115913-31-0Relevant articles and documents
Bridge-Chlorinated Bicyclo[1.1.1]pentane-1,3-dicarboxylic Acids
Kaleta, Ji?í,Ron?evi?, Igor,Císa?ová, Ivana,Dra?ínsky, Martin,?olínová, Veronika,Ka?i?ka, Václav,Michl, Josef
, p. 2448 - 2461 (2019)
Radical chlorination of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid is highly selective, and up to four chlorine atoms can be introduced relatively easily without damage to the strained bicyclic cage. Combined with hydrodechlorination with TMS3SiH, direct chlorination provides access to five of the 15 possible chlorinated diacids. Their configuration has been established by X-ray diffraction. Their pKa values have been measured by capillary electrophoresis and calculated at the B3LYP-D3BJ/6-311+G(d,p)-level. The results are in good agreement and reflect the expected trend, from 2.78 ± 0.08 and 4.14 ± 0.10 in the parent to 1.07 ± 0.03 and 2.31 ± 0.03 in the tetrachlorinated diacid. Strain energy relative to the parent diacid was calculated for all 15 chlorinated diacids and shows a dramatic increase with successive chlorination, due to nonbonded Cl-Cl repulsions.
DEOXYNOJIRIMYCIN DERIVATIVES AS GLUCOSIDASE INHIBITORS
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Paragraph 0655, (2022/01/22)
The present invention relates to novel iminosugars and their use as glucosidase inhibitors. The present inventors discovered that certain deoxynojirimycin derivatives may be effective in inhibiting glucosidases. In particular, such deoxynojirimycin derivatives may be useful for treating a disease or condition in which inhibition of glucosidase may play an important role.
Bifunctional cytotoxic agents
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Page/Page column 68; 95-96; 100, (2018/11/02)
Cytotoxic dimers comprising CBI-based and/or CPI-based sub-units, antibody drug conjugates comprising such dimers, and to methods for using the same to treat cancer and other conditions.
Preparation method for bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester
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Paragraph 0006; 0013, (2017/03/08)
The invention relates to a preparation method for bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester, and mainly solves the technical problem that a method suitable for industrial synthesis does not exist at present. The preparation method comprises the following six steps: firstly, reacting a compound (1) and bromoform under an alkaline condition to obtain a compound (2); secondly, reacting the compound (2) and lithium methide to obtain a compound (3); thirdly, illuminating the compound (3) and diacetyl by a high-pressure mercury lamp to obtain a compound (4); fourthly, treating with sodium hypochlorite to obtain a compound (5); fifthly, reacting the compound (5) and thionyl chloride to obtain a compound (6); and finally, treating the compound (6) under the effect of methanol to obtain a compound (7) which is a final product. A reaction formula is as shown in the specification, and the acquired bicyclo [1.1.1] pentane-1,3-dicarboxylic acid dimethylester is a useful midbody or product for synthesis of many drugs.
BIFUNCTIONAL CYTOTOXIC AGENTS CONTAINING THE CTI PHARMACOPHORE
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Paragraph 0278; 0279, (2016/10/11)
The present invention is directed to novel bifunctional CTI-CTI and CBI-CTI dimers of the formula: [in-line-formulae]F1-L1-T-L2-F2 [/in-line-formulae] where F1, L1, T, L2 and F2 are as defined herein, useful for the treatment for proliferative diseases, where the inventive dimers can function as stand-alone drugs, payloads in antibody-drug-conjugates (ADCs), and linker-payload compounds useful in connection with the production or administration of such ADCs; and to compositions including the aforementioned dimers, linker-payloads and ADCs, and methods for using these dimers, linker-payloads and ADCs, to treat pathological conditions including cancer.
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
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.
supporting information; experimental part, p. 3414 - 3424 (2012/06/01)
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.
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
Costantino, Gabriele,Maltoni, Katiuscia,Marinozzi, Maura,Camaioni, Emidio,Prezeau, Laurent,Pin, Jean-Philippe,Pellicciari, Roberto
, p. 221 - 227 (2007/10/03)
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.
Compounds and methods based on [1.1.1]propellane
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, (2008/06/13)
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.
