- A facile synthesis of the spiroindoline-based growth hormone secretagogue, MK-677
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A facile and improved route for the synthesis of the orally active spiroindoline-based growth hormone secretagogue, MK-677 was described. The key step adopted the Fischer indole/reduction strategy. The preparation of the key intermediates N-protected piperidine carboxaldehyde 5 and the N-Boc-O-benzyl-d-serine (2) are also optimized.
- Qi, Xian Liang,Yang, Er Qun,Zhang, Jun Tao,Wang, Tao,Cao, Xiao Ping
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Read Online
- Design and Synthesis of Novel N-(2-aminophenyl)benzamide Derivatives as Histone Deacetylase Inhibitors and Their Antitumor Activity Study
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Histone deacetylases (HDACs) are promising therapeutic targets for cancer therapy because inhibition of HDACs triggers growth arrest or apoptosis of tumor cells. In the present study, a new series of fluorinated N-(2-aminophenyl)benzamide derivatives were synthesized to investigate potential inhibition of HDACs and associated anticancer activity. Among the synthesized derivatives, compound 24a showed potent inhibitory activity of HDACs and higher antitumor efficacy in human cancer cell lines (HCT-116, MCF-7, and A549) compared with SAHA. Moreover, animal studies demonstrated that compound 24a showed potent in vivo antitumor efficacy in an HCT-116 colon cancer xenograft mouse model.
- La, Minh Thanh,Jeong, Byung-Hoon,Kim, Hee-Kwon
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supporting information
p. 740 - 743
(2021/03/16)
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- Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidine-based protein kinase D inhibitors
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The multiple roles of protein kinase D (PKD) in various cancer hallmarks have been repeatedly reported. Therefore, the search for novel PKD inhibitors and their evaluation as antitumor agents has gained considerable attention. In this work, novel pyrazolo[3,4-d]pyrimidine based pan-PKD inhibitors with structural variety at position 1 were synthesized and evaluated for biological activity. Starting from 3-IN-PP1, a known PKD inhibitor with IC50 values in the range of 94–108 nM, compound 17m was identified with an improved biochemical inhibitory activity against PKD (IC50 = 17–35 nM). Subsequent cellular assays demonstrated that 3-IN-PP1 and 17m inhibited PKD-dependent cortactin phosphorylation. Furthermore, 3-IN-PP1 displayed potent anti-proliferative activity against PANC-1 cells. Finally, a screening against different cancer cell lines demonstrated that 3-IN-PP1 is a potent and versatile antitumoral agent.
- Gilles, Philippe,Kashyap, Rudra S.,Freitas, Maria Jo?o,Ceusters, Sam,Van Asch, Koen,Janssens, Anke,De Jonghe, Steven,Persoons, Leentje,Cobbaut, Mathias,Daelemans, Dirk,Van Lint, Johan,Voet, Arnout R.D.,De Borggraeve, Wim M.
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supporting information
(2020/08/25)
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- THERAPEUTICS TARGETING MUTANT ADENOMATOUS POLYPOSIS COLI (APC) FOR THE TREATMENT OF CANCER
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The present disclosure reports an extensive medicinal chemistry evaluation of a large collection of Truncating APC-Selective Inhibitor (TASIN) compounds. The compounds were evaluated for activity against a series of colon cancer cell lines with and withou
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Paragraph 00435; 00596
(2020/07/04)
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- AZOLE-SUBSTITUTED PYRIDINE COMPOUND
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The present invention provides a compound represented by formula [I'| shown below or a pharmaceutically acceptable salt thereof that has an inhibitory effect on 20-HETE producing enzyme, wherein the structure represented by formula [III] shown below represents any of the structures represented by formula group [IV] shown below, wherein R1 represents a hydrogen atom, a fluorine atom, methyl, etc.; R2, R3, and R4 each independently represent a hydrogen atom, a fluorine atom, or methyl; W represents a single bond, C1-3alkanediyl, or the formula -O-CH2CH2-; and ring A represents (a) substituted C4-6cycloalkyl, (b) substituted 4- to 6-membered saturated nitrogen-containing heterocyclyl, (c) substituted phenyl, (d) substituted pyridyl, (e) substituted 2,3-dihydrobenzofuran, (f) 4- to 6-membered saturated oxygen-containing heterocyclyl, etc.
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Paragraph 0636; 0637
(2019/01/08)
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- Nickel-Catalyzed C-Alkylation of Nitroalkanes with Unactivated Alkyl Iodides
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Enabled by nickel catalysis, a mild and general catalytic method for C-alkylation of nitroalkanes with unactivated alkyl iodides is described. Compatible with primary, secondary, and tertiary alkyl iodides; and tolerant of a wide range of functional groups, this method allows rapid access to diverse nitroalkanes.
- Rezazadeh, Sina,Devannah, Vijayarajan,Watson, Donald A.
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supporting information
p. 8110 - 8113
(2017/06/28)
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- Highly regioselective gold-catalyzed formal hydration of propargylic: Gem -difluorides
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Herein, we report a highly regioselective gold-catalyzed formal hydration of propargylic gem-difluorides. Not only does this transformation provide access to versatile fluorinated building blocks that were difficult or hardly possible to access beforehand, but it also represents a rare case of a highly regioselective gold-catalyzed hydroalkoxylation of internal alkynes and puts forward the utility of the difluoromethylene unit as a directing group in catalysis.
- Hamel, Jean-Denys,Hayashi, Tatsuru,Cloutier, Mélissa,Savoie, Paul R.,Thibeault, Olivier,Beaudoin, Meggan,Paquin, Jean-Fran?ois
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supporting information
p. 9830 - 9836
(2017/12/08)
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- COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
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Compounds of formula I, defined herein, act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for treating broncho-obstructive and inflammatory diseases.
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Paragraph 0706; 0707; 0708
(2016/09/12)
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- INHIBITORS OF CYTOMEGALOVIRUS
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Compounds of Formula (I) wherein R1, R2, R3A, R3B, Y, Z1 and Z2 are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.
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Page/Page column 20
(2014/05/24)
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- A library of conformationally restricted saturated heterocyclic sulfonyl chlorides
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An approach to the synthesis of conformationally restricted saturated heterocyclic sulfonyl chlorides is described. Being guided by the principle of diversity-oriented conformational restriction, a mini-library of saturated heterocyclic sulfonyl chlorides
- Zhersh, Sergey,Buryanov, Volodymyr V.,Karpenko, Oleksandr V.,Grygorenko, Oleksandr O.,Tolmachev, Andrey A.
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scheme or table
p. 3669 - 3674
(2011/12/16)
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- ANTI VIRAL COMPOUNDS
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There is provided small molecule anti-human immunodeficiency virus (anti-HIV) compounds as well as a phenotypic cell-based high throughput screening (HTS) assay for their identification.
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Page/Page column 63-64
(2010/05/13)
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- Synthesis of α,α-difluoro-β-amino esters or gem-difluoro-β-lactams as potential metallocarboxypeptidase inhibitors
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The synthesis of gem-difluorinated β-lactams and gem-difluorinated β-amino acids, each possessing a potential basic functional group, from ethyl bromodifluoroacetate and either imines (for β-lactams) or N-(α-aminoalkyl)benzotriazoles (for β-amino esters) was investigated. A series of these compounds were used for the design of novel metallocarboxypeptidase inhibitors. N-Alkylation and N-acylation of these two versatile scaffolds were carried out, leading to the expected targets in moderate to good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Boyer, Nicolas,Gloanec, Philippe,De Nanteuil, Guillaume,Jubault, Philippe,Quirion, Jean-Charles
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experimental part
p. 4277 - 4295
(2009/04/10)
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- Azinyl-3-sulfonylindazole derivatives as 5-hydroxytryptamine-6 ligands
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The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the 5-HT6 receptor.
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Page/Page column 24
(2010/11/26)
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- 1-PHENETHYLPIPERIDINE DERIVATIVES AND THEIR USE AS OPIOID RECEPTOR LIGANDS
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This invention relates to novel 1-phenethylpiperidine derivatives of formuia (I) useful as opioid receptor ligands. More specifically, the invention provides compounds useful as μ opioid receptor ligands. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of pain, and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 15
(2010/11/28)
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- Synthesis of diarylazepan-4-ones
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Synthesis of several 3,3-diarylazepan-4-ones and 5,5-diarylazepan-4-ones has been established starting from two tetrasubstituted olefins, which is derived from commercially available piperidine-3-carboxylic acid ethyl ester and piperidine-4-carboxylic aci
- Chang, Meng-Yang,Kung, Yung-Hua,Ma, Chih-Chong
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p. 199 - 202
(2007/10/03)
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- 4-SUBSTITUTED PIPERIDINE DERIVATIVES
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Substituted piperidine compounds represented by the structure I are provided, wherein each of Rla, R1b, R1c, R1d, Rle, R1f, R1g, R1h, R2, R2A, R3, R4, A, X, a, x, and n is as defined in the specification. Substituted piperidine compounds of structure I may permeate or penetrate across a nerve cell membrane into the interior of a nerve cell, may inhibit intracellular Rho kinase enzyme found in nerve cells in mammals, and may find utility in repair of damaged nerves in the central and peripheral nervous system of such mammals. These compounds may induce the regeneration or growth of neurites in mammalian nerve cells and may thereby induce regeneration of damaged or diseased nerve tissue. These compounds also find additional utility as antagonists of the enzyme Rho kinase in treatment of disease states in which Rho kinase is implicated. Pharmaceutical compositions containing these substituted piperidine compounds may be useful to promote neurite growth and in the treatment of diseases in which Rho kinase inhibition is indicated.
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Page/Page column 131
(2008/06/13)
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- Synthesis and structure-activity relationships of novel selective factor Xa inhibitors with a tetrahydroisoquinoline ring
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A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were designed and synthesized. Among these derivatives, compounds 1 and 2 exhibited potent inhibitory activity against factor Xa (FXa) and good selectivity with respect to other serine
- Ueno, Hiroshi,Yokota, Katsuyuki,Hoshi, Jun-Ichi,Yasue, Katsutaka,Hayashi, Mikio,Hase, Yasunori,Uchida, Itsuo,Aisaka, Kazuo,Katoh, Susumu,Cho, Hidetsura
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p. 3586 - 3604
(2007/10/03)
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- Mild and chemoselective deacetylation method using a catalytic amount of acetyl chloride in methanol
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Efficient deacetylation of alcohol acetates under mild acidic conditions was accomplished with a catalytic amount of acetyl chloride in methanol. Acetates of various primary, secondary, aromatic and sugar alcohols were successfully deprotected. Highly chemoselective removal of acetyl groups in presence of other commonly employed esters was also achieved in excellent yields. The reactivity of this transesterification-mediated deacetylation was found to be directly dependent upon the electronic and steric nature of the acetates. Georg Thieme Verlag Stuttgart.
- Yeom, Chang-Eun,Lee, So Young,Kim, Young Jong,Kim, B. Moon
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p. 1527 - 1530
(2007/10/03)
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- NOVEL ANTIDIABETIC COMPOUNDS HAVING HYPOLIPIDAEMIC, ANTIHYPERTENSIVE PROPERTIES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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New thiazolidin-2,4-dione derivatives of formula (1) in which A, W, Q, B, D, X, Y, Z, R', k and p are defined as in claim 1; their tautomeric forms, their derivatives, their steroisomers, their polymorphs, their pharmaceutical acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. Methods for their preparation and their use as antidiabetic compounds are claimed.
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- QUINOLINE DERIVATIVES AS ANTIBACTERIALS
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A method of treatment of bacterial infections in mammals, particularly in man, which method comprises the administration to a mammal in need of such treatment of an effective amount of a quinoline of formula (I) or a pharmaceutically acceptable derivative thereof wherein: n is 0, 1 or 2; A is NR, O, S(O)x or CRR and B is NR, O, S(O)x or CRR where x is 0, 1 or 2 novel quinolines for use in the method.
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- Pyridyl-containing spirocyclic compounds as inhibitors of fibrinogen-dependent platelet aggregation
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Disclosed are certain substituted or unsubstituted pyridyl-containing spirocyclic compounds substituted with both basic and acidic functionality, which are useful in inhibiting platelet aggregation, inhibiting the binding of fibrinogen to blood platelets, and preventing or treating thrombosis
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- Amidine compounds
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A compound of the formula [I] wherein R1, R2and R3are the same or different and each is hydrogen atom, wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof. The compound of the presen
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- Nitric oxide donors, compositions and methods of use related applications
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The invention describes novel nitric oxide donors and novel compositions comprising at least one nitric oxide donor. The invention also provides novel compositions comprising at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating cardiovascular diseases, for the inhibition of platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune, inflammatory, proliferative, hyperproliferative, vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering the nitric oxide donor optionally in combination with at least one therapeutic agent. The invention also provides methods for treating inflammation, pain, fever, gastrointestinal disorders, respiratory disorders and sexual dysfunctions. The nitric oxide donors donate, transfer or release nitric oxide, and/or elevate endogenous levels of endothelium-derived relaxing factor, and/or stimulate endogenous synthesis of nitric oxide and/or are substrates for nitric oxide synthase and are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions. The therapeutic agent can optionally be substituted with at least one NO and/or NO2 group (i.e., nitrosylated and/or nitrosated). The invention also provides novel compositions and kits comprising at least one nitric oxide donor and/or at least one therapeutic agent.
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- Pyrrolidine modulators of chemokine receptor activity
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The present invention is directed to pyrrolidine compounds of the formula 1: (wherein R1, R2, R3, R4, R5, R6and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
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- Synthesis of diaminobutane derivatives as potent Ca2+-permeable AMPA receptor antagonists
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We synthesized diaminobutane derivatives as potent Ca2+-permeable AMPA receptor antagonists with non-hypotensive activity. Compound 10c showed selective Ca2+-permeable AMPA receptor antagonist activity and neuroprotective effects in transient global ischemia models in gerbils.
- Yoneda, Yoshiyuki,Kawajiri, Shinichi,Sugimura, Masunobu,Osanai, Ken,Kito, Fusako,Ota, Emi,Mimura, Tetuya
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p. 2663 - 2666
(2007/10/03)
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- Phosphonic acid derivatives
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A phosphonic acid derivative which is useful for medically treating hyperlipemia, represented by the following general formula (I) or a pharmacologically acceptable salt thereof: STR1 Representative example of the compound according to the present invention is one represented by the following formula: STR2
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- 2-SACCHARINYLMETHYL ARYL CARBOXYLATES USEFUL AS PROTEOLYTIC ENZYME INHIBITORS AND COMPOSITIONS AND METHOD OF USE THEREOF
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A compound having the formula: STR1 wherein Ar, R 4 and R 5 are defined herein have pharmaceutical utility as proteolytic enzyme inhibitors.
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- Pyridine compounds which are useful as anti-arrhythmic agents
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A series of novel aryloxyalkylamino- and arylaminoalkylamino-pyridine and imidazole compounds have been prepared, including their pharmaceutically acceptable salts, wherein the aryl moiety is further substituted by a sulphamoyl or sulphonylamino group or
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