59648-34-9

Upstream product

• 89-95-2 2-methyl-benzyl alcohol 
• 693-25-4 n-pentylmagnesium bromide 
• 66-25-1 hexanal 
• 108-95-2 phenol 
• 121-71-1 3-Hydroxyacetophenone 
• 90-02-8 salicylaldehyde 
• 59672-38-7 4-pentyl-2-phenyl-4H-benzo[1,3,2]dioxaborinine 

Downstream Products

• 3226-15-1 1-(2-hydroxyphenyl)hexan-1-one 
• 103119-33-1 3-[2-(1-Hydroxy-hexyl)-phenoxymethyl]-benzoic acid methyl ester 

Relevant academic research and scientific papers

Targeting the gatekeeper residue in phosphoinositide 3-kinases

A single residue in the ATP binding pocket of protein kinases-termed the gatekeeper-has been shown to control sensitivity to a wide range of small molecule inhibitors (Chem. Biol. 2004, 11, 691; Chem. Biol. 1999, 6, 671). Kinases that possess a small side chain at this position (Thr, Ala, or Gly) are readily targeted by structurally diverse classes of inhibitors, whereas kinases that possess a larger residue at this position are broadly resistant. Recently, lipid kinases of the phosphoinositide 3-kinase (PI3-K) family have become the focus of intense research interest as potential drug targets (Chem. Biol. 2003, 10, 207; Curr. Opin. Pharmacol. 2003, 3, 426). In this study, we identify the residue that corresponds structurally to the gatekeeper in PI3-Ks, and explore its importance in controlling enzyme activity and small molecule sensitivity. Isoleucine 848 of p110α was mutated to alanine and glycine, but the mutated kinase was found to have severely impaired enzymatic activity. A structural bioinformatic comparison of this kinase with its yeast orthologs identified second site mutations that rescued the enzymatic activity of the I848A kinase. To probe the dimensions of the gatekeeper pocket, a focused panel of analogs of the PI3-K inhibitor LY294002 was synthesized and its activity against gatekeeper mutated and wild-type p110α was assessed.

Certain unsymmetrical quinolinyl ethers having anti-inflammatory and anti-allergic activity

Compounds of the formula: and salts thereof, wherein Ar1 is a nitrogen, sulfur or oxygen heterocyclic ring; Ar is a phenyl ring or a nitrogen, oxygen or sulfur heterocyclic ring; Ar and Ar1 may be fully substituted or less than fully substituted with H, CH3, lower alkyl, aryl, aralkyl, halo, hydroxy, lower alkoxy, CF3, carboxy, alkylcarboxy, arylcarboxy, alkylcarbalkoxy, alkanoyl, formyl, oxo, nitrilo, amino, aminoalkyl, alkylamine, carboxamide, aryloxy, nitro, sulfonyl, sulfonamide, thio, alkylthio, hydroxyalkyl or oxyalkylcarbalkoxy; X= STR1 of up to 2 carbon atoms in the principal chain and up to a total of 4 carbon atoms, STR2 Z is an alkylene chain containing up to 10 carbon atoms in the principal chain and a total of up to 12 carbon atoms and from 0 to 2 double bonds and the said alkylene chain may be attached to Ar through an oxygen, sulfur or amino nitrogen atom, and when n'=2, one of the R substituents may be halogen on an omega carbon of the alkylene chain Z; when n'=1, R is a substituent attached to one of the carbon atoms of Z selected from the group consisting of =O, OR3, SR3, N(R2)2 and R1, --COR4 and when n'=2 one R is previously defined and the additional R is a substituent attached to one of the carbon atoms of Z selected from the group consisting of =O, OR3, SR3, N(R2)2, --COR4, lactone and halo; R1 is H or CH3 ; R2 is H, lower alkyl, aryl or aralkyl; R3 is H, lower alkyl, lower alkanoyl, aryl, aralkyl or substituted aryl in which the substituent is halo, lower alkyl or lower alkoxy; R4 is OR2 or N(R2)2 ; n=0 or 1; n'=1 to 7; and n"=0, 1 or 2.