- DRUG COMBINATIONS CONTAINING PDE4 INHIBITORS AND NSAIDS
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The present invention relates to new drug combinations which contain in addition to one or more PDE4-inhibitors at least one NSAID (=non-steroidal anti-inflammatory drug) (2), processes for preparing them and their use in treating in particular respiratory complaints such as for example COPD, chronic sinusitis and asthma. The invention particularly relates to those drug combinations which contain, in addition to one or more, preferably one PDE4 inhibitor of general formula 1 wherein X is SO or SO2, but preferably SO, and wherein R1, R2, R3 and R4 have the meanings given in claim 1, at least one NSAID (2), the preparation thereof and the use thereof for the treatment of respiratory complaints.
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- DERIVATIVES OF UREAS OF PIPERIDINE OR PYRROLIDINE, THEIR PREPARATION AND THEIR THERAPEUTICAL USE
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The present invention is related to a compound of formula (I): wherein i, j, n, o, p, q, r, R1a, R1b, R1c, R1d, R2a, R2b, R2c, R2d, R3a, R3b and R4 are as defined herein, or an addition salt with an acid thereof, or a hydrate or solvate thereof, its preparation, pharmaceutical composition, and uses for treating a disease in which the enzyme 11β-HSD1 is involved.
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Page/Page column 27-28
(2009/07/18)
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- 1,3-Dihydro-2H-Indole-2-One Compound and Pyrrolidine-2-One Compound Fused With Aromatic Heterocycle
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It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.
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Page/Page column 75-76
(2009/01/24)
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- The development of a manufacturing route for the GPIIb/IIIa receptor antagonist SB-214857-A. Part 2: Conversion of the key intermediate SB-235349 to SB-214857-A
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The process development to the manufacturing route to (2S)-7-([4,4′ -bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1, 4-benzodiazepine-2-acetic acid hydrochloride (SB-214857-A, lotrafiban) is described. The starting point is the previously reported intermediate (2RS)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester. The first stage is a lipase-catalysed resolution of the racemic ester to (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid and subsequent iodination using a pyridine iodine monochloride complex to give (2S)-2,3,4,5-tetrahydro-7-iodo-4-methyl-3-oxo-1H-1,4-benzodiazepine-2- acetic acid. The unreacted (R)-enantiomer of the starting ester is recovered and recycled to the racemate by treatment with sodium methoxide. The next stage describes the palladium-catalysed aminocarbonylation of the aryl iodide with 4,4′-pyridylpiperidine to give (2S)-2,3,4,5-tetrahydro-4-methyl-3-oxo-7-[[4-(4-pyridinyl)-1-piperidinyl] carbonyl]-1H-1,4-benzodiazepine-2-acetic acid dihydrate. The third stage is the hydrogenation of the pyridine subunit over palladium on charcoal to obtain the zwitterionic (2S)-7-([4,4′ -bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1, 4-benzodiazepine-2-acetic acid hexahydrate. The final stage is the formation of the hydrochloride salt to afford the drug substance.
- Atkins, Richard J.,Banks, Adam,Bellingham, Richard K.,Breen, Gary F.,Carey, John S.,Etridge, Stephen K.,Hayes, Jerome F.,Hussain, Nigel,Morgan, David O.,Oxley, Paul,Passey, Stephen C.,Walsgrove, Timothy C.,Wells, Andrew S.
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p. 663 - 675
(2013/09/05)
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- Heterocyclic compounds useful as oxido-squalene cyclase inhibitors
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This invention concerns heterocyclic derivatives of formula (I) which are useful in inhibiting oxido-squalene cyclase, processes for their preparation and pharmaceutical compositions containing them. The present invention is also concerned with heterocyclic derivatives capable of inhibiting cholesterol biosynthesis and hence in lowering cholesterol levels in blood plasma. The present invention also relates to methods of using such heterocyclic derivatives in diseases and medical conditions such as hypercholesterolemia and atherosclerosis.
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Page column 15
(2008/06/13)
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- A new synthesis of the GPIIb/IIIa receptor antagonist SB-214857-A
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A new synthesis of lotrafiban SB-214857-A is reported. The key steps are the preparation of racemic (4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-yl)-acetic acid methyl ester from 2-nitrobenzyl alcohol, a resolution using an immobilised li
- Andrews, Ian P,Atkins, Richard J,Badham, Neil F,Bellingham, Richard K,Breen, Gary F,Carey, John S,Etridge, Stephen K,Hayes, Jerome F,Hussain, Nigel,Morgan, David O,Share, Andrew C,Smith, Stephen A.C,Walsgrove, Timothy C,Wells, Andrew S
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p. 4915 - 4917
(2007/10/03)
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- Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol synthase derived by consideration of inhibitor pKa
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Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol synthase (OSC) was maintained after structural modification of the 4-piperidinopyridine OSC inhibitor series. These novel analogues with a much lower pKa range (5.8-6.7) gave
- Brown, George R.,Foubister, Alan J.,Johnson, Michael C.,Newcombe, Nicholas J.,Waterson, David,Wells, Stuart L.
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p. 2213 - 2216
(2007/10/03)
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- Substituted benzoylpiperidine derivatives and their use as Neurokinin antagonists
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The present invention provides a compound of the formula:- or a pharmaceutically acceptable acid addition salt thereof, whereinAr is phenyl substituted by 1 or 2 substituent(s) each independently selected from fluoro and chloro;X is NSO2(C1-C4 alkyl), NSO2(halo(C1-C4 alkyl)) or O;m is 0 or 1 ;n is 1 or 2;p is 1 or 2;q is 1 or 2; and r is 1 or 2, together with processes for the preparation of, intermediates used in the preparation of, compositions containing and uses of, such derivatives. The compounds have tachykinin receptor antagonist activity.
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- From bipyridines to tobacco alkaloids and related compounds
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Starting from structural considerations which led to the hypothesis that a chemical relationship could exist between two families of natural compounds (mainly pyridinic and pyrrolidinic alkaloids), experiments were carried out in order to establish a correlation route between the two studied classes. Of special interest was the central position of nicotine in these studies, and the main part of this work was devoted to the synthesis of nicotine starting from bipyridines. It was thus necessary to determine the conditions for selective reactions on one aromatic ring of bipyridines (N-methylation, N-oxidation and reduction of the heterocycle). Ring contraction procedure allowed us to obtain nicotine from the parent compound (3,3′-bipyridine). Complementary studies yielded various isomers of piperidinylpyridines (hexahydro derivatives of bipyridines) in a regiochemically controlled manner by means of original methods. Elsevier,.
- Plaquevent, Jean-Christophe,Chichaoui, Ilhame
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p. 369 - 379
(2007/10/03)
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- Reduction Regiospecifique des Bipyridines
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A method for the specific reduction of bipyridines through the use of the N-oxo derivatives is described.
- Plaquevent, Jean-Christophe,Chichaoui, Ilhame
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p. 5287 - 5288
(2007/10/02)
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