Abstract: Disclosed are multibinding compounds which are antibiotics effective against bacterial infections, in particular, Gram-negative bacterial infections. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is a polymyxin, circulin or octapeptin antibiotic or other suitable compound which binds to the LPS present in bacteria, in particular, Gram-negative bacteria. The multibinding compounds of this invention are useful for the prophylaxis and treatment of various bacterial infections caused by bacteria.

Abstract: The present invention is directed to multibinding compounds which are &bgr;2 adrenergic receptor agonists and are therefore useful in the treatment and prevention of respiratory diseases such asthma, bronchitis, and the like. They are also useful in the treatment of nervous system injury and premature labor.

Abstract: The present invention is directed to multibinding compounds which are &bgr;3 adrenergic receptor agonists and are therefore useful in the treatment and prevention of metabolic disorders such as obesity, diabetes, and the like.

Abstract: This invention provides novel quinazolinone compounds and pharmaceutically acceptable salts thereof, which are useful as local anesthetics. This invention also provides pharmaceutical compositions containing such compounds; methods for producing local anesthesia in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.

Abstract: Disclosed are multibinding compounds which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-COA reductase), the rate limiting enzyme in cholesterol biosynthesis. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is a moiety capable of binding to HMG-CoA reductase and the distance between ligands is at least 10 Å. The multibinding compounds of this invention are useful in the treatment and prevention of hypercholesterolemia, hyperlipidemia, atherosclerosis and the like.

Abstract: The present invention describes a protein kinase which catalyzes the in phosphorylation of BRCA-1 protein. The present invention also describes the use of the BRCA-1 protein kinase as a molecular target for therapeutic intervention and/or as a therapeutic tool for diagnosing and treating breast and/or ovarian cancer.

Abstract: The present invention is based of the discovery of two modified forms of human platelet factor-4, herein named MPF-4 and CPF-4, which were isolated from serum free culture medium of lipopolysaccharide-stimulated peripheral blood leukocytes. Amino acid sequence determination revealed that MPF-4 shares homology with platelet factor-4 beginning at N-terminal residue 17. CPF-4 consists of MPF-4 disulfide bonded to the 16 N-terminal residues of platelet factor-4. Both MPF-4 and CPF-4 are potent inhibitors of endothelial cell proliferation, approximately 10-100 fold more potent than native or recombinant platelet factor-4, making them useful in the treatment of angiogenic diseases.

Abstract: The present invention relates to therapeutically active azacyclic or azabicyclic compounds, a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating diseases in the central nervous system caused by malfunctioning of the muscarinic cholinergic system.

Abstract: The invention provides a pharmaceutically acceptable solid oral formulation of olanzapine and a process for making such formulation.

Abstract: The invention provides isolated nucleic acid compounds encoding a multiple drug resistance protein of Aspergillus fumigatus. Vectors and transformed host cells comprising the multiple drug resistance-encoding DNA of Aspergillus fumigatus AfuMDR1 are also provided. The invention further provides assays which utilize these transformed host cells.

Abstract: This invention relates to thrombin inhibiting compounds having the Formula IX--Y--NH--(CH.sub.2).sub.r --G Iwhere X, Y, r and G have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitors, coagulation inhibitors, and thromboembolic disorder agents.

Abstract: .alpha.,.alpha.-Difluoro-.beta.-hydroxy thiol esters of Formula (III): ##STR1## wherein: R.sup.c and R.sup.d are independently selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, S-tert-butyl difluorothioacet-2-yl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, substituted C.sub.3 -C.sub.8 cycloalkyl, substituted C.sub.3 -C.sub.8 cycloalkenyl, aryl, substituted aryl, C.sub.6 -C.sub.10 fused aromatic rings, and substituted C.sub.6 -C.sub.10 fused aromatic rings; orR.sup.c and R.sup.d together make up a ring selected from the group consisting of C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, substituted C.sub.3 -C.sub.8 cycloalkyl and substituted C.sub.3 -C.sub.8 cycloalkenyl;R.sup.e is selected from the group consisting of C.sub.1 -C.sub.10 alkyl, substituted C.sub.1 -C.sub.10 alkyl, aryl, substituted aryl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.3 -C.sub.8 cycloalkenyl, substituted C.sub.3 -C.sub.8 cycloalkyl and substituted C.sub.3 -C.sub.

Abstract: This invention relates to peptide derivatives, pharmaceutical formulations containing those compound and methods of their use as thrombin inhibitors.

Abstract: The present invention provides a method of treating anxiety and related disorders using an agonist which acts at negatively coupled cAMP-linked metabotropic glutamate receptors.

Abstract: The present invention provides a method for altering mammalian central and peripheral physiological and pathological functioning which is mediated by serotonin binding to the 5-HT.sub.7 receptor. Specifically, the invention provides a method for antagonizing serotonin binding to the 5-HT.sub.7 receptor.

Abstract: This invention provides novel 5-HT.sub.1F agonists of the Formula ##STR1## in which X, Y, E, R, A, B, and n are as defined in the specification, which are useful for the treatment of migraine and associated disorders.

Abstract: The invention provides isolated nucleic acid compounds encoding a glycosyltransferase enzyme of Amycolatopsis orientalis. Also provided are vectors carrying genes that encode said enzyme, transformed heterologous host cells for expressing said enzyme, and methods for producing glycopeptide compounds using the cloned genes that encode said enzyme.

Abstract: A pharmaceutical compound of the formula: ##STR1## in which R.sup.1 is hydrogen, hydroxy or C.sub.1-6 alkoxy, R.sup.2 is hydrogen, carboxy, tetrazolyl, --SO.sub.2 H, --SO.sub.3 H, --OSO.sub.3 H, --CONHOH, or --P(OH)OR', --PO(OH)OR', --OP(OH)OR' or --OPO(OH)OR' where R' is hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or aryl C.sub.1-6 alkyl,R.sup.3 is hydrogen, hydroxy or C.sub.1-4 alkoxy, andR.sup.4 is fluoro, trifluoromethyl, nitro, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkylthio, heteroaryl, optionally substituted aryl, optionally substituted aryl C.sub.1-6 alkyl, optionally substituted aryl C.sub.2-6 alkenyl, optionally substituted aryl C.sub.2-6 alkynyl, optionally substituted aryloxy, optionally substituted aryl C.sub.1-6 alkoxy, optionally substituted arylthio, optionally substituted aryl C.sub.1-6 alkylthio or --CONR"R'", --SO.sub.2 NR"R"", --NR"R'", --OCONR"R"' or --SONR"R'" where R" and R'" are each hydrogen, C.sub.1-6 alkyl or aryl C.sub.

Abstract: A device for aligning a syringe with a vessel having a variable internal volume and containing an injectable solution. The device includes one section for removably retaining a vessel of an injectable solution, one section for allowing insertion and extraction of a syringe, and another section adjoining the two aforementioned sections for accurately aligning the needle of the syringe with the opening of the vessel. The alignment device further includes a clip for both releasably retaining the vessel in the device and for enabling the device to be clipped to a shirt pocket.

Abstract: The present invention provides a method for treating a condition associated with muscarinic receptor modulation using a 3-?4-(butylthio)-1,2,5-thiadiazol-3-yl!-1-azabicyclo-?2.2.2!octane transdermal formulation. The invention provides desired transdermal 3-?4-(butylthio)-1,2,5-thiadiazol-3-yl!-1-azabicyclo?2.2.2!octane patch formulations.