- Bismuth(iii)-catalyzed regioselective alkylation of tetrahydroquinolines and indolines towards the synthesis of bioactive core-biaryl oxindoles and CYP19 inhibitors
-
Bismuth(iii)-catalyzed regioselective functionalization at the C-6 position of tetrahydroquinolines and the C-5 position of indolines has been demonstrated. For the first time, one pot symmetrical and unsymmetrical arylation of isatins with tetrahydroquinolines was accomplished giving a completely new product skeleton in good to excellent yields. Most importantly, this protocol leads to the formation of a highly strained quaternary carbon stereogenic center, which is a challenging task. Benzhydryl and 1-phenylethyl trichloroacetimidates have been used as the alkylating partners to functionalize the C-6 and C-5 positions of tetrahydroquinolines and indolines, respectively. The scope of the developed methodology has been extended for the synthesis of the bioactive CYP19-inhibitor and its analogue.
- Prusty, Namrata,Kinthada, Lakshmana K.,Meena, Rohit,Chebolu, Rajesh,Ravikumar, Ponneri Chandrababu
-
p. 891 - 905
(2021/02/09)
-
- Synthesis, Structure, and Properties of Amino-Substituted Benzhydrylium Ions – A Link between Ordinary Carbocations and Neutral Electrophiles
-
Optimized synthetic procedures for the straightforward access to eleven amino-substituted diarylmethylium tetrafluoroborates are described. These benzhydrylium ions cover a range of seven orders of magnitude in electrophilicity and provide a link between ordinary carbocations and neutral electrophiles. Five of these highly stabilized benzhydrylium tetrafluoroborates were characterized by single-crystal X-ray crystallography. While the experimentally determined bond lengths and angles in the solid state perfectly agree with those calculated by DFT methods for the gas phase and aqueous solution, crystal packing accounts for large differences in the twist angles of the aryl groups found in the solid state as compared to calculated structures.
- Mayer, Robert J.,Hampel, Nathalie,Mayer, Peter,Ofial, Armin R.,Mayr, Herbert
-
supporting information
p. 412 - 421
(2018/09/14)
-
- Synthesis and Biological Evaluation of Fused Tricyclic Heterocycle Piperazine (Piperidine) Derivatives As Potential Multireceptor Atypical Antipsychotics
-
Herein, a novel series of multireceptor ligands was developed as polypharmacological antipsychotic agents using the designed multiple ligand approach between dopamine receptors and serotonin receptors. Among them, compound 47 possessed unique pharmacological features, exhibiting high affinities for D2, D3, 5-HT1A, 5-HT2A, and 5-HT6 receptors and low efficacy at the off-target receptors (5-HT2C, histamine H1, and adrenergic α1 receptor). Compound 47 showed dose-dependent inhibition of apomorphine- and MK-801-induced motor behavior, and the conditioned avoidance response with low cataleptic effect. Moreover, compound 47 resulted nonsignificantly serum prolactin levels and weight gain change compared with risperidone. Additionally, compound 47 possessed a favorable pharmacokinetic profile with oral bioavailability of 58.8% in rats. Furthermore, compound 47 displayed procognition properties in a novel object recognition task in rats. Taken together, compound 47 may constitute a novel class of atypical antipsychotic drugs for schizophrenia.
- Cao, Xudong,Zhang, Yifang,Chen, Yin,Qiu, Yinli,Yu, Minquan,Xu, Xiangqing,Liu, Xin,Liu, Bi-Feng,Zhang, Liangren,Zhang, Guisen
-
p. 10017 - 10039
(2018/12/11)
-
- RADIOACTIVE QUINOLINONE DERIVATIVE AND PHARMACEUTICAL DRUG COMPRISING THE SAME
-
It is intended to provide a radioactive compound that has higher selectivity for CYP11B2 than that for CYP11B1, exhibits highly selective accumulation in the adrenal gland compared with blood and organs adjacent to the adrenal gland, and permits commercial supply. The present invention provides a radioactive quinolinone derivative represented by the predetermined general formula or a salt thereof.
- -
-
Paragraph 0088; 0089
(2014/07/08)
-
- Novel imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1-ij] quinolin-4-ones as potent and selective cyp11b1 inhibitors for the treatment of cushing's syndrome
-
CYP11B1 inhibition is a promising therapy for Cushing's syndrome. Starting from etomidate, references I and II, the title compounds were designed and synthesized. Cyclopropyl analogue 4 was identified as a CYP11B1 inhibitor more potent (IC50 = 2.2 nM) than leads and more selective (SF = 11) than I and metyrapone. Since it also showed potent inhibition of rat CYP11B1 and good selectivity over human CYP17 and CYP19, it is a promising candidate for further development.
- Yin, Lina,Lucas, Simon,Maurer, Frauke,Kazmaier, Uli,Hu, Qingzhong,Hartmann, Rolf W.
-
supporting information; experimental part
p. 6629 - 6633
(2012/09/21)
-
- Fine-tuning the selectivity of aldosterone synthase inhibitors: Structure-activity and structure-selectivity insights from studies of heteroaryl substituted 1,2,5,6-tetrahydropyrrolo[3,2,1- ij ]quinolin-4-one derivatives
-
Pyridine substituted 3,4-dihydro-1H-quinolin-2-ones (e.g., 1-3) constitute a class of highly potent and selective inhibitors of aldosterone synthase (CYP11B2), a promising target for the treatment of hyperaldosteronism, congestive heart failure, and myocardial fibrosis. Among these, ethyl-substituted 3 possesses high selectivity against CYP1A2. Rigidification of 3 by incorporation of the ethyl group into a 5- or 6-membered ring affords compounds with a pyrroloquinolinone or pyridoquinolinone molecular scaffold (e.g., 4 and 5). It was found that these molecules are even more potent and selective CYP11B2 inhibitors than their corresponding open-chain analogues. Moreover, pyrroloquinolinone 4 exhibits no inhibition of the six most important hepatic CYP enzymes as well as a bioavailability in the range of the marketed drug fadrozole. The SAR studies disclose that subtle changes in the heterocyclic moiety are responsible for either a strong or a weak inhibition of the highly homologous 11-hydroxylase (CYP11B1). These results are not only important for fine-tuning the selectivity of CYP11B2 inhibitors but also for the development of selective CYP11B1 inhibitors that are of interest for the treatment of Cushing's syndrome and metabolic syndrome.
- Lucas, Simon,Negri, Matthias,Heim, Ralf,Zimmer, Christina,Hartmann, Rolf W.
-
scheme or table
p. 2307 - 2319
(2011/06/20)
-
- 6-PYRIDIN-3-YL-3,4-DIHYDRO-1H-QUINOLIN-2-ONE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE HUMAN ALDOSTERONE SYNTHASE CYP11B2
-
The invention provides compounds of the general formula (I) which are inhibitors of the human aldosterone synthase, and also pharmaceutical compositions containing these compounds, and the use of these compounds and other heteroaryl substituted quinolinone derivatives for the treatment of hyperaldosteronism and/or disorders or diseases that are mediated by 11 β-hydroxylase (CYP11 B1 ).
- -
-
Page/Page column 47-48
(2010/01/29)
-
- FUSED TRICYCLIC HETEROCYCLES FOR THE TREATMENT OF SCHIZOPHRENIA
-
Disclosed are compounds of Formula (1), pharmaceutical compositions containing compounds of Formula (1), and the use of compounds of Formula (1) to treat central nervous system disorders, including schizophrenia and other psychotic disorders, wherein L, Z1, Z2, R1, R2, R3, R4, R5, R6, R7 R8, R9 and R10 in Formula (1) are defined in the specification.
- -
-
Page/Page column 36
(2010/11/30)
-
- 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.
- Zhao, He,Thurkauf, Andrew,He, Xiaoshu,Hodgetts, Kevin,Zhang, Xiaoyan,Rachwal, Stanislaw,Kover, Renata X.,Hutchison, Alan,Peterson, John,Kieltyka, Andrzej,Brodbeck, Robbin,Primus, Renee,Wasley, Jan W.F.
-
p. 3105 - 3109
(2007/10/03)
-
- Indane or dihydroindole derivatives
-
The present invention relates to substituted indane or dihydroindole compounds of Formula (I) wherein A is an indole. These compounds have high affinity for D4receptors.
- -
-
Page column 42
(2010/02/05)
-
- Microbiological Transformations, Part 9. Microbiological Transformations of 1,2,5,6-Tetrahydropyrroloquinolin-4-one and of Derivatives of 1,2,3,5,6,7-Hexahydropyridoquinoline with the Fungus Cunninghamella elegans
-
Incubation of 1,2,6,7-tetrahydropyridoquinolin-3(5H)-one with C. elegans resulted in oxidation at the C-7 benzylic position, whereas 1-methyl-1,2,6,7-tetrahydropyridoquinolin-5(3H)-one gave products resulting from oxidation at both benzylic positions. cis- and trans-1-Hydroxy-3-methyl-1,2,6,7-tetrahydropyridoquinolin-5(3H)-ones were produced on incubation of 5-methyl-1,2,6,7-tetrahydropyridoquinolin-3(5H)-one with C. elegans, in addition to trans-1-hydroxy-5-methyl-1,2,6,7-tetrahydropyridoquinolin-3(5H)-one.Incubation of 1,2,5,6-tetrahydropyrroloquinolin-4-one with C. elegans resulted in dehydrogenation to 1,2-dihydropyrroloquinolin-4-one.Incubation of 2,3,6,7-tetrahydropyridoquinolin-1(5H)-one with C. elegans resulted in benzylic attack at C-7.
- Crabb, Trevor A.,Soilleux, Stephanie L.
-
p. 5407 - 5414
(2007/10/02)
-