- Cholesteryl ester transfer protein (CETP) inhibitors based on cyclic urea, bicyclic urea and bicyclic sulfamide cores
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Cholesteryl ester transfer protein (CETP) inhibitors reduce the transfer of cholesteryl esters from the high-density lipoprotein (HDL-C) to apolipoprotein such as VLDL/LDL, with exchange of triglycerides. Thus, this inhibition increases the HDL-C levels, which is believed to lower the risk for heart disease and stroke. We report here a series of CETP inhibitors based on the cyclic, bicyclic urea and sulfamide cores. These CETP inhibitors exemplified by 15, 31, and 45 demonstrated in vitro potency in inhibiting the CETP transfer activity, and 15, 31 showing in vivo efficacy to increase HDL-C levels in cynomolgus-CETP transgenic mice. The synthesis and biological evaluations of these CETP inhibitors are described.
- Liu, Jian,Shao, Patrick P.,Guiadeen, Deodial,Krikorian, Arto,Sun, Wanying,Deng, Qiaolin,Cumiskey, Anne-Marie,Duffy, Ruth A.,Murphy, Beth A.,Mitra, Kaushik,Johns, Douglas G.,Duffy, Joseph L.,Vachal, Petr
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- Luminescent tungsten(vi) complexes as photocatalysts for light-driven C-C and C-B bond formation reactions
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The realization of photocatalysis for practical synthetic application hinges on the development of inexpensive photocatalysts which can be prepared on a large scale. Herein an air-stable, visible-light-absorbing photoluminescent tungsten(vi) complex which can be conveniently prepared at the gram-scale is described. This complex could catalyse photochemical organic transformation reactions including borylation of aryl halides, such as aryl chloride, reductive coupling of benzyl bromides for C-C bond formation, reductive coupling of phenacyl bromides, and decarboxylative coupling of redox-active esters of alkyl carboxylic acid with high product yields and broad functional group tolerance.
- Chan, Kaai-Tung,Che, Chi-Ming,Du, Lili,Liu, Yungen,Phillips, David Lee,To, Wai-Pong,Tong, Glenna So Ming,Wu, Liang-Liang,Yu, Daohong
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p. 6370 - 6382
(2020/07/15)
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- Visible-light-mediated borylation of aryl and alkyl halides with a palladium complex
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Palladium catalyzed visible-light-mediated borylation of inactivated aryl and alkyl halides is reported; the method provided high yields and excellent functional group compatibility. Furthermore, arylsilicates were synthesized selectively using dimethylphenylsilyl boronic ester via changing the reaction conditions. Finally, the possible reaction mechanism is determined through fluorescence quenching and turn on/off experiments.
- Zhao, Jia-Hui,Zhou, Zhao-Zhao,Zhang, Yue,Su, Xuan,Chen, Xi-Meng,Liang, Yong-Min
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supporting information
p. 4390 - 4394
(2020/10/20)
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- CANCER TREATMENTS TARGETING CANCER STEM CELLS
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Disclosed are compounds, methods, compositions, and kits that allow for treating cancer by, e.g., targeting cancer stem cells. In some embodiments, the cancer is colorectal cancer, gastric cancer, gastrointestinal stromal tumor, ovarian cancer, lung cancer, breast cancer, pancreatic cancer, prostate cancer, testicular cancer, or lymphoma. In some embodiments, the cancer is liver cancer, endometrial cancer, leukemia, or multiple myeloma. The compounds utilized in the disclosure are of Formula (0), (O'), and (I):
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Paragraph 0331; 0376-0377; 0605-0607
(2019/11/19)
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- Reversible Covalent End-Capping of Collagen Model Peptides
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The combination of supramolecular aggregation of collagen model peptides with reversible covalent end-capping of the formed triple helix in a single experimental set-up yielded minicollagens, which were characterized by a single melting temperature. In spite of the numerous possible reaction intermediates, a specific synthetic collagen with a leading, middle and trailing strand is formed in a highly cooperative self-assembly process.
- Priem, Christoph,Geyer, Armin
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supporting information
p. 14278 - 14283
(2019/11/03)
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- Small molecule compound
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The invention provides a small molecular compound, The small molecular compound is characterized by having a structure as shown in the following molecular general formula, wherein X1 and X2 are selected from carbon or nitrogen, G1 is a carbon ring or a heterocyclic ring with aromaticity, any one or more hydrogen atoms on the G1 ring are substituted by R1, wherein R1 is selected from nitrogen-containing groups. The small molecule compound can be used as an efficient and specific JAK kinase inhibitor, especially a Tyk2 inhibitor, and/or a JAK1 inhibitor, and/or a JAK1/Tyk2 dual inhibitor, or a Tyk2/JAK1 dual inhibitor or a Tyk2/Jak2 dual inhibitor.
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Paragraph 0395-0396; 0397-0398
(2020/01/12)
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- Diverse Multi-Functionalized Oligoarenes and Heteroarenes for Porous Crystalline Materials
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A modular synthesis of multi-functionalized biphenyl, terphenyl and higher linear oligophenylene dicarboxylic acids and pyridine-terminated oligoarenes by stepwise palladium–catalyzed borylation/Suzuki–Miyaura cross-coupling reactions is described. The presence of several distinct functional groups such as azide, hydroxy, and alkyne, as well as coordinative functional end groups (carboxylic acid or pyridine) combined in a single oligoarene molecular unit at strategic positions offer an advantageous dual-utility. First, these compounds can serve as useful molecular bricks (ditopic organic linkers) in the construction of complex porous crystalline materials. Second, after the assembly into the crystalline coordination networks, orthogonal functional sites within the linker-backbone offer tremendous potential from application perspectives as they can be modified by a wide range of post-synthetic modifications including azide–alkyne click chemistry. This allows further tailoring of the supramolecular assemblies to yield novel multifunctional materials.
- Grosjean, Sylvain,Hassan, Zahid,W?ll, Christof,Br?se, Stefan
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p. 1446 - 1460
(2018/10/24)
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- Porphyrin sensitizers containing an auxiliary benzotriazole acceptor for dye-sensitized solar cells: Effects of steric hindrance and cosensitization
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Dye-sensitized solar cells (DSSCs) have attracted intensive attention in developing photovoltaic devices for employing solar energy. For developing panchromatic and efficient porphyrin sensitizers, it has been demonstrated to be an effective approach to i
- Song, Heli,Tang, Weiqiang,Zhao, Shuangliang,Liu, Qingyun,Xie, Yongshu
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p. 323 - 331
(2018/04/12)
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- Self-assembly of peptide boroxoles on cis-dihydroxylated oligoamide templates in water
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We develop templates that can be used to stabilize consistent oligomers of a bioactive peptide. In the present study, we synthesize oligomers of an antibody epitope from the amyloidogenic prion protein. Dynamic covalent chemistry is the basis for the spontaneous condensation of 2, 3, 4 or 6 peptides with qualified polyol templates presenting the required number of bioorthogonal ligation sites. To study this process in aqueous solution, the N-terminal amino acid of a 13-mer peptide is first acylated with 4-carboxy-benzoboroxole (1-hydroxy-1,3-dihydrobenzo[c][1,2] oxaborole-5-carboxylic acid) and then mixed with the template to obtain self-assembled miniamyloids of specified degree of oligomerization. The template is assembled from bicyclic dipeptides of alternating d- and l-stereochemistry. The cis-diol group of this dipeptide hot=Tap (hot: d-hydroxythreonine, Tap: l-thiaproline) has sufficiently high affinity for boroxoles in water. A single N3-hot=Tap-OMe dipeptide template forms a 1?:?1 complex with 4-carboxy-benzoboroxole with excellent diastereoselectivity. The oligomeric template N3-(hot=Tap)n-OMe (n?=?2, 3, 4 or 6) presents a regular pattern of 2, 3, 4 or 6 cis-diol groups for the spontaneous esterification with the same number of boronic acids. Nuclear magnetic resonance identifies the homogenous regioselectivity and stereoselectivity of this ligation process. The combination of electron-poor benzoboroxoles with this optimized cis-diol template allows for the complete ligation under high-dilution conditions in water with only 1.3 equivalents of peptide-boroxole per diol functionality. Copyright
- Wuttke, André,Geyer, Armin
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p. 549 - 555
(2017/08/15)
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- MOLECULAR GAUGE BLOCKS FOR BUILDING ON THE NANOSCALE
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Disclosed herein is a way to produce a series of discrete sized slender, rigid oligoparaxylene molecules ranging from 1-5 nm in length. Molecules, based on 1-7, 9-11 paraxylene rings, have been synthesized as part of a homologous series of oligoparaxylenes (OPXs) with a view to providing a molecular tool box for the construction of nano architectures—such as spheres, cages, capsules, metal-organic frameworks (MOFs), metal-organic polyhedrons (MOPs) and covalent-organic frameworks (COFs), to name but a few—of well-defined sizes and shapes. Twisting between the planes of contiguous paraxylene rings is generated by the steric hindrance associated with the methyl groups and leads to the existence of soluble molecular gauge blocks without the need—at least in the case of the lower homologues—to introduce long aliphatic side chains onto the phenylene rings in the molecules.
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Paragraph 0033; 0083
(2013/05/22)
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- Giving substance to the Losanitsch series
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A series of oligoparaxylene model compounds with two to six paraxylene units was synthesised and the resulting mixtures of atropisomers with one to five axes of chirality were analysed by dynamic 1H NMR spectroscopy. The number of atropisomers was found to constitute part of the Losanitsch series. The Royal Society of Chemistry 2012.
- Grunder, Sergio,Stoddart, J. Fraser
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supporting information; experimental part
p. 3158 - 3160
(2012/04/17)
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- Molecular gauge blocks for building on the nanoscale
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Molecular gauge blocks, based on 1-7, 9-11 paraxylene rings, have been synthesized as part of a homologous series of oligoparaxylenes (OPXs) with a view to providing a molecular tool box for the construction of nano architectures-such as spheres, cages, capsules, metal-organic frameworks (MOFs), metal-organic polyhedrons (MOPs) and covalent-organic frameworks (COFs), to name but a few-of well-defined sizes and shapes. Twisting between the planes of contiguous paraxylene rings is generated by the steric hindrance associated with the methyl groups and leads to the existence of soluble molecular gauge blocks without the need, at least in the case of the lower homologues, to introduce long aliphatic side chains onto the phenylene rings in the molecules. Although soluble molecular gauge blocks with up to seven consecutive benzenoid rings have been prepared employing repeating paraxylene units, in the case of the higher homologues it becomes necessary to introduce hexyl groups instead of methyl groups onto selected phenylene rings to maintain solubility. A hexyl-doped compound with seven substituted phenylene rings was found to be an organogelator, exhibiting thermally reversible gelation and a critical gelation concentration of 10 mM in dimethyl sulfoxide. Furthermore, control over the morphology of a series of hexyl-doped OPXs to give microfibers, microaggregates, or nanofibers, was observed as a function of their lengths according to images obtained by scanning electron microscopy. The modular syntheses of the paraphenylene derivatives rely heavily on Suzuki-Miyaura cross-coupling reactions. The lack of π-π conjugation in these derivatives that is responsible for their enhanced solubilities was corroborated by UV/Vis and fluorescent spectroscopy. In one particular series of model OPXs, dynamic 1H NMR spectroscopy was used to probe the stereochemical consequences of having from one up to five axes of chirality present in the same molecule. The Losanitsch sequence for the compounds with 1-3 chiral axes was established, and a contemporary mathematical way was found to describe the sequence. The development of the ways and means to make molecular gauge building blocks will have positive repercussions on the control of nanostructures in general. Their incorporation into extended structures with the MOF-74 topology provides an excellent demonstration of the potential usefulness of these molecular gauge blocks. Walking along a fine line: The synthesis and characterization of a series of high-aspect-ratio oligoparaxylenes as molecular gauge blocks are reported. The lengths of the molecules range from 10 A? for the shortest member of the series with two phenylene rings up to 50 A? for the longest member with eleven phenylene units (see figure). Minimalistic design criteria led to a walk along a fine line between keeping the molecules slender, yet also rendering them soluble. Copyright
- Grunder, Sergio,Valente, Cory,Whalley, Adam C.,Sampath, Srinivasan,Portmann, Jürg,Botros, Youssry Y.,Stoddart, J. Fraser
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p. 15632 - 15649
(2013/01/16)
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- OXADIAZOLE DIARYL COMPOUNDS
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The invention relates to compounds of formula (I): wherein R1, R2, Ra , Rb,Rc and W, have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.
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Page/Page column 74
(2009/05/29)
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- 7-SUBSTITUTED INDOLE MCL-1 INHIBITORS
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Compounds which inhibit the activity of anti-apoptotic Mcl-1 protein, compositions containing the compounds, and methods of treating diseases involving overexpressed or unregulated Mcl-1 protein are disclosed
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Page/Page column 152
(2008/12/08)
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- Discovery of a novel series of biphenyl benzoic acid derivatives as potent and selective human β3-adrenergic receptor agonists with good oral bioavailability. Part I
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A novel class of biphenyl analogues containing a benzoic acid moiety based on lead compound 8i have been identified as potent and selective human β3 adrenergic receptor (β3-AR) agonists with good oral bioavailability and long plasma half-life. After further substituent effects were investigated at the terminal phenyl ring of lead compound 8i, we have discovered that more lipophilic substitution at the R position improved potency and selectivity. As a result of these studies, 10a and 10e were identified as the leading candidates with the best balance of potency, selectivity, and pharmacokinetic profiles. In addition, compounds 10a and 10e were evaluated to be efficacious for a carbachol-induced increase of intravesical pressure, such as an overactive bladder model in anesthetized dogs. This represents the first demonstrated result dealing with β3- AR agonists.
- Imanishi, Masashi,Tomishima, Yasuyo,Itou, Shinji,Hamashima, Hitoshi,Nakajima, Yutaka,Washizuka, Kenichi,Sakurai, Minoru,Matsui, Shigeo,Imamura, Emiko,Ueshima, Koji,Yamamoto, Takao,Yamamoto, Nobuhiro,Ishikawa, Hirofumi,Nakano, Keiko,Unami, Naoko,Hamada, Kaori,Matsumura, Yasuhiro,Takamura, Fujiko,Hattori, Kouji
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p. 1925 - 1944
(2008/12/20)
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- Amine Compounds
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There is provided a compound exhibiting an activity of suppressing immune response with reduced adverse drug reactions, which compound is useful in the chemotherapy for preventing or treating, for example, a wide range of various autoimmune diseases including systemic erythematodes, chronic rheumatoid arthritis, Type I diabetes, inflammatory bowel disease, biliary cirrhosis, uveitis, multiple sclerosis or other disorders, or chronic inflammatory diseases, or cancers, lymphoma or leukemia, or resistance to organ or tissue transplantation or rejection against transplantation. Novel amine compounds having an S1P1/Edg1 receptor agonist effect, possible stereoisomers or racemic bodies of the compounds, or pharmacologically acceptable salts, hydrates or solvates of the compound, the stereoisomers or the racemic bodies, or prodrugs of the compounds, the stereoisomers, the racemic bodies, the salts, the hydrates or the solvates, are provided.
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Page/Page column 179
(2008/12/08)
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- CETP INHIBITORS
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Compounds having the structure of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compounds of Formula (I), B is a cyclic group other than phenyl, and B has a cyclic substituent at a position that is ortho to the position at which B is connected to the remainder of the structure of Formula (I). The 5-membered ring of Formula (I) has a second cyclic substituent in addition to B.
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Page/Page column 106-107
(2008/06/13)
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- CETP INHIBITORS
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Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. The compounds have 3 cyclic groups connected by single bonds, as for example triphenyl, which are attached directly to the ring of formula I or attached at the position B.
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Page/Page column 53
(2008/06/13)
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- NOVEL THIOPHENE AMIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATING COMPLEMENT-MEDIATED DISEASES AND CONDITIONS
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Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula (I) or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4 and R7 are defined in the specification, Z is SO or SO2, and Ar is an aromatic or heteroaromatic group as defined herein.
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Page 300-301
(2010/02/05)
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- An improved preparation of arylboronates: Application in one-pot Suzuki biaryl synthesis
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We have developed a modification of the Miyaura arylboronate synthesis1a by substituting a ligandless palladium catalyst for PdCl2(dppf). Palladium acetate, free of ligand, was found highly effective for such coupling reactions. This modified procedure is advantageous over the original Miyaura synthesis in ease of workup, catalyst removal, and low catalyst cost. Furthermore, the boronates formed in this manner can be used directly for Suzuki coupling reactions in a one-pot fashion. The biaryl products have improved impurity profiles and reduced heavy metal contamination.
- Zhu, Lei,Duquette, Jason,Zhang, Mingbao
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p. 3729 - 3732
(2007/10/03)
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- Novel cyclohexenyl phenyl diazepines vasopressin and oxytocin receptor modulators
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The present invention provides novel tricyclic diazepine compounds and methods and pharmaceutical compositions utilizing them for the treating or preventing disorders including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleedi
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