197359-43-6

Upstream product

• 100-39-0 benzyl bromide 
• 498-02-2 1-(3-methoxy-4-hydroxyphenyl)ethanone 
• 75665-73-5 1-(2-amino-4-(benzyloxy)-5-methoxyphenyl)ethanone 
• 75665-88-2 1-(4-(benzyloxy)-5-methoxy-2-nitrophenyl)ethanone 
• 1835-11-6 4-benzyloxy-3-methoxyacetophenone 

Downstream Products

• 197359-42-5 7-benzyloxy-4-chloro-6-methoxycinnoline hydrochloride 
• 398127-72-5 7-(benzyloxy)-4-chloro-6-methoxycinnoline 
• 1378294-21-3 7-(benzyloxy)-4-(6-fluoro-5-methylpyridin-3-yl)-6-methoxycinnoline 

Relevant academic research and scientific papers

Heterocyclic compound, preparation method and application thereof

The invention relates to a heterocyclic compound in the technical field of medicines. The compound is represented by a structural general formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, X, Y, Z, Cy1, Cy2, m, n and t have the meanings given in the specification; in addition, the invention also discloses an application of the compound and the pharmaceuticallyacceptable salt thereof in preparation of drugs for treating diseases caused by abnormal high expression of tyrosine kinase, especially application in preparation of drugs for treating and preventingcancers.

Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors

Fifteen cinnoline analogues and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined. Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds 26a, 26b, and 33c were 1.52 ± 0.18, 2.86 ± 0.10, and 3.73 ± 0.60 nM, respectively; these three compounds also showed high in vitro selectivity (>1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacological behavior and ability to quantify PDE10A in the brain.

Cinnoline compounds

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.

Cinnoline derivatives and use as medicine

The invention relates to the use of cinnoline derivatives of formula (I) wherein Z represents —O—, —NH—, —S— or —CH2—; m is a n integer from 1 to 5; R1represents hydrogen, hydroxy, halogeno, nitro, cyano, trifluoromethyl, Cp1-3alkyl, C1-3alkoxy, C1-3alkylthio or NR6R7(wherein R6and R7, which may be the same or different, each represents hydrogen or C1-3alkyl); R2represents hydrogen, hydroxy, auoro, chioro, methoxy, amino or nitro; R3represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; R4represents hydrogen, hydroxy, halogeno, cyano, nitro, amino, trifluoromethyl, C1-3alkyl or a group R5—X1(wherein X1represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR8CO—, —CONR9—, —SO2NR10—, —NR11SO2— or NR12— (wherein R8, R9, R10, R11and R12each independently represents hydrogen, C1-3alkyl or C1-3alkoxy C2-3alkyl) and R5is an optionally substituted alkyl, carbocylic or heterocylic group which may be saturated or unsaturated and may be directly linked to the cinnoline ring or be linked via a carbon chain which may have heteroatom linking groups within it and salts thereof, in the manufacture of a medicament for use in the production of an anti angiogenic and/or vascular permeability reducing effect in a warmn-blooded animal such as a human being, processes for the preparation of such derivatives, pharmnaceutical compositions containing a compound of formula (I) or a pharmnaceutically 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.