Synthesis and antirheumatic activity of novel tetrahydroquinoline-8-carboxylic acid derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 12, 1997, Pages 1515-1518

  Kohno, Yasushi ^a   Awano, Katsuya ^a   Miyashita, Mitsutomo ^a   Fujimori, Shizuyoshi ^a   Kuriyama, Kazuhiko ^a   Sakoe, Yasuhiko ^a   Kudoh, Shinji ^a   Saito, Koji ^a   Kojima, Eisuke ^a  

^a KYORIN PHARMACEUTICAL CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRHEUMATIC AGENT; INTERLEUKIN 1BETA; TETRALIN DERIVATIVE;

ADJUVANT ARTHRITIS; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE DESTRUCTION; CONTROLLED STUDY; DRUG SYNTHESIS; IN VITRO STUDY; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT;

EID: 0030988272     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00261-8     Document Type: Article

References (10)

1. If the test compounds had COX inhibition, it would be vague whether their effects on adjuvant arthritis exhibited by COX inhibition or immunomodulating activity. In order to distinguish DMARDs from NSAIDs definitely, we selected the compounds without COX inhibition.
2. -5 M.
3. Adjuvant arthritis was induced in SD rats according to the method of Kameyama et al.: Kameyama, T.; Nabeshima T.; Yamada S.; Sato M., Arzneim-Forsch/Drug Res., 37, 19 (1987). After the adjuvant injection, drug treatment (10 mg/kg and 50 mg/kg p.o.) was started on Day 14 and continued until Day 20 (once daily, 7 treatments). Suppressive rates on edema were calculated on Day 21. Some of the compounds listed in Table 1 and 2 did not show a dose-dependent suppression. In order to simplify comparison of the inhibitory effects, Table 1 and 2 were expressed by better inhibitory effect obtained at the above doses.
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9. The bone resorption was measured according to a modification of the method described by Tsuda et al.: Tsuda M.; Kitazaki T.: Ito T.; Fujita T., J. Bone Miner. Res., 1, 207 (1986).
10. On day 24, radiographic assessments of non-injected paws were done by a modification of the method of Tanaka et al.: Tanaka A.; Kakushi H.; Shike T.; Yoshida T.; Kojima Y.; Nishiyama S.; Yahara I., Oyo Yakuri-Pharmacometrics, 24, 571 (1982). Bone damage was assessed blindly on a scale of 0-4+ (with 0 equaling normal and 4+ equaling severe changes) for metatarsus, tarsus, calcaneum, and the end of the distal tibia of the non-injected paw. The maximum total severity score by this method was 16+.