On March 20, 2003, Shimano, Masanao; Kamei, Noriyuki; Tanaka, Tomohiro; Harada, Tatsuhiro; Haino, Makoto; Okuyama, Akihiko; Arakawa, Yoshio; Murakami, Yoshiko published a patent.Computed Properties of 37480-41-4 The title of the patent was Preparation of reverse hydroxamic acid derivatives as selective inhibitors of TNF-α converting enzyme (TACE). And the patent contained the following:
Reverse hydroxamic acid derivatives, i.e. N-[2-[[(hetero)arylalkoxy](hetero)arylsulfonyl]ethyl] hydroxamic acid derivatives having specific structures represented by the general formula A-CON(OH)C(R1)(R2a)CH2SO2-Ar1-OCH2Ar2 [A = H, lower alkyl, cycloalkyl, (un)substituted NH2; Ar1 = arylene or heteroarylene; Ar2 = (un)substituted aryl, aralkyl, heteroaryl, or heteroarylalkyl; R1 = H, (un)substituted lower alkyl, lower alkenyl, or cycloalkyl; R2a = Q, Q1; wherein R5, R6, R16 = H, halo, OH, cyano, CF3, (un)substituted lower alkyl or alkoxy; R17 = H, halo, (un)substituted lower alkyl; R68, R69, R70, R71 = H, (un)substituted lower alkyl; X1, X2, Y1, Y2 = a single bond, O, S, (un)substituted CH2 or NH; Z1, Z2 = O, S, (un)substituted :CH or :NH, O(CH2)rO, S(CH2)r1S, O(CH2)t1S; wherein r, r1, t1 = an integer of 2-4; m1, m2 = an integer of 0-6; n1, n2, q1, q2 = an integer of 0-3; p1, p2 = 0, 1] are prepared These compounds are useful for the treatment of diseases caused by TNF-α. Thus, 4-(4-methanesulfonylphenoxymethyl)-2-methylquinoline was treated with lithium diisopropylamide/hexane-heptane-ethylbenzene in THF at -78° for 30 min, treated dropwise with a solution of (tetrahydro-4-ylidene)acetaldehyde in THF, and stirred for 30 min to give 77% 1-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonyl]-3-(tetrahydropyran-4-ylidene)propan-2-ol (I). To a solution of I and Et3N in CH2Cl2 was added methanesulfonyl chloride at -10° and stirred at room temperature for 12 h to give 100% 2-methyl-4-[4-[3-(tetrahydropyran-4-ylidene)prop-1-en-1-ylsulfonyl]phenoxymethyl]quinoline which was stirred with hydroxylamine in aqueous THF at room temperature for 64 h and then formylated by a mixture of formic acid and acetic anhydride at room temperature for 1 h to give 27.0% N-hydroxy-N-[2-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonyl]-1-(tetrahydropyran-4-ylidene)ethyl]formamide (II). II and optically active II showed IC50 of 3.5 and 2.2 μM, resp., against TACE and were inactive against MMP1, 2, 3, 8, 9, 13, 14, and 17. II at 3 mg/kg (s.c. injection) in vivo inhibited the Escherichia coli-derived lipopolysaccharide (LPS)-induced production of TNF-α by 74.8% in male Lewis rats. The experimental process involved the reaction of Methyl 1-methyl-4-oxocyclohexanecarboxylate(cas: 37480-41-4).Computed Properties of 37480-41-4
The Article related to reverse hydroxamic acid preparation selective tnf converting enzyme inhibitor, tace selective inhibitor reverse hydroxamic acid preparation, tnf production inhibitor hydroxyquinolinylmethoxybenzenesulfonylethylformamide preparation, hydroxyformamide reverse hydroxamic acid preparation tace inhibitor and other aspects.Computed Properties of 37480-41-4
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