- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
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The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
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- METHOD FOR TREATING CHRONIC PAIN USING MEK INHIBITORS
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The invention features a method for treating chronic pain using a compound selected from formulae (I), (II)A, (I)B and (I)C.
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- Benzenesulfonamide derivatives and their use as MEK inhibitors
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Benzenesulfonamides of formula (I), in which W is OR1, NR2OR1, NRARB, NR2NRARB, or NR2(CH2)2-4NRARBand the other variables as defined in the claims, are inhibitors of MEK and are effective in the treatment of proliferative diseases, cancer, stroke, heart failure, xenograft rejection, arthritis, cystic fibrosis, hepatomegaly, cardiomegaly, Alzheimer's disease, complications of diabetes, septic shock, and viral infection.
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- 2-aminopyridine derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
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- Synthesis, characterization, and biological evaluation of a novel class of N-(arylethyl)-N-alkyl-2-(1-pyrrolidinyl)ethylamines: Structural requirements and binding affinity at the σ receptor
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By synthesizing and testing a part-structure, N-[2-(3,4- dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3), derived from our previously reported high affinity σ receptor ligands (1S,2R)-(-)-N-[2- (3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine [(-)- 2] and (+)-2, we have identified a novel class of superpotent (subnanomolar affinity) σ ligands specific for the σ receptor labeled by [3H]-(+)-3-PPP. When 3 was tested for its capacity to displace [3H]-(+)-3-PPP from guinea pig brain membranes, it exhibited a K(i) of 0.34 nM, which is better than either of its parent compounds (-)-2 (K(i) = 1.3 nM) and (+)-2 (K(i) = 6.0 nM). Other compounds related to 3 such as N-[2-(3,4-dichlorophenyl)ethyl]-N- methyl-2-(1-homopiperidinyl)ethylamine (19) exhibited K(i) = 0.17 nM ([3H]- (+)-3-PPP). The determinants for high σ receptor affinity of 3 were examined by manipulation of this structure in a number of different ways. The high efficacy of these compounds for the σ receptor, their relative chemical simplicity and ease of synthesis, and their high degree of selectivity identifies N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)ethylamine (3) and related compounds as a highly promising base for determination of the functional role of σ receptors as well as the development of novel therapeutic agents.
- De Costa,Radesca,Di Paolo,Bowen
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- N-(amino)alkyl)-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) with sulfur linked substitution in the 2, 3 or 4-positions
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Novel pyrrolidine, piperidine and homopiperidinecarboxamide and thiocarboxamide compounds having the formula: STR1 wherein X is --S--, --S(O)-- or --S(O)2 --; A is a loweralkalene chain and A1 and A2 are alkalene chains when p and d are one; R, R1 and R2 are hydrogen, loweralkyl, phenyl cycloalkyl or phenylalkyl and R1 and R2 may form a heterocyclic residue with the adjacent nitrogen atom; Q is a selected aromatic radical, and the pharmaceutically acceptable acid addition salts useful as cardiac antiarrhythmia agents are disclosed. Novel chemical intermediates, unsubstituted on pyrrolidine, piperidine and homopiperidine nitrogen but with --(A2)p --X--(A2)d --Q side chain are also disclosed.
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- Substituted sulfonamidobenzamides and method of treating arrhythmias
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Novel substituted sulfonamidobenzamides are described as useful antiarrhythmic agents. Their use in the treatment of cardiac arrhythmias, especially re-entrant arrhythmias, via the prolongation of the action potential of cardiac tissue is provided. Pharmaceutical formulations containing such compounds are also disclosed.
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- N-[(amino)alkyl]-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) with sulfur linked substitution in the 2, 3 or 4-position
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Novel pyrrolidine, piperidine and homopiperidinecarboxamide and thiocarboxamide compounds having the formula: STR1 wherein X is --S--, --S(O)-- or --S(O)2 --; A is a loweralkalene chain and A1 and A2 are alkalene chains when p and d are one; R, R1 and R2 are hydrogen, loweralkyl, phenyl cycloalkyl or phenylalkyl and R1 and R2 may form a heterocyclic residue with the adjacent nitrogen atom; Q is a selected aromatic radical, and the pharmaceutically acceptable acid addition salts useful as cardiac antiarrhythmia agents are disclosed. Novel chemical intermediates, unsubstituted on pyrrolidine, piperidine and homopiperidine nitrogen but with --(A2)p --X--(A2)d --Q side chain are also disclosed.
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- Substituted sulfonamidobenzamides, antiarrhythmic agents and compositions thereof
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Novel substituted sulfonamidobenzamides are described as useful antiarrhythmic agents. Their use in the treatment of cardiac arrhythmias, especially re-entrant arrhythmias, via the prolongation of the action potential of cardiac tissue is provided. Pharmaceutical formulations containing such compounds are also disclosed.
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- Long-range anisotropic effects of long chain amides
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In 1H-NMR spectra of amids with long-chain aliphatic N-substituents one observes - despite of the free mobility of the aliphatic chain - splitting of the signals of the terminal methyl groups which is caused by the hindered rotation of the amide bond. - Keywords: Amides; Hindered rotation; 1H-NMR
- Budzikiewicz, Herbert,Vieth, Peter-Eric,Krueger, Uwe
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p. 825 - 840
(2007/10/02)
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