4133-34-0Relevant academic research and scientific papers
Synthesis and Bioactivity of a Brasilicardin A Analogue Featuring a Simplified Core
Jung, Michael E.,Chamberlain, Brian T.,Koch, Pierre,Niazi, Kayvan R.
, p. 3608 - 3611 (2015)
An analogue 2 of Brasilicardin A, 1 (BraA), a potent immunosuppressive and cytotoxic agent, was synthesized in which the natural tricyclic skeleton was replaced with a synthetically more accessible substituted tetrahydronaphthalene core. BraA, this analogue (BraL), and cyclosporine A were tested for their ability to inhibit the proliferation of human T cells upon CD3/CD28 activation. Although BraL did not impact T cell activation over the dose range tested, this study shows the inhibitory activity of BraA on human T cells for the first time.
IMPROVED PROCESS FOR THE PREPARATION OF 9-ETHYL-6,6-DIMETHYL-8-[4-(MORPHOLIN-4-YL) PIPERIDIN-1-YL]-11-OXO-6,11-DIHYDRO-5H-BENZO[B]CARBAZOLE-3-CARBONITRILE HYDROCHLORIDE
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Page/Page column 19, (2019/11/19)
The present invention relates to novel process for the preparation of 9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride compound of formula-1a, represented by the following structural formula: The present invention also provides an improved process for the preparation of tert-butyl-4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoate having the following structural formula which is useful in the preparation of Alectinib and its pharmaceutical acceptable salts.
Gold-Catalyzed Oxidation Terminal Alkyne: An Approach to Synthesize Substituted Dihydronaphthalen-2(1H)-ones and Phenanthrenols
Ling, Hui-Bo,Chen, Zi-Sheng,Yang, Fang,Xu, Bin,Gao, Jin-Ming,Ji, Kegong
, p. 7070 - 7076 (2017/07/15)
A facile gold-catalyzed oxidation terminal alkynes to synthesize substituted dihydronaphthalen-2(1H)-ones 3 and phenanthrenols 5 was realized. Various useful structures and drug precursors were generated in up to 99% yield under mild condition and low catalyst loading.
Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen- 2-one as a new class of microtubule-targeting agents
Liu, Jia,Zheng, Can-Hui,Ren, Xiao-Hui,Zhou, Feng,Li, Wei,Zhu, Ju,Lv, Jia-Guo,Zhou, You-Jun
experimental part, p. 5720 - 5733 (2012/07/30)
A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC50 = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC50 = 3.93 μM), and significantly induced cell cycle arrest in G2/M phase. In addition, compound 22b could inhibit the tumor growth in colon nude mouse xenograft tumor model significantly and seemed safer than CA-4 when achieving a similar tumor suppression. This study provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
A concise method for the synthesis of 2-tetralone by titanium tetrachloride-promoted cyclization of 4-aryl-2-hydroxybutanal diethyl acetal
Hon, Yung-Son,Devulapally, Rammohan
scheme or table, p. 5713 - 5715 (2009/12/09)
4-Aryl-2-hydroxybutanal diethyl acetal, prepared from the reaction of benzyl Grignard reagent and glycidaldehyde diethyl acetal, was treated with titanium tetrachloride to give 2-tetralone in good yield. This highly efficient transformation involves tande
TiCl4-promoted intramolecular cyclization of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones: an expedient method to prepare 2-tetralones
Hon, Yung-Son,Devulapally, Rammohan
experimental part, p. 2831 - 2834 (2009/09/30)
DABCO is a very effective catalyst in the formation of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones 12 from the corresponding α-carbonatoaldehyde. Intramolecular cyclization of cyclic carbonates 12 promoted by TiCl4 affords 2-tetralones 13 contain
Discovery of a novel series of benzoic acid derivatives as potent and selective human β3 adrenergic receptor agonists with good oral bioavailability. 3. Phenylethanolaminotetraline (PEAT) skeleton containing biphenyl or biphenyl ether moiety
Imanishi, Masashi,Nakajima, Yutaka,Tomishima, Yasuyo,Hamashima, Hitoshi,Washizuka, Kenichi,Sakurai, Minora,Matsui, Shigeo,Imamura, Emiko,Ueshima, Koji,Yamamoto, Takao,Yamamoto, Nobuhiro,Ishikawa, Hirofumi,Nakano, Keiko,Unami, Naoko,Hamada, Kaori,Matsumura, Yasuhiro,Takamura, Fujiko,Hattori, Kouji
experimental part, p. 4804 - 4822 (2009/07/11)
We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds (10c, 10m) with a good balance of potency, selectivity, and pharmacokinetic profile. Further optimization of the two lead compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of high potency (EC50 = 0.38 nM) for β3, high selectivity over β1 and β2, and good pharmacokinetic properties in rats, dogs, and monkeys.
Synthesis and antifungal activities of novel 2-aminotetralin derivatives
Yao, Bin,Ji, Haitao,Cao, Yongbin,Zhou, Youjun,Zhu, Jü,Lü, Jiaguo,Li, Yaowu,Chen, Jun,Zheng, Canhui,Jiang, Yuanying,Liang, Rongmei,Tang, Hui
, p. 5293 - 5300 (2008/03/18)
Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14α-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.
A convenient strategy for the total synthesis of pisiferic acid type diterpenes
Zhu, Hui,Tu, Pengfei
, p. 71 - 78 (2007/10/03)
A practical method for the total synthesis of pisiferic acid type diterpenoids is described. This involves Robinson annulation of the keto ester for the key intermediate.
New platelet fibrinogen receptor glycoprotein IIb-IIIa antagonists: Orally active series of N-alkylated amidines with a 6,6-bicyclic template
Okumura, Kunio,Shimazaki, Toshiyuki,Aoki, Yoji,Yamashita, Hiroyuki,Tanaka, Eishi,Banba, Shinichi,Yazawa, Kouhei,Kibayashi, Kenji,Banno, Hitoshi
, p. 4036 - 4052 (2007/10/03)
The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3- yl]acetate hydrochloride ((S)-4·HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4- tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4·HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)4·HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4·HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.
