- Large-Scale Synthesis and Modifications of Bicyclo[1.1.1]pentane-1,3-dicarboxylic Acid (BCP)
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In flow photochemical addition of propellane to diacetyl allowed construction of the bicyclo[1.1.1]pentane (BCP) core in a 1 kg scale within 1 day. Haloform reaction of the formed diketone in batch afforded bicyclo[1.1.1]pentane-1,3-dicarboxylic acid in a
- Ripenko, Vasyl,Vysochyn, Daniil,Klymov, Ivan,Zhersh, Serhii,Mykhailiuk, Pavel K.
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p. 14061 - 14068
(2021/07/20)
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- SUBSTITUTED BICYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
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Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein Q is C2-6 alkenyl or C2-6 alkynyl, each substituted with zero to 2 R1; and the other variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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Page/Page column 220-222
(2020/08/28)
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- CYCLOBUTYL CARBOXYLIC ACIDS AS LPA ANTAGONISTS
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The present invention provides compounds of Formula (I): (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.
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Page/Page column 140
(2021/01/22)
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- NLRP3 MODULATORS
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The present invention provides compounds of Formula (I): (I) wherein all of the variables are as defined herein. These compounds are modulators of NLRP3, which may be used as medicaments for the treatment of proliferative disorders, such as cancer in a subject (e.g., a human).
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Page/Page column 110-111
(2020/07/31)
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- A DNA toxicity dimer compound (by machine translation)
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The invention discloses a DNA toxicity dimer compound, with the previous technology disclosed benzo hypnotic benzodiazepines compared with the conjugates, the cytotoxic compound display much higher in vivo therapeutic index (the maximum tolerance dose and the lowest effective dose of ratio). (by machine translation)
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Paragraph 0077-0079
(2019/01/22)
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- Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry
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Syntheses of bicyclo[1.1.1]pentane-derived azides and terminal alkynes – interesting substrates for click reactions – are described. With a few exceptions, these compounds were prepared in two or three steps starting from common synthetic intermediates – the corresponding carboxylic acids. The key step in the synthesis of 1-azidobicyclo[1.1.1]pentanes is a copper-catalysed diazo-transfer reaction with imidazole-1-sulfonyl azide. The preparation of bicyclo[1.1.1]pentyl-substituted alkynes relies on a Seyferth–Gilbert homologation with dimethyl 1-diazo-2-oxopropylphosphonate (Ohira–Bestmann reagent). Both types of target compounds were found to be suitable substrates for click reactions, and thus they are promising building blocks for medicinal, combinatorial and bioconjugate chemistry. A practically important side result of this study was a multigram preparation of Boc-monoprotected 1,3-diaminobicyclo[1.1.1]pentane – a representative bicyclic conformationally restricted diamine derivative.
- Kokhan, Serhii O.,Valter, Yevheniia B.,Tymtsunik, Andriy V.,Komarov, Igor V.,Grygorenko, Oleksandr O.
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p. 6450 - 6456
(2017/12/01)
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- HETEROARYL DERIVATIVES AS SEPIAPTERIN REDUCTASE INHIBITORS
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Inhibitors of sepiapterin reductase of formula (I) or (I'), wherein the substituents are defined as in the claims, and uses of sepiapterin reductase inhibitors in analgesia, treatment of acute and chronic pain, anti-inflammation, and immune cell regulation are disclosed.
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Paragraph 001004-00106
(2017/05/31)
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- METHOD OF PREPARING SUBSTITUTED BICYCLO[1 1 1]PENTANES
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The invention relates to a new and efficient process for the preparation of a class of molecules, namely bicyclo[1.1.1]pentanes and derivatives thereof by reaction of [1.1.1]propellane with a variety of reagents under irradiation and/or in the presence of radical initiators to obtain bicyclo[1.1.1]pentanes asymmetrically substituted at position 1 and 3, which are useful as intermediates for the preparation of asymmetrically 1,3-disubstituted bicyclo[1.1.1]pentane derivatives and various physiologically active substances or materials containing these structures.
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Page/Page column 27
(2017/10/11)
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- COMPOUNDS
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The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example Alzheimer's disease.
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Page/Page column 171; 172
(2016/02/12)
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- Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring bioisostere in the design of a potent and orally active γ-secretase inhibitor
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Replacement of the central, para-substituted fluorophenyl ring in the γ-secretase inhibitor 1 (BMS-708,163) withthe bicyclo[1.1.1]pentane motif led to the discovery of compound 3, an equipotent enzyme inhibitor with significant improvements in passive permeability and aqueous solubility. The modified biopharmaceutical properties of 3 translated into excellent oral absorption characteristics (~4-fold Cmax and AUC values relative to 1) in a mouse model of γ-secretase inhibition. In addition, SAR studies into other fluorophenyl replacements indicate the intrinsic advantages of the bicyclo[1.1.1]pentane moiety over conventional phenyl ring replacements with respect to achieving an optimal balance of properties (e.g., γ-secretase inhibition, aqueous solubility/permeability, in vitro metabolic stability). Overall, this work enhances the scope of the [1.1.1]-bicycle beyond that of a mere spacer unit and presents a compelling case for its broader application as a phenyl group replacement in scenarios where the aromatic ring count impacts physicochemical parameters and overall drug-likeness.
- Stepan, Antonia F.,Subramanyam, Chakrapani,Efremov, Ivan V.,Dutra, Jason K.,O'Sullivan, Theresa J.,Dirico, Kenneth J.,McDonald, W. Scott,Won, Annie,Dorff, Peter H.,Nolan, Charles E.,Becker, Stacey L.,Pustilnik, Leslie R.,Riddell, David R.,Kauffman, Gregory W.,Kormos, Bethany L.,Zhang, Liming,Lu, Yasong,Capetta, Steven H.,Green, Michael E.,Karki, Kapil,Sibley, Evelyn,Atchison, Kevin P.,Hallgren, Andrew J.,Oborski, Christine E.,Robshaw, Ashley E.,Sneed, Blossom,O'Donnell, Christopher J.
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supporting information; experimental part
p. 3414 - 3424
(2012/06/01)
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- 3-Aminobicyclo[1.1.1]pentane-1-carboxylic Acid Derivatives: Synthesis and Incorporation into Peptides
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We have developed an efficient synthesis of derivatives of 3-aminobicyclo[1.1.1]pentane-1-carboxylic acid (7, 8, 9, and 10) starting from [1.1.1]propellane (3). These rigid analogues of γ-aminobutyric acid have been incorporated into linear and cyclic peptides using solution chemistry and solid-phase techniques. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Paetzel, Michael,Sanktjohanser, Maximilian,Doss, Alexander,Henklein, Peter,Szeimies, Guenter
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p. 493 - 498
(2007/10/03)
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- Synthesis and biological evaluation of 2-(3′-(1H-tetrazol-5-yl)bicyclo[1.1.1]pent-1-yl)glycine (S-TBPG), a novel mGlu1 receptor antagonist
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The design and synthesis of 2-(3′-(1H-tetrazol-5-yl)bicyclo[1.1.1]pent-1-yl)glycine (S-TBPG), a novel mGluR1 antagonist is reported. S-TBPG is characterized by the bioisosteric replacement of the distal carboxy group of 2-(3′-carboxybicyclo[1.1.1]pent-1-yl)glycine (S-CBPG) by a tetrazolyl moiety. Despite a moderate reduction in potency, S-TBPG is a selective mGluR1 antagonist (69 μM), with no activity at other mGluR subtypes. The interesting biological profile of S-TBPG, coupled with its peculiar chemical structure, is discussed in terms of the structure-activity relationship (SAR) of mGluR1 antagonists.
- Costantino, Gabriele,Maltoni, Katiuscia,Marinozzi, Maura,Camaioni, Emidio,Prezeau, Laurent,Pin, Jean-Philippe,Pellicciari, Roberto
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p. 221 - 227
(2007/10/03)
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- Compounds and methods based on [1.1.1]propellane
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Molecular bulding beams, liquid crystals, and surfactants in the form of compounds based on [1.1.1]propellane, including poly[1.1.1]propellanes. Molecular building beams having a telomeric or polymeric chain staff, and linking groups functionalized on one or both ends of the staff. A system for linking the beams to connecting units to construct molecular structures of various forms, such as whips, combs, scaffoldings, nets, or stars. Other broad aspects of the invention provide liquid crystals and surfactants. The liquid crystals include telomeric or polymeric compounds functionalized with flexible end groups, while the surfactant compounds are functionalized with surface active end groups. Methods of synthesizing the various compounds ar also provided.
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- Polar Substituent Effects in 1,3-Disubstituted Bicyclopentanes
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The pKa's of eight 3-substituted bicyclopentanecarboxylic acids have been measured and found to correlate well with ?I constants.The value of ρI (2.23 +/- 0.12) is large but not large enough to propose any special perturbation of normal field-inductive effects by the close proximity (about 1.88 Ae) of the bridgehead carbons.Also determined were the products and rates of solvolyses of the p-nitrobenzoates of three 3-substituted 1-pentanes.The products were primarily unrearranged, and the rates again showed no surprisingsubstituent effects.A practical synthesis of 1,3-disubstituted bicyclopentanes has been developed and is described.
- Applequist, Douglas E.,Renken, Terry L.,Wheeler, James W.
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p. 4985 - 4995
(2007/10/02)
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