- 64Cu-AMD3100-A novel imaging agent for targeting chemokine receptor CXCR4
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CXCR4 is a chemokine receptor which has been shown to be exploited by various tumors for increased survival, invasion, and homing to target organs. We developed a one step radiosynthesis for labeling the CXCR4-specific antagonist AMD3100 with Cu-64 to pro
- Jacobson, Orit,Weiss, Ido D.,Szajek, Lawrence,Farber, Joshua M.,Kiesewetter, Dale O.
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Read Online
- Facile N-1 protection of cyclam, cyclen and 1,4,7-triazacyclononane
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An exceptionally high yielding method for the tri-protection of cyclam and cyclen using ethyl trifluoroacetate is described. The selective reaction also applies to the di-protection of 1,4,7-triazacyclononane. The application of this method in the synthesis of AMD3100, a clinical candidate for stem cell mobilization is presented.
- Yang, Wen,Giandomenico, Christen M.,Sartori, Michael,Moore, Dennis A.
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Read Online
- Octahydropyrazine bipyrimidine molecular clip compound as well as preparation method and application thereof
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The invention discloses an octahydropyrazine bipyrimidine molecular clip compound as well as a preparation method and application thereof. The chemical structure of the octahydropyrazine bipyrimidine molecular clip compound is shown in the description, wherein X is selected from fluorine, chlorine, bromine and iodine. The octahydropyrazine bipyrimidine molecular clip compound has the advantages of reasonable route design, safe and easily available raw materials, high process safety, high reaction selectivity, high product purity and high product yield, and can fully meet the requirements of industrial production of products.
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Paragraph 0152; 0153; 0162; 0163; 0164; 0165; 0166
(2021/09/26)
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- Preparation method of Plerixafor
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The invention discloses a preparation method of Plerixafor, and belongs to the technical field of Plerixafor preparation. Common agents such as ethylenediamine and diethyl malonate are used as starting raw materials; Michael addition and ring formation are performed; then, the materials are bridged with 1,4-bis(halogenated methyl) benzene; then, reduction is performed through an I2-NaBH4 reduction system to obtain the Plerixafor. The cost of the I2-NaBH4 reduction system is low; the operation is safe, simple and convenient; the pure product can be obtained through recrystallization. The preparation method of the Plerixafor provided by the invention has the advantages that the production cost is low; the operation is safe, simple and convenient; byproducts are few; environment protection and economization are realized; the method can be widely applied to medicine development; good application effects can be achieved; good popularization and application values are realized.
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Paragraph 0011; 0046; 0050
(2017/12/29)
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- A PROCESS FOR THE PREPARATION OF XYLENE LINKED CYCLAM COMPOUNDS
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The present invention relates to an improved process for the preparation of xylene linked cyclam compounds. More particularly the invention provides a process for preparation of high purity plerixafor which does not involve the use of expensive chemicals, hazardous reagents or tedious purification techniques. Invention also provides novel intermediate useful for preparation of desired compound in high purity.
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Paragraph 20; 21
(2017/03/28)
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- IMPROVED AND COMMERCIALLY VIABLE PROCESS FOR THE PREPARATION OF HIGH PURE PLERIXAFOR BASE
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The present invention relates to an improved and commercially viable process for the preparation of ≥ 99.8% pure plerixafor base (1) by HPLC. The process of the present invention involves simple crystallization techniques to isolate the compounds at each step without employing the laborious column chromatography technique. The solid state characteristics of plerixafor base also discussed by PXRD, DSC and I.R spectroscopy.
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Page/Page column 16; 17
(2014/09/03)
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- Chemokine combinations to mobilize progenitor/stem cells
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Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 in combination with the CXCR2 chemokine GROβ, including its modified forms, are disclosed.
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Page/Page column 24
(2008/06/13)
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- Regioselective N-functionalization of tetraazacycloalkanes
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Bisaminal type compounds obtained by condensation of pyruvic aldehyde with the suitable open-chain tetraamine followed by cyclization with either dibromoethane or dibromopropane can be regioselectively quaternized by a wide range of alkylating agents. Removal of the bisaminal bridge yields the monosubstituted tetraazamacrocycle or bismacrocycle. Further functionalization allows the preparation of bifunctional ligands or trisubstituted macrocycles. The structure of six compounds was solved by X-ray diffraction, and the unexpected results are rationalized according to the molecular modeling calculations.
- Boschetti, Frederic,Denat, Franck,Espinosa, Enrique,Tabard, Alain,Dory, Yves,Guilard, Roger
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p. 7042 - 7053
(2007/10/03)
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- Methods to mobilize progenitor/stem cells
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Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula [in-line-formulae]Z-linker-Z′??(1)[/in-line-formulae] or pharmaceutically acceptable salt thereof wherein Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′ is of the formula [in-line-formulae]—Ar(Y)j;[/in-line-formulae] wherein Ar is an aromatic or heteroaromatic moiety, and each Y is independently a non-interfering substituent and j is 0-3; and “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.
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- METHODS AND COMPOSITIONS TO ENHANCE WHITE BLOOD CELL COUNT
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Methods to elevate white blood cell counts in animal subjects using compounds of formula (1) are disclosed. These compounds have the formulaor pharmaceutically acceptable salt thereofwherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;Z' may be embodied in a form as defined by Z above, or alternatively may be of the formulawherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan;"linker" represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms;in an amount effective to elevate said WBC count in said subject.
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- Methods to mobilize progenitor/stem cells
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Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z′??(1) or pharmaceutically acceptable salt thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system; or Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula —N(R)—(CR2)n—X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan; “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.
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- Process for preparation of N-1 protected N ring nitrogen containing cyclic polyamines and products thereof
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Cyclic polyamines containing N nitrogens on the ring are protected with high yields in a N-1 manner, e.g. all protected but one amino group, by using certain fluoro-containing agents that offer easy deprotection. Preferably, a new process for preparing 1,1′-[1,4-phenylenebis (methylene)]-bis1,4,8,11-tetraazacyclotetradecane is disclosed.
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- Methods to enhance white blood cell count
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Methods to elevate white blood cell counts in animal subjects using compounds of formula (1) are disclosed. These compounds have the formula Z-linker-Z′??(1) or pharmaceutically acceptable salt thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system; Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula —N(R)—(CR2)n—X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan; “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms; in an amount effective to elevate said WBC count in said subject.
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- Bis-aminals: Efficient tools for bis-macrocycle synthesis
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Tetraazamacrocyclic bis-aminals prove to be excellent tools for the synthesis of symmetrical, dissymmetrical or functionalized bis-tetraazamacrocycles. The key feature of the process is the separation of insoluble mono- or bis-quaternary ammonium salts from solution during the course of the alkylation reaction.
- Le Baccon,Chuburu,Toupet,Handel,Soibinet,Dechamps-Olivier,Barbier,Aplincourt
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p. 1168 - 1174
(2007/10/03)
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- Process for preparing 1,1'-[1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane
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An improved process for preparing 1,1'-[1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane comprising the selective functionalization of an acyclic tetraamine, and subsequent dimerization and hydrolyzation/tosylation to obtain a 1,4-phenylenebis-methylene bridged hexatosyl acyclic precursor in a first step, the cyclization of said precursor to obtain a hexatosyl cyclam dimer in a second step, and the detosylation of said cyclam dimer in a third step followed by basification to obtain the desired 1,1'-[1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane.
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- An expeditious synthesis of a biscyclam with an aromatic linker
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An efficient synthesis of 1 starting from N,N'-bis(3-aminopropyl)ethylenediamine 2 is described. Two salient features of the present work are the selective bis or tris-trifluoroacetylation of 2 and a novel bis-macrocyclization of the hexatosyl intermediate 5 using ethylene glycol ditosylate.
- Xu, Daqiang,Mattner, Paul G.,Prasad, Kapa,Repic, Oljan,Blacklock, Thomas J.
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p. 5301 - 5304
(2007/10/03)
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- Trivalent protecting groups for the synthesis of symmetrical and unsymmetrical bis-tetraazamacrocycles
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Facile syntheses of bis-tetraazamacrocycles are reported starting from tripotection of tetraazamacrocycles. The triprotected macrocycle was mono N-alkylated and then this compound reacted with another macrocycle to give symmetrical or unsymmetrical bis-tetraazamacrocycles.
- Gardinier,Roignant,Oget,Bernard,Yaouanc,Handel
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p. 7711 - 7714
(2007/10/03)
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- New facile and convenient synthesis of bispolyazamacrocycles using Boc protection. Determination of geometric parameters of dinuclear copper(II) complexes using ESR spectroscopy and molecular mechanics calculations
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A new facile and convenient synthetic route has been designed for the preparation of bispolyazamacrocycles in high yields by direct condensation of the readily available intermediate //,W-diboctriazamacrocycle or N,N',N"triboctetraazamacrocycles with aromatic biselectrophiles, ie, o-, m-, p-xylyl and anthracenyl derivatives. The use of a versatile group, such as ferf-butyloxycarbonyl (Boc), which is easily removed within l h by treatment with 6 M HC1 or TFA, leads to polyazamacrocycles in which one nitrogen is discriminated from the others. The anthracenyl and o-xylyl dimers were synthesized by reacting diacyl chloride to give the corresponding diamides. Further reduction of the amide groups and elimination of the protecting Boc moieties were carried in a one-pot reaction with BHa-THF followed by acid treatment. In parallel, exclusive mono-JV-alkylation of the available secondary amine of the same protected macrocycle with the corresponding dibromoxylene gave the meta and para dimers; the protecting moieties were eliminated in a similar way. ESR measurements of spin-spin distances of the dicopper complexes were determined from the ratio of the intensity of the forbidden transition to the intensity of the allowed transitions. Molecular mechanics calculations were also undertaken in order to evaluate the Cu-Cu distance by using a new rule-based force field. Eisevier,.
- Brandes, Stephane
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- Mono N-Functionalization of Cyclic and Linear Tetraamines via Their Tridentate Tricarbonylchromium Complexes
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The fac-LCr(CO)3 tridentate complexes of 1,4,7,10-tetraazacyclododecane 1, 1,4,8,11-tetraazacyclotetradecane 2, 1,4,7,10-tetraazadecane 3 and 1,5,8,12-tetraazadodecane 4 have been shown selectively alkylated in high yield at the uncomplexed nitrogen atom, giving rise to mono N-functionalized tetraamines and bis-macrocyclic compounds.
- Yaouanc, Jean-Jacques,Bris, Nathalie Le,Gall, Guenaelle Le,Clement, Jean-Claude,Handel, Henri,Abbayes, Herve des
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p. 206 - 207
(2007/10/02)
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