Whitby Research, Inc.

Nelson Research & Development Company

Other

Lts Lohmann Therapie-systeme Ag

Discovery Therapeutics, Inc.

Ucb Biopharma Sprl

Aderis Pharmaceuticals, Inc.

Schwarz Pharma Limited

Nelson Research & Development

Ucb Manufacturing Ireland Limited

Whitby, Inc.

Durham Pharmaceuticals LLC

James V Peck

Gevork Minaskanian

Vithal J Rajadhyaksha

Eric L Nelson

Walter Mueller

Ibrahim M Uwaydah

Ronald J Wysocki

Noel J Cusack

Walter Muller

Walter Müller

Alan S Horn

Mark C Sleevi

Margarita L Dubocovich

William D Fairbairn

Atef A Helmy

Paul A Jerabek

Jonathan Hadgraft

Julia J Chouw

A substantially solvent-free matrix layer containing (&#x2212;)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol is produced by adding an active substance to an adhesive solution, coating the resultant active substance-containing adhesive solution onto a suitable sheet, and removing the solvents in a drying process to give said substantially solvent-free matrix layer.

Method for producing a transdermal therapeutic system which contains a D2 agonist

Transdermal therapeutic system and method of use thereof for treating parkinsonism

A transdermal therapeutic system (TTS) comprises a silicone-based polymer adhesive system having distributed therein (&#x2212;)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base in an amount of about 5% to 40% by weight. The adhesive system comprises a silicone adhesive and an additive having increased solubility for the active substance, in an amount effective to increase dissolving capacity of the matrix for the active substance.

Transdermal therapeutic system for treating Parkinsonism

A transdermal therapeutic system, comprising a backing layer inert to the components of the matrix, a self-adhesive matrix layer containing (&#x2212;)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol in an effective amount and a protective foil or sheet to be removed prior to use, is characterised by a matrix that is based on a non-aqueous, acrylate-based or silicone-based polymer adhesive system having a solubility of &#x2267;5% (w/w) for (&#x2212;)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]-amino]-1-naphthalenol, and said matrix is substantially free of inorganic silicate particulates.

Transdermal therapeutic system which contains a d2 agonist and which is provided for treating parkinsonism, and a method for the production thereof

Methods for preventing the penetration of toxic chemicals through the stratum corneum of the skin of a mammal are disclosed which employ, as a penetration prevention agent, at least one compound selected from the group consisting of compounds represented by the formula: ##STR1## wherein W.sub.1 is a divalent oxygen, sulfur or nitrogen radical, W.sub.2 and W.sub.3 are independently a divalent oxygen or sulfur radical, R' is an alkyl radical comprising from 1 to 4 carbon atoms, y is 0 or 1, R.sub.1 and R.sub.2 are alkyl radicals comprising from 1 to 10 carbon atoms and R and R.sub.3 are individually a hydrocarbyl radical containing from 1 to 20 carbon atoms or a heteroatom-substituted derivative thereof wherein at least one but not two adjacent carbon atoms may be replaced by a divalent oxygen or sulfur radical or by NR', wherein R' is hydrogen or R', n is an integer from 2 to 5 and compounds represented by the above formula in which the ring and/or R includes one to three carbon carbon double bonds.

Topical compositions useful as skin penetration barriers

Optically active or racemic compounds represented by the formula ##STR1## where R.sub.1 is C.sub.1 to C.sub.4 straight chain or branched alkyl; R.sub.2 is selected from the group consisting of H, --OR.sub.1, --SR.sub.1, --NH(R.sub.1), --N(R.sub.4)(R.sub.5), aminocarbonyl, halogen, and --CN, where R.sub.4 and R.sub.5 are independently C.sub.1 to C.sub.6 straight chain or branched alkyl, or taken together form a 3- to 7-membered heterocycloalkyl substituent, such heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, optionally including an additional heteroatom which is selected from the group consisting of nitrogen, oxygen, and sulfur; R.sub.3 is cyclopentyl or: ##STR2## where R' and R' are independently H, .dbd.O, --OH, or --NH.sub.2, with the proviso that R' and R' can be taken together form the following structure as R.sub.3 : ##STR3## where R'' is --OH or --NH.sub.2 ; and with the further proviso that when R.sub.3 is cyclopentyl or norbornyl, then R.sub.2 cannot be H or halogen; and pharmaceutically-acceptable salts thereof. These compounds are useful as diuretics, renal protectives against acute or chronic renal failure, as well as agents to facilitate recovery from coma, to improve the therapeutic outcome resulting from defibrillation or cardiopulmonary resuscitation by preventing post-resuscitation bradycardia, bradyarrhythmia and cardioplegia, to restore cardiac function following a cardioplegic procedure, and to treat or prevent intermittent claudication.

Substituted 9-alkyladenines

Compounds, topical compositions and methods useful for preventing the penetration of toxic chemicals through the skin of a mammal are disclosed. The compounds of the invention provide an enhanced barrier for the skin of a mammal to further inhibit or decrease the passage of bioactive agents through the skin of a mammal either from the outside environment into the systems of said mammal or from the mammal into the outside environment.

Cyclic amides and derivatives thereof

N-substituted 9-alkyladenines

This invention relates to compounds and a method for their use in carrying physiologically active agents through body membranes such as skin and for retaining these agents in body tissues. More specifically, the invention relates to carboxylic acid derivatives and salts thereof, which compounds are useful in topically administering a physiologically active agent to a human or animal via a composition comprising the agent and an effective amount of a compound represented in one embodiment by the general formulae: ##STR1## wherein W represents oxygen, sulfur, or two hydrogen radicals; Z represents oxygen, sulfur, or --CH.sub.2 --;

Transdermal penetration enhancers

This invention relates to a method for administering systemically active agents through the skin or mucosal membranes of humans and animals and into the bloodstream in a transdermal device or formulation comprising topically administrating with said systemic agent an effective amount of a membrane penetration enhancer having the structural formula ##STR1## or the pharmaceutically acceptable salt thereof wherein W represents oxygen, sulfur or two hydrogen radicals; Z represents --CH.sub.2 --; R represents alkyl optionally substituted with one to three double or triple bonds, --SR'', --OR'', --NHR'', or --COOR.sub.1 ; R'' represents alkyl, alkylthioalkyl, alkoxyalkyl, amino alkyl, optionally substituted with a phenyl, or benzoyl; R' represents hydrogen, alkyl, alkoxy, acyloxy, alkylthio, hydroxy or --(CH.sub.2).sub.y COOR.sub.1 ; R' represents hydrogen or --(CH.sub.2).sub.y COOR.sub.1 ; R.sub.1, in each instance, independently represents hydrogen or lower alkyl; y, in each instance, is between zero and 3, inclusive; m is between one and 3, inclusive; n is between one and 24, inclusive; and x is zero or one, inclusive; with the provisos that when R' is hydrogen, then W is two hydrogen radicals and R' is not hydrogen; and when R' is hydrogen, then R' is not hydrogen. It has been found that the penetration enhancers are sufficient to carry physiologically active agents through body membranes and into the bloodstream.

Penetration enhancers for transdermal delivery of systemic agents

This invention relates to a method for administering systemically active agents including therapeutic agents through the skin or mucosal membranes of humans and animals and into the blood stream in a transdermal device or formulation comprising topically administering with said systemic agent an effective amount of a membrane penetration enhancer.

Optically active or racemic compounds are provided having the formula ##STR1## where R.sub.1 is ##STR2## where Y is hydrogen, halogen or C.sub.1 to C.sub.6 linear or branched alkyl; R.sub.6 is C.sub.1 to C.sub.4 linear or branched alkyl; X is oxygen or sulfur; a is an integer from zero to 3; and n is an integer from 1 to 4. The compounds are capable of binding selectively to dopamine D.sub.2 receptors and are useful in treatment of disorders of the central nervous, cardiovascular and endocrine systems, such as intraocular pressure, schizophrenia and Parkinsonism, and for inducing anorexia and weight loss in humans and other mammals.

Substituted 2-aminotetralins

Optically active or racemic compounds are provided having the formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are selected from the group consisting of H and OA with the provision that at least one of R.sub.2, R.sub.3 and R.sub.4 is H, that R.sub.2 and R.sub.4 are not both OA; A is H or is selected from the group consisting of hydrocarbyl radicals, said hydrocarbyl radicals being further optionally substituted with radicals selected from the group consisting of ##STR2## R.sub.5 is selected from the group consisting of alkyl and aromatic residues, preferably radicals having between 1 and 12 carbon atoms, including alkyl, alkyl substituted with aryl radicals, and aryl radicals substituted with alkyl radicals; n is an integer between 1 and 4; R.sub.6 is an alkyl chain comprising between 1 and 4 carbon atoms; X is oxygen; and R.sub.1 is selected from the group consisting of ##STR3## wherein Y is as defined in the specification, and a is an integer of from zero to 3. These compounds are useful in treatment of disorders of the central nervous, cardiovascular, and endocrine systems, such as for inducing anorexia and weight loss in humans.

This invention relates to novel melatonin derivatives, such as 2-aryl substituted N-acetyltryptamines, having pharmacological activity, e.g., melatonin antagonist activity, and methods for the synthesis thereof.

2-aryl substituted N-acetyltryptamines and process of preparing such

Optically active or racemic compounds are provided having the formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H and OH with the provision that at least one of R.sub.2, R.sub.3 and R.sub.4 is H, that R.sub.2 and R.sub.4 are not both OH; X is oxygen; and R.sub.1 is selected from the group consisting of ##STR2## wherein Z is oxygen, nitrogen or sulfur, wherein Y is selected from the group consisting of hydroxy, nitro, cyano, azido, amino, acylamino, carboxyamido, trifluoromethyl, sulfate, sulfonamido, halogen, hydrocarbyl and heteroatom-substituted hydrocarbyl radicals, wherein said heteroatoms are selected from the group consisting of halogen, nitrogen, oxygen, sulfur and phosphorus and said hydrocarbyl radicals comprise from 1 to 12 carbon atoms, and a is an integer of from zero to 3. These compounds are capable of binding selectivity of one or more dopamine D.sub.2 receptors, for instance, in humans. They are useful in treatment of disorders of the central nervous, cardiovascular, and endocrine systems, such as elevated intraocular pressure, schizophrenia and Parkinsonism, and for inducing anorexia and weight loss in humans and other mammals.

Growing community of inventors

Costa Mesa, CA, United States of America

James V Peck