Abstract: The present invention provides methods and compositions for inhibiting the proliferation of smooth muscle cells at a site of vascular injury. The methods include intravascular administration of a reactive compound to the site of injury, without the requirement for activation or sustained release of the compound.

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

Abstract: This invention relates to substituted bis-acridines and related compounds which are ligands, in particular, antagonists of the CCR5 receptor. In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5, including, but not limited to, asthma and atopic disorders (for example, atopic dermatitis and allergies), rheumatoid arthritis, atherosclerosis, psoriasis, autoimmune disease such as multiple sclerosis, and inflammatory bowel disease, all in mammals, by the use of substituted bis-acridines and related compounds which are CCR5 receptor antagonists. Also, since CCR5 is a co-receptor for the entry of HIV into cells, selective receptor ligands may be useful in the treatment of HIV infection.

Abstract: The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4c, R4d, and R4f are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.

Abstract: The present invention provides methods for inhibiting restenosis at a site of vascular recanalization. The methods include intravascular administration of a reactive acridine compound to the site of injury, without the requirement for activation or sustained release of the compound.

Abstract: The invention relates to a method of treating neurological disorders associated with neurotransmitter deficit in a mammal comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one neurotransmitter release enhancer, and (ii) at least one acetylcholinesterase inhibitor. The invention also relates to compositions and kits containing the same.

Abstract: Disclosed herein are methods for identifying a patient for the treatment of cognitive impairments.

Abstract: The invention provides an isolated gene encoding Mch6 as well as functional fragments thereof. Also provided are isolated nucleic acid sequences encoding Mch6 or functional fragments thereof. The gene or nucleic acid sequences can be single or double stranded nucleic acids corresponding to coding or non-coding strands of the Mch6 nucleotide sequences. The invention further provides an isolated Mch6 polypeptide and isolated large and small subunits of the Mch6 polypeptide, including functional fragments thereof.

Abstract: There are disclosed compounds having the formula wherein n is 1-4; X is hydrogen, loweralkyl, cycloalkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, formyl, loweralkylcarbonyl, arylcarbonyl, —SH, loweralkylthio, —NHCOR2 or —NR3R4 where R2 is hydrogen or loweralkyl, and R3 and R4 are independently hydrogen, loweralkyl or cycloalkyl; R is hydrogen, loweralkyl or loweralkylcarbonyl; and R1 is hydrogen, loweralkyl, aryl, diloweralkylaminoloweralkyl, arylloweralkyl, furylloweralkyl, thienylloweralkyl, pyridinylloweralkyl, diarylloweralkyl, oxygen-bridged arylloweralkyl or oxygen-bridged diarylloweralkyl; stereo, optical and geometrical isomers thereof, and pharmaceutically acceptable acid addition salts thereof which are useful for enhancing memory.

Abstract: This invention relates to substituted bis-acridines and related compounds which are ligands, in particular, antagonists of the CCR5 receptor. In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5, including, but not limited to, asthma and atopic disorders, rheumatoid arthritis, atherosclerosis, psoriasis, auto immune diseases such as multiple sclerosis, and inflammatory bowel disease, all in mammals, by the use of substituted bis-acridines and related compounds which are CCR5 receptor antagonists. Also, since CCR5 is a co-receptor for the entry of HIV into cells, selective receptor ligands may be useful in the treatment of HIV infection.

Abstract: The use of certain heterocyclic derivatives for treating parasitic protozoa infections in mammals, in particular bovine trichomoniasis and giardiasis, is disclosed.

Abstract: The compounds are N-substituted azaheterocyclic compounds of formula I wherein R1 and R2 independently are hydrogen, halogen, trifluoromethyl, hydroxy, C1-6-alkyl or C1-6-alkoxy; and Y is >N—CH2— wherein only the underscored atom participates in the ring system; and X is —C(R6R7)—, —CH2CH2—, —CH═CH—CH2—, —CH2—CH═CH—, —CH2—(C═O)—, —(C═O)—CH2—, —CH2CH2CH2—, —CH═CH—, CH(R10)CH2—, —CH2CH(R10) or —(C═O)— wherein R6 and R7 independently are hydrogen or C1-6-alkyl and wherein R10 is C1-6-alkyl or phenyl; and r is 0, 1 or 2; and Z is selected from wherein A is —CH2—, —O—, —S— or —N(R5)— wherein R5 is H or C1-6-alkyl; and R3 is —(CH2)pCOR4 wherein p is 1, 2, 3 or 4 and R4 is OH, NH2, NHOH or C1-6-alkoxy; or a pharmaceutically acceptable salt th

Abstract: The present invention provides covalent conjugates of topoisomerase I and topoisomerase II inhibitors. Such compounds have a structure according to formula I: TI—L—TII  (I) wherein: TI is a topoisomerase I inhibitor such as a camptothecin group; TII is a topoisomerase II inhibitor such as an amsacrine, ellipticine, epipodophyllotoxin, or anthracycline antibiotic group; and L is a linking group. The compounds are useful for inhibiting topoisomerase I and II enzymes, for promoting cellular differentiation, and for treating cancer.

Abstract: A pharmaceutical composition in the form of a solid dispersion comprising a macrolide, e.g. a rapamycin or an ascomycin, and a carrier medium.

Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.

Abstract: A series of tacrine derivatives has be synthesized and disclosed. These tacrine derivatives were claimed to be new and be useful for the treatment of Alzheimer's disease alone or in combination with other drugs for Alzheimer's disease. These tacrine derivatives may be formulated into suitable pharmaceutical dosage forms for the treatment of Alzheimer's disease.

Abstract: The present invention provides novel compounds of formula I which may be useful in hyperpolarizing cell membranes, opening potassium channels, relaxing smooth muscle cells, and inhibiting bladder contractions.

Abstract: A series of bis-acridinyl DNA intercalating agents with anticancer cell activity represented by formula (I), where Z is a linear arrangement of multiple aromatic rings, containing at least three aromatic rings, or at least two alicyclic rings, said rings being linked in a 1,4 or 1,3 manner are provided. Methods of inhibiting cancer cells and treating patients having cancer with these agents are also provided.

Abstract: A gonadotropin-releasing hormone antagonistic composition, which comprises an optionally substituted condensed-bicyclic compound consisting of a homo or hetero 5 to 7 membered ring and a homo or hetero 5 to 7 membered ring is effective as a propylactic or therapeutic agent for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, cancer of uterine cervix, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; is effective as a fertility controlling agent in both sexes (e.g.

Abstract: Methods and compositions for treating pathogens in material are described, including methods of decontaminating human fluids prior to processing in the clinical laboratory and methods for decontaminating blood products prior to in vivo use. The techniques handle large volumes of human serum without impairing the testing results.

Abstract: A pharmaceutical compound of the formula in which R1 is C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-10 alkyl, C3-10 cycloalkyl-C2-10 alkenyl, C3-10 cycloalky-C2-10 alkynyl, optionally substituted phenyl-C1-10 alkyl, optionally substituted phenyl-C2-10 alkenyl, optionally substituted phenyl-C2-10 alkynyl, optionally substituted naphthyl, optionally substituted naphthyl-C1-10 alkyl, C1-10 alkoxy-C1-10 alkyl, C3-10 cycloalkoxy-C1-10 alkyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl-C1-10 alkyl, optionally substituted phenyl fused to C5-10 cycloalkyl, optionally substituted tricyclic, optionally substituted tricyclic-C1-10 alkyl, or [optionally substituted phenyl(CH2)n]2-C1-10 alkyl, where n is 0 or 1 to 4, and R2 is hydrogen or one of the values for R1; or a salt or ester thereof.

Abstract: The present invention relates to genetic mutations in mitochondrial cytochrome c oxidase genes that segregate with Alzheimer's disease (AD). The invention provides methods for detecting such mutations, as a diagnostic for Alzheimer's Disease, either before or after the onset of clinical symptoms. The invention further provides treatment of cytochrome c oxidase dysfunction.

Abstract: Compositions for controlling harmful fungi which comprise, as active ingredients, at least one compound which inhibits respiration on the cytochrome complex III and at least one amide compound of the formula II A—CO—NR1 R2 where A, R1 and R2 have the meanings given in the description. The compositions according to the invention can be used, in particular, for controlling botrytis.

Abstract: Compounds of Formula (I), methods for their preparation, pharmaceutical formulations and use thereof.

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: A pharmaceutical formulation for the prophylaxis and preliminary treatment of a poisoning caused by organophosphorus cholinesterase inhibitors is characterized in that it consists of an active substance combination of at least one parasympathomimetic and at least one parasympatholytic.

Abstract: A compound which is a bis(acridinecarboxamide) or bis(phenazinecarboxamide) derivative of formula (I): ##STR1## wherein each X, which may be the same or different in a given molecule, is --CH.dbd. or --N.dbd. each of R.sub.1 to R.sub.4 which may be the same or different, H, C.sub.1 -C.sub.4 alkyl, OH, SH, NH.sub.2, C.sub.1 -C.sub.4 alkoxy, aryloxy, NHR, N(R).sub.2, SR, SO.sub.2 R wherein R is C.sub.1 -C.sub.4 alkyl, CF.sub.3, NO.sub.2 or halogen, or R.sub.1 and R.sub.2 together form a methylenedioxy group; each of R.sub.5 and R.sub.6, which may be the same or different, is H or C.sub.1 -C.sub.4 alkyl; Z is (CH.sub.2).sub.n, (CH.sub.2).sub.n O(CH.sub.2).sub.n, (CH.sub.2).sub.n N(R.sub.7)(CH.sub.2).sub.n, (CH.sub.2).sub.n N(R.sub.7)(CH.sub.2).sub.m N(R.sub.7)(CH.sub.2).sub.n or (CH.sub.2).sub.n N(CH.sub.2 CH.sub.2).sub.2 N(CH.sub.2).sub.n wherein R.sub.7 is H or C.sub.1 -C.sub.

Abstract: Compounds and methods for inactivating pathogens in materials are described, including compositions and methods for inactivating pathogens in biological materials such as red blood cell preparations and plasma. The compounds and methods may be used to treat materials intended for in vitro or in vivo use, such as clinical testing or transfusion. The compounds are designed to specifically bind to and react with nucleic acid, and then to degrade to form breakdown products. The degradation reaction is preferably slower than the reaction with nucleic acid.

Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.

Abstract: This invention relates to acridin derivatives of general formula ##STR1## or pharmaceutically acceptable salts thereof, to a method of producing them and to their use as analgesics.

Abstract: The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description, or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for treatment of indications caused by or related to the secretion and circulation of insulin antagonising peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

Abstract: The invention relates to a composition which is a pharmaceutical combination preparation comprising a compound which has an acetylcholinesterase-inhibitory action or exhibits muscarinergic action and a compound which increases the endogenous extracellular adenosine level, wherein the combination preparation is suitable for the treatment of dementia. The invention further relates to a process for the production of the combination preparation. The invention additionally relates to a process for treating patients in need of suitable therapy with the combination preparation.

Abstract: Mammalian hair growth is reduced by applying to the skin an inhibitor of a DNA topoisomerase.

Abstract: This invention relates to a method for treating snoring, sleep apnea and other form of sleep-disordered breathing, which comprises administration of a therapeutically effective dose of an acetyl choline esterase inhibitor (CEI) such as pyridostigmine or a pharmaceutically acceptable salt thereof.

Abstract: Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, Q.sup.4, and Q.sup.5 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of SP and NKA are useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.

Abstract: Therapeutic compositions for the treatment of infectious diseases are disclosed. These compositions comprise xanthones and xanthone derivatives, such as 2,3,4,5,6-pentahydroxyxanthone. Also disclosed are methods for the treatment of infectious diseases using such compounds.

Abstract: Amyloid aggregation in animals is inhibited by administering a 9-acridinone compound of formula I, defined herein. The compounds are especially useful in preventing and treating Alzheimer's disease.

Abstract: Parkinson's disease can be treated with an at least one cholinesterase inhibitor. The cholinesterase inhibitor has been found to alleviate both any symptoms of dementia as well as to reduce rigidity and improve motor function.

Abstract: Mammalian hair growth is reduced by applying an inhibitor of aminoacyl-tRNA synthetase to the skin.

Abstract: The invention provides a compound of the following formula: ##STR1## wherein R.sup.1 is C.sub.1-6 alkyl; or phenyl;R.sup.2 is hydrogen;an acyl group of the formula --COR.sup.a wherein R.sup.a is C.sub.1-6 alkyl or phenyl; oran acetylalkylcarbonyl group of the formula --CO(CH.sub.2).sub.n COCH.sub.3 wherein n=1-3; andR.sup.3 and R.sup.4 are substituents at different position(s) of the acridine ring (i.e. C-1'-C-8'), and R.sup.3 and R.sup.4 may be the same or different and independently represent:hydrogen;C.sub.1-6 alkyl;C.sub.1-6 alkyloxy;a nitro group;an amino group of the formula --NR.sup.b R.sup.c wherein R.sup.b and R.sup.c may be the same or different and independently represent hydrogen or C.sub.1-6 alkyl;an aminoalkylamino group of the formula --NH(CH.sub.2).sub.n NR.sup.d R.sup.e wherein R.sup.d and R.sup.e may be the same or different and independently represent hydrogen, C.sub.1-6 alkyl, a hydroxyalkyl group of the formula --(CH.sub.2).sub.n OH wherein n=1-3, or C.sub.

Abstract: The present invention relates to a method for the identification of human subjects to be responsive to cholinomimetic therapy comprising determining the absence of apolipoprotein E4 (apoE4) alleles in a biological sample of the patient where the absence of at least one apoE4 allele indicates a predisposition to respond to cholinomimetic therapy and methods of administering cholinomimetics to such identified subjects.

Abstract: Novel pharmaceutically/cosmetically-active polycyclic polyenic compounds have the structural formula (I): ##STR1## and are useful for modulating cellular hormone receptors.

Abstract: The present invention relates to an anti-cancer composition containing acridine derivatives and guanosine compounds. In the composition of the present invention, the acridine derivative and the guanosine compound are present in the weight ratio of 1:0.1-5.0, preferably 1:0.3-3.0 and more preferably 1:0.5-1.5. In the composition of the present invention, most preferably the acridine derivative is acriflavine neutral and the guanosine compound is guanosine hydrate. Although acridine derivatives and guanosine compounds used as an active ingredient in the present composition have substantially no anti-cancer effect when they are used individually, the combination of acriflavine neutral and guanosine hydrate which potentiates the effect of acriflavine neutral, i.e. the composition(AG60) according to the present invention, exhibits reduced toxicity and increased anti-cancer effect in comparison to the use of acriflavine neutral or guanosine hydrate alone.

Abstract: A new treatment schedule for administration of N-?2-(dimethylamino)ethyl!acridine-4-carboxamide and other related carboxamide anticancer drugs in which the drug is administered in a divided-dose schedule comprising two or more administrations at frequent intervals, for example every hour. Schedules to produce cyclic peaks/troughs in plasma levels are mentioned. The compounds can be used for circumventing multidrug resistance in cancers and may, for example, be used in combination with other cytotoxic drugs, especially non-topo II inhibitors. Treatment of melanoma and advanced colon cancer is included.

Abstract: The invention concerns pharmaceutically useful N-heterocyclyl sulphonamide derivatives, their pharmaceutically acceptable salts, processes for their manufacture, their use for antagonising one or more actions of endothelin in a human or other warm-blooded animal, their use in methods of treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role.

Abstract: Novel tricyclic heterocyclic sulfonamide derivatives and sulfonic ester derivatives which have each an antitumor action and are represented by the following general formula (I) and processes for producing the same are provided. These compounds have each an excellent antitumor activity.A sulfonamide derivative or a sulfonic ester derivative represented by the following general formula (I): ##STR1## {G represents an aromatic 5- or 6-membered ring; L represents 0 or --N(R.sup.1)-- (R.sup.1 represents hydrogen or lower alky); and M represents a tricyclic structure selected from among the following ones; ##STR2## ?rings A and B represent each an unsaturated 5- or 6-membered ring; X represents N(R.sup.2), (wherein R.sup.2 represents hydrogen or lower alkyl), or NHCO;Y represents O, S(O).sub.n, C(R.sup.3)(R.sup.4), C(O), N(R.sup.5), CH(R.sup.6)CH(R.sup.7), C(R.sup.8).dbd.C(R.sup.9), N(R.sup.10)C(O), N.dbd.C(R.sup.11), OCH(R.sup.12), S(O).sub.n CH(R.sup.13) or N(R.sup.14)CH(R.sup.15);Z represents nitrogen or C(R.sup.

Abstract: The present invention provides a novel method for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.

Abstract: The present invention provides cholinesterase inhibitors of general formula (I): ##STR1## wherein R is H or (C.sub.1 -C.sub.4)alkyl, Y is a linking group and Z is an alkyl or aryl group, including heteroaryl groups, and the pharmaceutically acceptable salts thereof.

Abstract: Polyhydroxylated and dehydrogenated metabolites of 9-amino-1,2,3,4-tetrahydro-acridine (Tacrine) in which attached to at least two of the carbon atoms numbered 1,2,3 and 4 is a hydroxyl group and to the others either hydrogen, hydroxyl or double bonded oxygen the residual valencies being occupied by hydrogen or double bonds between carbon atoms 1 and 2 and/or 3 and 4 are disclosed as being useful medicaments for enhancing memory and cognitive function in Alzheimer's disease because they have retained the anticholinesterase activity of their metabolic precursor while circumventing its hepatotoxicity. Related compounds to which this disclosure also applies include those in which the aromatic ring is substituted with lower alkyl, lower alkoxy, halogen, hydroxy, nitro, trifluoromethyl, alkyl-N-substituted carboxamides and where the 9-amino group is mono or di-substituted independently.

Abstract: A composition for use as a fungistat for the treatment and prevention of infections such as sporotrichosis, onychomycosis infections, white line disease, hoof rot, jungle rot, pseudallecheria boydii, scopulariopsis, athletes foot, canker sole and fungal infections generally. The fungistat composition includes acriflavine and gentian violet.