955978-78-6

Basic information

• Product Name: 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzene
• Synonyms: 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzene
• CAS NO: 955978-78-6
• Molecular Weight: 250.134
• Mol File: 955978-78-6.mol
• Article Data: 7

Chemical Properties

• CAS DataBase Reference: 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzene(CAS DataBase Reference)
• NIST Chemistry Reference: 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzene(955978-78-6)
• EPA Substance Registry System: 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzene(955978-78-6)

Safety Data

• Hazardous Substances Data: 955978-78-6(Hazardous Substances Data)

Upstream product

• 16533-71-4 3,5-dinitro-p-toluic acid 
• 99-94-5 p-Toluic acid 
• 6140-17-6 4-methylbenzotrifluoride 

Downstream Products

• 955978-79-7 4-amino-6-trifluoromethylindole 
• 1332493-16-9 3-(4-methylpiperazin-1-yl)-N-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-7-(trifluoromethyl)quinolin-5-amine 
• 1332493-07-8 5-bromo-3-(4-methylpiperazin-1-yl)-2-phenyl-7-(trifluoromethyl)quinoline 
• 1332493-09-0 1,7-dibromo-3,9-bis(trifluoromethyl)-5,6,11,12-tetrahydro-6,12-epoxydibenzo[b,f][1,5]diazocine 
• 1332492-86-0 2-amino-6-bromo-4-(trifluoromethyl)benzaldehyde 
• 1332492-85-9 2-bromo-6-nitro-4-(trifluoromethyl)benzaldehyde 
• 239079-89-1 1-bromo-2-methyl-3-nitro-5-(trifluoromethyl)benzene 
• 1332492-84-8 2-methyl-3-nitro-5-(trifluoromethyl)aniline 
• 1332492-93-9 5-bromo-3-(4-phenylpiperazin-1-yl)-7-(trifluoromethyl)quinoline 
• 1332492-92-8 5-bromo-3-(4-benzylpiperazin-1-yl)-7-(trifluoromethyl)quinoline 
• 1268264-10-3 Zgwatinib 

Relevant articles and documents

X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson’s Disease

Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) have been closely linked to the pathogenesis of Parkinson’s disease (PD); nevertheless, development of dual hIDO1 and hTDO inhibitors to evaluate their potential efficacy against PD is still lacking. Here, we report biochemical, biophysical, and computational analyses revealing that 1H-indazole-4-amines inhibit both hIDO1 and hTDO by a mechanism involving direct coordination with the heme ferrous and ferric states. Crystal structure-guided optimization led to23, which manifested IC50values of 0.64 and 0.04 μM to hIDO1 and hTDO, respectively, and had good pharmacokinetic properties and brain penetration in mice.23showed efficacy against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse motor coordination deficits, comparable to Madopar, an anti-PD medicine. Further studies revealed that different from Madopar,23likely has specific anti-PD mechanisms involving lowering IDO1 expression, alleviating dopaminergic neurodegeneration, reducing inflammatory cytokines and quinolinic acid in mouse brain, and increasing kynurenic acid in mouse blood.

Synthesis of 2-methyl-1,5-dinitro-3- and 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzenes and their transformation into 6-nitro-4-(trifluoromethyl)- and 4-nitro-6-(trifluoromethyl)-1H-indoles

A facile two-step synthesis of 2-methyl-1,5-dinitro-3- and 2-methyl-1,3-dinitro-5-(trifluoromethyl)benzenes is described. The first step is the nitration of otho- and para-methylbenzoic acids to furnish the corresponding dinitroacids. The dinitroacids then react with sulfur tetrafluoride to provide the corresponding trifluoromethylated products. The latter are easily transformed into 6-nitro-4-(trifluoromethyl)- and 4-nitro-6-(trifluoromethyl)-1H-indoles by applying the Batcho-Leimgruber synthetic protocol.

PHARMACEUTICAL COMPOUNDS

The invention provides compounds which are pyrimidines of formula (I): wherein R2 is bonded at ring position 2 and -YR1 is bonded at ring position 5 or 6, or YR1 is bonded at ring position 2 and R2 is bonded at ring position 6; R is an indol-4-yl group which is substituted at the 5- or 6-position; either: (a) Y is selected from -O-(CH2)n-, -NH-(CH2)n-,. -NHC(O)-(CH2)n and -C(O)NH-(CH2)n- wherein n is 0 or an integer of 1 to 3, and R1 is selected from an unsaturated 5- to 12-membered carbocyclic or heterocyclic group which is unsubstituted or substituted and a group -NR3R4 wherein R3 and R4, which are the same or different, are each independently selected from H, C1-C6 alkyl which is unsubstituted or substituted, C3 - C10 cycloalkyl which is unsubstituted or substituted, -C(O)R, -C(O)N(R)2 and -S(O)mR, or R3 and R4 together form, with the nitrogen atom to which they are attached, a saturated 5-, 6- or 7- membered N-containing heterocyclic group which is unsubstituted or substituted; (b) Y is a direct bond and R1 is selected from an unsaturated 5- to 12-membered carbocyclic or heterocyclic group which is unsubstituted or substituted, and a group -NR3R4 wherein R3 and R4, which are the same or different, are each independently selected from H, C1-C6 alkyl which is unsubstituted or substituted, C3-C10 cycloalkyl which is unsubstituted or substituted, -C(O)R, -C(O)N(R)2 and -S(O)mR; R is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl and a 5- to 12-membered aryl or heteroaryl group, which group is unsubstituted or substituted; and m is 1 or 2; or a pharmaceutically acceptable salt thereof. These compounds are inhibitors of PO K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PB kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.