- Development of a scalable synthesis of a vascular endothelial growth factor receptor-2 kinase inhibitor: Efficient construction of a 6-etherified [1,2,4]triazolo[1,5-a]pyridine-2-amine Core
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A practical and scalable synthesis of the vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor 1 has been developed. The key features of the process development include facile preparation of the key raw material 3-amino-4- fluorophenol, chemoselective nucleophilic aromatic substitution of 5-chloro-2-nitropyridine with phenol, a safe one-pot synthesis of a substituted urea using an isothiocyanate generated in situ from inexpensive materials, and improvement of the yield of acylation in the end game. The optimized six-step synthesis afforded 1·H2O in 54% overall yield, twice as much as the yield of the original synthesis, without chromatographic purification. In addition, a robust recrystallization procedure to afford the desired crystal form of 1 was also developed.
- Ishimoto, Kazuhisa,Fukuda, Naohiro,Nagata, Toshiaki,Sawai, Yasuhiro,Ikemoto, Tomomi
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p. 122 - 134
(2014/05/20)
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- Compounds and Methods of Treatment
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A derivative, which is useful as a ret kinase inhibitor is described herein. The described invention also includes methods of using the same in the treatment of diseases mediated by inappropriate ret kinase activity.
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Page/Page column 15
(2008/12/08)
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- Quinoline derivatives inhibiting the effect of growth factors such as VEGF
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Compounds of the formula (I): wherein: R2represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; n is an integer from 0 to 5; Z represents —O—, —NH—, —S— or —CH2—; G1represents phenyl or a 5-10 membered heteroaromatic cyclic or bicyclic group; Y1, Y2, Y3and Y4each independently represents carbon or nitrogen; R1represents fluoro or hydrogen; m is an integer from 1 to 3; R3represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR4R5(wherein R4and R5, can each be hydrogen or C1-3alkyl), or a group R6—X1— wherein X1represents —CH2— or a heteroatom linker group and R6is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R6is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals such as humans, processes for the preparation of such derivatives, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. 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.
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Page column 43
(2010/02/08)
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- Production of pyridazine herbicides
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PCT No. PCT/JP97/03726 Sec. 371 Date Apr. 9, 1999 Sec. 102(e) Date Apr. 9, 1999 PCT Filed Oct. 16, 1997 PCT Pub. No. WO98/17632 PCT Pub. Date Apr. 30, 1998Carboxylic acids of formula (1): wherein R2 and R3 are independently hydrogen or C1-C3 alkyl, and Q
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- A facile synthetic method of herbicidal 2,-dihydro-3-methylene-2-substituted - phenyl-1hisoindol-1-one derivatives
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Herbicidal 2,3-dihydro-3-methylene-2-substitutedphenyl-1 H-isoindol-1-one derivatives 7 have been synthesized. They were prepared from the easily available phenol derivatives 1 in 5 steps in moderate yields.
- Kim, Jae Nyoung,Ryu, Eung K.
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- Tetrahydrophthalimide compounds, as post-emergence herbicides for use in soybean fields
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A tetrahydrophthalimide compound of the formula: STR1 wherein R is methyl or n-pentyl, which is useful as a post emergent herbicide for a soybean field.
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- Tetrahydrophthalimides, and their production and use
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A compound of the formula: STR1 wherein X is a chlorine atom or a bromine atom, which is useful as a herbicide.
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