- Rh(III)-catalyzed, 1,2,3-triazole-assisted directed C–H coupling with diazo diphosphonates
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A mild and efficient procedure was developed for the [Cp?Rh(III)]-catalyzed, 1,2,3-triazole directed C–H coupling with diazomethylene-diphosphonates. This protocol provided a step- and atom-economical protocol for C–C bond formation and led to structurally diverse 2-(1,2,3-triazol-2-yl)benzyl diphosphonates in good to excellent yields.
- Yu, Zhu-Jun,Zhang, Chen,Li, Jiang-Lian,Liu, Yan-Zhao,Yu, Xin-Ling,Guo, Li,Li, Guo-Bo,Wu, Yong
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Read Online
- Selenophosphonates as building blocks for the preparation of bis-methylene analogs of triphosphates
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A new route to bis-methylene analogs of triphosphate esters involving carbanion chemistry is described. Lithiated methaneselenophosphonate anion is condensed several times with chlorophosphites and phosphoramidous chlorides prior to esterification/transesterification and selenation or oxidation.
- Mons, Stéphane,Klein, Emmanuel,Mioskowski, Charles,Lebeau, Luc
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Read Online
- Bisphosphonate prodrugs: A new synthetic strategy to tetraacyloxymethyl esters of methylenebisphosphonates
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A concise and simple method to prepare Cl2C[P(O)(OCH2O2CCMe3)2]2 starting from H2C[P(O)(OMe)2]2 with high selectivity and reasonable yield is developed.
- Vepsaelaeinen, Jouko J.
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Read Online
- COMPOSITIONS AND METHODS OF MODULATING THE IMMUNE RESPONSE BY ACTIVATING ALPHA PROTEIN KINASE 1
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The disclosure provides compositions and methods related to activating alpha-kinase 1 (ALPK1) for modulating an immune response and treating or preventing cancer, infection, inflammation and related diseases and disorders as well as potentiating an immune response to a target antigen. The disclosure also provides heterocyclic compounds of formula (I) as agonists of alpha protein kinase 1 (ALPK1) and their use in activating ALPK1, modulating an immune response and treating diseases such as cancer, wherein A1, A2, L1, L2, L3, Z1, Z2, W1, W2, R1, R2, R3, R4, R5, R6 and R7 are defined herein.
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Paragraph 239
(2019/05/15)
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- PET bone imaging agent precursor and synthesis method thereof
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The invention discloses a PET bone imaging agent precursor, wherein a linking agent tripolyethanol is introduced between a macrocyclic polyamine ligand and a targeting carrier diphosphonic acid, and the diphosphonic acid bone-seeking group with targeting effect can form the macrocyclic polyamine cooperation group of a stable chelate with a plurality of metal nuclides so as to form a bone imaging agent. According to the present invention, the synthesized precursor compound contains the bone-seeking group (diphosphonic acid) and the cooperation group (DOTA), and the two functional groups are linked by PFG3, such that the precursor compound has remarkable structural characteristics; the precursor compound has strong bone-seeking property, and can form a complex (marker) with kinetic and thermodynamic stability with metal nuclides; the marker formed by marking the precursor with different metal nuclides can be used as a bone imaging agent (marked with Cu, Ga and other positron emission metal nuclides) with powerful functions, and can further be used as an ideal bone tumor treatment drug (marked with In, Y, Zr, Sm and other radioactive treatment metal nuclides).
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Paragraph 0059
(2019/12/10)
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- PHOSPHONATED RIFAMYCINS AND USES THEREOF FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS
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The present invention relates to phosphonated Rifamycins, and methods of making and using such compounds. These compounds are useful as antibiotics for prophylaxis and/or the treatment of bone and joint infections, especially for the prophylaxis and/or treatment of osteomyelitis.
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Page/Page column 77
(2011/11/06)
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- METAL COMPLEX COMPOUND, CANCER THERAPEUTIC COMPOSITION COMPRISING THE METAL COMPLEX COMPOUND AS ACTIVE INGREDIENT, AND INTERMEDIATE FOR PRODUCTION OF THE METAL COMPLEX COMPOUND
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A metal complex compound which exhibits a high degree of adsorption to bone or inhibition of cell growth, and is highly effective for therapy of a cancer metastasized to bone and therapy of the primary carcinoma thereof; a therapeutic agent composition for a cancer containing as an active ingredient the metal complex compound or a physiologically acceptable salt thereof; and an intermediate for the metal complex compound are provided. More concretely, a metal complex compound represented by the following General Formula (1): (wherein R1 independently represents C1-C10 alkyl which may be branched or have a substituent; or a C3-C30 cyclic group which may have a substituent; and X represents CHR2, an oxygen atom or NR5); a therapeutic agent composition for a cancer containing it as an active ingredient; and an intermediate for the metal complex compound are provided.
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Page/Page column 8
(2010/05/13)
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- An osteoclast-targeting agent for imaging and therapy of bone metastasis
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A hybrid compound (DO3A-BP) featuring a radiometal bifunctional chelator (1,4,7,10-tetraazacyclotetradecane-N,N′,N″,N?-tetraac etic acid, DOTA) and an osteoclast-targeting moiety (bisphosphonate) was designed and synthesized. The 111In-labeled complex of DO3A-BP showed significantly elevated uptake in osteoclasts compared to the undifferentiated adherent bone marrow derived cells. Biodistribution studies revealed a favorable tissue distribution profile in normal mice with high bone uptake and long retention, and low or negligible accumulation in non-target organs.
- Liu, Wei,Hajibeigi, Asghar,Lin, Mai,Rostollan, Cynthia L.,Kovacs, Zoltan,Oez, Orhan K.,Sun, Xiankai
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experimental part
p. 4789 - 4793
(2009/05/26)
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- ORALLY AVAILABLE SPHINGOSINE 1-PHOSPHATE RECEPTOR AGONISTS AND ANTAGONISTS
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The present invention relates to S1P analogs that have activity as S1Preceptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure (I) wherein R11 is C5-C18 alkyl or C5-C18 alkenyl; Q is selected from the group consisting of C3-C6 optionally substituted cycloalkyl, C3-C6 optionally substituted heterocyclic, C3-C6 optionally substituted aryl C3-C6 optionally substituted heteroaryl and; R2 is selected from the group consisting of H, C1-C4 alkyl, (C1-C4 alkyl)OH and (C1-C4 alkyl)NH2; R23 is H or C1-C4 alkyl, and R15 is a phosphonate ester or a phosphate ester or a pharmaceutically acceptable salt or tautomer thereof.
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Page/Page column 138-140
(2008/06/13)
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- Synthesis of new potential chelating agents: Catechol-bisphosphonate conjugates for metal intoxication therapy
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In a quest for better chelating therapy drugs for the treatment of intoxication by Fe, Al, or actinides, three new series of bisphosphonates conjugated with catechol were synthesized.
- Xu, Guangyu,Yang, Chunhao,Liu, Bo,Wu, Xihan,Xie, Yuyuan
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p. 251 - 257
(2007/10/03)
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- PROSTAGLANDIN CONJUGATES FOR TREATING OR PREVENTING BONE DISEASES
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This invention relates to prostaglandin-bisphosphonate conjugates. These conjugates are effective for treating or preventing bone diseases such as osteoporosis. These conjugates simultaneously deliver a prostaglandin agent for increasing bone formation and a bisphosphonate agent for inhibiting bone resorption.
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- Synthesis of stable analogues of thiamine di- and triphosphate as tools for probing a new phosphorylation pathway
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Thiamine (vitamin B1) is an essential nutritional factor metabolized inside the body in its mono-, di-, and triphosphate forms. Although the action of thiamine and thiamine diphosphate have been intensely investigated, many questions remain unanswered and
- Klein, Emmanuel,Nghiem, Hoang-Oanh,Valleix, Alain,Mioskowski, Charles,Lebeau, Luc
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p. 4649 - 4655
(2007/10/03)
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- Simple synthesis of oxiranylidene-2,2-bis(phosphonic acid): Tetrabenzyl geminal bisphosphonate esters as useful intermediates
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Tetrabenzyl geminal bisphosphonate esters are shown to be useful synthetic equivalents of 1,1-bis(phosphonic acid)s which may be easily functionalized at the central carbon atom without phosphonate ester hydrolysis. The parent bis(phosphonic acid) unit is readily regenerated by hydrogenolysis. The chemistry is used to prepare the elusive epoxide oxiranylidene-2,2-bis(phosphonic acid) by a short and reliable procedure.
- Bulman Page, Philip C.,McKenzie, Michael J.,Gallagher, James A.
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p. 211 - 218
(2007/10/03)
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- Novel synthesis of bis(phosphonic acid)-steroid conjugates
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An efficient synthesis has been realized for several members of a new class of potential bone resorption inhibitors consisting of steroidal oestrogenic units linked at the 3 and 17 positions to a geminal bisphosphonate moiety through an ester linkage of variable length. The convergent synthesis utilizes benzyl bisphosphonates, transesterification, and Meldrum's acid chemistry and has the potential to allow many oestrogenic derivatives as well as other biologically active compounds to be coupled to the geminal bisphosphonate moeity.
- Page,McKenzie,Gallagher
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p. 3704 - 3708
(2007/10/03)
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- Prostaglandin conjugates for treating or preventing bone disease
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This invention relates to prostaglandin-bisphosphonate conjugates. These conjugates are effective for treating or preventing bone diseases such as osteoporosis. These conjugates simultaneously deliver a prostaglandin agent for increasing bone formation and a bisphosphonate agent for inhibiting bone resorption.
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- The assembly of β-methylene-TAD, a metabolically stable analogue of the antitumor agent TAD, by the stepwise esterification of monodeprotected methylenebis-(phosphonate) benzyl esters under Mitsunobu conditions
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Synthesis of the metabolically stable analogue of thiazole-4-carboxamide adenine dinucleotide (β-methylene-TAD) was achieved via the sequential monodeprotection of tetrabenzyl methylenebis(phosphonate) after two rounds of Mitsunobu esterifications with th
- Ikeda, Hisafumi,Abushanab, Elie,Marquez, Victor E.
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p. 3069 - 3074
(2007/10/03)
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- Prostaglandin E2-bisphosphonate conjugates: Potential agents for treatment of osteoporosis
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Conjugates of bisphosphonates (potential bone resorption inhibitors) and prostaglandin E2 (a bone formation enhancer) were prepared and evaluated for their ability to bind to bone and to liberate, enzymatically, free PGE2. The conjugate 3, an amide at C-1 of PGE2 proved to be too stable in vivo while conjugate 6, a thioester, was too labile. Several PGE2, C-15 ester-linked conjugates (18, 23, 24 and 31) were prepared and conjugate 23 was found to bind effectively to bone in vitro and in vivo and to liberate PGE2 at an acceptable rate. A 4-week study in a rat model of osteoporosis showed that 23 was better tolerated and more effective as a bone growth stimulant than daily maximum tolerated doses of free PGE2. Copyright (C) 1999 Elsevier Science Ltd.
- Gil, Laurent,Han, Yongxin,Opas, Evan E.,Rodan, Gideon A.,Ruel, Rejean,Seedor, J. Gregory,Tyler, Peter C.,Young, Robert N.
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p. 901 - 919
(2007/10/03)
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- First Use of Benzyl Phosphites in the Michaelis-Arbuzov Reaction Synthesis of Mono-, Di-, and Triphosphate Analogs
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Benzyl phosphites were used in the Michaelis-Arbuzov reaction.Special experimental conditions allowed preparation of a set of phosphonate analogs of mono-, di-, and triphosphate.Furthermore, regioselective mono-deprotection mades these molecules useful building blocks for the synthesis of analogs of polyphosphorylated compounds of biological interest (e.g. nucleotides), after removal of all phosphonate benzyl ester groups under very mild conditions and high yields.
- Saady, Mourad,Lebeau, Luc,Mioskowski, Charles
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p. 670 - 678
(2007/10/02)
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- Synthesis of Di- and Triphosphate Ester Analogs via a Modified Michaelis-Arbuzov Reaction
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For the first time, benzyl phosphites allowed the preparation of a set of polyphosphonates from chloromethyl halides via the Michaelis-Arbuzov reaction performed under vacuum.Regioselective mono-deprotection or complete deprotection of these phosphonates provide useful building blocks for the synthesis of biological phosphate analogs.
- Saady, Mourad,Lebeau, Luc,Mioskowski, Charles
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p. 5183 - 5186
(2007/10/02)
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