Abstract: The present invention relates to novel naphthopyran-type compounds, annelated in position C5-C6 by an indene- or dihydronaphthalene-type carbocycle, which are of the formulae (I) and (II) given below: These compounds (I) and (II) have interesting photochromic properties. The invention also relates to their preparation, to their applications as photochromes, as well as to the compositions and (co)polymer matrices containing them.

Abstract: Novel sulfatase inhibitor/estrogen receptor blocker compounds useful in the treatment of estrogen dependent illnesses are disclosed. The compounds generally comprise a sulfamate moiety and an aromatic, estrogen receptor blocker moiety. Methods for synthesizing these compounds and using them in the therapeutic and/or prophylactic treatment of an estrogen-dependent disease are also disclosed.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention relates to novel compounds of formula (I): 1

Abstract: This invention is directed to substituted (aminoiminomethyl or aminomethyl) dihydrobenzofurans and benzopyrans that inhibit Factor Xa, pharmaceutical compositions comprising these compounds and their use for inhibiting Factor Xa or treating pathological conditions in a patient that may be ameliorated by administration of such compounds. This invention is also is also directed to substituted (aminoiminomethyl or aminomethyl) dihydrobenzofurans and benzopyrans which directly inhibit both Factor Xa and Factor IIa (thrombin), to pharmaceutical compositions comprising these compounds, to intermediates useful for preparing these compounds and to a method of simultaneously directly inhibiting both Factor Xa and Factor IIa (thrombin).

Abstract: The subject invention pertains to novel enantiomerically pure compounds, and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns a method of making and purifying the compounds. The enantiomerically purified compounds, and compositions of these compounds, exhibit unexpectedly distinct and advantageous characteristics, such as a markedly superior ability to reduce or inhibit ventricular premature beats, as compared to racemic mixtures of the compounds.

Abstract: Compounds of formula (I) 1

Abstract: This invention provides estrogen receptor modulators of formula 1, having the structure 1

Abstract: The invention relates to novel 2-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole derivatives of the formula (I) in which Ar represents substituted phenyl, to a plurality of processes for their preparation and to their use as pesticides.

Abstract: The present invention is concerned with compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein R1 is hydrogen, hydroxy, C1-6alkyl or aryl; R2 is hydrogen; optionally substituted C1-12alkyl; C3-7cycloalkyl; C2-8alkenyl, optionally substituted pyrrolidinyl or aryl; R3 is hydrogen, optionally substituted C1-6alkyl or aryl; Het is an optionally substituted unsaturated heterocycle selected from imidazolyl, triazolyl, tetrazolyl and pyridinyl; is an optionally substituted unsaturated mono- or bicyclic heterocycle; and aryl is optionally substituted phenyl. The present invention also relates to processes for their preparation and compositions comprising said new compounds, as well as their use as a medicine.

Abstract: The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-[4-(2-aminoethoxy)benzoyl]benzo[b]-thiophenes. The present invention is also directed to crystalline solvates and a non-solvated crystalline form of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]-benzo[b]thiophene hydrochloride, as well as processes for their preparation.

Abstract: Compounds of formula (I) 1

Abstract: The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-[4-(2-aminoethoxy)benzoyl]benzo[b]-thiophenes. The present invention is also directed to crystalline solvates and a non-solvated crystalline form of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]-benzo[b]thiophene hydrochloride, as well as processes for their preparation.

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: A compound represented by the general formula (I), a pharmaceutically acceptable acid addition salt thereof or a pharmaceutically acceptable C1-C6 alkyl addition salt thereof, and their medical applications. These compounds inhibit the action of chemokines such as MIP-1&agr; and/or MCP-1 on target cells, and are useful as therapeutic and/or preventative drugs in diseases, such as atherosclerosis, rheumatoid arthritis, and the like where blood monocytes and lymphocytes infiltrate into tissues.

Abstract: The instant invention provides compounds of formula I wherein R1 is OH, O—C(O)—(C1-C6 alkyl), O—C(O)—O(C1-C6 alkyl), O—C(O)—Ar, or O—C(O)—O—Ar; R2 is H, OH, O(C1-C6 alkyl), O—C(O)—(C1-C6 alkyl), O—C(O)—O(C1-C6 alkyl), O—C(O)—Ar, O—C(O)—O—Ar, O—SO2—(C4-C6 alkyl), chloro, fluoro, or bromo; V is S, O, or CH2CH2; W is CHOH, C(O), or CH2; X is (CH2)n; R3 and R4 each, independently, are H, C1-C6 alkyl, C(O)—(C1-C6 alkyl), C(O)—NH—(C1-C6 alkyl), C(O)—Ar, or together with the nitrogen to which they are attached form a 5- or 6-membered imide or cyclic amide; n is 1, 2, or 3; and Ar is optionally substituted phenyl; povided that at least one of R3 and R4 contains a carbonyl functional group, and their use in the treatment of estrogen deficiency pathologies.

Abstract: Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1

Abstract: This invention is directed to a class of acrylic and propionic acid compounds and their use in the treatment of post-menopausal symptoms and restenosis. In other embodiments, the invention is directed to intermediates and to processes for the preparation of the acrylic and propionic acid compounds.

Abstract: Cyclohexenonedioxothiochromanoyl derivatives of the formula I where X is oxygen, sulfur, S═O, S(═O)2, CR4R5, C═O or C═NR6, the other substituents are as defined in the specification, and and agriculturally useful salts thereof; processes for preparing the cyclohexenonedioxotheiochromanoyl derivatives; compositions comprising them, and the use of these derivatives or of compositions comprising them for controling undesirable piants.

Abstract: The instant invention provides compound of formula I wherein: R1 is —H, —OH, —O(C1-C4 alkyl), —O—CO—(C1-C6 alkyl), —O—CO—O(C1-C6 alkyl), —O—CO—Ar in which Ar is optionally substituted phenyl, or —O—SO2—(C4-C6 alkyl); R2 is —H, —OH, —O(C1-C4 alkyl), —O—CO—(C1-C6 alkyl), —O—CO—O(C1-C6 alkyl), —O—CO—Ar in which Ar is optionally substituted phenyl, —O—SO2—(C4-C6 alkyl), —F, —Cl, or —Br; n is an integer from 5 to 8; R3 and R4 each are independently C1-C4 alkyl, or combine to form, with the nitrogen to which they are attached, piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, or hexamethyleneimino; or a pharmaceutically acceptable salt or solvate thereof, intermediates, pharmaceutical formulations, processes, and methods of use.

Abstract: The invention provides novel benzothiophenes of the formula: wherein R1 is —H, —OH, —O(C1-C4 alkyl), —O—CO(C1-C6 alkyl), —OSO2(C4-C6 alkyl, or —OCOAr where Ar is optionally substituted phenyl; R2 is —H, —OH, —Cl, —Br, —O(C1-C4 alkyl), —OCO(C1-C6 alkyl), —OSO2(C4-C6 alkyl, or —OCOAr where Ar is optionally substituted phenyl; R3 is —H, —F, —Cl, —(C1-C4 alkyl), —CN, or —O(C1-C3 alkyl); R4 is —H, —F, —Cl, —(C1-C4 alkyl), —CN or —O(C1-C3 alkyl); R5 is —H, —F, —Cl, —(C1-C4 alkyl), or —O(C1-C3 alkyl); and R6 is —H, —F, —Cl, —(C1-C4 alkyl), or —O(C1-C3 alkyl); with the provisos that R3, R4, R5 and R6 can not all be hydrogen, and that when one of R3, R4, R5 or R6 is C1-C4 alkyl, no more than two of R3, R4, R5 and R6 can be hydrogen; Y is —CO—, —CHOH—, or &mda

Abstract: The present invention relates to a fused thiophene derivative of the formula (I) (wherein all the symbols are defined as described in the specification) and an inhibitor of producing interleukin-6 and/or interleukin-12 comprising the said derivative as an active ingredient. A fused thiophene derivative of the formula (I) is useful as an agent for the prevention and/or treatment of various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi's sarcoma, rheumatoid arthritis, gammopathy, Castleman's disease, atrial myxoma, diabetes mellitus, autoimmune diseases, hepatitis, multiple sclerosis, colitis, graft versus host immune diseases, infectious diseases.

Abstract: This invention relates to the fields of pharmaceutical and organic chemistry and provides novel 3-benzyl-benzothiophenes which are a-substituted with ether, thioether amino, hydrazino, cyano or halo that are useful for the treatment of the various medical indications associated with post-menopausal syndrome, as well as estrogen dependent diseases including cancer of the breast, uterus and cervix. The present invention further relates to intermediate compounds and processes useful for preparing the pharmaceutically active compounds of the present invention, and pharmaceutical compositions.

Abstract: Process for the preparation of compounds of formula (I), wherein the general symbols are as defined in claim 1, which process comprises reacting a compound of formula (V), wherein the general symbols are as defined in claim 1, with carbon monoxide in the presence of a catalyst.

Abstract: Compounds of Formula 1 1

Abstract: The present invention provides novel compound of the formula: wherein Ra is —OH or —O—(C1-C4 alkyl); R1a is —OH or —O—(C1-C4 alkyl); n is 2 or 3; R2 and R3 are each independently: —C1-C4 alkyl, or combine to form 1-piperidinyl, 1-pyrrolidinyl, 1-pyrrolidinyl substituted with one or two methyl groups, 4-morpholino or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof.

Abstract: This invention provides novel benzothiophene compounds of formula I: which are useful for the inhibition of the various medical conditions associated with postmenopausal syndrome, as well as estrogen dependent diseases including cancer of the breast, uterus, and cervix. The present invention further. relates to pharmaceutical formulations of compounds of formula I.

Abstract: The present invention relates to the compounds of formula (I) in which X, R1, R2 and R3 are as defined in claim 1. These compounds are cholesteryl acyl transferase (ACAT) inhibitors.

Abstract: The present invention provides method of treating endometriosis using novel benzothiophene compounds of formula I wherein R is —H, —OH, —O(C1-C4 alkyl), —O—CO—(C1-C6 alkyl), —O—CO—Ar in which Ar is optionally substituted phenyl, or —O—SO2—(C4-C6 alkyl); R1 is —H, —OH, —O(C1-C4 alkyl),, —O—CO—(C1-C6 alkyl), —O—CO—Ar in which Ar is optionally substituted phenyl, —O—SO2—(C4-C6 alkyl) chloro or bromo; R2 is —H or —OH; n is 2 or 3; and R3 and R4 each are independently C1-C4 alkyl, or combine to form 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof.

Abstract: The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-[4-(2-aminoethoxy)benzoyl]benzo[b]-thiophenes. The present invention is also directed to crystalline solvates and a non-solvated crystalline form of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]-benzo[b]thiophene hydrochloride, as well as processes for their preparation.

Abstract: Novel compounds that are potent and selective inhibitors of PDE4, as well as methods of making the same, are disclosed. Use of the compounds in the treatment of inflammatory diseases and other diseases involving elevated levels of cytokines, as well as central nervous system (CNS) disorders, also is disclosed.

Abstract: The present invention provides a compound of formula I wherein R1 is H, OH, halo, OCO(C1-C6 alkyl), OCO(aryl), OSO2(C4-C6 alkyl), OCOO(C1-C6 alkyl), OCOO(aryl), OCONH(C1-C6 alkyl), or OCON(C1-C6 alkyl)2; R2 is aryl, C1-C6 alkyl, C3-C6 cycloalkyl, or 4-cyclohexanol; R3 is O(CH2)2 or O(CH2)3; R4 and R5 are optionally CO(CH2)3, CO(CH2)4, C1-C6 alkyl, or R4 and R5 combine to form, with the nitrogen to which they are attached, piperidine, morpholine, pyrrolidine, 3-methylpyrrolidine, 3,3-dimethylpyrrolidine, 3,4-dimethylpyrrolidine, azepine, or pipecoline; R6 is and pharmaceutically acceptable salts thereof; useful in treating estrogen deficient pathology.

Abstract: A pharmaceutical compound of formula (I) in which R1 and R2 are each hydrogen or C1-4 alkyl, or R1 and R2 together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholino group, said group being optionally substituted with 1 to 3 C1-4alkyl substituents, R3 is a naphythyl, indolyl, benzothienyl, benzofuranyl, benzothiazolyl, quinolinyl or isoquinolinyl group, said group being optionally substituted, and n is 1 or 2; or a salt or ester thereof.

Abstract: Compounds that modulate gene expression through the estrogen receptor (ER) are disclosed having the following structure, as well as pharmaceutical compositions containing the same: wherein R1, R2, R3, n and p are as defined here. Methods are also disclosed for modulating ER in cells and/or tissues expressing the same, such as bone, breast, prostate, uterus, CNS or the cardiovascular system. Methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, and adverse reproductive effects associated with exposure to environmental chemicals or natural hormonal imbalances.

Abstract: The present invention provides novel crystalline (−)-3R,4R-trans-7-methoxy-2,2-dimethyl-3-phenyl-4-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}chromane, hydrogen maleate useful for reducing or preventing bone loss as well as pharmaceutical compositions containing the same. A process for preparing (−)-3R,4R-trans-7-methoxy-2,2-dimethyl-3-phenyl-4-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}chromane, hydrogen maleate is described.

Abstract: The invention relates to a compound having formula (I) wherein A is an optionally unsaturated 5- or 6-membered ring, which may comprise a heteroatom selected from N, O and S and which may be substituted with oxo or (1-6C)alkyl; R1, R2 and R3 are independently H, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkoxy-(1-6C)alkyl, carbo(1-6C)alkoxy or halogen; X is O or S; and n is 1 or 2; or a pharmaceutically acceptable salt thereof, with the exception of 3-(naphth-1-yl-oxy)-pyrrolidin and 3-(5,6,7,8-tetrahydro-napth-1-yl-oxy)-pyrrolidin. The compounds of the invention have antidepressant activity and can be used in treating or preventing serotonin-related diseases.

Abstract: A process for the production of a Mannich reagent comprises reacting formaldehyde, especially paraformaldehyde, with a secondary amine in the complete or almost complete absence of a solvent. An alternative comprises reacting a diaminomethane produced from a secondary amine, formaldehyde, especially paraformaldehyde, as well as water with one another in about equimolar amounts. The invention is also concerned with a process for the aminomethylation of &dgr;-tocopherol or of tocopherol mixtures containing this and comprises using a Mannich reagent which has been produced in the above manner. After completion of this aminomethylation process excess Mannich reagent can be separated by distillation and can be reacted with water and formaldehyde, especially paraformaldehyde, in order to regenerate further Mannich reagent suitable for use in the aminomethylation, this regeneration representing a further aspect of the invention. Finally, the invention includes certain novel bis(aminomethyl)-&ggr;-tocopherols.

Abstract: The present invention provides a medicament exhibiting excellent retinoic acid receptor agonism. A Carboxylic acid derivative having a fused ring which is represented by the following formula or a pharmacologically acceptable salt thereof: {wherein the symbol represents a single bond or a double bond; X, Y, Z, P, Q, U, V and W are each a group represented by the formula: —O— or —S—, or a group represented by the formula: [wherein Rk (k: 1 to 8) is hydrogen, halogeno, optionally substituted lower alkyl or the like, with either of R7 and R8 being a group represented by the formula: (wherein A and B are each independently an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and D is optionally protected carboxyl)]}.

Abstract: Described are novel photochromic naphtho[1,2-b]pyran compounds having certain substituents at the 2 position of the pyran ring, certain substituents at the 5 and 6 positions and optionally at the 7, 8, 9 and 10-positions of the naphtho portion of the compound. These compounds may be represented by the following graphic formula: Also described are polymeric organic host materials that contain or that are coated with such compounds. Optically clear articles such as ophthalmic lenses or contact lenses that incorporate the novel naphthopyran compounds or combinations thereof with complementary photochromic compounds, e.g., certain other naphthopyrans, benzopyrans, and spiro(indoline)type compounds, are also described.

Abstract: The present invention provides the compounds of the following formula (I): and a method for inhibiting the reuptake of seretonin, antagonizing the 5-HT1A receptor and antagonizing the 5-HT2A receptor which comprises administering to a subject in need of such treatment an effective amount of formula (I).

Abstract: This invention is directed to a class of acrylic and propionic acid compounds and their use in the treatment of post-menopausal symptoms and restenosis. In other embodiments, the invention is directed to intermediates and to processes for the preparation of the acrylic and propionic acid compounds.

Abstract: This application relates to novel compounds of formula (I) (and their pharmaceutically acceptable salts), as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula (I), and the use of the compounds of formula (I) as thrombin inhibitors.

Abstract: The present invention provides novel crystalline (−)−3R,4R-trans-7-methoxy-2, 2-dimethyl-3-phenyl-4-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}chromane, hydrogen maleate useful for reducing or preventing bone loss as well as pharmaceutical compositions containing the same. A process for preparing (−)−3R,4R-trans-7-methoxy-2,2-dimethyl-3-phenyl-4-{4-[2-(pyrrolidin-1-yl) ethoxy]phenyl}chromane, hydrogen maleate is described.

Abstract: Compounds that modulate gene expression through the estrogen receptor (ER) are disclosed having the following structure, as well as pharmaceutical compositions containing the same: wherein R1, R2, R3, n and p are as defined here. In a specific embodiment, the compounds are selective modulators for Er-&bgr; over ER-&agr;. Methods are also disclosed for modulating ER-&bgr; in cells and/or tissues expressing the same, including cells and/or tissues that preferentially express ER-&bgr;. More generally, methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, testicular cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, urinary incontinence, hairloss, cataracts, natural hormonal imbalances, and adverse reproductive effects associated with exposure to environmental chemicals.

Abstract: The present invention relates to therapeutically active compounds of formula I a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in the prevention or treatment of estrogen related diseases or syndromes.

Abstract: The photochromic compounds of the invention correspond to the formula: in which Th2 represents a bithienyl group in one of the positions 5 to 10 of the naphthenic ring system system, R1 denotes a bithienyl or trithienyl group and R2 denotes a bithienyl, trithienyl, aryl, naphthyl, thienyl, furyl, pyrrolyl or N-alkylpyrrolyl group.

Abstract: This invention relates to neurotrophic low molecular weight, small molecule N-linked sulfonamides of heterocyclic thioesters having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.

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. wherein Q is an un-natural amino acid. More particurlarly, 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 aneurism, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, arthiritis, or other autoimmune or inflammatory diseases dependent upon tissue invasion by leukocytes.

Abstract: This invention provides novel benzothiophene compounds of the formula I: which are useful for the treatment of the various medical conditions associated with postmenopausal syndrome, as well as estrogen dependent diseases including cancer of the breast, uterus, and cervix. The present invention further relates to pharmaceutical formulations of compounds of formula I.

Abstract: Compounds that modulate gene expression through the estrogen receptor (ER) are disclosed having the following structure, as well as pharmaceutical compositions containing the same: wherein R1, R2, R3, n and p are as defined here. Methods are also disclosed for modulating ER in cells and/or tissues expressing the same, such as bone, breast, prostate, uterus, CNS or the cardiovascular system. Methods for treating estrogen-related conditions are also disclosed, including conditions such as is breast cancer, osteoporosis, endometriosis, cardiovascular disease, hypercholesterolemia, prostatic hypertrophy, prostatic carcinomas, obesity, hot flashes, skin effects, mood swings, memory loss, and adverse reproductive effects associated with exposure to environmental chemicals or natural hormonal imbalances.