Abstract: The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, R4, R6, R11, X1, X2, and X3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

Abstract: The disclosure relates to methods and materials useful for polymerizing a monomer. In one embodiment, for example, the disclosure provides a method for polymerizing a monomer containing a plurality of electrophilic groups, wherein the method comprises contacting the monomer with a nucleophilic reagent in the presence of a guanidine-containing catalyst. The methods and materials of the disclosure find utility, for example, in the field of materials science.

Abstract: The disclosure relates to methods and materials useful for depolymerizing a polymer. In one embodiment, for example, the disclosure provides a method for depolymerizing a polymer containing electrophilic linkages, wherein the method comprises contacting the polymer with a nucleophilic reagent in the presence of a guanidine-containing compound. The methods and materials of the disclosure find utility, for example, in the field of waste reclamation and recycling.

Abstract: The disclosure relates to methods and materials useful for polymerizing a monomer. In one embodiment, for example, the disclosure provides a method for polymerizing a monomer containing a plurality of electrophilic groups, wherein the method comprises contacting the monomer with a nucleophilic reagent in the presence of a guanidine-containing catalyst. The methods and materials of the disclosure find utility, for example, in the field of materials science.

Abstract: The disclosure relates to methods and materials useful for depolymerizing a polymer. In one embodiment, for example, the disclosure provides a method for depolymerizing a polymer containing electrophilic linkages, wherein the method comprises contacting the polymer with a nucleophilic reagent in the presence of a guanidine-containing compound. The methods and materials of the disclosure find utility, for example, in the field of waste reclamation and recycling.

Abstract: Prodrugs of guanfacine, pharmaceutical compositions containing such prodrugs and a method for providing therapeutic benefit in the treatment of ADHD/ODD (attention deficient hyperactivity disorder and oppositional defiance disorder) with guanfacine prodrugs are provided herein. Additionally, methods for improving the pharmacokinetics of guanfacine or minimizing or avoiding the adverse gastrointestinal side effects associated with guanfacine administration are provided herein.

Abstract: The present invention relates to novel inhibitors of glutaminyl cyclase and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Chorea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.

Abstract: The present invention relates to a family of guanidine-based F1F0-ATPase inhibitors, e.g., mitochondrial F1F0-ATPase inhibitors, methods for their discovery, and their use as therapeutic agents for treating certain disorders.

Abstract: Provided herein are methods and compounds for post-translational regulation of cytochrome P450 46A1 (CYP46A1) enzyme activity in the brain and retina. Also, a method for identifying a potential regulator of a CYP46A1 enzyme using crystal structures of the enzyme and a subsequent method for screening for a regulatory activity in the presence of CYP46A1 enzyme are provided. In addition, the regulator compounds that either inhibit or stimulate cholesterol hydroxylation by the CYP46A1 enzyme are provided. Further provided is a method of treating a pathoneurological condition associated with increased cholesterol levels in the brain and retina using the stimulatory compounds.

Abstract: Imidazole-based compounds, compositions comprising them, and methods of their use for the treatment, prevention and management of inflammatory and autoimmune diseases and disorders are disclosed.

Abstract: This invention provides compounds and methods for treating melanocortin receptor associated disorders, such as weight loss disorders including cachexia resulting from cancer and other chronic illnesses. The compounds are represented by formula I: wherein X is oxygen or sulfur; G is G1 or G2: L1, L2, L3 and Q are linker groups, and Rings A, B and C, and R1-R14 are described in the specification. The compounds are antagonists of melanocortin receptors.

Abstract: Compounds of the formula wherein the substituents are as defined in the specification which are useful for the treatment of pain.

Abstract: Transport reagents and conjugates of therapeutic agents linked to transport reagents are described. In particular, the transport reagents have a plurality of guanidinium moieties that are either contiguous or spaced along a backbone, but are sufficiently removed from the backbone via tethers, to allow their interaction with a cell or tissue surface, leading to uptake of the therapeutic agent.

Abstract: Compounds having the formula (I), and pharmaceutically acceptable salts thereof, are useful for modulating mitochondrial F1F0 ATPase activity and treating ischemic conditions including myocardial infarction, congestive heart failure, and cardiac arrhythmias.

Abstract: The invention relates to compounds of formula (2) in which R1, R2, R3 and R4 have the meanings indicated in the description, their preparation and their further reaction to give compounds of formula (1), in which A1, A2 and R4 have the meanings indicated in the description. The compounds of the formula (1) are valuable intermediates for the preparation of medicaments.

Abstract: Heterocyclically substituted benzoylguanidines of the formula I in which the substituents R(1) to R(4) have the meanings indicated in the claims. These compounds I are suitable as antiarrhythmic pharmaceuticals having a cardioprotective component for infarct prophylaxis and infarct treatment, and also for the treatment of angina pectoris. They also preventively inhibit the pathophysiological processes in the formation of ischemically induced damage, in particular in the elicitation of ischemically induced cardiac arrhythmias.

Abstract: The invention relates to &bgr;-alaninamides of general formula (I), wherein: R1 represents hydrogen or C1-C6 alkyl which is optionally substituted by hydroxy, amino, carboxy, carbamoyl, methylmercapto, guanidino, or by optionally substituted aryl or heteroaryl; R2 represents hydrogen or R1 and R2, together, form a group of formula —(CH2)n, wherein n represents 3 or 4, and; R3 represents hydrogen, a negative charge compensated for by an equivalent of an inorganic or organic cation or represents C1-C6 alkyl. The &bgr;-alaninamides are produced without using an amino protective group by reacting the corresponding &agr;-amino acid or the corresponding &agr;-amino acid ester with a cyanoacetic acid to form a cyanoacetic acid amide and by a subsequent catalytic hydrogenation. The method is particularly suited for producing carnosine (&bgr;alanyl-L-histidine, R1=imidazol-4-yl-methyl, R2═R3═H), a naturally occurring dipeptide, which is used as a food additive having an antioxidant effect.

Abstract: Alkenyl and alkynyl compounds as potent and highly selective inhibitors of factor Xa isolated or assembled in the prothrombinase complex and compositions containing such alkenyl and alkynyl compounds are described. Such compounds show selectivity for factor Xa over other proteases of the coagulation (e.g., thrombin, fvIIa, flXa) or the fibrinolytic cascades (e.g., plasminogen activators, plasmin). Methods for using such alkenyl and alkynyl compounds as diagnostic or therapeutic agents for prevention or treatment of a condition in a mammal characterized by undesired coagulation disorders, such as thrombosis, are also described.

Abstract: Compounds having formula I: are useful in treating diseases prevented by or ameliorated with &agr;1A agonists. Also disclosed are &agr;1A agonist compositions and a method of activating &agr;1 adrenoceptors in a mammal.

Abstract: The invention relates to compounds of formula (I), wherein the symbols have the meanings indicated in the specification. The inventive compounds exhibit dramatic antiarrhythmic proprieties and contain a cardioprotective compound. They can preventively inhibit or strongly reduce pathophysiologic processes upon occurrence of ischemic injuries, especially ischemic cardiac arrhythmia. Said compounds also exhibit a strong inhibiting effect on cellular proliferation.

Abstract: The invention relates to compounds of formula (I), wherein the symbols have the meanings indicated in the specification. The inventive compounds exhibit dramatic antiarrhythmic proprieties and contain a cardioprotective compound. They can preventively inhibit or strongly reduce pathophysiologic processes upon occurrence of ischemic injuries, especially ischemic cardiac arrhythmia. Said compounds also exhibit a strong inhibiting effect on cellular proliferation.