227956-83-4

Upstream product

• 32692-19-6 5-nitro-2,3-dihydro-1H-indole 
• 100-39-0 benzyl bromide 
• 1021389-36-5 2-(2-bromoethyl)-1-fluoro-4-nitrobenzene 
• 108-24-7 acetic anhydride 
• 100-46-9 benzylamine 

Downstream Products

• 512787-53-0 N-(1-benzyl-2,3-dihydro-1H-indole-5-yl)-methanesulfonamide 
• 741692-09-1 (S)-2-[3-(1-Benzyl-2,3-dihydro-1H-indol-5-yl)-ureido]-4-methyl-pentanoic acid ((S)-2-oxo-tetrahydro-furan-3-yl)-amide 
• 741692-06-8 2-[3-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-ureido]-4-methyl-pentanoic acid 
• 741692-03-5 2-[3-(1-benzyl-2,3-dihydro-1H-indol-5-yl)-ureido]-4-methyl-pentanoic acid methyl ester 
• 1025997-45-8 N-[4-(1-benzyl-2,3-dihydro-1H-indol-5-ylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-acetamide 
• 848133-83-5 6-amino-4-(1-benzyl-2,3-dihydro-1H-indol-5-ylamino)-7-ethoxyquinoline-3-carbonitrile 
• 21909-45-5 1-benzyl-2,3-dihydro-1H-indol-5-ylamine 

Relevant academic research and scientific papers

Indole derivatives or salts thereof as well as preparation method and application of indole derivatives or salts thereof

The invention belongs to the technical field of chemical medicine, and relates to an Hh (Hedgehog) signal pathway Smoothed (SMO) receptor small molecule inhibitor, in particular to indole derivativesor salts thereof with Smoothed inhibitory activity, which are shown in chemical general formula (I) in the description, as well as a preparation method and pharmaceutical composition of the indole derivatives or salts thereof. Tests on inhibitory activity of Hh signal pathways show that most compounds have better inhibitory activity on the Hh signal pathways. The invention further discloses the application of the compounds to preparation of medicines for treating diseases associated with Hh, wherein the diseases are BCC (basal cell carcinoma), MB (medullblastoma), SCLC (small cell lung cancer), medulloblastoma, rhabdomyosarcoma, or a combination of the diseases.

Benzo-fused heterocycles and carbocycles by intramolecular SNAr and tandem SN2-SNAr reactions

(Chemical Equation Presented) Benzo-fused heterocyclic and carbocyclic systems have been synthesized by intramolecular SNAr and tandem SN2-SNAr reactions. Treatment of 3-(2-fluoro-5- nitrophenyl)-1-propanol with sodium hydride in N,N-dimethylformamide gave 6-nitrochroman in 80% yield by an intramolecular SNAr reaction. Treatment of 2-(3-bromopropyl)-1-fluoro-4-nitrobenzene with benzylamine in N,N-dimethylformamide gave 1-benzyl-6-nitrotetrahydroquinoline in 98% yield by a tandem SN2-SNAr reaction. Finally, in a similar process, reaction of this same bromide with dimethyl malonate under basic conditions gave 1,1-bis(methoxycarbonyl)-6-nitro-1,2,3,4-tetrahydronaphthalene in 80% yield. Further studies exploring ring size effects are also presented.

Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activity

A series of new 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitrile derivatives that function as irreversible inhibitors of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) kinases have been prepared. These compounds demonstrated enhanced activities for inhibiting HER-2 kinase and the growth of HER-2 positive cells compared to our EGFR kinase inhibitor 86 (EKB-569). Three synthetic routes were used to prepare these compounds. They were prepared mostly by acylation of 6-amino-4-(arylamino) quinoline-3-carbonitriles with unsaturated acid chlorides or by amination of 4-chloro-6-(crotonamido)-quinoline-3-carbonitriles with monocyclic or bicyclic anilines. The third route was developed to prepare a key intermediate, 6-acetamido-4-chloroquinoline-3-carbonitrile, that involved a safer cyclization step. We show that attaching a large lipophilic group at the para position of the 4-(arylamino) ring results in improved potency for inhibiting HER-2 kinase. We also show the importance of a basic dialkylamino group at the end of the Michael acceptor for activity, due to intramolecular catalysis of the Michael addition. This, along with improved water solubility, resulted in compounds with enhanced biological properties. We present molecular modeling results consistent with the proposed mechanism of inhibition. Binding studies of one compound, 25o (C-14 radiolabeled), showed that it binds irreversibly to HER-2 protein in BT474 cells. Furthermore, it demonstrated excellent oral activity, especially in HER-2 overexpressing xenografts. Compound 25o (HKI-272) was selected for further studies and is currently in phase I clinical trials for the treatment of cancer.

Novel dual inhibitors of calpain and lipid peroxidation

A series of molecules with dual inhibitory activities on calpain and lipid peroxidation were synthesized. These hybrid compounds were built on the calpain pharmacophore 2-hydroxytetrahydrofuran linked to a set of antioxidants via a L-leucine linker. Compo

1H-indole derivatives as a highly selective cyclooxygenase-2 inhibitor

The present invention relates to a novel 1H-indole derivative having a structure of formula 1 and its pharmaceutically acceptable salts as a highly selective cyclooxygenase-2 inhibitor. Wherein, X, Y, and Q are defined in this specification respectively.