2-aminothiophenes by the gewald reaction

Compounds are disclosed having formula (I) wherein D, E, G, L, M, A, R'1, L', and M' are defined herein. The compounds of the invention are angiotensin II receptor antagonists.

Angiotensin ii receptor antagonists

This invention relates to a novel group of imidazole compounds, processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and pharmaceutical compositions for use in such therapy.

Substituted imidazole compounds

N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula (I). Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-a expression utilizing compounds of the present invention are also disclosed.

N-heterocyclic inhibitors of tnf-alpha expression

Substituted sulfonamides having formula (I), are selective .beta.3 adrenergic receptor agonists with very little .beta.1 and .beta.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduce neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.

Substituted sulfonamides as selective .beta.3 agonists for the treatment of diabetes and obesity

Thieno[2,3‐d]pyrimidines. I. A new method for the preparation of esters and amides of thieno[2,3‐d] pyrimidine‐6‐carboxylic acids

The syntheses of 2-oxo-1,8-naphthyridine-3-carboxylic acid derivatives having potent gastric antisecretory properties in the pyloric-ligated (Shay) rat model are described. Two of the more potent compounds tested that were selected for more detailed dose-response evaluation were 4-amino-1-ethyl-1,2-dihydro-2-oxonaphthyridine-3-carboxylic acid ethyl ester (35) and 1-ethyl-1,2-dihydro-7-methyl-4-(4-methyl-1-piperazinyl)-2- oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester (77). These compounds lowered total acid output in the rat in a dose-related fashion. Both compounds were more potent than cimetidine when tested in the rat. Both 35 and 77 showed inhibitory activity in food-stimulated acid secretion in the Pavlov-pouch, conscious dog. The mechanism of action for this series is not known. Details of structure-activity relationships are described.

2-Oxo-1,8-naphthyridine-3-carboxylic acid derivatives with potent gastric antisecretory properties

Substituted 4-oxy-3-carboxy or cyano-1,2-dihydro-2-oxo-1,8-naphthyridine derivatives as gastric antisecretory agents for use in the treatment of peptic ulcer disease.

Antisecretory 4-oxy-3-carboxy or cyano-1,2-dihydro-2-oxo-1,8-naphthyridine derivatives

Further exploration of the cycloalkanol ethylamine scaffold, of which venlafaxine ( 1) is a member, was undertaken to develop novel and selective norepinephrine reuptake inhibitors (NRIs) for evaluation in a variety of predictive animal models. These efforts led to the discovery of a piperazine-containing analogue, 17g (WY-46824), that exhibited potent norepinephrine reuptake inhibition, excellent selectivity over the serotonin transporter, but no selectivity over the dopamine transporter. Synthesis and testing of a series of cyclohexanol ethylpiperazines identified ( S)-(-)- 17i (WAY-256805), a potent norepinephrine reuptake inhibitor (IC 50 = 82 nM, K i = 50 nM) that exhibited excellent selectivity over both the serotonin and dopamine transporters and was efficacious in animal models of depression, pain, and thermoregulatory dysfunction.

Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors.

Compounds of formula
 in which R' is hydrogen, alkyl, cycloalkyl of 5 to 6 carbon atoms, alken(3,4,5 or 6)-yl of 3 to6 carbon atoms oralkyn(3,4,5 or 6)-yl of 3 to 6 carbon atoms; R 2 is-CN,-CO 2 H,-CO 2 R 7 where R 7 is alkyl, -CONHNH 2 or
 where R 8 and R 9 are independently hydrogen or alkyl; R 3 and R 4 are independently hydrogen, alkyl, hydroxyalkyl, dialkylaminoalkyl of 4 to 8 carbon atoms, alkanoyl of 2 to carbon atoms, haloalkanoyl of 2 to 4 carbon atoms, or when taken together with the nitrogen atom to which they are attached. R 3 and R 4 complete a defined heterocyclic group; R 6 and R 6 are independently hydrogen; alkyl of 1 to 4 carbon atoms, halo, alkylamino of 1 to4 carbon atoms, or alkoxy; or a pharmaceutically acceptable saltthereof are disclosed which have gastric anti-secretory, and in some cases diuretic, activity and are useful in pharmaceutical compositions especially for treatment of peptic ulcers. Also described are processes for preparing the compounds and 4-halo-1, 8-naphthyridine intermediates useful in some of the processes.

Arthur A. Santilli

Papers

Thieno[2,3‐d]pyrimidines. I. A new method for the preparation of esters and amides of thieno[2,3‐d] pyrimidine‐6‐carboxylic acids

2-Oxo-1,8-naphthyridine-3-carboxylic acid derivatives with potent gastric antisecretory properties

Antisecretory 4-oxy-3-carboxy or cyano-1,2-dihydro-2-oxo-1,8-naphthyridine derivatives

Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors.

1,8-naphthyridine derivatives, their preparation, pharmaceutical compositions containing them