- PYRIMIDINE TBK/IKKε INHIBITOR COMPOUNDS AND USES THEREOF
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The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.
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- AZAINDOLE DERIVATIVES AS INHIBITORS OF P38 KINASE
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The invention is directed to methods to inhibit p38 kinase, preferably p38-α using compounds which are azaindoles wherein the azaindoles are coupled through an azacyclic linker to another cyclic moiety.
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Page/Page column 59
(2010/11/24)
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- 2-ALKOXY-6-AMINO-5-HALOGENO-N-(1-SUBSTITUTED-4-PIPERIDINYL)PYRIDINE-3-CARBOXAMIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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PROBLEM TO BE SOLVED: To provide a compound exhibiting high affinity for serotonin 4 receptor and useful as a digestive tract motion promoting agent or digestive tract function ameliorating agent. SOLUTION: The compound is represented by the formula(I), or an acid addition salt thereof and an intermediate thereof are provided. In formula(I), R1 is a halogen atom; R2 is H or a lower alkyl; R3 is H, a lower alkyl or the like; R4 is a lower alkyl; A is a group represented by the formula: Z-N(Q1)(Q2) or CO-R5, wherein Z is CO, CS or the like; Q1 and Q2 are each H, a lower alkyl or the like, or joined together with the nitrogen atom to which Q1 and Q2 are bound to form a pyrrolidine ring, piperidine ring or the like; and R5 is H, a lower alkyl, lower alkoxy, lower alkoxycarbonyl or the like.
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Page/Page column 22
(2010/02/11)
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- A practical preparation of methyl 2-methoxy-6-methylaminopyridine-3-carboxylate from 2,6-dichloro-3-trifluoromethylpyridine
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An effective and practical synthetic route to methyl 2-methoxy-6-methylaminopyridine-3-carboxylate (7), the key intermediate of 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxylic acid (1), from 2,6-dichloro-3-trifluoromethylpyridine (12) was undertaken. Process improvements were highlighted by regioselectivity of 12 with a nitrogen nucleophile and conversion of the 3- trifluoromethyl group into the methoxycarbonyl group. The reaction of 12 with N-benzylmethylamine provided the 6-(N-benzyl-N-methyl)aminopyridine 26a and the regioisomer 26b in >98: 2 ratio in a quantitative yield. Treatment of 2-methoxy-6-methylamino-3-trifluoropyridine (14a) with a large excess of sodium methoxide followed by acid hydrolysis gave the pyridine-3-carboxylic ester 7 in an excellent yield. The potential application of this reaction is also described.
- Horikawa,Hirokawa,Kato
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p. 1621 - 1627
(2007/10/03)
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- Synthesis of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6- yl)nicotinamides and their affinities for 5-HT3 and dopamine D2 receptors
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A series of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)nicotinamide derivatives were prepared and evaluated for their binding to 5-HT3 and dopamine D2 receptors. Among them, the 5-bromo-2-methoxy-6- methylaminonicotinamide 16 and its (R)-isomer were found to have potent affinities for both receptors. The affinities of (R)-16 for 5-HT3 and dopamine D2 receptors are approximately 3-fold higher than those of the corresponding benzamide (R)-1 (IC50: 1.1 and 12 nM vs. 2.9 and 35 nM, respectively).
- Hirokawa, Yoshimi,Yoshida, Naoyuki,Kato, Shiro
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p. 1551 - 1554
(2007/10/03)
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