Abstract: This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.

Abstract: This invention is directed to certain physiologically active compounds of formula (I) wherein represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring is an azaheterocycle, and the ring represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; and N-oxides thereof, and their prodrugs, and pharmaceutically acceptable salts and solvates of the compounds of formula (I) and N-oxides thereof, and their prodrugs. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.

Abstract: Compounds of formula (I) are described wherein R1 is hydrogen, -(lower alkyl)q(CO2R6 or OH), —CN, —C(R7)═NOR8, NO2, —O(lower alkyl)R9, —C≡C—R10, —CR11═C(R12)(R13), —C(═O)CH2C(═O)CO2H, —CO(R14), alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, thiocarbamoyl, substituted carbamoyl, substituted thiocarbamoyl, sulphamoyl or an optionally substituted nitrogen-containing ring, m, n, o and p are independently zero or 1 and R2, R3, R4 and R5 are various groups; and physiologically acceptable salts, N-oxides and prodrugs thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.

Abstract: This invention is directed to compounds of formula I ##STR1## wherein R.sup.1 is CN, CH.sub.2 CN, CH.dbd.CHCN, CHO, or CH.dbd.CHCO.sub.2 H;R.sup.2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted;R.sup.3 is halogen;R.sup.4 is optionally substituted aryl or optionally substituted heteroaryl;R.sup.5 is carboxy or an acid isostere;X is oxygen or sulphur; andn is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.

Abstract: This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.

Abstract: An inhaler for inhaling pulverulent medicament from within a capsule comprises a chamber 24 within which the capsule is free to rotate while having its longitudinal axis in the median plane of the chamber and thus generally parallel to the front and rear walls 30 and 31 of the chamber, by virtue of the fact that the spacing between said front and rear walls is less than the axial length of the capsule but just greater than the diameter of the capsule. The device includes pins 21 serving as opening means to pierce the ends of the capsule while it is seated in a recess 25, whereupon the retraction of the pins 21 allows the capsule to be entrained into swirling airflow in the chamber 24 during inhalation of air through air inlets 26 and out through a mouthpiece nozzle 27.

Abstract: This invention is directed to compounds of formula I ##STR1## wherein R.sup.1 is CN, CH.sub.2 CN, CH.dbd.CHCN, CHO, or CH.dbd.CHCO.sub.2 H;R.sup.2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted;R.sup.3 is halogen;R.sup.4 is optionally substituted aryl or optionally substituted heteroaryl;R.sup.5 is carboxy or an acid isostere;X is oxygen or sulphur; andn is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.

Abstract: This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.

Abstract: A powder composition for inhalation comprising at least one microfine drug and a carrier, in which at least a portion of the said carrier comprises an antistatic agent.

Abstract: An inhaler for inhalation of a medicament from a pierced capsule has a swirling or emptying chamber where the capsule is emptied by inhalation action of an operator. A rotary magazine for a multi-unit does inhaler which holds a number of capsules containing a medicament in a number of recesses arranged around the periphery of the magazine. The capsules are held in place by pins or plugs at both ends. Either the capsules are pierced before being loaded into the magazine or they are pierced by the pins when they are loaded into the magazine. In either case a seal may be provided around the ends of the capsules near the holes which are plugged to keep them fresh. When a recess is rotated to a particular position within the magazine then it releases its capsule. Contents of a capsule are drawn out during inhalation when the capsule is in the swirling chamber. A motor can be used to operate the magazine.

Abstract: This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.

Abstract: Compounds of formula I ##STR1## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, n, and are as defined herein, their use as antiinflammatory, immunosuppressive, and antiallergic agents, pharmaceutical compositions comprising them, and methods for their preparation comprising irradiating compounds of formula II ##STR2## under an inert atmosphere, in the presence or absence of a compound of formula R.sub.3 --S--S(O).sub.m --R.sub.8, where R.sub.7, R.sub.8, and m are as defined herein, and methods for their preparation comprising oxidizing, reducing, halogenating, or alkylating compounds of formula I are disclosed.

Abstract: An inhaler for powdered medicament in capsules has a swirling chamber which can be opened to allow access of a closed capsule into the swirling chamber for operation of capsule-opening means in the swirling chamber. Access to the swirling chamber is gained by a pivoting cover member (22) which is provided with interlock means associated with the capsule-opening means to ensure that the capsule opening means cannot be operated while the cover member is in its open position to allow access of the user's finger to the region (28) of the swirling chamber (26,28) where the capsule-opening pins (30) could damage the user's finger. A further embodiment of an inhaler has a removable capsule reservoir having a container portion (74) with a closure (76) removable to reveal the interior of said reservoir and closable to define one entire side face of said reservoir, the closure member (76) being hinged to the container portion at thin film hinge (78).

Abstract: The invention relates to a process for the preparation of intermediates useful in the preparation of (1R,2R)-2-(3-pyridyl)-N-alkyltetrahydro-2H-thiopyran-2-carbothioamide 1-oxides, which possess useful pharmaceutical properties, for example antihypertensive properties, and to intermediates and pharmaceutical products prepared using said process.

Abstract: A process is described for the preparation of a compound of formula (I) or a stereoisomeric compound thereof, in which the 1,2-position is saturated or is a double bond; X.sup.1 and X.sup.2 are each independently hydrogen or halogen; R.sup.1 is hydrogen or acyl; R.sup.2 is hydroxyl, acyloxy or oxo; and R.sup.3 is alkyl, by reacting a compound of formula (II) with an aldehyde R.sup.3 CHO in either phosphoric acid or about 60% to about 75% w/w sulphuric acid. Compounds of formula (I) are either pharmacologically active steroids or are intermediates in the synthesis of pharmacologically active steroids.

Abstract: This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.

Abstract: A process is described for the preparation of a compound of formula (IX) from 4-hydroxybutyl 3-pyridyl ketone. The compound of formula (IX) is an intermediate useful in the preparation of (1R,2R)-2-(3-pyridyl)-N-alkyl-tetrahydro-2H-thiopyran-2-carbothioamide 1-oxides which possess useful pharmaceutical properties, for example anti-hypertensive properties.

Abstract: This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.

Abstract: This invention is directed to 1-alkoxy-2-(alkoxy- or cycloalkyloxy-)-4-(cyclothioalkyl- or cyclothioalkenyl-)benzene compounds that inhibit cyclic AMP phosphodiesterase or tumor necrosis factor (TNF) and are useful in treating patients suffering from disease state capable of being modulated by inhibiting production of cyclic AMP phosphodiesterase or TNF by administering the compound to the patient. The invention is also directed to the preparation of these compounds, pharmaceutical compositions containing these compounds and methods for their pharmaceutical use.