- The new method of the preparation of oxazole derivatives
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The invention particularly relates to a method for synthesizing oxazole derivative, belonging to the field of synthesis of heterocyclic compounds. The technical scheme is as follows: the method comprises the following steps: reacting the raw material tosyl methyl isonitrile derivative disclosed as Formula (I) with acyl chloride disclosed as Formula (II) to obtain alpha-ketoimine chloride disclosed as Formula (III); and reacting the intermediate alpha-ketoimine chloride disclosed as Formula (III) with aldehyde (IV) in the presence of a protonic solvent and alkali to obtain 2-substituted oxazole (V). Compared with the prior art, the method uses cheap and accessible raw materials, avoids using the catalyst, lowers the cost, reduces the environmental pollution, has the advantage of mild reaction conditions, and is simple to operate and beneficial to industrial production.
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Paragraph 0054; 0055; 0056
(2017/08/25)
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- COMBINATION OF A MUSCARINIC RECEPTOR ANTAGONIST AND A BETA-2-ADRENOCEPTOR AGONIST
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The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is a selected muscarinic receptor antagonist selected, and a second active ingredient which is a β2-adrenoceptor agonist, of use in the treatment of respiratory diseases such as chronic obstructive pulmonary disease and asthma.
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Page/Page column 31
(2008/12/08)
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- CHEMICAL COMPOUNDS
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The present invention provides compounds of formula (Ia): wherein A, X, and R1-R8 are as defined herein, such compounds having utility in the treatment of diseases where M3 and beta2 receptors are implicated, such as respiritory tract diseases; compositions comprising such compounds; uses of such compounds in therapy (such as asthma or COPD); and methods of treating a patient with such compounds.
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Page/Page column 69
(2008/06/13)
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- HETEROCYCLIC DERIVATIVES AS M3 MUSCARINIC RECEPTORS
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This invention relates to M3 antagonists of formula (I) wherein R2, R4, R5, R6, W, V, A, D, X, t, u and v are as defined herein; pharmaceutical compositions containing them; methods for their preparation; and their use in the treatment of diseases where enhanced M3 receptor activation is implicated.
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Page/Page column 55-56
(2008/12/08)
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- OXAZOLE AND THIAZOLE DERIVATIVES AND THEIR USES
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A quaternary ammonium compound of formula (I) having M3 receptor antagonist activity; a composition comprising such a compound; the use of such a compound in therapy (such as asthma or COPD); and a method of treating a patient with such a compound.
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Page/Page column 19-20
(2008/12/08)
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- OXAZOLE AND THIAZOLE DERIVATIVES AND THEIR USES 2
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Compounds of formula (I): wherein A, X, R1, R2, R3, R4, R5, R6 and R8 are as defined in the Specification are useful in the treatment of diseases where enhanced M3 receptor activ
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Page/Page column 43-44
(2008/12/08)
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- NAPADISYLATE SALT OF A MUSCARINIC M3 ANTAGONIST
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The invention provides [2-((R)-Cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-ylmethyl]- dimethyl-(3-phenoxy-propyl)-ammonium napadisylate, pharmaceutical compositions containing it, and its use in therapy.
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Page/Page column 20-21
(2008/12/08)
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- AZOLE AND THIAZOLE DERIVATIVES AND THEIR USE
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Compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiritory tract diseases: wherein (i) R1 is C1-C6-alkyl or hydrogen; and R2 is hydrogen or a group -R7, -Z-Y-R7, -Z-NR9R10; -Z-CO-NR9R10, -Z-NR9-[AE11]C(O)O-R7, or -Z-C(O)-R7; and R3 is a lone pair, or C1C6-alkyl; or (ii) R1 and R3 together with the nitrogen to which they are attached form a heterocycloalkyl ring, and R2 is a lone pair or a group -R7, -Z-Y-R7, -Z-NR9R10, -Z-CO-NR9R10, -Z-NR9-[AE12]C(O)O-R7; or; -Z-C(O)-R7; or (iii) R1 and R2 together with the nitrogen to which they are attached form a heterocycloalkyl ring, said ring being substituted by a group -Y-R7, -Z-Y-R7, -Z-NR9R10; -Z-CO-NR9R10; -Z-NR9-[AE13]C(O)O-R7; or; -Z-C(O)-R7; and R3 is a lone pair, or C1-C6-aIkyl; R4 and R5 are independently selected from the group consisting of aryl, arytfused-heterocycloalkyl, heteroaryl, C1-C6-alkyl, cycloalkyl; R6 is -OH, C1-C6-alkyl, C1-C6-alkoxy, hydroxy-C1-C6-alkyl, nitrile, a group CONR82 or a hydrogen atom; A is an oxygen or a sulfur atom; X is an alkylene, alkenylene or alkynylene group; R7 is an C1-C6-alkyl, aryl, aryl-fused-cycloalkyl, aryl-ffused-heterocycloalkyl, heteroaryl, aryl(C1-C8-alkyl)-, heteroaryl(C1-C8-alkyl)-, cycloalkyl or heterocycloalkyl group; R8 is C1-C6-alkyl or a hydrogen atom; Z is a C1-C16-alkylene, C2-C16-alkenylene or C2-C16-alkynylene group; Y is a bond or oxygen atom; R9 and R10 are independently a hydrogen atom, C1-C6-alkyl, aryl, aryl-fused-heterocycloalkyl, aryl-fused-cycloalkyl, heteroaryl, aryl(C1-C6-alkyl)-, or heteroaryl(C1-C6-alkyl)- group; or R9 and R10 together with the nitrogen atom to which they are attached form a heterocyclic ring of 48 atoms, optionally containing a further nitrogen or oxygen atom.
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Page/Page column 41-42
(2010/11/25)
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