66684-61-5

Usage

Uses

Used in Pharmaceutical Industry:
1,5-Difluoro-3-methoxy-2-nitro-benzene is used as a precursor in the synthesis of pharmaceuticals, contributing to the development of new drugs due to its unique chemical structure and properties.
Used in Agrochemical Industry:
1,5-DIFLUORO-3-METHOXY-2-NITRO-BENZENE is also utilized as a precursor in the synthesis of agrochemicals, playing a role in the production of pesticides and other agricultural chemicals to protect crops and enhance yields.
Used in Antiseptic and Disinfectant Production:
1,5-Difluoro-3-methoxy-2-nitro-benzene is used as an active ingredient in the formulation of antiseptics and disinfectants, leveraging its ability to inhibit the growth of various microorganisms and promote hygiene and sanitation.
Used in Dye and Polymer Production:
Furthermore, this chemical is employed in the production of dyes and polymers, contributing to the coloration and material properties of various products across different industries.
It is crucial to handle 1,5-difluoro-3-methoxy-2-nitro-benzene with care due to its toxic nature and potential to cause irritation to the skin, eyes, and respiratory system upon exposure. Proper safety measures should be implemented during its use and production.

Upstream product

• 151414-46-9 3,5-Difluoro-2-nitrophenol 
• 74-88-4 methyl iodide 
• 93343-10-3 3,5-difluoroanisol 
• 67-56-1 methanol 
• 315-14-0 1,3,5-trifluoro-2-nitrobenzene 
• 124-41-4 sodium methylate 
• 2713-34-0 3,5-difluorophenol 
• 372-38-3 1,3,5-trifluorobenzene 

Downstream Products

• 862270-96-0 N-(2,4-dimethoxybenzyl)-5-fluoro-3-methoxy-2-nitrobenzenamine 
• 256454-00-9 5-fluoro-3-methoxy-2-nitrophenol 
• 1159795-35-3 2-bromo-1-(5-fluoro-3-methoxy-2-nitrophenyl)-4-methyl-1H-imidazole 
• 1226805-66-8 1-(5-fluoro-3-methoxy-2-nitrophenyl)-4-methyl-1H-imidazole 
• 1226803-99-1 8-fluoro-6-methoxy-1-(2-methoxyphenyl)-3-methylimidazo[5,1-c][1,2,4]benzotriazine 
• 1226803-97-9 8-fluoro-6-methoxy-1-(3-methoxyphenyl)-3-methylimidazo[5,1-c][1,2,4]benzotriazine 
• 1226804-27-8 8-fluoro-1-(3-fluoro-2-methylphenyl)-6-methoxy-3-methylimidazo[5,1-c][1,2,4]benzotriazine 

Relevant academic research and scientific papers

Amino pyrimidine compound and preparation method and application thereof

The invention relates to an amino pyrimidine compound and a preparation method and application thereof. The amino pyrimidine compound has a structure as shown in a formula I. The formula is shown in the description. The compound is an inhibitor of an epidermal growth factor receptor (EGFR) kinase. The invention further relates to a medicine composition comprising the compound, a preparation methodand application thereof in preparation of anti-tumor medicines.

HYDANTOIN AND THIOHYDANTOIN DERIVATIVES AS ANTIVIRAL DRUGS

The present invention relates to a compound of the following formula (I), or a salt, solvate, tautomer, enantiomer, diastereoisomer or racemic mixture thereof: as well as its use as a drug, notably in the treatment of hepatitis C, its preparation process, and the pharmaceutical compositions containing such a compound.

5 OXO-5,8-DIHYDROPYRIDO[2,3-d]PYRIMIDINE DERIVATIVES AS CAMKII KINASE INHIBITORS FOR TREATING CARDIOVASCULAR DISEASES

The present invention relates to 5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine derivatives, to their preparation and to their therapeutic use.

Novel triazines as potent and selective phosphodiesterase 10A inhibitors

The identification of highly potent and orally active triazines for the inhibition of PDE10A is reported. The new analogs exhibit low-nanomolar potency for PDE10A, demonstrate high selectivity against all other members of the PDE family, and show desired drug-like properties. Employing structure-based drug design approaches, we investigated the selectivity of PDE10A inhibitors against other known PDE isoforms, by methodically exploring the various sub-regions of the PDE10A ligand binding pocket. A systematic assessment of the ADME and pharmacokinetic properties of the newly synthesized compounds has led to the design of drug-like candidates with good brain permeability and desirable drug kinetics (t1/2, bioavailability, clearance). Compound 66 was highly potent for PDE10A (IC50 = 1.4 nM), demonstrated high selectivity (>200×) for the other PDEs, and was efficacious in animal models of psychoses; reversal of MK-801 induced hyperactivity (MED = 0.1 mg/kg) and conditioned avoidance responding (CAR; ID50 = 0.2 mg/kg).

Highly potent, selective, and orally active phosphodiesterase 10A inhibitors

The identification of highly potent and orally active phenylpyrazines for the inhibition of PDE10A is reported. The new analogues exhibit subnanomolar potency for PDE10A, demonstrate high selectivity against all other members of the PDE family, and show desired druglike properties. Employing structure-based drug design approaches, we methodically explored two key regions of the binding pocket of the PDE10A enzyme to alter the planarity of the parent compound 1 and optimize its affinity for PDE10A. Bulky substituents at the C9 position led to elimination of the mutagenicity of 1, while a crucial hydrogen bond interaction with Glu716 markedly enhanced its potency and selectivity. A systematic assessment of the ADME and PK properties of the new analogues led to druglike development candidates. One of the more potent compounds, 96, displayed an IC50 for PDE10A of 0.7 nM and was active in predictive antipsychotic animal models.

ARYL AND HETEROARYL FUSED IMIDAZO[1,5-a]PYRAZINES AS INHIBITORS OF PHOSPHODIESTERASE 10

The invention relates to imidazo[1,5-a]pyrazine derivatives, to processes for preparing them, to pharmaceutical preparations which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phosphodiesterase 10 (PDE10), as active compounds for treating central nervous system diseases of mammals, including humans.

VANILLOID RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS

Pyrimidine ethers and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

VLA-4 INHIBITORS

The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.

Chemical compounds

Compound of formula (I) wherein: A is a bicyclic heteroaryl, optionally substituted with one or more substituents; B is linker group connecting group A to group D and comprising a 3 or 4 atom linker where each atom is independently selected from carbon, oxygen, nitrogen and sulphur and is optionally subsituted with one or more C1-6alkyl groups or two of such adjacent alkyl substituents may form a ring; C is aryl or a mono or bicyclic heteroaryl, each of which can be optionally substituted; D is an aryl or heteroaryl, both of which are optionally substituted R1is hydrogen, C1-5alkyl, C1-3alkanoyl or C1-3alkoxycarbonyl; R2to R5are each independently selected from hydrogen, C1-6alkyl, aryl and heteroaryl containing up to 2 heteroatoms chosen from oxygen, sulphur and nitrogen, the aryl and heteroaryl optionally substituted with C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-4alkoxy, C1-4alkanoyl, C1-6alkylamino, C1-4alkylC1-6alkyoxyl, C1-6alkylaminoC1-6alkyl, nitro, cyano, halogeno, trifluoromethyl, hydroxy, (CH2)pOH where p is 1 or 2, —CO2Ra, and —CONRaRb, where Raand Rbare independently selected from hydrogen and C1-6alkyl or two of R2to R5can be taken together to form a 3 to 7 membered ring; R6is an acidic functional group; r and s are each independently 0 or 1 with the proviso that r and s cannot both be 0; or a pharmaceutically acceptable salt or in vivo hydrolysable derivative thereof.

The Effect of Fluorine Substitution on the Metabolism and Antimalarial Activity of Amodiaquine

Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial which causes adverse side effects such as agranulocytosis and liver damage.The observed drug toxicity is believed to be related to the formation of an electrophilic metabolite, amodiaquine imine (AQQI), which can bind to cellular macro-molecules and initiate hypersensitivity reactions. 5'-Fluoroamodiaquine (5'-FAQ, 3), 5',6'-difluoroamodiaquine (5',6'-DIFAQ, 4), 2',6'-difluoroamodiaquine (2',6'-DIFAQ, 5), 2',5',6'-trifluoroamodiaquine (2',5',6'-TRIFAQ, 6) and 4'-dehydroxy-4'-fluoroamodiaquine (4'-deOH-4'-FAQ, 7) have been synthesized to assess the effect of fluorine substitution on the oxidation potential, metabolism, and in vitro antimalarial activity of amodiaquine.The oxidation potentials were measured by cyclic voltammetry, and it was observed that substitution at the 2',6'- and 4'-positions (2',6'-DIFAQ and 4'-deOH'4'-FAQ) produced analogues with significantly higher oxidation potentials than the parent drug.Fluorine substitution at the 2',6'-positions and 4'-position also produced analogues that were more resistant to bioactivation.Thus 2',6'-DIFAQ and 4'-deOH-4'-FAQ produced thioether conjugates corresponding to 2.17percent (SD: +/-0.27percent) and 0percent of the dose compared with 11.87percent (SD: +/-1.31percent) of the dose for amodiaquine.In general the fluorinated analogues had similar in vitro antimalarial activity to amodiaquine against the chloroquine resistant K1 strain of Plasmodium falciparum and the chloroquine sensitive T9-96 strain of P. falciparum with the notable exception of 2',5',6'-TRIFAQ (6).The data presented indicate that fluorine substitution at the 2',6'-positions and replacement of the 4'-hydroxyl of amodiaquine with fluorine produces analogues ( 5 and 7) that maintain antimalarial efficacy in vitro and are more resistant to oxidation and hence less likely to form toxic quinone imine metabolites.