Abstract: This invention relates to novel PDE-IV inhibitors having the formula: ##STR1## where: R.sup.1 =H, C.sub.1 -C.sub.6 alkyl;R.sup.2 =C.sub.3 -C.sub.7 alkyl, C.sub.3 -C.sub.7 cycloalkyl or C.sub.4 -C.sub.8 cycloalkylidene when Y is CH; ##STR2## R.sup.4 =H, OR.sup.5, NHR.sup.5, NHOH, NHNH.sub.2 or ##STR3## R.sup.5 =H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl or ##STR4## W=N or CH; X=CH.sub.2, O, S, or NH;Y=CH.sub.2, CH, O, S, or NH;Q=a bond or CH.dbd.CH;n=0, 1, 2, 3 or 4;M=O, NOH or H.sub.2 ;Z=H or halogen;or a pharmaceutically acceptable salt thereof, as antiasthmatic agents.

Abstract: This invention relates to benzyl and naphthalenylmethyl thiophenones and cyclopentenones, some of which are novel, which have oral antihyperglycemic activity in diabetic mice, a genetic animal model of non-insulin dependent diabetes mellitus. These compounds are represented by the formula ##STR1## wherein: R.sup.2 and R.sup.3 are independently selected from hydrogen, C.sub.1-6 alkyl, halogen, C.sub.1-6 alkoxy, thio-C.sub.1-6 alkyl, or trifluoromethyl or R.sup.2 together with R.sup.3 forms a benzo ring fused to the phenyl ring and optionally substituted with one or two substituents independently selected from C.sub.1-6 alkyl, halogen, C.sub.1-6 alkoxy, thio-C.sub.1-6 alkyl, or trifiuoromethyl;R.sup.1 is selected from hydrogen, C.sub.1-6 alkyl, halogen, C.sub.1-6 alkoxy, thio-C.sub.1-6 alkyl, or trifluoromethyl;andR.sup.4 is selected from the group consisting of: ##STR2## wherein R.sup.5 is H or C.sub.1-6 alkyl or a pharmaceutically acceptable salt thereof.

Abstract: Derivatives of 4-anilinoquinoline having the formula: ##STR1## where X is O or H.sub.2 and Z is 1-substituted-4-piperidinylamino or diloweralkylaminoloweralkyl inhibit binding of tritiated bradykinin to guinea pig ileum and inhibit bradykinin-induced writhing in mice. Bradykinin is a nonapeptide formed in plasma as a result of inflammation or injury and produces pain when it binds with pain receptors. A drug which inhibits the binding of bradykinin therefore has analgetic properties.

Abstract: Piperazine derivatives of formula I ##STR1## and their pharmaceutically acceptable acid addition salts are 5-HT.sub.1A binding agents, particularly 5-HT.sub.1A antagonists and may be used, for example, as anxiolytics. In the formula R is hydrogen or one or two lower alkyl groups, R.sup.1 is a mono of bicyclic aryl or heteroaryl radical, R.sup.2 is aryl and A is a C.sub.2-5 alkylene chain optionally substituted by lower alkyl.

Abstract: This invention relates to compounds which inhibit lipoxygenase in the metabolism of arachidonic acid and thus inhibits formation of leukotrienes which are implicated in inflammatory processes and bronchoconstriction and inhibits the oxidation of LDL which is implicated in formation of atherosclerotic plaque.The compounds useful in this invention are represented by the formula: ##STR1## wherein: R.sup.2 is hydrogen, halogen or C.sub.1 -C.sub.6 alkyl; Y of O or S; R.sup.5 is hydrogen or methyl R.sup.6 is --NH.sub.2, --CH.sub.3 or --OCH.sub.3 ;and R.sup.1 is ##STR2## wherein R.sup.7, R.sup.8 and R.sup.10 are independently halogen, trifluoromethyl, alkyl, alkoxy, methanesulfonyl or trifiuoromethanesulfonyl; R.sup.9 is hydrogen or methyl; and Z is O or S,or a pharmaceutically acceptable salt thereof.Compounds of the above formula where R.sup.1 is not ##STR3## when R.sup.3 is H and R.sup.6 is --NH.sub.2 are novel.

Abstract: The compounds of this invention which have the formula: ##STR1## wherein: R.sup.1 and R.sup.2 are independently hydrogen, C.sub.1 -C.sub.8 alkyl, halogen, C.sub.1 -C.sub.8 alkoxy, or trifluoromethyl;R.sup.3 is --OH or --NHCO.sub.2 CH.sub.3 ;X is --CH.sub.2 -- or --OCH.sub.2 --;n is 1 or 2;or a pharmaceutically acceptable salt thereof,are useful in treating or inhibiting the long-term complications of diabetes such as diabetic retinopathy, nephropathy and neuropathy through the inhibition of the enzyme aldose reductase. Aldose reductase inhibitors have been shown to prevent the biochemical, functional and morphological changes induced by hyperglycemia.

Abstract: A derivative of rapamycin of general formula (1) and (2) ##STR1## wherein ##STR2## or hydrogen; R.sup.2 =hydrogen, or lower alkyl having 1 to 6 carbon atoms; ##STR3## wherein X=hydrogen, lower alkyl having 1 to 6 carbon atoms, --CF.sub.3, --NO.sub.2, --OR.sup.2, NR.sup.2, SR.sup.2, or halogen; R.sup.4 =lower alkyl, alkenyl or alkynyl having 1 to 6 carbon atoms or an aromatic or heterocyclic moiety selected from the group consisting of phenyl, naphthyl, thiophenyl and quinolinyl;Y-=halide, methanesulfonate, toluene sulfonate or maleate; andZ=oxygen or OH and H.which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host versus graft disease, autoimmune diseases, and diseases of inflammation.

Abstract: This invention relates to substituted 4-aminopyrimidines, which by virtue of their ability to antagonize angiotensin II are useful for the treatment of hypertension, congestive heart failure, and restenosis. The compounds are also useful for reducing lipid levels in the blood plasma and are thus useful for treating hyperlipidemia and hypercholesterolemia. Also disclosed are processes for the production of said compounds and pharmaceutical compositions containing said compounds.

Abstract: This invention relates to 4-phenoxy (and 4-substituted phenoxy)5-hydroxy-2(5H)-furanones of the formula: ##STR1## where Z is ##STR2## where R is H, halogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, trifluoromethyl, or ##STR3## and X is H, C.sub.1 -C.sub.8 alkyl, --O--C.sub.1 -C.sub.8 alkyl, or halogen; a process for their preparation, their use in the treatment of osteoporosis, and pharmaceutical compositions thereof.

Abstract: This invention provides novel 2-substituted-3-quinuclidinyl arylcarboxamides and arylthiocarboxamides and corresponding arylcarboxylates which have utility as therapeutic agents which exhibit gastric prokinetic, antiemetic, anxiolytic and 5-HT (serotonin) antagonist effects in warm blooded animals.Illustrative of an invention compound is 5-chloro-2-methoxy-4-(methylamino)-N-[2-(1-piperidinylmethyl)-1-azabicyclo [2.2.2]oct-3-yl]benzamide: ##STR1## or a pharmaceutically acceptable salt thereof.

Abstract: Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula:(HO)p--A--[--OS(O).sub.2 NR.sup.1 R.sup.2 ].sub.zwherein A encompasses a wide range of values including but not limited to aryl, loweralkyl, cycloalkyl, and carbohydrates including sucrose and fructose; p is equal to the number of unreacted hydroxy groups contained on the molecule and may be zero; z is the number of --OS(O).sub.2 NR.sup.1 R.sup.2 groups and is always at least one; R.sup.1 and R.sup.2 are selected from hydrogen, loweralkyl, carboxy and the like; a novel process for preparing the compounds is provided wherein an appropriate sulfamic acid aryl ester is reacted with a hydroxy substituted A radical which may or may not contain thereon protected carboxyl, amino or hydroxy substituents, in an aprotic solvent containing a tertiary amine base. Pharmaceutical compositions for the treatment of chronic arthritis and osteoporosis are also provided.

Abstract: N-arylcarbonyl and N-alkylcarbonyl carbamates of rapamycin of the formula shown below wherein ##STR1## R.sup.1 and R.sup.2 are both ##STR2## and where A is lower alkoxy or aryl or heteroaryl, R.sup.3 is H or methyl and R.sup.4 is C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl possess immunosuppressive and/or antifungal and/or antitumor and/or antiinflammatory activity in vitro and/or inhibit thymocyte proliferation in vivo. These compounds are thus expected to be useful in the treatment of transplantation rejection, autoimmune diseases, fungal infections, cancer, and diseases of inflammation.

Abstract: Carbonate esters with rapamycin at position 42 or positions 31 and 42 have been shown to have immunosuppressant properties and are useful in the treatment of transplant rejections and autoimmune diseases. These esters are represented by the formula below: ##STR1## wherein: R.sup.1 and R.sup.2 are independently H or --COOR.sup.3 but both R.sup.1 and R.sup.2 cannot be H, andR.sup.3 is C.sub.1 -C.sub.6 alkyl where 1 to 3 hydrogens may be replaced by fluorine, chlorine, bromine or iodine, C.sub.3 -C.sub.8 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, or Ar--(CH.sub.2).sub.n -- where n is 0 to 6 and Ar is phenyl, phenyl substituted by fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, cyano, C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkoxy; pyridinyl, indolyl, quinolyl or furanyl;or a pharmaceutically acceptable salt thereof.

Abstract: Antiviral activity against respiratory syncytial virus has been found in some substituted 6-aminopyrimidines having the formula: ##STR1## wherein R.sup.1 is lower alkyl, preferably methyl or t-butyl, R.sup.2 is halogen or cyano, and R.sup.3 is C.sub.1 -C.sub.6 alkyl or --(CH.sub.2).sub.n R.sup.4 where n is 1 or 2 and R.sup.4 is phenyl, phenyl substituted by lower alkoxy, lower alkyleneoxy, bromo, or 3,4-methylenedioxy; 3 or 4-pyridinyl, pyridinyl substituted by cyano or bromo, thienyl, or di-(C.sub.1 -C.sub.6 alkyl)amino.

Abstract: Novel 1-azabicyclo[3.2.1]octan-5-ylmethyl and 1-azabicyclo[3.3.1]nonan-5-ylmethyl amines and alcohols are coupled with aryl carboxylic acids to obtain compounds having the formula: ##STR1## wherein X is --O-- or --NH-- and n is 1 or 2 which are useful in increasing gastric motility, in preventing emesis and emesis caused by anticancer treatments, anxiety, certain arrhythmias, and disorders caused by serotonin imbalances.

Abstract: 5-(2-Hydroxy-1-phenyl (or-1-naphthalenyl)ethylidene) and 5-(2-oxo-1-phenyl (or 1-naphthalenyl)ethylidene)-2,4-thiazolidinediones and derivatives thereof are useful in lowering blood glucose levels in a hyperglycemic laboratory animal model and are thus useful in the treatment of diabetes mellitus.

Abstract: This invention provides novel 3-quinuclidinyl benzamides and benzoates which have utility as therapeutical agents which exhibit anxiolytic, antipsychotic, cognition improvement, antiemetic and gastric prokinetic effects in warm blooded animals.The compounds useful in the methods and composition of this invention are represented by the formula: ##STR1## where X is oxygen or sulfur; Y is --NH or --O--; when Y is --O--, R.sup.1 is ##STR2## and when Y is --NH, R.sup.1 is ##STR3## and R.sup.2 is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl; the geometrical and optical isomers, or a pharmaceutically acceptable salt thereof.

Abstract: Reduction of the C-33 ketone of rapamycin gives the C-33 hydroxy analog of Formula I. ##STR1## The reduction product prevents cleavage of the C-31/C-32 bond due to base degradation. The Formula I compounds exhibit immunosuppressant, antifungal, and antiinflammatory activities.

Abstract: Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula:(HO)p--A--[--OS(O).sub.2 NR.sup.1 R.sup.2 ].sub.zwherein A encompasses a wide range of values including but not limited to aryl, loweralkyl, cycloalkyl, and carbohydrates including sucrose and fructose; p is equal to the number of unreacted hydroxy groups contained on the molecule and may be zero; z is the number of --OS(O).sub.2 NR.sup.1 R.sup.2 groups and is always at least one; R.sup.1 and R.sup.2 are selected from hydrogen, loweralkyl, carboxy and the like; a novel process for preparing the compounds is provided wherein an appropriate sulfamic acid aryl ester is reacted with a hydroxy substituted A radical which may or may not contain thereon protected carboxyl, amino or hydroxy substituents, in an aprotic solvent containing a tertiary amine base. Pharmaceutical compositions for the treatment of chronic arthritis and osteoporosis are also provided.