201404-86-6Relevant articles and documents
6,7-DIHYDRO-5H-PYRIDO[2,3-C]PYRIDAZINE DERIVATIVES AND RELATED COMPOUNDS AS BCL-XL PROTEIN INHIBITORS AND PRO-APOPTOTIC AGENTS FOR TREATING CANCER
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Page/Page column 204-205, (2021/02/05)
The present invention discloses 6,7-dihydro-5H-pyrido[2,3- c]pyridazine, 1,2,3,4-tetrahydroquinoline, 1H-indole, 3,4- dihydro-2H-1,4-benzoxazine, 1H-pyrrolo[2,3-b]pyridin-1-yl, 7H- pyrrolo[2,3-c]pyridazine, 5H,6H,7H,8H,9H-pyridazino[3,4-b]azepine derivatives and related compounds of formula (I) as Bcl-xL protein inhibitors for use as pro-apoptotic agents for treating cancer, autoimmune diseases or immune system diseases. Formula (I). The description discloses the preparation of exemplary compounds (e.g. pages 113 to 354 examples 1 to 221) as well as pharmacological studies with relevant data (e.g. pages 355 to 367; examples A to E; tables 1 to 5). Exemplary compounds are e.g. 2-{6-[(1,3-benzothiazol-2-yl) amino]-1,2,3,4-tetrahydroquinolin-1-yl}-1,3-thiazole-4-carboxylic acid (example 1) or e.g. 3-{1-[(adamantan-1-yl)methyl]-5- methyl-1H-pyrazol-4-yl}-6-{3-[(1,3-benzothiazol-2-yl)amino]-4- methyl-5H,6H,7H,8H-pyrido[2,3-c]pyridazin-8-yl]pyridine-2-carboxylic acid (example 24).
A west he row sandbank intermediate preparation method
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Paragraph 0065; 0066; 0067; 0076; 0084, (2017/08/25)
The invention discloses a preparation method for a sitagliptin intermediate and belongs to the field of drug synthesis. The preparation method comprises the following steps: (1) carrying out a ring-opening reaction: carrying out Grignard reaction on 2,4,5-trifluorobromobenzene and a Grignard reagent RMgX in a medium of tetrahydrofuran and methyl tertiary-butyl ether at (-20) DEG C to 50 DEG C by taking cuprous chloride as a catalyst, wherein R2 is isopropyl and X is halogen, and then carrying out the ring-opening reaction on the generated compound and a compound shown in a formula 3 to obtain a compound shown in a formula 4; and (2) carrying out an oxidizing reaction: carrying out the oxidizing reaction on the compound shown in the formula 4 and potassium permanganate in an acetone medium, quenching and neutralizing the product by using reducing agents sodium sulfite and sodium hydrogen sulfite, and extracting the product by methyl tertiary butyl ether to obtain the sitagliptin intermediate. The method is low in cost, high in yield, mature in process and suitable for industrial production.
A new stereocontrolled approach to a key intermediate in the synthesis of (25,3R)-capreomycidine
Martinkova, Miroslava,Gonda, Jozef,Dzoganova, Martina
, p. 1199 - 1210 (2008/03/27)
A new stereocontrolled approach to the synthesis of advanced intermediate in the synthesis of nonproteinogenic amino acid (2S,3R)-capreomycidine via the novel domino reaction has been developed.