- Process development of a disease-modifying antirheumatic drug, TAK-603, based on optimization of Friedel-Crafts reaction and selective substitution of a triazole ring
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A practical method for the preparation of TAK-603, an antirheumatic drug, has been developed. As a result of optimizing the Friedel-Crafts reaction in the presence of SnCl4/POCl3, 2-aminobenzophenone skeleton, the key intermediate of
- Mizuno, Masahiro,Inagaki, Atsushi,Yamashita, Makoto,Soma, Norie,Maeda, Yoshiharu,Nakatani, Hiroshi
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p. 4065 - 4070
(2007/10/03)
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- Production of benzophenone derivatives
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A method for producing a compound of the formula: wherein R is an acyl group or a silyl group, the rings A and B respectively may have one to four substituent(s), or a salt thereof, which comprists reacting a compound of the formula: wherein R has the same meaning as defined above, the ring A may have one to four substituents at the position(s) other than 2-position, or a salt thereof, with a compound of the formula: wherein Y is a hydroxyl group or a halogen atom, the ring B may have one to four substituent(s), or its salt, in the presence of a catalyst other than polyphosphonic acid. The method produces aminobenzophenone derivative of the formula (I) in a high purity, a high yield, with a conventional and commercially advantageous procedure.
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- Pharmaceutical composition containing quinoline or quinazoline derivatives
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The present invention provides a pharmaceutical composition for inhibiting bone resorption or for preventing or treating osteoporosis which comprises a quinoline or quinazoine derivative as an active ingredient.
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- Processes for production of quinoline or quinazoline derivatives and intermediates therefor
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Processes for production of quinoline or quinazoline derivatives and intermediates therefor STR1 A process for producing a compound of formula (2) of value as antiinflammatory agents, which comprises reacting a compound of formula (3) or a salt thereof wi
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- Studies on disease-modifying antirheumatic drugs: Synthesis of novel quinoline and quinazoline derivatives and their anti-inflammatory effect
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In the course of our study aimed at developing new types of DMARDs (disease-modifying antirheumatic drugs), we found that quinoline derivative 1a had a potent anti-inflammatory effect in an adjuvant arthritis (AA) rat model, starting from the potent bone resorption inhibitors justicidins as the lead compounds. Further modification of 1a was performed, and various quinoline and quinazoline derivatives having a heteroaryl moiety on the alkyl side chain at the 2-position of the skeleton were prepared. These compounds were evaluated for antiinflammatory effects using the AA rat model. Most of these compounds, especially those having an imidazole or a triazole moiety on the 2-alkyl chain, exhibited a potent effect. Among the compounds synthesized, ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1- yl-methyl)quinoline-3-carboxylate (12d), having an ED50 value of 2.6 mg/kg/day (anti-inflammatory effect in an AA rat model, po), was selected as a candidate for further investigation. In vitro, 12d inhibited mitogen- induced proliferation at 10-7-10-5 M but not prostaglandin E2 production at 10-5 M. Moreover, 12d preferentially inhibited the IFN-γ production by Th1-type clones over the IL-4 production by Th2-type clones. This preferential suppression of Th1 cytokine production is considered the essential immunomodulating action of 12d for the present. Synthesis and structure-activity relationships for this novel series of quinoline and quinazoline derivatives are detailed.
- Baba, Atsuo,Kawamura, Noriaki,Makino, Haruhiko,Ohta, Yoshikazu,Taketomi, Shigehisa,Sohda, Takashi
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p. 5176 - 5182
(2007/10/03)
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- Quinoline or quinazoline derivatives, their production and use
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A compound represented by the general formula: STR1 wherein Y represents a nitrogen atom or C--G (G represents a carboxyl group which may be esterified); ring R is a nitrogen-containing unsaturated heterocyclic group which may be substituted or unsubstituted; each of rings A and B may have a substituent; n represents an integer from 1 to 4; k represents the integer 0 or 1, or a salt thereof, which serves well as an anti-inflammatory agent, particularly a therapeutic agent for arthritis.
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