120635-74-7Relevant articles and documents
NOVEL PROCESS FOR THE PREPARATION OF IMIDAZOLYL COMPOUNDS
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Page 9, (2008/06/13)
The present invention relates to a method for the preparation of an imidazolyl compound of the general formula (I), wherein: Ra and Rb each separately are (C1-C6)alkyl, (C1-C6)alkoxyalkyl, optionally substituted aryl or heteroaryl; or wherein Ra and Rb together form a further homocyclic or heterocyclic system comprising one or more rings; Ra’ and Rb’ each are hydrogen or together form a carbon-carbon double bond, said carbon-carbon double bond optionally being part of an aromatic system; Rc is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1,-C6)alkoxyalkyl or halogen; Rd is hydrogen or (C1-C4)aIkyl; Re is hydrogen or (C1-C4)aIkyl; m is 1 or 2; and R1, is hydrogen or (C1-C4)aIkyl; as well as its acid addition salt;characterized in that a compound of the general formula (II) is reacted with a compound of the formula (III), wherein: R is a hydrogen, a (C1-C4)alkyl group optionally substituted with a hydroxygroup or an optionally substituted aryl group, R', R", R'" and R"" each individually are a hydrogen or a (C1-C4)aIkyl group; followed by a reaction with a compound of the formula (IV), wherein R1, Rd and Re have the meanings defined above; and optionally followed by a reaction with a suitable acid. De method according to the present invention is especially useful for the preparation of ondansetron and cilansetron.
Formulations of adenosine a1 agonists
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, (2008/06/13)
The present invention provides a method of treating conditions associated with pain and alleviating the symptoms associated therewith which comprises administering to a mammal, including man, an adenosine A1 agonist or a physiologically acceptable salt or solvate thereof and a 5HT3 antagonist or a physiologically acceptable salt or solvate thereof. The present invention also provides pharmaceutical formulations and patient packs comprising said combinations.
USE OF ONDANSETRON IN THE MANUFACTURE OF A MEDICAMENT FOR THE TREATMENT OF TREMOR
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, (2008/06/13)
The invention provides the use of a 5-HT3 receptor antagonist or a pharmaceutically acceptable derivative thereof for use in the treatment of dyskinesia.
Development of high-affinity 5-HT3 receptor antagonists. Structure- affinity relationships of novel 1,7-annelated indole derivatives. 1
Van Wijngaarden,Hamminga,Van Hes,Standaar,Tipker,Tulp,Mol,Olivier,De Jonge
, p. 3693 - 3699 (2007/10/02)
On the basis of the structures of ondansetron and GR 65,630, its ring- opened C-linked methylimidazole analogue, novel 1,7-annelated indole derivatives were synthesized as potential 5-HT3 antagonists. Receptor binding studies show that all compounds display a high affinity for the 5- HT3 receptors. In both series annelation results in compounds being 7 and 4 times more potent than the references ondansetron and GR 65,630, respectively. Similar to ondansetron, the 1,7-annelated indoles show little stereoselectivity. The (-)-isomers are only slightly more potent than the (+)-isomers. The receptor binding profile of l-10-[(2-methyl-1H-imidazol-1- yl)methyl]-5,6,8,9,10,11-hexahydro-4H-pyrido[3,2,1-jk]carbazol-11-one hydrochloride (24b) (INN cilansetron) shows that the compound displays, besides a high affinity for 5-HT3 receptors (K(i) = 0.19 nM), a weak affinity for σ-receptors (K(i) = 340 nM), muscarine M1 receptors (K(i) = 910 nM), and 5-HT4 receptors (K(i) = 960 nM) and no affinity (K(i) ≥ 5000 nM) for all the other receptor types tested (n = 37). The new compounds fit the proposed necessary chemical template for binding: a heteroaromatic ring system, a coplanar carbonyl group, and a nitrogen center at well-defined distances. The enhanced potency of the annelated 1,7-indole derivatives indicates that the extra ring provides a favorable hydrophobic area for interaction with the 5-HT3 receptor site. In vivo cilansetron is more potent and induces less central side effects than ondansetron. At present cilansetron is in clinical trials.
New anellated indole derivatives
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, (2008/06/13)
The invention relates to new anellated indole derivatives of general formula 2, STR1 wherein p1 R 0 is alkyl or alkoxy having 1-4 C-atoms, phenylalkoxy having 1-3 C-atoms in the alkoxy group, hydroxy, halogen, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, or a group R 7 S(O) p, wherein R 7 is alkyl having 1-4 C-atoms and p has the value 0, 1 or 2, or R 0 is a group R 8 R 9 N, R 8 R 9 N--CO--CH 2 -- or R 8 R 9 --N--CO wherein R 8 and R 9 are hydrogen or alkyl having 1-4 C-atoms or R 8 R 9 N forms a saturated 5- or 6-membered ring and n has the value 0, 1 or 2, Z together with the carbon atom and nitrogen atom to which Z is bound and the intermediate carbon atom, forms a heterocyclic group consisting of 5-8 ring atoms, in which, in addition to the nitrogen atom already present, a --CO--group or a second hetero atom from the group N, O, S, S-O or SO 2 may be present, which ring may be substituted with 1-3 alkyl groups having 1-4 C-atoms, a phenyl group or a spiroalkyl group (C 2 -C 5), or which ring may be anellated with a saturated or non-saturated carbocyclic or heterocyclic ring which consists of 5- or 6-ring atoms and which may be substituted with halogen, alkyl or alkoxy having 1-4 C-atoms, andm has the values 1-5,one of the groups R 2, R 3 and R 4 is hydrogen, alkyl having 1-6 C-atoms, cycloalkyl having 3-7 C-atoms, alkenyl having 2-6 C-atoms or phenylalkyl having 1-3 C-atoms in the alkyl group, and the two other groups independently of each other are hydrogen or alkyl having 1-6 C-atoms,and the pharmaceutically acceptable acid addition salts thereof. These compounds are strong and selective antagonists of ""neuronal"" 5-hydroxytryptamine (5-HT) receptors, and have a considerably longer-lasting effect and lower toxicity in comparison with related known compounds.
