120729-52-4

Upstream product

• 352-33-0 1-Chloro-4-fluorobenzene 
• 64792-49-0 Ethyl (2,2-dimethyl-4-tetrahydropyranylidene)cyanoacetate 
• 352-34-1 4-fluoro-1-iodobenzene 
• 1581258-45-8 (Z)-ethyl 2-cyano-2-(2,2-dimethyltetrahydropyran-4-ylidene)acetate 
• 105-56-6 ethyl 2-cyanoacetate 
• 1194-16-7 2,2-dimethyltetrahydropyran-4-one 

Downstream Products

• 1581258-25-4 6-(2,5-difluorophenyl)-N-(2-(4-(4-fluorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)ethyl)pyrazin-2-amine 
• 1581258-50-5 6-chloro-N-(2-(4-(4-fluorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)ethyl)pyrazin-2-amine 
• 1313603-11-0 {2-[4-(4-fluorophenyl)-2,2-dimethyltetrahydropyran-4-yl]ethyl}-(3-methoxyphenyl)amine 
• 330998-24-8 2-(4-(4-fluorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)acetonitrile 
• 368837-34-7 2-(4-(4-fluorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl)ethanamine 
• 120729-59-1 3-Amino-2-[4-(4-fluoro-phenyl)-2,2-dimethyl-tetrahydro-pyran-4-yl]-propan-1-ol 

Relevant academic research and scientific papers

TETRAHYDROPYRAN-4-YLETHYLAMINO- OR TETRAHYDROPYRANYL-4-ETHYLOXY-PYRIMIDINES OR -PYRIDAZINES AS ISOPRENYLCYSTEINCARBOXYMETHYL TRANSFERASE INHIBITORS

A compound of formula (I): wherein: R1 is selected from: (i) phenyl, optionally substituted by one fluoro group; (ii) thienyl; (iii) furanyl; (iv) C1-4 alkyl; and (v) H; R2 is selected from: (II), R3 is selected from: (III), X is selected from NH and O; R4 is selected from phenyl, a 5-membered heteroaryl or a 6-membered heteroaryl, all of which are optionally substituted by one or more substituents selected from the group consisting of: methyl, methoxy, trifluoromethyl, trifluoromethoxy, cyano, fluoro, -OC2H4OMe, and pyrazolyl.

Discovery and SAR of methylated tetrahydropyranyl derivatives as inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT)

A series of tetrahydropyranyl (THP) derivatives has been developed as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT) for use as anticancer agents. Structural modification of the submicromolar hit compound 3 led to the potent 3-methoxy substituted analogue 27. Further SAR development around the THP ring resulted in an additional 10-fold increase in potency, exemplified by analogue 75 with an IC50 of 1.3 nM. Active and potent compounds demonstrated a dose-dependent increase in Ras cytosolic protein. Potent ICMT inhibitors also reduced cell viability in several cancer cell lines with growth inhibition (GI50) values ranging from 0.3 to >100 μM. However, none of the cellular effects observed using ICMT inhibitors were as pronounced as those resulting from a farnesyltransferase inhibitor.