- Enantioselective Synthesis of N-Alkylamines through β-Amino C-H Functionalization Promoted by Cooperative Actions of B(C6F5)3and a Chiral Lewis Acid Co-Catalyst
-
We disclose a catalytic method for β-C(sp3)-H functionalization of N-alkylamines for the synthesis of enantiomerically enriched β-substituted amines, entities prevalent in pharmaceutical compounds and used to generate different families of chiral catalysts. We demonstrate that a catalyst system comprising of seemingly competitive Lewis acids, B(C6F5)3, and a chiral Mg- or Sc-based complex, promotes the highly enantioselective union of N-alkylamines and α,β-unsaturated compounds. An array of δ-amino carbonyl compounds was synthesized under redox-neutral conditions by enantioselective reaction of a N-alkylamine-derived enamine and an electrophile activated by the chiral Lewis acid co-catalyst. The utility of the approach is highlighted by late-stage β-C-H functionalization of bioactive amines. Investigations in regard to the mechanistic nuances of the catalytic processes are described.
- Chang, Yejin,Cao, Min,Chan, Jessica Z.,Zhao, Cunyuan,Wang, Yuankai,Yang, Rose,Wasa, Masayuki
-
supporting information
p. 2441 - 2455
(2021/02/16)
-
- A phosphine-free iron complex-catalyzed synthesis of cycloalkanes: Via the borrowing hydrogen strategy
-
Herein we report a diaminocyclopentadienone iron tricarbonyl complex catalyzed synthesis of substituted cyclopentane, cyclohexane and cycloheptane compounds using the borrowing hydrogen strategy in the presence of various substituted primary and secondary 1,n diols as alkylating reagents. Deuterium labeling experiments confirm that the diols were the hydride source in this cascade process. This journal is
- Bettoni, Léo,Gaillard, Sylvain,Renaud, Jean-Luc
-
supporting information
p. 12909 - 12912
(2020/11/07)
-
- 3-(5-HYDROXY-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF
-
The present disclosure provides a compound of Formula (I′): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein Rx, X1, X2, and R1 are as defined herein, and methods of making and using same.
- -
-
Paragraph 1766-1767
(2020/02/05)
-
- N-(PYRIDIN-2-YLSULFONYL)CYCLOPROPANECARBOXAMIDE DERIVATIVES AND THEIR USE IN THE TREATMENT OF A CFTR MEDIATED DISEASE
-
The invention relates to heterocyclic compounds of the formula (I), in which all of the variables are as defined in the specification; capable of modulating the activity of CFTR. The invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including Cystic fibrosis and related disorders.
- -
-
Page/Page column 149
(2020/07/14)
-
- Compounds and Their Use in Treating Cancer
-
The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts and prodrugs thereof, where R1, R4, R5, R6, R7, Linker, X, Y, A, G, D and E have any of the meanings defined herein. This specification also relates to the use of such compounds and pharmaceutically acceptable salts and prodrugs thereof in methods of treatment of the human or animal body, for example in prevention or treatment of cancer. This specification also relates to processes and intermediate compounds involved in the preparation of such compounds and to pharmaceutical compositions containing them.
- -
-
Paragraph 0731; 0732
(2019/07/10)
-
- Stereoselective synthesis of alicyclic ketones: A hydrogen borrowing approach
-
A highly diastereoselective annulation strategy for the synthesis of alicyclic ketones from diols and pentamethylacetophenone is described. This process is mediated by a commercially available iridium(III) catalyst, and provides efficient access to a wide range of cyclopentane and cyclohexane products with high levels of stereoselectivity. The origins of diastereoselectivity in the annulation reaction have been explored by a series of control experiments, which provides an explanation for how each stereocentre around the newly forged ring is controlled.
- Armstrong, Roly J.,Akhtar, Wasim M.,Frost, James R.,Christensen, Kirsten E.,Stevenson, Neil G.,Donohoe, Timothy J.
-
supporting information
(2019/11/13)
-
- PRODRUGS OF FUSED-BICYCLIC C5aR ANTAGONISTS
-
The present disclosure provides, inter alia, Compounds of Formulae IA, IB, IC, IIA, IIB and IIC or pharmaceutically acceptable salts thereof that are modulators of the C5a receptor. Also provided are pharmaceutical compositions and methods of use including the treatment of diseases or disorders involving pathologic activation from C5a and non-pharmaceutical applications.
- -
-
Paragraph 0197
(2019/10/23)
-
- SALT FORM AND CRYSTAL FORM OF 1,2,5-THIADIAZOLIDIN-1,1-DIOXIDE, PREPARATION METHOD THEREOF AND INTERMEDIATE
-
The present invention discloses a salt form, crystal form and intermediate of the compound 1, and preparation method thereof.
- -
-
Paragraph 0065; 0067
(2018/06/04)
-
- Stereoselective Synthesis of Cyclohexanes via an Iridium Catalyzed (5 + 1) Annulation Strategy
-
An iridium catalyzed method for the synthesis of functionalized cyclohexanes from methyl ketones and 1,5-diols is described. This process operates by two sequential hydrogen borrowing reactions, providing direct access to multisubstituted cyclic products with high levels of stereocontrol. This methodology represents a novel (5 + 1) strategy for the stereoselective construction of the cyclohexane core.
- Akhtar, Wasim M.,Armstrong, Roly J.,Frost, James R.,Stevenson, Neil G.,Donohoe, Timothy J.
-
supporting information
p. 11916 - 11920
(2018/09/27)
-
- ANTI-ENTEROVIRUS 71 THIADIAZOLIDINE DERIVATIVE
-
Disclosed is a novel anti-enterovirus 71 (EV71) 1,2,5-thiadiazolidine-1,1-dioxide derivative or a pharmaceutically acceptable salt thereof; and specifically, a compound represented by formula (II) or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0325-0326
(2017/03/28)
-
- Stereocontrolled Total Synthesis of Muraymycin D1 Having a Dual Mode of Action against Mycobacterium tuberculosis
-
A stereocontrolled first total synthesis of muraymycin D1 (1) has been achieved. The synthetic route is highly stereoselective, featuring (1) selective β-ribosylation of the C2-methylated amino ribose, (2) selective Strecker reaction, and (3) ring-opening
- Mitachi, Katsuhiko,Aleiwi, Bilal A.,Schneider, Christopher M.,Siricilla, Shajila,Kurosu, Michio
-
supporting information
p. 12975 - 12980
(2016/10/13)
-
- N-SUBSTITUTED PYRROLIDINES
-
Compounds of formula and enantiomers and pharmaceutically acceptable salts thereof are described, as well as the pharmaceutical compositions containing said compounds and their pharmaceutically acceptable salts, and the use of said compounds and pharmaceu
- -
-
Page/Page column 28
(2012/01/15)
-
- Cyclopropenium-activated cyclodehydration of diols
-
The dehydrative cyclization of diols to cyclic ethers via cyclopropenium activation is described. Using 2,3-diphenylcyclopropene and methanesulfonic anhydride, a series of 1,4-and 1,5-diols are rapidly cyclized to furnish tetrahydrofurans and tetrahydropyrans in high yield. Eleven total substrates are shown, including a gram scale cyclization of a diterpene derivative.
- Kelly, Brendan D.,Lambert, Tristan H.
-
supporting information; experimental part
p. 740 - 743
(2011/05/04)
-
- SUBSTITUTED SPIROINDOLINONES
-
There is provided a compound of the formula wherein X, Y, W, R1, R2 and R3 are as described herein. The compounds have activity as anticancer agents.
- -
-
Page/Page column 19-20
(2011/09/14)
-
- Design, synthesis, and anti-HCV activity of thiourea compounds
-
A series of thiourea derivatives were synthesized and their antiviral activity was evaluated in a cell-based HCV subgenomic replicon assay. SAR studies revealed that the chain length and the position of the alkyl linker largely influenced the in vitro anti-HCV activity of this class of potent antiviral agents. Among this series of compounds synthesized, the thiourea derivative with a six-carbon alkyl linker at the meta-position of the central phenyl ring (10) was identified as the most potent anti-HCV inhibitor (EC50 = 0.047 μM) with a selectivity index of 596.
- Kang, Iou-Jiun,Wang, Li-Wen,Lee, Chung-Chi,Lee, Yen-Chun,Chao, Yu-Sheng,Hsu, Tsu-An,Chern, Jyh-Haur
-
scheme or table
p. 1950 - 1955
(2009/11/30)
-
- Catalytic, asymmetric transannular aldolizations: Total synthesis of (+)-hirsutene
-
We report an asymmetric, catalytic transannular aldolization that provides polycyclic products useful for natural product synthesis. We found that a proline-derivative catalyzes the transannular aldol reaction of 1,4-cyclooctanediones to the corresponding cyclic β-hydroxy ketones in good yields and with high enantioselectivities. The utility of our reaction has been demonstrated in a total synthesis of (+)-hirustene. Copyright
- Chandler, Carley L.,List, Benjamin
-
p. 6737 - 6739
(2008/12/22)
-
- Design, synthesis, and antipicornavirus activity of 1-[5-(4-arylphenoxy) alkyl]-3-pyridin-4-ylimidazolidin-2-one derivatives
-
A series of pyridylimidazolidinone derivatives was synthesized and tested in vitro against enterovirus 71 (EV71). On the basis of compound 33 (DBPR103), introduction of a methyl group at the 2- or 3-position of the linker between the imidazolidinone and the biphenyl resulted in markedly improved antiviral activity toward EV71 with IC50 values of 5.0 nM (24b) and 9.3 nM (14a), respectively. Increasing the branched chain to propyl resulted in a progressive decrease in activity, while inserting different heteroatoms entirely rendered the compound only weakly active. The introduction of a bulky group (cyclohexyl, phenyl, or benzyl) led to loss of activity against EV71. The 4-chlorophenyl moiety in 14a was replaced with bioisosteric groups such as oxadiazole (28a-d) or tetrazole (32a,b), dramatically improving anti-EV71 activity and selectivity indices. Compounds 14a, 24b, 28b, 28d, and 32a exhibited a strong activity against lethal EV71, and no apparent cellular toxicity was observed. Three of the more potent imidazolidinone compounds, 14a, 28b, and 32b, were subjected to a large group of picornaviruses to determine their spectrum of antiviral activity.
- Chang, Chih-Shiang,Lin, Ying-Ting,Shih, Shin-Ru,Lee, Chung-Chi,Lee, Yen-Chun,Tai, Chia-Liang,Tseng, Sung-Nien,Chern, Jyh-Haur
-
p. 3522 - 3535
(2007/10/03)
-
- Synthesis and antipicornavirus activity of (R)- and (S)-1-[5-(4′- chlorobiphenyl-4-yloxy)-3-methylpentyl]-3-pyridin-4-yl-imidazolidin-2-one
-
The new pyridyl imidazolidinone derivative, 1-[5-(4′-chlorobiphenyl- 4-yloxy)-3-methylpentyl]-3-pyridin-4-yl-imidazolidin-2-one (±)-1a, was synthesized and found to have an excellent antiviral activity against EV71 (IC50 = 0.009 μM). Therefore, both the enantiomers, (S)-(+)-1a and (R)-(-)-1a, have been prepared starting from readily available monomethyl (R)-3-methylglutarate (7) as a useful chiral building block and their antiviral activity was evaluated in a plaque reduction assay. Interestingly, we observed that the enantiomer (S)-(+)-1a was 10-fold more active against enterovirus71 (EV71) (IC50 = 0.003 μM) than the corresponding enantiomer (R)-(-)-1a (IC50 = 0.033 μM). Similar results were found against all five strains (1743, 2086, 2231, 4643, and BrCr) of EV71 tested. This demonstrated that the absolute configuration of the chiral carbon atom at the 3-position of the alkyl linker considerably influenced the anti-EV71 activity of these pyridyl imidazolidinones.
- Chern, Jyh-Haur,Chang, Chih-Shiang,Tai, Chia-Liang,Lee, Yen-Chun,Lee, Chung-Chi,Kang, Iou-Jiun,Lee, Ching-Yin,Shih, Shin-Ru
-
p. 4206 - 4211
(2007/10/03)
-
- Indoline derivatives
-
This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure: wherein R1and R2may be single substituents or fused to form spirocyclic rings.
- -
-
-
- CYCLIC REGIMENS UTILIZING INDOLINE DERIVATIVES
-
This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure: wherein R 1 and R 2 may be single substituents or fused to form spirocyclic rings, in combination with progestins, estrogens, or both. These methods of treatment may be used for contraception or for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake.
- -
-
-
- Tricyclic nitrogen ring compounds, their production and use
-
Tricyclic compound of the formula: STR1 wherein ring A is a nitrogen-containing heterocyclic ring, having two nitrogen atoms as the hetero-atoms, which is optionally substituted with oxo or thioxo; ring Q may optionally be substituted; Y is an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group or an optionally substituted mecapto group, excluding for methyl group as Y; R1 is a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon group or an acyl group, or a salt thereof, having excellent PDGF-inhibiting activities, antihypertensive activities, activities of ameliorating renal diseases and activities of lowering lipid level.
- -
-
-
- Imidazopyridine or imidazopyrimidine compounds, their production and use
-
This invention provides a new condensed imidazole compound possessing inhibitory activity of adhesion molecule expression. This invention also provides a therapeutic and prophylactic agent for diabetic nephritis and/or autoimmune disease and an immunosuppressor for organ transplantation.
- -
-
-
- Oxidation of putrescine and cadaverine derivatives by diamine oxidases
-
A range of putrescine and cadaverine derivatives has been synthesized and assayed as substrates for the diamine oxidases from pea seedlings and pig kidney. KM and Vmax data are reported, mainly for the pea enzyme. N-Alkylputrescines and C-alkylcadaverines are generally poorer substrates than the parent compounds with up to 4500-fold reduction in Vmax. There is significantly less variation in KM values, indicating that the binding site of the pea enzyme is relatively non-specific and that enzymic specificity lies at the catalytic stage. This suggests that poor substrates might act as convenient, short-lived inhibitors of diamine oxidases.
- Equi, Angela M.,Brown, Alison M.,Cooper, Alan,Her, Surjit K.,Watson, Allan B.,Robins, David J.
-
p. 507 - 518
(2007/10/02)
-
- Organosulfur Chemistry. II. Use of Dimethyl Sulfoxide; a Facile Synthesis of Cyclic Sulfides
-
A versatile and short-reaction-time synthesis of twelve four-, five- and six-membered thiacycloalkanes (IIa-l)from the appropriate α,ω-dibromoalkanes (Ia-l)has been developed.Technical-grade dimethyl sulfoxide was proved to be by far the best for this cyclization.The pronounced effect for ring formation was recognized to be in order of five-membered ring (thiolanes) > six-membered ring (thianes) > four-membered ring (thietanes).Startling were 2-methylthiolane (IIf) and 2,5-dimethylthiolane (IIg; cis/trans mixture), both obtained in high yields although α-methyl - and α,α'-dimethyl substitution in general showing a remarkable retardation for cyclization.On the other hand, in both 3,3-dimethylthietane (IId) and 4,4-dimethylthiane (IIl) cyclization was much more efficient than other counterparts in each series, which is referred to as the gem-dimethyl effect.Keywords: thiacycloalkane; thietane; thiolane; thiane; dimethyl sulfoxide; cyclization: α,ω-dibromoalkane; sodium sulfide nonahydrate; refractive index
- Nagasawa, Kazuo,Yoneta, Akemi
-
p. 5048 - 5052
(2007/10/02)
-
- Alkylsubstituted Cyclopentanones via Hydrocarbonylating Cyclization of 1,4-Pentadiene Systems Mediated by Metal Carbonyls
-
3,3-Dialkyl-1,4-pentadienes 8 under the influence of metal carbonyls can be converted to unsymmetrically substituted cyclopentanones 9 by hydrocarbonylating cyclization with carbon monoxide and hydrogen or water.Starting from 1,1-divinylcycloalkanes of type 8 this method can also be used for the synthesis of spirocyclopentanones.The yields of cyclic ketones with the here used dienes are markedly better than with the unsubstituted 1,4-pentadiene itself.
- Eilbracht, Peter,Acker, Michael,Totzauer, Walter
-
p. 238 - 242
(2007/10/02)
-
