On January 7, 2021, Zhong, Wenge; Zhu, Xiaotian; Feng, Song; Wu, Lei; Huang, Wei; Liu, Hao; Liu, Rongqiang; Wen, Kate Xin; Zhou, Hua published a patent.Safety of 6-Chloro-2,3-dihydro-1H-indole The title of the patent was Preparation of substituted tetrahydroisoquinolinylaminopyridines and pyrrolopyridinylphenyldialkyl phosphine and their analogs as HPK1 inhibitors for treating cancers. And the patent contained the following:
The invention is related to the preparation of compounds I [X = CR2R3, NR3; A = CR2, N; R = 8-10 membered bicyclic N-containing heteroaryl or 8-10 membered bicyclic N-containing heterocyclyl optionally substituted with oxo, wherein the heteroaryl or heterocyclyl represented by R has 1 to 3 heteroatoms selected from N, O, and S, and is further optionally substituted, and wherein R is either connected with the pyrimidine ring via a nitrogen ring atom or R = (un)substituted quinolin-4-yl, indol-1-yl, isoquinolin-1-yl, etc.; R1 = H, D, halo,, OH, CN, NH2, NO2, etc.; or R and R1 together with the carbon atoms to which they are attached, form a ring selected from II, III, IV, etc.; Rb = independently at each occurrence H, D, COOH, etc.; Rc = independently Ph, 5-6 membered monocyclic heterocyclyl having 1-3 heteroatoms selected from N and O; 5-6 membered monocyclic heteroaryl having 1-3 heteroatoms selected from N and O; wherein the Ph, heterocyclyl, or heteroaryl represented by R is optionally substituted with one to three substituents independently selected from the group consisting of halogen, OH, CN, etc.; m = 0-3; Y = (CH2)p; p = 1-3; Z = (CH2)q; q = 1-3 and p+q ≤4], their pharmaceutically acceptable salts and stereoisomers as hematopoietic progenitor kinase 1 (HPK1)inhibitors for treating cancers. The invention is also related to the preparation of compounds V [A1 = CR’, N; X = P(O)R3R4; R’ = H, D, halo, CN, NO2, etc.; R1′ = independently at each occurrence H, D, OH, (un)substituted alk(en/yn)yl, etc.; R2′ = independently at each occurrence H, NO2, alkoxycarbonyl, etc.; m, n = independently 0-2] as HPK1 inhibitors for treating cancers. Thus, reaction of (1H-indol-3-yl)dimethylphosphine oxide (preparation given) with [1-(2,5-dichloropyrimidin-4-yl)-1H-indol-3-yl]dimethylphosphine oxide and treatment of the resulting [1-[5-chloro-2-[(6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)amino]pyrimidin-4-yl]-1H-indol-3-yl]dimethylphosphine oxide with 6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-amine gave VI. VI inhibited HPK1 and JAK3 kinases with IC50 of ≤100μ=nM and > 1μM, resepctively. Certain HPK1 inhibitors I and V are selective against one or more kinases selected from: Lck, ZAP70, JAK3, PKC-theta, TBK1, and MAP4K3. The experimental process involved the reaction of 6-Chloro-2,3-dihydro-1H-indole(cas: 52537-00-5).Safety of 6-Chloro-2,3-dihydro-1H-indole
The Article related to tetrahydroisoquinolinylaminopyrimidine pyrrolopyridinylphenyldialkyl phosphine preparation hpk1 inhibitor antitumor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Safety of 6-Chloro-2,3-dihydro-1H-indole
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Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles