31380-91-3

Basic information

• Product Name: 4-amino-5-chloro-2-methoxybenzonitrile
• Synonyms: 4-amino-5-chloro-2-methoxybenzonitrile
• CAS NO: 31380-91-3
• Molecular Weight: 182.609
• Mol File: 31380-91-3.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: 4-amino-5-chloro-2-methoxybenzonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 4-amino-5-chloro-2-methoxybenzonitrile(31380-91-3)
• EPA Substance Registry System: 4-amino-5-chloro-2-methoxybenzonitrile(31380-91-3)

Safety Data

• Hazardous Substances Data: 31380-91-3(Hazardous Substances Data)

Upstream product

• 7206-70-4 4-amino-5-chloro-2-methoxybenzoic acid 
• 171351-19-2 1H-1,2,3-benzotriazol-1-yl 4-amino-5-chloro-2-methoxybenzoate 
• 24190-74-7 4-amino-5-chloro-2-methoxybenzamide 

Downstream Products

• 950662-34-7 4-(2-chloro-4-cyano-5-methoxy-phenyl)-2-methylsulfanyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile 
• 1057339-08-8 4-(2-chloro-4-cyano-5-methoxy-phenyl)-2-methanesulfonyl-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile 
• 1057339-09-9 4-iodo-5-chloro-2-methoxybenzonitrile 
• 147805-12-7 2-Methoxy-4-amino-5-chlorobenzamide-oxime 
• 147805-12-7 4-amino-5-chloro-N-hydroxy-2-methoxybenzamidine 
• 174822-16-3 2-chloro-5-methoxy-4-<5-(2-piperidylmethyl)-1,2,4-oxadiazol-3-yl>aniline 

Relevant articles and documents

Targeting conserved water molecules: Design of 4-aryl-5-cyanopyrrolo[2,3-d] pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization

Inhibitors of the Hsp90 molecular chaperone are showing promise as anti-cancer agents. Here we describe a series of 4-aryl-5-cyanopyrrolo[2,3-d] pyrimidine ATP competitive Hsp90 inhibitors that were identified following structure-driven optimization of purine hits revealed by NMR based screening of a proprietary fragment library. Ligand-Hsp90 X-ray structures combined with molecular modeling led to the rational displacement of a conserved water molecule leading to enhanced affinity for Hsp90 as measured by fluorescence polarization, isothermal titration calorimetry and surface plasmon resonance assays. This displacement was achieved with a nitrile group, presenting an example of efficient gain in binding affinity with minimal increase in molecular weight. Some compounds in this chemical series inhibit the proliferation of human cancer cell lines in vitro and cause depletion of oncogenic Hsp90 client proteins and concomitant elevation of the co-chaperone Hsp70. In addition, one compound was demonstrated to be orally bioavailable in the mouse. This work demonstrates the power of structure-based design for the rapid evolution of potent Hsp90 inhibitors and the importance of considering conserved water molecules in drug design.

PYRROLOPYRIMIDINE DERIVATIVES USED AS HSP90 INHIBITORS

Compounds of formula (I) have HSP90 inhibitory activity and are therefore useful in the treatment of, inter alia, cancer: Formula (I) wherein Ri is hydrogen, fluoro, chloro, bromo, or a radical of formula -X-Alk1-(Z)m-(Alk2)n-Q wherein X is -O-, -S- -S(O)-, -SO2-, or -NH-, Z is -O-, -S-, -(C=O)-, -(C=S)-, -S(O)-, -SO2-, -NRA-, or, in either orientation -C(=O)O-, -C(=O)NRA- , -C(=S)NRA-, -SO2NRA-, -NRAC(=O)-, or -NRASO2- wherein RA is hydrogen or C1-C6 alkyl AIk1 and AIk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals, m, n and p are independently 0 or 1 , and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is a radical of formula -(Ar1)p-(Alk1)q-(Z)r-(Alk2)s-Q wherein Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1, Alk2, Z, and Q are as defined above, and p, q, r and s are independently 0 or 1 ; and R3 is cyano (-CN), fluoro, chloro, bromo, methyl in which in which one or more hydrogen atoms are optionally replaced by fluorine atoms, ethyl in which in which one or more hydrogen atoms are optionally replaced by fluorine atoms, cyclopropyl, -OH, -CH2OH, -C(O)NH2, -C(O)CH3, Or -NH2.