On January 12, 2017, Bradner, James; Buckley, Dennis; Winter, Georg published a patent.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid The title of the patent was Preparation of bifunctional molecules for inducing targeted protein degradation. And the patent contained the following:
The title bifunctional compounds Degron-Linker-Targeting Ligand [Degron = I (ring A = II, III; Y = a bond, O, NH, etc.; X = C(O), C(R3); X1-X2 = C(R3):N or C(R3)2C(R3)2; R1 = halo, NO2, NH2, etc.; R3 = H, alkyl optionally substituted with aryl or 5-10 membered heteroaryl; each R31 = (independently) alkyl; R4 = (independently) H or alkyl; or two R4, together with the carbon atom to which they are attached, form C(O), carbocycle, or 4-6 membered heterocycle comprising 1-2 heteroatoms selected from N and O; R5 = H, alkyl, F or Cl; n = 0-2; m = 0-3; t = 0-1); Linker = IV (p1 = 0-12; p2 = 0-12; p3 = 0-6; each W = (independently) absent, CH2, O, S, NH or NR5; Z = absent, CH2, O, NH or NR5; each R5 = (independently) alkyl; Q = absent, C(O)NH, C(O)O, etc.); Targeting Ligand = V (ring containing T1-T5 = (a) T1, T2, T4 = N; T3, T5 = C, or (b) T1 = N, T2 = O; T3-T5 = C; A1 = S or C:C; A2 = NR15 or O; nn1 = 0-2; each R11 = (independently) alkyl, (CH2)0-3CN, (CH2)0-3halogen, etc.; R12 = H, alkyl, (CH2)0-3heterocyclyl, etc.; nn2 = 0-3; each R13 = alkyl, (CH2)0-3CN, (CH2)0-3halogen, etc.; R14 = alkyl; R15 = H or alkyl); with the proviso] which act as protein degradation inducing moieties, were prepared E.g., a multi-step synthesis of VI, starting from JQ1 (VII), was described. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the title bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. Exemplified compounds I demonstrated to have potent biol. activities, e.g., binding to the protein target (e.g. BRD4), mediating protein degradation, etc. (data given). The present application also provides methods for making compounds of the application and intermediates thereof. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid
The Article related to bifunctional compound preparation targeted protein degradation inducer cereblon binding, e3 ubiquitin ligase binding bifunctional compound preparation proliferative disorder, bromodomain brd4 protein degradation inducer bifunctional compound preparation and other aspects.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem