87866-11-3

Upstream product

• 17133-48-1 2-Chloro-1-(2,3-dihydro-1H-1-indolyl)-1-ethanone 
• 6146-52-7 5-nitroindole 
• 32692-19-6 5-nitro-2,3-dihydro-1H-indole 
• 79-04-9 chloroacetyl chloride 

Relevant academic research and scientific papers

Regioselective C5 nitration of N-protected indolines using ferric nitrate under mild conditions

An efficient and facile process has been developed for the regioselective C5 nitration of the N-protected indolines using ferric nitrate as the nitrating reagents. The reaction proceeded smoothly in moderate to excellent yields with high efficiency and broad substrate scope under mild conditions. In addition, the synthesized nitration products can be further transformed to 5-nitroindolines and C5-nitroindole derivatives. The method is operationally simple, efficient, and might have potential application in industry production.

Discovery of Indolinone-Based Multikinase Inhibitors as Potential Therapeutics for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a serious and deadly disease for which treatment options are limited. The recent approval of antifibrosis agent nintedanib represents one of the first therapeutic approaches for the treatment of IPF. Here, we report novel indolinone-based multikinase inhibitors that target angiogenesis and fibrosis pathways and may serve as potential therapeutics for IPF. KBP-7018 is a novel, tyrosine kinase-selective inhibitor with potent effects on three fibrotic kinases (c-KIT, PDGFR, and RET). The pharmacokinetics (PK) properties of KBP-7018 were favorable in mice, rats, and dogs. In a bleomycin (BLM)-induced mouse pulmonary fibrosis model, 10, 30, and 100 mg/kg daily doses (q.d.) of KBP-7018 improved the 28-day survival rate in a dose-dependent manner. The improved efficacy of KBP-7018 compared to nintedanib provided a certain level of chemical validation for the involvement of PDGFR, c-KIT, and RET in IPF. Thus, KBP-7018 represents a novel multikinase inhibitor with differentiated activity, highly enhanced selectivity, and acceptable PK profiles that will enter phase I clinical trials.

Synthesis method for acylindoline-type compound with C-5 position substituted by nitro group

The invention discloses a synthesis method for an acylindoline-type compound with a C-5 position substituted by a nitro group, wherein a reaction general formula is represented as follows, R referring to alkyl groups including hydrogen (H), 4-methyl and 7-methyl groups. The synthesis method is simple and high-effective, wherein by means of ferric nitrate nonahydrate, the acylindoline-type compound with the C-5 position substituted by a nitro group is produced directly through one step. The reaction has strong zone selectivity and high synthesis efficiency. The raw materials are easy to prepare, and the nitration reagent, ferric nitrate nonahydrate, is low-cost and easy-to-obtained, has wide source and is stable and low-toxic. The reaction is free of protection by inert gas and can be directly carried out in air, has simple operations and gentle conditions, employs a low-cost and easy-to-obtained solvent, and has wide adaptable range of a substrate. The method is low in requirement on reaction conditions, has wide adaptable range, has significant advantages than known methods, and has a potential wide application prospect.

INDOLE FULL KETONE DERIVATIVE USED AS TYROSINE-KINASE INHIBITOR

The present invention relates to a compound represented by general formula (I), a method for preparing said compound, a pharmaceutical formulation containing said compound, and the use of said compound in manufacture of a medicament for treating or preven

Discovery of a potent, orally bioavailable and highly selective human neuronal nitric oxide synthase (nNOS) inhibitor, N-(1-(piperidin-4-yl)indolin-5- yl)thiophene-2-carboximidamide as a pre-clinical development candidate for the treatment of migraine

We recently reported a series of 1,6-disubstituted indoline-based thiophene amidine compounds (5) as selective neuronal nitric oxide synthase (nNOS) inhibitors to mitigate the cardiovascular liabilities associated with hERG K+ channel inhibition (IC50 = 4.7 μM) with previously reported tetrahydroquinoline-based selective nNOS inhibitors (4). The extended structure-activity relationship studies within the indoline core led to the identification of 43 as a selection candidate for further evaluations. The in vivo activity in two different pain (spinal nerve ligation and migraine pain) models, the excellent physicochemical and pharmacokinetic properties, oral bioavailability (Fpo = 91%), and the in vitro safety profile disclosed in this report make 43 an ideal candidate for further evaluation in clinical applications related to migraine pain.

AMIDE COMPOUNDS

A compound of the formula (I) wherein R1 is hydrogen, lower alkyl, lower alkenyl, halo(lower)alkyl, cyclo(lower)alkyl, lower alkoxy, lower alkylthio, acyl, optionally substituted aryl or NR3R4; R2 is hydrogen; or aryl or heteroaryl, each of which may be substituted; X is direct bond or bivalent residue derived from piperazine; Y is -(A1)n#191-(A2?)?m#191-, wherein n and m are independently 0 or 1); is bivalent residue derived from arene or heteroarene; and is bivalent residue derived from arene or heteroarene, or a salt thereof. The compound of the present invention and a salt thereof inhibit apolipoprotein B (Apo B) secretion and are useful as a medicament for prophylactic and treatment of diseases or conditions resulting from elevated circulating levels of Apo B.

Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure-activity relationships

Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 7b. Their related synthesis was also reported.