Abstract: The present invention relates to novel heterocyclic fluoroalkenyl thioethers of the formula (I) 1

Abstract: The use of compounds of formula (1) is described, in which compounds R1, R2 and R3 are each independently of the others hydrogen; C1-C20alkyl; C3-C7cycloalkyl; C2-C20alkenyl; C4-C7cycloalkenyl; C2-C20alkynyl, C4-C7cycloalkynyl; or unsubstituted or C1-C5alkyl-, C3-C7cylcoalkyl-, C1-C5alkoxyl-, C3-C7cycloakoxy-, halo-, oxo-, carboxy-, carboxy-C1-C7alkyl ester-, carboxy-C3-C7cylcloalkyl ester-, cyano-, trifluoromethyl-, pentafluoroethyl-, amino-, N,N-mono- or di-C1-C20alkylamino- or nitro-substituted phenyl-C1-C5alkyl, naphthyl-C1-C5alkyl, phenylcarbonyl-C1-C5alkyl, naphthylcarbonyl-C1-C5alkyl, pyrrolylalkyl, furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl, oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl, 1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl, 1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl, 1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl, pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl, pyrrolyl, furanyl,

Abstract: This invention relates to novel heterocyclic derivatives of the formula (VII), (VIII) or (IX) 1

Abstract: Compounds having the general structure 1

Abstract: The present invention relates to 3-heteroarylidenyl-2-indolinone compounds that modulate the enzymatic activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer. Furthermore, these compounds are expected to enhance the efficacy of other chemotherapeutic agents, in particular, fluorinated pyrimidines, in the treatment of cancer.

Abstract: This invention relates to novel heteroatom containing compounds and compositions thereof, and their use for the prevention and treatment of disease. The invention also provides for methods of making the compounds. The invention is based on the discovery that certain heteroatom containing compounds, 3-oxoacetamideindolyl compounds, have potent anticancer, cytotoxic, and anti-angiogenic activity.

Abstract: The invention relates to nitrofuran-containing compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds and compositions comprising them are useful for treating disease or disease symptoms. The invention also provides for methods of making the compounds, and methods for identifying compounds with desired biological activity.

Abstract: A compound of the formula (1): 1

Abstract: The invention concerns a compound of the formula (I): wherein, for example: T is of the formula (IA), (IB), or (IC); R1 is of the formula —NHC(═O)Rb wherein Rb is (1-4C)alkyl; R2 and R3 are hydrogen or fluoro; >A—B— is >C═CH— (but not when T is (IA)) or >CH—CH2—; wherein when T is of the formula (IA) or (IB); R6 is, for example, (1-4C)alkyl; R5 is hydrogen, R10CO—, R10SO2— or R10CS— wherein R10 is, for example, optionally substituted phenyl, or (1-10C)alkyl, or when T is of the formula (IA), (IB); or (IC): R5 and R6 are linked to give a 5- or 6-membered ring which is fused to the ring shown in (IA), (IB), or (IC) so as to give an optionally substituted bicyclic ring; and pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them, and their use as antibacterial agents.

Abstract: Compounds of the general formula I where the index and the substituents have the following meanings: n is 0 or 1 to 4; X is O or S; Y is a five-membered heteroaromatic ring; R1 is nitro; cyano; halogen; alkyl; haloalkyl; alkoxy; haloalkoxy; alkylthio; phenyl or phenoxy; R2 is hydrogen; alkyl, alkenyl or alkynyl; or a saturatedy,or unsaturated ring which, in addition to carbon atoms, can also contain hetero atoms as ring members are described.

Abstract: This invention is directed to a method of retarding or preventing the transformation of a colonic adenoma to a colonic adenocarcinoma comprising the administration to a patient with FAP or a patient with one or more of said adenomas a non-toxic therapeutically effective amount of NSAID, said amount effective to inhibit the PGHS-2 in said adenoma. The preferred method comprises the administration of a specific PGHS-2 inhibiting agent as defined herein.

Abstract: The present invention relates to compounds with the formula (I) 1

Abstract: The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.

Abstract: The present invention relates to substituted pyrazolyl derivatives, compositions comprising such, intermediates, methods of making substituted pyrazolyl derivatives, and methods for treating cancer, inflammation, and inflammation-associated disorders, such as arthritis.

Abstract: The present invention is directed to novel inhibitors and methods for inhibiting serine elastases. These compounds and methods achieve a novel approach to enzyme inhibition; namely, balanced inhibition of a plurality of serine elastases. Balanced inhibition of a plurality of elastases offers a novel approach to therapeutic treatment of diseases that involve abnormal activities of a plurality of elastases resulting in pathological changes such as occur in inflammatory and vascular conditions. These pathological changes are not limited to the breakdown of elastin but may include the processing of other proteins by serine elastases which in turn results in adverse effects. The opportunity of targeting a plurality of enzymes using single inhibitor offers therapeutic advantages over administering multiple therapeutic against where each agent has a single specificity for an individual target enzyme.

Abstract: Compounds of formula (I) or pesticidally acceptable salts thereof, compositions containing them and methods of use.

Abstract: Microbicide composition for plants, containing at least two active ingredient components in an amount producing synergistic activity, together with an appropriate filler, characterized in that

Abstract: Methods of treating exercise-induced asthma using a PDE-4 inhibitor are disclosed.

Abstract: In accordance with the present invention, there are provided compounds and pharmaceutical compositions useful for the selective inhibition of COX-2 in the presence of COX-1. As a result, invention compounds and compositions provide anti-inflammatory relief to a subject in need thereof while dramatically reducing the occurrence of side effects in the subject. Compounds contemplated for use in the practice of the present invention are substituted heterocyclic compounds containing amidinyl and imidazolyl groups.

Abstract: Disclosed is a pharmaceutical composition, comprising a combination of a dose of rofecoxib or a pharmaceutically acceptable salt thereof and a dose of oxcodone or a pharmaceutically acceptable salt thereof, said combination in an amount sufficient to provide an analgesic effect in a human patient. Also disclosed is a method of effectively treating pain in humans or other mammals, comprising administering to the patient a combination of a dose of rofecoxib or a pharmaceutically acceptable salt thereof and a dose of oxycodone or a pharmaceutically acceptable salt thereof such that the dosing interval of the rofecoxib overlaps with the dosing interval of the oxycodone, said combination in an amount sufficient to provide an analgesic effect in a human patient.

Abstract: The invention provides a method for modulating attentive cognition comprising administering a compound that alters intraneuronal carbonic anhydrase activity thereby affecting establishment of a theta rhythm. The metabolic pathway of the compound preferably involves bicarbonate-mediated GABAergic depolarization. The term “attentive cognition” is meant to encompass memory formation, learning, spatial memory, and attention. The modulating may be stimulating, or the compound may have the multiple effects of inhibiting intraneuronal carbonic anhydrase activity, establishment of a theta rhythm, and memory acquisition. The invention further provides a method of modulating memory and attention comprising switching theta rhythm on and off, the switching comprising potentiating or inhibiting intraneuronal carbonic anhydrase activity.

Abstract: Compounds, compositions, and methods for inhibiting the glycine transporter 2 and for inhibiting glycine transporter mediated neuronal activity. These compounds are particularly useful for treating diseases of the nerve and muscle, including psychoses, pain, epilepsy, neurodegenerative diseases, stroke, head trauma, multiple sclerosis and the like, and of muscle disorders, including diseases or conditions associated with increased muscle contraction, such as spasticity and myoclonus. In addition, the compounds may be used to discover other agents with improved activity in assays in which the compounds of the invention are active.

Abstract: The invention provides compounds of Formula I: compounds of the Formula I: 1

Abstract: The invention provides 1,3,4-thiadiazoles and 1,3,4-oxadiazoles having the following Formula I: 1

Abstract: A series of activated iodo-benzamide derivatives are described as antineoplastic and antiviral drug compounds. The compounds generally possess a chelating group, a thiol trapping group and an activating group. The presumptive mechanism of action in preventing cancer cell and virus replication is through inhibition of the binding of transcription factors to zinc finger binding domains. The compounds are effective in inhibiting growth of a variety of human and animal tumor and leukemia cell lines at low concentrations.

Abstract: Antiatherosclerotic agents are provided which are represented by Formulas I or II: 1

Abstract: The present invention concerns antiviral compounds, their compositions, and use in the treatment of viral infections. More particularly, the invention provides benzimidazolone derivatives for the treatment of respiratory syncytial virus infection.

Abstract: A method is disclosed for rational design of a PPAR, FXR, LXR-alpha, or LXR-beta antagonist comprising chemical modification of a PPAR, FXR, LXR-alpha, or LXR-beta agonist to: a) prevent formation of a hydrogen bond between the agonist and tyrosine or histidine, or tryptophan involved in receptor activation; and/or b) displace the tyrosine or histidine, or tryptophan involved in receptor activation from its agonist bound position. Preferably, little or no additional changes are made in the structure of the agonist so that the resulting antagonist is a close structural analogue of the agonist.

Abstract: Provided, among things, is a method of decreasing intraocular pressure in an animal, including a human, comprising administering an intraocular pressure decreasing amount of a compound of the formula I: 1

Abstract: Provided, among things, is a method of treating or ameliorating an indication of the invention in an animal, including a human, comprising administering an effective amount of a compound of formula I: 1

Abstract: The invention concerns compounds of formula (I), wherein, for example, R1 is of the formula —NHC(═O)Ra wherein Ra is (1-4C)alkyl; R2 and R3 are independently hydrogen or fluoro; R5 and R6 are, for example, hydrogen; R4 is —X—Y—Het.; wherein, for example, X is a direct bond and Y is —(CH2)m— or —CONH—(CH2)m—; or X is —(CH2)n— and Y is —S(O)p—(CH2)m—; or X is —CH2O—or —CH2NH— and Y is —CO—(CH2)m—; wherein n is 1, 2 or 3; m is 0, 1, 2 or 3 and p is 0, 1 or 2; wherein Het. is a heterocyclic ring, unsaturated or saturated, optionally substituted by, for example, (1-4C)alkyl, halo, cyano, nitro or amino; pharmaceutically acceptable salts and in vivo hydrolysable ester thereof; processes for their preparation; pharmaceutical compositions containing them and their use as antibacterial agents.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds aslo inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The intention relates to bacterial antibiotic resistance and, in particular, to compositions and methods for overcoming bacterial antibiotic resistance. The invention provides novel &bgr;-lactamase inhibitors, which are structurally unrelated to the natural product and semi-synthetic &bgr;-lactamase inhibitors presently available, and which do not require a &bgr;-lactam pharmacophore. The invention also provides pharmaceutical compositions and methods for inhibiting bacterial growth.

Abstract: The present invention relates to a series of peptidyl heterocyclic ketones which are inflammatory cell serine protease inhibitors and their compositions and methods for the prevention and treatment of a variety of immunomediated inflammatory disorders. More particularly, these compounds are potent and selective inhibitors of tryptase and are therefore effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis.

Abstract: The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.

Abstract: The present invention relates to a method of treating Multiple Sclerosis, other demyelinating disorders and peripheral neuropathy in a mammal by administering to the mammal a neurotransmitter-inducing or precursor agent in combination with an (SRI) antidepressant or an anxiolytic agent with improvement in efficiency. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a neurotransmitter-inducing or precursor agent, and an SRI antidepressant or anxiolytic agent.

Abstract: Potent inhibitors of fatty acid amide hydrolase (FAAH) are constructed having Ki's below 200 pM and activities 102-103 times more potent than the corresponding trifluoromethyl ketones. The potent inhibitors combine several features, viz.: 1.) an &agr;-keto heterocylic head group; 2.) a hydrocarbon linkage unit employing an optimal C12-C8 chain length; and 3.) a phenyl or other &pgr;-unsaturation corresponding to the arachidonyl &Dgr;8.9/&Dgr;11.12 and/or oleyl &Dgr;9.10 positions. A preferred &agr;-keto heterocylic head group is &agr;-keto N4 oxazolopyridine, with incorporation of a second weakly basic nitrogen. Fatty acid amide hydrolase is an enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid) and anandamide (an endogenous ligand for cannabinoid receptors).

Abstract: Compounds are disclosed which efficiently inhibit glutaminase but which have no effect, at higher levels, on various mechanistically and functionally related enzymes. The compounds, which are useful for neuroprotection and in treatment of hepatic encephalopathy, have the general formula I: as defined further herein.

Abstract: 2-Hydrazino-1,3-thiazoles, or their salts, can be used as effective constituents in cosmetic and dermatological preparations, and in preparations which are of use in nutrition or consumption, for protecting mammalian cells and tissues, and also the preparations, from the harmful effect of reactive oxygen species and free radicals.

Abstract: Oxazolidinones and methods for their synthesis are provided. Further provided are methods of making biologically active oxazolidinones as well as pharmaceutically acceptable compositions comprising the oxazolidinones. Oxazolidinones as disclosed herein can be readily synthesized and used in a variety of applications including use as antimicrobial agents. In one embodiment, a variety of thioamidomethyloxazolidinones and methods for their synthesis and use are provided.

Abstract: Compounds are disclosed which efficiently inhibit glutaminase but which have no effect, at higher levels, on various mechanistically and functionally related enzymes.

Abstract: This invention relates to a method for the prophylaxis of or reducing the severity of post-viral bacterial infection by administering a PDE 4-specific inhibitor prior to or during the course of a viral infection or thereafter during the course of the bacterial infection.

Abstract: The invention provides a method for modulating attentive cognition comprising administering a compound that alters intraneuronal carbonic anhydrase activity thereby affecting establishment of a theta rhythm. The metabolic pathway of the compound preferably involves bicarbonate-mediated GABAergic depolarization. The term “attentive cognition” is meant to encompass memory formation, learning, spatial memory, and attention. The modulating may be stimulating, or the compound may have the multiple effects of inhibiting intraneuronal carbonic anhydrase activity, establishment of a theta rhythm, and memory acquisition. The invention further provides a method of modulating memory and attention comprising switching theta rhythm on and off, the switching comprising potentiating or inhibiting intraneuronal carbonic anhydrase activity.

Abstract: Minor groove binding molecules are covalently bound to oligonucleotides which in their base sequence are complementary to a target sequence of single stranded or double stranded DNA, RNA or hybrids thereof. The covalently bound oligonucleotide minor groove binder conjugates strogly bind to the target sequence of the complementary strand.

Abstract: A method for inhibiting the action of TNF for treating neurological conditions in a human by administering a TNF antagonist for reducing the inflammation of neuronal tissue of said human, or for modulating the immune response affecting neuronal tissue of said human, comprising the step of: administering a therapeutically effective dosage level to said human of said TNF antagonist selected from the group consisting of etanercept, infliximab, and D2E7 (a human anti-TNF mAb from Knoll Pharmaceuticals) for reducing the inflammation of neuronal tissue of said human, or for modulating the immune response affecting neuronal tissue of said human. In addition, for the viral-associated neurological disorders, the following additional step is performed: administering a therapeutically effective dosage level to said human of an antiviral agent or anti-retroviral agents for reducing the inflammation of neuronal tissue of said human, or for modulating the immune response affecting neuronal tissue of said human.

Abstract: This invention relates to pharmaceutical compositions and methods for treating alopecia and promoting hair growth using N-linked ureas or carbamates of heterocyclic thioesters.

Abstract: A method for treating COPD is disclosed comprising administering compounds of Formula (I) wherein the terms R1, R3, X, X2 and Z are herein defined.

Abstract: A compound of Formula (I): or pharmaceutical acceptable salts thereof wherein X is NR1; R1 is H, C1-6 alkyl optionally substituted with one or more OH, CN, or halo, or R1 is —(CH2)h-aryl, —COR1-1, —COOR1-2, —CO—(CH2)h—COR1-1, C1-6 alkyl sulfonyl, —SO2—(CH2)h-aryl, or —(CO)i-Het; R2 is H, C1-6 alkyl, —(CH2)h-aryl, or halo; R3 and R4 are independently H or halo; R5 is H, C1-12 alkyl optionally substituted with one or more halo, C3-12 cycloalkyl, C1-6 alkoxy; m and n taken together are 1 or 2. The compounds are useful antimicrobial agents.

Abstract: A benzimidazole compound represented by the formula (I): wherein R3 is a carboxyl group, a esterified carboxyl group, an amidated carboxyl group, an amino group, an amido group, or a sulfonyl group, or their pharmaceutically acceptable salts. Because of their blood sugar-depressing effect or PDE5 inhibitory effect, these compounds or salts thereof are useful as medicines for treating impaired glucose tolerance, diabetes, diabetic complications, syndrome of insulin resistance, hyperlipidemia, atherosclerosis, cardiovascular disorders, hyperglycemia, or hypertension; or stenocardia, hypertension, pulmonary hypertension, congestive heart failure, glomerulopathy, tubulointerstitial disorders, renal failure, atherosclerosis, angiostenosis, distal angiopathy, cerebral apoplexy, chronic reversible obstructions, allergic rhinitis, urticaria, glaucoma, diseases characterized by enteromotility disorders, impotence, diabetic complications, nephritis, cancerous cachexia, or restenosis after PTCA.

Abstract: Compounds of formula (I) or pesticidally acceptable salts thereof, compositions containing them and methods of use.