On August 10, 2021, Moriyama, Akihiro; Kawabe, Yusuke; Otsuki, Shinobu; Takikawa, Yasushi published a patent.Computed Properties of 1198284-94-4 The title of the patent was Preparation of (hetero)arylimidazolone compounds as inhibitors of prolyl hydroxylases (PHDs). And the patent contained the following:
The (hetero)arylimidazolone compounds represented by the following formula I [m, u = independently 0, 1, 2, or 3; p, q = independently 1 or 2; r = an integer from 0 to 6; R1 = halo, C1-6 alkyl, cyano, hydroxy, or carboxy (m = 2 or 3, two or more R1s may be different from each other); E, G, Q, T are groups selected from the group consisting of the following (1) to (7): (1) E = CR2e, Q = CR2q, T = CR2t, G = N; (2) E = CR2e, G = CR2g, T = CR2t, Q = N; (3) E = CR2e, G = CR2g, Q = CR2q, T = N; (4) E = CR2e, Q = CR2q, G = T = N, (5) G = CR2g, T = CR2t, E = Q = N; (6) G = CR2g, Q = CR2q, E = T = N; and (7) E = CR2e, G = CR2g, Q = CR2q, T = CR2t; R2e, R2g, R2q, R2t = independently H, halogen, C1-6 alkyl, Halo-C1-6 alkyl, C1-6 alkoxy, halo-C1-6 alkoxy, hydroxy, CO2H, C1-6 alkoxycarbonyl, or (un)substituted NH2; ring W = C6-10 aryl, 5- or 6-membered ring heteroaryl, 9 or 10-membered ring heteroaryl, C3-8 cycloalkyl, or 3- to 8-membered heterocycloalkyl; ring Z = Q1, Q2, or Q3; Ra, Rb, Rc = independently H, halogen, C1-6 alkyl, cyano, Hydroxy, or carboxy; Rd = H or C1-6 alkyl; R3 = halogen, C1-6 alkyl, halo-C1-6 alkyl, C1-6 alkoxy, halo-C1-6 alkoxy, C2-6 alkoxy, C2-6 alkynyl, C1-6 alkylsulfanyl, C1-6 alkylsulfinyl, C1-6 alkoxysulfonyl, hydroxy, cyano, nitro, CO2H, C1-6 alkoxycarbonyl, or each (un)substituted or CONH2, etc.] or pharmacol. acceptable salts thereof. The compounds I or pharmacol. acceptable salts thereof have an inhibitory action on prolyl hydroxylases (PHDs) and are useful as therapeutic agents for inflammatory bowel disease such as ulcerative colitis and Crohn’s disease. Thus, (S)-3-[3-[6-[4-(methoxycarbonyl)phenyl]pyridin-3-yl]-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl]pyrrolidine-1-carboxylic acid tert-Bu ester was treated with 4 M HCl/1,4-dioxane solution at room temperature for 8 h to give (S)-3-[3-[6-[4-(methoxycarbonyl)phenyl]pyridin-3-yl]-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl]pyrrolidine which underwent reductive alkylation with 2-formylisonicotinic acid Me ester using NaBH(OAc)2 in the presence of Et3N in THF at room temperature for 2 h to give (S)-2-[[3-[3-[6-[4-(methoxycarbonyl)phenyl]pyridin-3-yl]-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl]pyrrolidin-1-yl]methyl]isonicotinic acid Me ester (II; R = Me). II (R = Me) was stirred with LiOH in aqueous methanol at 65° for 1 h, cooled to room temperature, treated with concentrated HCl, and stirred at 50° for 30 min to give (S)-2-[[3-[3-[6-(4-Carboxyphenyl)pyridin-3-yl]-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl]pyrrolidin-1-yl]methyl]isonicotinic acid II (R = H). II (R = H) showed IC50 of 0.12μM against human PHD2184-418. The experimental process involved the reaction of tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate(cas: 1198284-94-4).Computed Properties of 1198284-94-4
The Article related to heteroarylimidazolone preparation inhibitor prolyl hydroxylases phd, arylimidazolone preparation inhibitor prolyl hydroxylase phd, inflammatory bowel disease treatment imidazolone preparation, ulcerative colitis crohn disease treatment imidazolone preparation and other aspects.Computed Properties of 1198284-94-4
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