Category: 1198284-94-4

On January 30, 2014, Ding, Fa-Xiang; Dong, Shuzhi; Frie, Jessica; Gu, Xin; Jiang, Jinlong; Pasternak, Alexander; Tang, Haifeng; Wu, Zhicai; Yu, Yang; Suzuki, Takao published a patent.Safety of tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate The title of the patent was Preparation of 2,8-diazaspiro[4.5]decan-1-one derivatives as inhibitors of the renal outer medullary potassium channel. And the patent contained the following:

The present invention provides compounds of Formula I [ R1 = H, halo, OH or C1-3 alkoxy; m = 0 or 1; n = 1 or 2; R2 = H, oxo, OH, etc.; R3a = H, oxo, C3-4 cycloalkyl, etc.; R3b = H, or C1-3 alkyl; R4 = H or oxo; R5 = H, halo, (un)substituted C1-3 alkyl, etc.; R6 = H or C1-3 alkyl; R7a = H, or (un)substituted C1-3 alkyl; R7b = H or C1-3 alkyl; R8 = H, halo or C1-3 alkyl; R9 = H, F, OH, etc.; R10 = H, halo, CN, etc.; R11 and R12 = H, CH2OH, CH2OCH3 or C1-3 alkyl optionally substituted with 1- 3 of F; R13 = H, SO2Me, (un)substituted C1-3 alkyl, etc.] and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. Compound II was prepared in a multi-step synthesis and had IC50 of 0.01μM in Thallium Flux assay. Compounds I may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention. The experimental process involved the reaction of tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate(cas: 1198284-94-4).Safety of tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate

The Article related to diazaspirodecanone preparation romk inhibitor cardiovascular disease treatment, Heterocyclic Compounds (More Than One Hetero Atom): Fused-Ring Systems With Two Or More Hetero Atoms, No More Than One Hetero Atom Per Ring and other aspects.Safety of tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

On August 4, 2016, Dejesus, Reynalda K.; Fu, Qinghong; Jiang, Jinlong; Tang, Haifeng published a patent.Synthetic Route of 1198284-94-4 The title of the patent was Preparation of novel spirocyclic compounds as inhibitors of the renal outer medullary potassium channel. And the patent contained the following:

The title compounds I [R1 = H, halo, OH, alky, alkoxy; R2 = H, alkyl; R3 = H, or alkyl optionally substituted with OH, OMe or 1-3 halo; or R3 and R4 are joined together to form CH2CH2; R4 = H, or alkyl optionally substituted with OH, OMe or 1-3 halo; n = 1-2; m = 1-2, wherein when m = 2, X3 = CH2; R5 = H, halo, cycloalkyl or alkyl; X1 = C(O), CH2; X2 = O, CH2; X3 = C(O), CH2, wherein when X3 = CH2, m = 2;X4 = C(O), SO2; Z = II or III (Y1-Y4 = (independently) CR9 or N; provided that at most two of Y1-Y4 are N; R9 = (independently) H, halo, alkoxy or alkyl optionally substituted with 1-3 halo; R10 = H, halo, alkyl optionally substituted with 1-3 halo; R11 = H, alkyl optionally substituted with 1-3 halo; R12 = H or alkyl)] which are inhibitors of the ROMK (Kir1.1) channel, were prepared For example, microwaving a solution of (1R,3r,5S)-1′-(2-methyl-3-oxocyclopent-1-en-1-yl)-8-azaspiro[bicyclo[3.2.1]octane-3,3′- pyrrolidin]-2′-one and (R)-4-methyl-5-(oxiran-2-yl)isobenzofuran- 1(3H)-one in EtOH at 145°C for 4.5 h afforded IV. Exemplified compounds I were tested in the thallium flux assay (data given). The compounds I may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions comprising I, alone or in combination with other therapeutic agent, are disclosed. The experimental process involved the reaction of tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate(cas: 1198284-94-4).Synthetic Route of 1198284-94-4

The Article related to spirocyclic compound preparation renal outer medullary potassium channel inhibitor, romk inhibitor diuretic natriuretic cardiovascular antihypertensive spirocyclic compound preparation, heart failure chronic kidney disease treatment spirocyclic compound preparation, excessive salt water retention treatment spirocyclic compound preparation and other aspects.Synthetic Route of 1198284-94-4

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics