrier or diluent therefor.

Abstract: The instant invention is concerned with aryl and heteroaryl oxyacetic acid type compounds which are useful antidiabetic compounds. Compositions and methods for the use of the compounds in the treatment of diabetes and related diseases and for lowering triglyceride levels are also disclosed.

Abstract: A compound comprising a non-steroidal antiinflammatory agent to which is directly or indirectly linked an NO group, a pharmaceutical composition including the compounds and methods of treatment of pain and/or inflammation using the compounds and compositions are disclosed. Also disclosed is a composition comprising a non-steroidal antiinflammatory agent and a compound that donates, transfers or releases nitric oxide.

Abstract: Novel meta substituted arylakylamine compounds are disclosed. These compounds can be administered as small molecule drugs to treat diseases or conditions associated with insufficient serotonin mediated nerve transmission, such as depression and obesity.

Abstract: Described herein are compounds selective for a 5-HT.sub.1D -like receptor, which have the general formula: ##STR1## wherein A is selected from a six-membered, non-aromatic, optionally substituted carbocycle and a six-membered, non-aromatic, optionally substituted heterocycle having one or two heteroatoms selected from O, S, SO, SO.sub.2 and N.sup.4 ;R.sup.1 is selected from H and OH;n is 0 or 1 as permited by chemical structure;R.sup.2 is selected from CR.sup.5 CR.sup.6 CH.sub.2 NR.sup.7 R.sup.8 or a group of formula II, III or IV: ##STR2## R.sup.3 is selected from H and benzoyl; R.sup.4 is selected from H, loweralkyl, benzyl, loweralkylcarbonyl, loweralkylaminocarbonyl, loweralkylaminothiocarbonyl, loweralkanoyl, loweralkylaminoimide and loweralkoxy-substituted loweralkylene;R.sup.5 and R.sup.6 are independently selected from H, loweralkoxy and hydroxy;R.sup.7 and R.sup.8 are independently selected from H and loweralkyl or R.sup.7 and R.sup.

Abstract: The present application describes m-amidino phenyl analogs of formula I: ##STR1## wherein D can be amidino and E can be phenyl, which are useful as inhibitors of factor Xa.

Abstract: The present invention relates to novel substituted indole compounds of formula (I) ##STR1## having pharmacological activity, to processes for their preparation, to solid phase methods for preparing libraries of the compounds, to utilizing libraries of the compounds for drug discovery, and to pharmaceutical compositions thereof.

Abstract: The present invention relates to a traceless solid phase process for the preparation of an indole derivative, which comprises the following steps:(1) reaction of an optionally substituted 2-iodoaniline derivative via the nitrogen atom of the NH.sub.2 moiety thereof with a dihydropyran-functionalized polymeric resin under conditions effective to form an aminal linkage;(2) reaction of the tetrahydropyran aminal derivative thereby obtained with an acetylene derivative in the presence of a transition metal catalyst under conditions effective to promote indole formation;(3) treatment of the product thereby obtained with acid, whereby the aminal linkage is cleaved and the desired indole derivative is liberated from the resin; and(4) isolation of the desired indole derivative thereby obtained.

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: The present invention provides novel tetrahydro-beta-carboline compounds having useful central nervous system activity. Further, there is provided tetrahydro-beta-carboline related compounds which are useful intermediates and have beneficial central nervous system activity. The invention provides formulations and methods for using the novel tetrahydro-beta-carboline and related compounds. Such compounds are particularly useful for the modulation of a 5-HT.sub.2B receptor.

Abstract: Described herein are compounds selective for 5-HT.sub.1D -like receptors, which have the general formula: ##STR1## wherein: R.sup.1 is selected from H, aryl and aryl substituted with 1, 2 or 3 substituents independently selected from loweralkyl, loweralkoxy, loweralkylcarbonyl, loweralkyl-S--, loweralkyl-S(O)--, loweralkyl-SO.sub.2 -, S.dbd.C.dbd.N--, O.dbd.C.dbd.N--, halo, loweralkoxycarbonyl, nitro, amino, loweralkyl-NH--, (loweralkyl).sub.2 --N--, loweralkyl-SO.sub.2 -loweralkyl-;A is a double or triple bond;R.sup.2 is selected from a group of Formula II, III, IV and V: ##STR2## R.sup.3 is selected from H and loweralkyl; R.sup.4 is selected from H and loweralkyl;One of R.sup.5 and R.sup.6 is H and the other is independently selected from H, loweralkoxy, loweralkyl and hydroxy; andR.sup.7 and R.sup.8 are independently selected from H and loweralkyl or R.sup.7 and R.sup.

Abstract: The present invention relates to new aromatic ethers derived from indole and having general formula (I) as well as to their preparation methods, pharmaceutical compositions containing them and their utilization as a medicament for the treatment of diseases linked to the dysfunction of the 5HT.sub.1 -like receptors.

Abstract: The present invention relates to novel classes of compounds which are inhibitors of interleukin-1.beta. converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

Abstract: There are disclosed compounds of formula (I) ##STR1## and pharmaceutically acceptable salts thereof which are useful as antagonists of GnRH and as such may be useful for the treatment of a variety of sex-hormone related and other conditions in both men and women.

Abstract: Compounds of the formula ##STR1## where W is ##STR2## n is 0, 1, or 2; m is 0, 1, 2, or 3: Y and G are each independently oxygen or sulfur; Z is --O--, --S--, --NH, or --CH.sub.2 ; R.sub.1 is hydrogen, C.sub.1 to C.sub.8 alkyl, substituted C.sub.1 to C.sub.8 alkyl substituted with one hydroxy, C.sub.3 to C.sub.8 alkenyl, C.sub.3 to C.sub.8 alkynyl, aryl, C.sub.1 to C.sub.3 alkylaryl, C.sub.1 to C.sub.3 alkylheteroaryl, or --Q--R.sub.4 ; R.sub.2 and R.sub.3 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, aryl, C.sub.1 to C.sub.3 alkylaryl, or C.sub.1 to C.sub.3 alkylheteroaryl; R.sub.4 is cyano, trifluoromethyl, --COR.sub.9, --CO.sub.2 R.sub.9, --CONR.sub.9 R.sub.10, --OR.sub.9, --SO.sub.2 NR.sub.9 R.sub.10, or --S(O).sub.q R.sub.9 ; R.sub.9 and R.sub.10 are each independently hydrogen, C.sub.1 to C.sub.8 alkyl, C.sub.1 to C.sub.3 alkylaryl, aryl, or R.sub.9 and R.sub.

Abstract: Compounds of formula (I) ##STR1## wherein R and R.sup.1 are hydrogen, C.sub.1-4 alkyl or are linked to form a ring,A is a cycloalkyl or alkyl-cycloalkyl group,n is an integer from 0 to 3,W is an optionally substituted 5-or 6-membered heterocyclic ring; or W is an optionally substituted aryl, heteroaryl, aryloxy or thiophenoxy group; orW is a group --SO.sub.2 NR.sup.6 R.sup.7 --NHC(O)R.sup.6 R.sup.7 or --C(O)NHR.sup.6 R.sup.7 ;are useful in treating clinical conditions for which a "5-HT.sub.1 -like" receptor agonist is indicated.

Abstract: The invention relates to a compound selected from those of formula (I): ##STR1## in which A, R.sub.1, R'.sub.1, R.sub.2, R.sub.3 and n are as defined in the description, and medicinal product containing the same useful for treating a mammal afflicted with a disorder of the melatoninergic system.

Abstract: The present invention relates to a pharmaceutical composition for rectal administration in solid dosage form which comprises a compound acting as a 5HT-1 like receptor agonist in the form of its free base or a physiologically acceptable hard fat base carrier having a hydroxyl value of more than 15 in the method for the treament of a mammal suffering from a susceptible to conditions associated with cephalic pain.

Abstract: The present invention, relates to 3-?2-(dimethylamino)ethyl!-N-methyl-1H-methanesulphonamide sulphate salt (2:1) and pharmaceutically acceptable solvates thereof, and to pharmaceutical compositions containing same. The compound is useful in the treatment of conditions associated with cephalic pain, in particular migraine. The pharmaceutical compositions are particularly useful as intranasal formulations.

Abstract: A compound selected from those of formula (I): ##STR1## in which A, R, Y, R.sup.1, R.sup.2 and R.sup.3 are as defined in the description,and a medicinal product containing the same useful for treating a disorder of the melatoninergic system.

Abstract: A compound of structure (I), in which A.sup.1 is O, S(O).sub.n in which n is 0, 1 or 2, NR, CH.sub.2, or CH(OH); A.sup.2 is a bond or CH.sub.2 ; or A.sup.1 A.sup.2 is CH.dbd.CH; R is hydrogen or C.sub.1-4 alkyl; R.sup.1 is an optionally substituted 6- to 10-membered aryl or heteroaryl ring; suitably R.sup.1 is an optionally substituted 6- 10-membered aryl ring such as phenyl or naphthyl; suitably R.sup.1 is optionally substituted 6- to 10-membered heteroaryl ring, containing from 1 to 4 nitrogen atoms; R.sup.2 is hydrogen, halogen, C.sub.1-4 alkyl, CN, NO.sub.2 or CF.sub.3 ; R.sup.3 is C(R.sup.4)(R.sup.5)CH.sub.2 NR.sup.6 R.sup.7, --CH.dbd.NNHC(NH)NH.sub.2 or a; R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-4 alkyl; R.sup.6 and R.sup.7 are the same or different and are each hydrogen or C.sub.1-4 alkyl or together with the nitrogen atom to which they are attached form a ring; R.sup.8 is hydrogen, C.sub.1-4 alkyl, or C.sub.

Abstract: 3-Ethanamine and 3-ethanamine related compounds are provided that are useful intermediates and have beneficial central nervous system activity.

Abstract: The invention relates to N-acyl-N-heterocyclylalkylamino acids of the formula ##STR1## wherein Y.sub.1 is O, S or N(R) and R is hydrogen or C.sub.1 -C.sub.7 alkyl;X.sub.1 is --CO-- or --S(O).sub.m -- and the index m is 0, 1 or 2;one of the variables X.sub.2 and X.sub.4 is C.sub.1 -C.sub.4 alkylene and the other of the variables X.sub.2 and X.sub.4 is a bond; or each of the variables X.sub.2 and X.sub.4 is a bond;X.sub.3 is C.sub.3 -C.sub.7 cycloalkylidene or the structural element --C(X.sub.a)(X.sub.b)-- and X.sub.a is hydrogen or C.sub.1 -C.sub.7 alkyl and X.sub.b is C.sub.1 -C.sub.7 alkyl;and the rings A, B and C, with the exception of the substituents indicated in the formula, and also aromatic substituents are, independently of one another, unsubstituted or mono- or poly-substituted by substituents selected from the group consisting of halogen, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.7 alkenyloxy, phenoxy, benzyloxy, trifluoromethyl and S(O).sub.

Abstract: Novel 1-alkyl-, 1-alkenyl-, and 1-alkynylaryl-2-amino-1,3-propanediols, intermediates and processes for the preparation thereof, and methods of reducing inflammation and cell proliferation, and relieving memory dysfunction, and inhibiting bacterial and fungal growth are disclosed.

Abstract: Certain 3-amino-cycloalkanyl and cycloalkenyl derivatives of 5-cyano-substituted indoles of Formula I are useful antidepressant agents. ##STR1## The substituent R.sup.1 is hydrogen or C.sub.1-4 alkyl and R.sup.2 is C.sub.1-4 alkyl or --(CH.sub.2).sub.p --Ar with Ar being a phenyl, pyridinyl, pyrimidinyl or 1,4-benzodioxan-2-yl moiety. The symbol m is zero or 1, n is 1 to 3 and p is zero or 1 to 4.

Abstract: Compounds of the formula (I): Ar.sub.1 --CH(OH)--CH.sub.2 --NH--CH.sub.2 --X--CH.sub.2 --E--(CH.sub.2).sub.n --Y--Ar.sub.2, in which the substituents and symbols have the meanings given in the description, are novel active compounds having, in particular, a broncholytic action.

Abstract: The present invention relates to known and novel tryptamine analogues, processes and intermediates useful in their preparation, pharmaceutical compositions containing them and their use in therapy, in particular for the treatment and/or prophylaxis of disorders characterized by excessive vasodilatation, such as migraine and portal hypertension.

Abstract: The invention is drawn to an antibiotic, NEMATOPHIN, 3-indoleethyl 3'-methyl-2-oxo-pentanamide (+stereoisomer, -stereoisomer and racemic mixture) and its derivatives, 3-indoleethyl 2-oxo-alkanamides, 3-indoleethyl 2-oxo-alkanoates with or without substitute(s) on the indole ring, produced by bacterial symbiont Xenorhabdus nematophilus and/or other Xenorhabdus species or synthesized by reaction of tryptamine or substituted tryptamine and 2-oxo-alkanoic acid or its derivative, the additional salts thereof, the pharmaceutical compositions thereof and their use as medicaments, particularly in the treatment of infectious diseases involving microorganisms susceptible to them, including antibiotic-resistant Staphylococcus.

Abstract: Disclosed are indole derivatives having activity on the cannabinoid receptors and the methods of their preparation. The compounds are useful for lowering ocular intra ocular pressure and treating glaucoma because of the activity on the cannabinoid receptor.

Abstract: Novel 1-alkyl-, 1-alkenyl-, and 1-alkynylaryl-2-amino-1,3-propanediols, intermediates and processes for the preparation thereof, and methods of reducing inflammation and cell proliferation, and relieving memory dysfunction, and inhibiting bacterial and fungal growth are disclosed.

Abstract: Described herein are tryptamine analogs that display high binding affinity and selectivity for the 5-HT1D.beta. receptor, of the formula: ##STR1## wherein R.sup.1 is a group selected from aryl-C.sub.1-7 alkyl; aryl-C.sub.2-7 alkoxy; aryl-C.sub.2-7 alkanoyl and aryl-C.sub.1-7 alkanoyloxy, wherein said alkyl, alkoxy, alkanoyl and alkanoyloxy groups are optionally substituted by a C.sub.1-4 alkyl substituent and wherein said aryl group is optionally substituted by one or more substituent selected from hydroxyl, halogen, mercapto, linear or branched C.sub.1-4 alkyl, linear or branched C.sub.1-4 alkoxy, linear or branched C.sub.1-4 alkylthio, thiol substituted C.sub.1-4 alkyl and nitro substituted C.sub.1-4 alkyl;R.sup.2 and R.sup.3 are selected independently from H and C.sub.1-4 alkyl; andR.sup.4 is selected from H, C.sub.1-4 alkyl, aryl and arylC.sub.1-4 alkyl.

Abstract: The present invention provides HIV protease inhibitors, pharmaceutical formulations containing those compounds and methods of treating and/or preventing HIV infection and/or AIDS.

Abstract: Novel 1-alkyl-, 1-alkenyl-, and 1-alkynylaryl-2-amino-1,3-propanediols, intermediates and processes for the preparation thereof, and methods of reducing inflammation and cell proliferation, and relieving memory dysfunction, and inhibiting bacterial and fungal growth are disclosed.

Abstract: Novel indole and indoline nonpeptide antagonists of endothelin I are described, as well as novel intermediates used in their preparation, methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, essential renovascular malignant and pulmonary hypertension, cerebral infarction, cerebral ischemia, congestive heart failure and subarachnoid hemorrhage.

Abstract: A series of novel serotonergic indolyl derivatives of cycloalkanyl- and cycloalkenyl-amines of Formula I are intended for use in the alleviation of vascular headaches.

Abstract: Compounds of the formula ##STR1## where R.sub.1 -R.sub.5 are hydrogen, lower alkyl of 1-6 carbons, or halogen; A is (CH.sub.2).sub.n where n is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds; B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR.sub.8, CONR.sub.9 R.sub.10, --CH.sub.2 OH, CH.sub.2 OR.sub.11, CH.sub.2 OCOR.sub.11, CHO, CH(OR.sub.12).sub.2, CHOR.sub.13 O, --COR.sub.7, CR.sub.7 (OR.sub.12).sub.2, or CR.sub.7 OR.sub.13 O, where R.sub.7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R.sub.8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R.sub.8 is phenyl or lower alkylphenyl, R.sub.9 and R.sub.10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R.sub.11 is lower alkyl, phenyl or lower alkylphenyl, R.sub.

Abstract: This invention relates to novel substituted tryptamine and phenalkylamine and related compounds, pharmaceutical compositions thereof and methods of using said compounds and compositions for a number of pharmaceutical indications including (but not limited to): 1. central nervous system and psychiatric disorders (e.g., sleep disorders, epilepsy and other convulsive disorders, anxiety, psychiatric diseases, neurodegenerative diseases, fever); 2. chronobiological-based disorders (e.g., jet lag, delayed sleep syndrome, shift-work, seasonal affective disorder); 3. endocrine indications (e.g., contraception and infertility, precocious puberty, premenstrual syndrome, hyperprolactinemia, growth hormone deficiency); 4. cancer and other proliferative diseases; 5. immune system disorders and conditions associated with senescence; 6. ophthalmological diseases; 7. animal breeding (e.g., regulation of fertility, puberty, pelage color).

Abstract: A method of synthesizing an indole derivative of the tryptamine type particularly .?.melatonine,.!. .Iadd.melatonin .Iaddend.comprising the steps of 1) reacting potassium phthalimide and 1,3-di-bromopropane to obtain 3-bromopropylphthalimide; 2) reacting 3-bromopropylphthalimide with sodium acetoacetic ester in ethanol to obtain ethyl-2-acetyl-5-phthalimidopentanoate; 3) reacting the product from step 2) with diazo-p-anisidine to obtain 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole; 4) reacting the 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole with 2N/NaOH and then 20% H.sub.2 SO.sub.4 to obtain impure 5-methoxytriptamine, which is purified by means of hexamethyldisilazane. The mono and disubstituted derivatives are obtained and the monosubstituted derivative is hydrolyzed with aqueous methanol and then recrystallized from ethanol. The N-acetyl derivative is prepared by reaction with acetic anhydride. .?.Melatonine.!. .Iadd.Melatonin .Iaddend.