865712-96-5

Upstream product

• 387-44-0 7-fluoro-1H-indole 
• 98-09-9 benzenesulfonyl chloride 

Downstream Products

• 865712-97-6 1-benzenesulfonyl-3-bromo-7-fluoro-1H-indole 
• 896138-34-4 (5-benzyloxy-1H-indol-2-yl)-(7-fluoro-1H-indol-2-yl)methanone 
• 896138-06-0 (5-benzyloxy-1-phenylsulfonyl-1H-indol-2-yl)-(7-fluoro-1-phenylsulfonyl-1H-indol-2-yl)methanone 

Relevant academic research and scientific papers

Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase

FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors 98 and 102 show IC 50 values of 0.06 and 0.04 μM, respectively, and 1 order of magnitude lower PDGFR inhibiting activity. The derivatives 76 and 82 are 20- to 40-fold PDGFR selective. Docking at the recent FLT3 structure suggests a bidentate binding mode with the backbone of Cys-694. Activity and selectivity can be related to interactions of one indole moiety with a Hydrophobic pocket including Phe-691, the only different binding site residue (PDGFR Thr-681). Compound 102 inhibited the proliferation of 32D cells expressing wildtype FLT3 or FLT3-ITD similarly as FLT3 autophosphorylation, and induced apoptosis in primary AML patient blasts.

(INDOL-3-YL)-HETEROCYCLE DERIVATIVES AS AGONISTS OF THE CANNABINOID CB1 RECEPTOR

The invention relates to (indol-3-yl)-heterocycle derivatives having general Formula (I) wherein A represents a 5-membered aromatic heterocyclic ring, wherein X1, X2 and X3 are independently selected from N, O, S and CR; R is H or (C1-4)alkyl; or R, when present in X2 or X3, may form together with R3 a 5-8 membered ring; R1 is a 5-8 mem-bered saturated carbocyclic ring, optionally containing a heteroatom selected from O and S; R2 is H, CH3 or CH2-CH3;or R2 is joined together with R7 to form a 6-mem-bered ring, optionally containing a heteroatom selected from O and S, and which heteroatom is bonded to the 7-position of the indole ring; R3 and R4 are independent-ly H, (C1-6)alkyl or (C3-7)cycloalkyl, the alkyl groups being optionally substituted with OH, (C1-4)alkyloxy, (C1-4)alkylthio, (C1-4)alkylsulfonyl, CN or halogen; or R3 together with R4 and the N to which they are bonded form a 4-8 membered ring optionally containing a further heteroatom selected from O and S, and which is optionally sub-stituted with OH, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy- (C1-4)alkyl, or halogen; or R3 together with R5 forms a 4-8 membered ring optionally containing a further hetero-atom selected from O and S, and which is optionally substituted with OH, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy- (C1-4)alkyl, or halogen; or R3 together with R, when present in X2 or X3, forms a 5-8 membered ring; R5 is H or (C1-4)alkyl; or R5 together with R3 forms a 4-8 membered ring optionally containing a further heteroatom select-ed from O and S, and which is optionally substituted with OH, (C1-4)alkyl, (C1-4)alkyl-oxy, (C1-4) alkyloxy- (C1-4)alkyl, or halogen; R5' is H or (C1-4)alkyl; R6 represents 1-3 substituents independently selected from H, (C1-4 alkyl, (C1-4) alkyloxy, CN and halogen; R7 is H, (C1-4)alkyl, (C1-4)alkyloxy, CN or halogen; or R7 is joined together with R2 to form a 6-membered ring, optionally containing a further heteroatom selected from O and S, and which heteroatom is bonded to the 7-position of the indole ring; or a pharmaceutically acceptable salt thereof, as agonists of the cannabinoid CB1 receptor, which can be used in the treatment of pain such as for example peri-operative pain, chronic pain, neuropathic pain, cancer pain and pain and spasticity associated with multiple sclerosis.