- 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; 00597
(2020/07/04)
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- Drastic fluorine effect: Complete reversal of the selectivity in the Au-catalyzed hydroalkoxylation reaction of fluorinated haloalkynes
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The gold-catalyzed hydration reaction of haloalkynes is highly regioselective producing 2-halomethylketones as the sole products. Herein, we document a drastic fluorine effect where the reaction of 1-halo-3,3-difluoroalkynes as substrates leads to a complete reversal of selectivity and produces 3,3-difluoroesters as the unique products.
- Cloutier, Mélissa,Mamone, Marius,Paquin, Jean-Fran?ois
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supporting information
p. 5969 - 5972
(2020/06/04)
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- Ugi-type reactions of spirocyclic indolenines as a platform for compound library generation
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A simple and efficient method for the synthesis of highly substituted spiroindoline derivatives is presented. A Fischer indolization is combined with Ugi-type reactions to explore the chemical space concerning this privileged structure. Moreover, spiropip
- Estévez, Verónica,Kloeters, Laura,Kwietniewska, Natalia,Vicente-García, Esther,Ruijter, Eelco,Orru, Romano V.A.
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supporting information
p. 376 - 380
(2017/02/10)
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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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p. 9830 - 9836
(2017/12/08)
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- SULFONAMIDE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 0244
(2016/02/16)
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- RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 0375
(2015/09/28)
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- 7-HYDROXY-SPIROPIPIPERIDINE INDOLINYL ANTAGONISTS OF P2Y1 RECEPTOR
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The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are antagonists of Ρ2Y1 receptor and may be used as medicaments in the treatment and/or prophylaxis of thromboembolic disorders.
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Paragraph 00158
(2014/02/16)
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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; 21
(2014/05/24)
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- 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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p. 661 - 664
(2012/07/03)
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- Substituted Disulfonamide Compounds
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Substituted disulfonamide compounds corresponding to formula I: In which R1, R2, R3, R4a, R4b, R5a, R5b, R8, R9a, R9b, R10, R11, a, b, s, t and A have defined meanings, pharmaceutical compositions containing one or more such compounds, processes for preparing such compounds, and a method of using such compounds for the treatment or inhibition of pain and/or other conditions mediated by the bradykinin receptor 1 (BR1).
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Page/Page column 31
(2010/06/22)
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- Substituted Pyrimidine and Triazine Compounds
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Substituted pyrimidine and triazine compounds corresponding to formula I wherein R1, R2, R3, R4a, R4b, R5a, R5b, R7, R8, R9a, R9b, R10, R11, A, a, b, s, t, V, W1, W2 and W3 have defined meanings, pharmaceutical compositions comprising such compounds, a process for preparing such compounds, and the use of such compounds and compositions to treat or inhibit pain and/or other disorders or disease states.
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Page/Page column 60
(2010/07/10)
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- Substituted Indole Compounds
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Substituted indole compounds corresponding to the formula I: In which R8, R9a, R9b, R10, R11, R200, R210, A, D, T, q, s and t have defined meanings, processes for the preparation thereof, pharmaceutical compositions containing such compounds and the use of substituted indole compounds for the treatment or inhibition of pain and other conditions which are at least partly mediated by Bradykinin 1 receptors (B1R).
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Page/Page column 57
(2010/09/07)
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- Substituted Spiroamide Compounds
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Substituted spiroamide compounds corresponding to formula (I): wherein A, B, Q1, Q2, Q3, Q4, R1, R8, R9a, R9b, R12, R13, R200 and R210 have defined meanings, processes for their preparation, pharmaceutical compositions containing such compounds, and the use of such compounds for treating or inhibiting pain or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).
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Page/Page column 41
(2010/09/18)
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- Substituted Spiro-amide Compounds
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Substituted spiro-amide compounds corresponding to formula I in which R5 through R8, D, X, Y and Z have defined meanings, processes for preparing such spiro-amide compounds, pharmaceutical compositions containing such compounds, and methods of using such spiro-amide compounds for treating and/or inhibiting disorders or disease states mediated at least in part by the bradykinin 1 receptor.
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Page/Page column 120
(2010/10/19)
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- SUBSTITUTED BENZIMIDAZOLES, BENZOTHIAZOLES AND BENZOXAZOLES
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The present invention relates to substituted benzimidazoles, benzothiazoles and benzoxazoles, processes for their preparation, medicaments containing these compounds and the use of these compounds for the preparation of medicaments.
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Page/Page column 143
(2010/12/29)
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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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- 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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- 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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- MODULATORS OF HCV REPLICATION
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The present invention is directed to the use of certain 2,4,5-trisubstituted imidazole derivatives in modulating the replication of Hepatitis C virus RNA and/or virus production in cells.
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Page/Page column 7
(2008/06/13)
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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 131-132
(2008/06/13)
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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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- Aryl and biaryl piperidines with MCH modulatory activity
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In one embodiment, this invention provides a novel class of compounds as antagonists of the MCH receptor, methods of preparing such compounds, pharmaceutical compositions containing one or more of the compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention or amelioration or one or more of diseases associated with the MCH receptor. An illustrative inventive compound is shown below: 1
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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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- Synthesis of the orally active spiroindoline-based Growth Hormone Secretagogue, MK-677
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The preparation of the Merck Growth Hormone Secretagogue; MK-677 is described. A Fischer indole/reduction based strategy provides the novel spiroindoline nucleus of this potent compound. This optimized sequence necessitates the isolation of only one intermediate 10 and provides MK-677 in 48% overall yield from isonipecotic acid 3.
- Maligres, Peter E.,Houpis, Ioannis,Rossen, Kai,Molina, Audrey,Sager, Jess,Upadhyay, Veena,Wells, Kenneth M.,Reamer, Robert A.,Lynch, Joseph E.,Askin, David,Volante,Reider, Paul J.,Houghton, Peter
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p. 10983 - 10992
(2007/10/03)
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- Indole and indazole derivatives, for the treatment and prophylaxis of cerebral disorders, their preparation and their use
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Compounds of formula (I) : [in which R1 and R2 are each hydrogen or various organic groups, pis 0, 1, 2 or 3, U is -CO- or -CH(OR3)- where R3 is hydrogen or a hydroxy-protecting group, V is an optionally unsaturated aliphatic hydrocarbon group and W is a nitrogen-containing group] are useful in the treatment and prophylaxis of dementia especially of the Alzheimer's type.
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- Analogues of the low-efficacy partial GABAA agonist 4-PIOL. Syntheses and in vitro pharmacological studies
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4-PIOL (3-hydroxy-5-(4-piperidyl)isoxazole) is a low-efficacy GABAA agonist showing a dominating GABAA antagonist profile.Three dihydro analogues of 4-PIOL were synthesized, including (RS)-3-hydroxy-5-(4-piperidyl)-2-isoxazoline (1).The synthesis of 1 was based on a regioselective 1,3-dipolar cyclo-addition reaction between 1-benzyloxycarbonyl-4-vinylpiperidine (7) and bromonitrile oxide, prepared in situ from dibromoformoxime.Furthermore, the spiro analogues of 1 3-hydroxy-1-oxa-2,8-diazaspirodec-2-ene (2) and (RS)-3-hydroxy-1-oxa-2,7-diazaspirodec-2-ene (3) were synthesized regiospecifically via cycloaddition of bromonitrile oxide to the N-benzyloxycarbonyl-protected forms of 4-methylenepiperidine (11) and 3-methylenepiperidine (15) respectively.In contrast to 4-PIOL, none of the new compounds 1-3 showed detectable effects on the binding of 3H-GABAA or the subunit-selective GABAA agonist, 3H-THIP, to GABAA receptor sites, and they did not significantly affect the muscimol-stimulated binding of 3H-diazepam to the benzodiazepine site of the GABAA receptor complex.
- Amici, M De,Froelund, B,Hjeds, H,Krogsgaard-Larsen, P
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p. 625 - 631
(2007/10/02)
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