53485-05-5Relevant articles and documents
Preparing method for N,N-diisopropyl-1,3-propane diamine
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Paragraph 0023; 0025; 0026; 0027; 0029; 0030; 0032; 0033, (2019/10/02)
The invention discloses a preparing method for N,N-diisopropyl-1,3-propane diamine. Acrylonitrile and diisopropylamine serve as raw materials, a reflux reaction is conducted at the temperature of 80 DEG C to 84 DEG C in the inert environment under an effect of a micro water catalyst, and N,N-diisopropyl propionitrile is prepared; in an absolute ethyl alcohol solvent system, sodium borohydride serves as a reducing agent, a reduction reaction is conducted on the N,N-diisopropyl propionitrile, and the N,N-diisopropyl-1,3-propane diamine is prepared. According to the preparing method, the raw materials are easy to obtain, a preparing technology is simple, reaction conditions are mild, and the production cost is low.
Structure-activity relationship study of hypoxia-activated prodrugs for proteoglycan-targeted chemotherapy in chondrosarcoma
Ghedira, Donia,Voissière, Aurélien,Peyrode, Caroline,Kraiem, Jamil,Gerard, Yvain,Maubert, Elise,Vivier, Magali,Miot-Noirault, Elisabeth,Chezal, Jean-Michel,Farhat, Farhat,Weber, Valérie
, p. 51 - 67 (2018/09/13)
Due to an abundant chondrogenic, poorly vascularized and particularly hypoxic extracellular matrix, chondrosarcoma, a malignant cartilaginous tumour, is chemo- and radio-resistant. Surgical resection with wide margins remains the mainstay of treatment. To address the lack of therapy, our strategy aims to increase anticancer drugs targeting and delivery in the tumour, by leveraging specific chondrosarcoma hallmarks: an extensive cartilaginous extracellular matrix, namely the high negative fixed charge density and severe chronic hypoxia. A dual targeted therapy for chondrosarcoma was investigated by conjugation of a hypoxia-activated prodrug (HAP) to quaternary ammonium (QA) functions which exhibit a high affinity for polyanionic sites of proteoglycans (PGs), the major components of the chondrosarcoma extracellular matrix. Based on preclinical results, an imidazole prodrug, ICF05016, was identified and provided the basis for a lead optimization study. A series of 27 QA-phosphoramide mustard conjugates, differing by the type of QA function and the length of the alkyl linker, was yielded by a common multi-step sequence involving phosphorylation of a key 2-nitroimidazole alcohol. Then, a screening was realized by surface plasmon resonance technology to assess biomolecular interactions between QA derivatives and aggrecan, the most abundant PG in chondrosarcoma. Results revealed that affinity depends more on the type of QA function, than on the linker length. Moreover, the presence of a benzyl group enhanced affinity to aggrecan. Twelve compounds were shortlisted and evaluated for antiproliferative activity (i.e., growth inhibiting concentration 50), under normoxic and hypoxic conditions using the human extraskeletal myeloid chondrosarcoma cell line (HEMC-SS). For all prodrugs, hypoxic selectivity was maintained and even increased, compared with the lead. From this study, compound 31f emerged as the most effective PG-targeted HAPs with a dissociation constant of 2.10 μM in the SPR experiment, a hypoxia cytotoxicity ratio of 24 and an efficient reductive cleavage under chemical and enzymatic conditions.
Salicylamide inhibitors of influenza virus fusion
Combrink, Keith D.,Gulgeze, H. Belgin,Yu, Kuo-Long,Pearce, Bradley C.,Trehan, Ashok K.,Wei, Jianmei,Deshpande, Milind,Krystal, Mark,Torri, Albert,Luo, Guangxiang,Cianci, Christopher,Danetz, Stephanie,Tiley, Laurence,Meanwell, Nicholas A.
, p. 1649 - 1652 (2007/10/03)
Structural variation of the quinolizidine heterocycle of the influenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identification of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a plaque reduction assay. (C) 2000 Elsevier Science Ltd. All rights reserved.
Compounds for the treatment of urinary incontinence
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, (2008/06/13)
The invention concerns compounds having the formula I STR1 wherein Ar is a phenyl or benzyl group which is optionally substituted with hydroxy or alkoxy;R 1 is hydrogen, lower alkyl, lower alkoxy, hydroxy;R 2 is hydrogen, lower alkyl;R 3 is NR 4 R 5, whereinR 4 and R 5 which can be the same or different, are lower alkyl, or wherein R 4 and R 5, when taken together, form a ring with the nitrogen atom, whereby said ring optionally is substituted with lower alkyl;n is 0 or 1;m is 2 or 3 andtheir salts with physiologically acceptable acids and when the compounds can be in form of optical isomers, the racemic mixture and the individual isomers, for the treatment of disorders of the urinary bladder.
