Karo Bio Ab

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Abbott Healthcare Products B.v.

Karo Pharma Ab

Konrad Koehler

Johan Malm

Neeraj Garg

Minsheng Zhang

Denis E Ryono

Jon J Hangeland

Yolanda V Caringal

Chris Litten

Yi-Lin Li

Ana Maria Garcia Collazo

Ye Liu

Josephus H M Lange

Frank Narjes

Marco Poma

Joakim Löfstedt

Peter Brandt

Michael Mlinaric

Theresa Apelqvist

Sandra Gordon

Lars Krüger

Aiping Cheng

Lars Hagberg

Karin Edvinsson

Andrei Sanin

Pieter Smid

Sara Nuñez Garcia

Elmar Wegener

Eva Koch

Daniel Nöteberg

Victor Matassa

Jesus Ontoria

Antonella Marchetti

Jinchang Wu

Lars KRÜGER

Joakim LÖFSTEDT

Daniel NÖTEBERG

Compounds of formula (I) or a pharmaceutically acceptable ester, amide, carbamate or salt thereof, including a salt of such an ester, amide or carbamate in which Rto Rhave meanings as defined in the Specification, are useful as estrogen receptor ligands. 

Estrogen receptor ligands

This invention concerns spiro azepane-ox-azolidinones as voltage gated Kv1.3 potassium channel blockers, pharmaceutical compositions containing these compounds, methods for preparing the compounds, methods for preparing novel intermediates useful for their synthesis, and methods for preparing compositions. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in the treatment of diabetes, psoriasis, obesity, transplant rejection and inflammatory neuropathies, including T-cell mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The compounds have formula (1): wherein R, R, (R), and (R)have the meanings given in the specification.

Spiro azepane-oxazolidinones as Kv1.3 potassium channel blockers

New thyroid receptor ligands are provided which have general formula (I) in which: n is an integer from 0 to 4; Ris halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; Rand Rare the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, at least one of Rand Rbeing other than hydrogen; Ris a carboxylic acid amide (CONR'R&#x2033;) or an acylsulphonamide (CONHSOR&#x2032;) derivative, or a pharmaceutically acceptable salt thereof, and all stereolsom thereof; or when n is equal to or greater than one, Rmay be heteroaromatic moiety which may be substituted or unsubstituted, or an amine (NR&#x2032;R&#x2033;). Ris hydrogen or an acyl (such as acetyl or benzoyl) or other group capable of bioconversion to generate the free phenol structure (wherein R&#x2014;H). In addition, a method is provided for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependant upon the expression of a Tregulated gene, wherein a compound as described above is administered in a therapeutically effective amount. Examples of such diseases associated with metabolism dysfunction or are dependent upon the expression of a Tregulated gene include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma, congestive heart failure and skin disorders. 

Thyroid receptor ligands and method II

This invention relates to novel compounds which are thyroid receptor ligands, preferably antagonists, and to methods for using such compounds in the treatment of cardiac and metabolic disorders, such as cardiac arrhythmias, thyrotoxicosis, subclinical hyperthyrodism and liver diseases.

Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders

New thyroid receptor ligands are provided which have general formula (I) in which: n is an integer from 0 to 4; Ris halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; Rand Rare the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, at least one of Rand Rbeing other than hydrogen; Ris a carboxylic acid amide (CONR'R&#x2033;) or an acylsulphonamide (CONHSO2R&#x2032;) derivative, or a pharmaceutically acceptable salt thereof, and all stereoisomers thereof; or when n is equal to or greater than one, Rmay be a heteroaromatic moiety which may be substituted or unsubstituted, or an amine (NR&#x2032;R&#x2033;). Ris hydrogen or an acyl (such as acetyl or benzoyl) or other group capable of bioconversion to generate the free phenol structure (wherein R=H). In addition, a method is provided for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependent upon the expression of a Tregulated gene, wherein a compound as described above is administered in a therapeutically effective amount. Examples of such diseases associated with metabolism dysfunction or are dependent upon the expression of a Tregulated gene include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma, congestive heart failure and skin disorders.

Fluorinated oligopeptides, especially those having 4,4-difluoro-2-amino butyric acid at the C terminus, may be effective inhibitors of hepatitis C virus NS3 protease. Examples of hexapeptides of the invention, optimized for binding in the S1 specificity pocket of the enzyme, may display ICs at the sub-micromolar level. Embodiments of tripeptides of the invention, having a keto-acid group at the C-terminus are, likewise, potent inhibitors of NS3 protease.

Peptide inhibitors of hepatitis C virus NS3 protease

Liver specific bile acid derivatives of the glucocorticoid antagonist RU486

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Huddinge, Sweden

Konrad Koehler