288385-88-6Relevant academic research and scientific papers
Preparation method of 4-fluoro-5-hydroxy-2-methyl-1H-indole
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, (2019/11/13)
The invention provides a preparation method of 4-fluoro-5-hydroxy-2-methyl-1H-indole. The preparation method comprises the steps that 2-fluoro-3-halo-6-nitrotoluene is used as a raw material and subjected to a substitution reaction with alcohol to prepare 2-fluoro-3-GO substituent-6-nitrotoluene, then 2-fluoro-3-GO substituent-6-nitrotoluene is subjected to a condensation reaction with trimethyl orthoacetate or triethyl orthoacetate to obtain 1-(2-fluoro-3-GO substituent-6-nitrophenyl)-2-alkoxy propylene, and then 1-(2-fluoro-3-GO substituent-6-nitrophenyl)-2-alkoxy propylene is further subjected to a reduction-cyclization reaction to obtain 4-fluoro-5-hydroxy-2-methyl-1H-indole. The preparation method is safe and green, simple in operation, low in cost, high in selectivity and high in yield and purity of a final product.
Design, synthesis and biological evaluation of O-linked indoles as VEGFR-2 kinase inhibitors (I)
Gao, Guo-Rui,Li, Meng-Yuan,Tong, Lin-Jiang,Wei, Li-Xin,Ding, Jian,Xie, Hua,Duan, Wen-Hu
supporting information, p. 1165 - 1168 (2015/09/01)
Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a series of O-linked indoles as potent inhibitors of VEGFR-2. Among these compounds, 18 showed significant anti-angiogenesis activities via VEGFR-2 in enzymatic proliferation assays, with IC50 value of 3.8 nmol/L. Kinase selectivity profiling revealed that 18 was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-α and β.
Commercial synthesis of a pyrrolotriazine-fluoroindole intermediate to brivanib alaninate: Process development directed toward impurity control
Pesti, Jaan A.,LaPorte, Thomas,Thornton, John E.,Spangler, Lori,Buono, Frederic,Crispino, Gerard,Gibson, Frank,Lobben, Paul,Papaioannou, Christos G.
, p. 89 - 102 (2014/05/20)
The development of a practical, commercial process for the preparation of 4-fluoro-2-methyl-indol-5-ol and its subsequent coupling with a pyrrolotriazine to form an advanced intermediate of the oncology therapy brivanib alaninate is described. A key aspect is the multikilogram-scale preparation of the fluoroindole intermediate from trifluoronitrobenzene and the subsequent coupling while achieving impurity minimalization. As brivanib alaninate is a high-dose drug, the synthesis of highquality API with low levels of impurities is critical.
VEGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
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Page/Page column 28, (2009/04/24)
The present invention relates to VEGFR inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.
CHEMICAL PROCESS
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Page/Page column 41-42, (2008/12/05)
The present invention relates to chemical processes for the manufacture of certain quinazoline derivatives, or pharmaceutically acceptable salts thereof. The invention also relates to processes for the manufacture of certain intermediates useful in the manufacture of the quinazoline derivatives and to processes for the manufacture of the quinazoline derivatives utilising said intermediates. In particular, the present invention relates to chemical processes and intermediates useful in the manufacture of the compound 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline.
PROCESS FOR PREPARING CERTAIN PYRROLOTRIAZINE COMPOUNDS
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Page 35, (2008/06/13)
The present invention relates to a process for preparing certain pyrrolotriazine compounds of the formula (I) and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2 and FGFR-1, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.
Quinoline derivatives having vegf inhibiting activity
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, (2008/06/13)
The invention relates to compounds of formula (I) wherein: either any one of G1, G2, G3, G4 and G5 is nitrogen and the other four are —CH—, or G1, G2, G3, G4 and G5 are all —CH—; Z is —O—, —NH—, —S—, —CH2— or a direct bond; Z is linked to any one of G1, G2, G3 and G4; n is an integer from 0 to 5; m is an integer from 0 to 3; Ra represents hydrogen or fluoro; Rb, R1 and R2 are defined herein and salt thereof, process for the preparation so such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and the use of a compound of formula I in the manufacture of a medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blodded animals. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of diseases states including cancer and rheumatoid arthritis.
Cinnoline compounds
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, (2008/06/13)
The invention relatest to compounds of the formula (I) wherein either any one of G1, G2, G3, G4 and G5 is nitrogen and the other four are —CH—, or G1, G2, G3, G4 and G5 are all —CH—; Z is —O—, —NH—, —S—, —CH2— or a direct bond; Z is linked to any one of G1, G2, G3 and G4 which is a free carbon atom; n is an integer from 0 to 5; any of the substitutents R1 may be attached at any free carbon atom of the indole, azaindole or indazole group; m is an integer from 0 to 3; Ra represents hydrogen; Rb represents hydrogen or another value as defined herein; R1 represents hydrogen, oxo, hydroxy, halogeno, C1-4alkyl, C1-4alkoxy, C1-4alkoxy, C1-4-alkyl, aminoC1-4alkyl, C1-3alkylaminoC1-4alkyl, di(C1-3alkyl)aminoC1-4alkyl, —C1-5alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinly, N-ethylpiperazinyl, morpholino and thiomorpholino; R2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3aklylsulphanyl, —NR3R4 (wherein R3 and R4, which may be the same or different, each represents hydrogen or C1-3alkyl), or R5X1— (wherein R5 and X1 are as defined herein) and salts thereof, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and the use of a compound of formula I in the manufacture of medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Chemical compounds
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, (2008/06/13)
The invention relates to compounds of the formula (I): wherein: ring C is 9 or 10-membered bicyclic heteroaromatic group containing at least one nitrogen atom in the ring attached to Z and optionally containing a further 1-3 heteroatoms, selected independently from O, S, and N, with the proviso that ring C is not a quinazoline, quinoline or cinnoline group; either any one of G1, G2, G3, G4 and G5 is nitrogen and the other four are —CH—; or G1, G2, G3, G4 and G5 are all —CH—; Z is —O—, NH—, —S—, CH2— or a direct substituents R1 may be attached at any free carbon atom of the indole, azaindole or indazole group; m is an integer from 0 to 2; Rb represents hydrogen or another value as defined herein; R1 represents hydrogen, hydroxy, halogeno, C1-4alkyl, or any other value as defined herein; R2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylsulphanyl, —NR3R4 (wherein R3 and R4, which may be the same or different, each represents hydrogen or C1-3alkyl), or R5X1— (wherein R5 and X1 are as defined herein) and salts thereof, processes for the preparation of such compounds, pharmaceutical compositions
