- An ESR Study of the Aziridine and Azetidine Radical Cations: Evidence for the C...C Ring-Opened Aziridine Radical Cation
-
The radical cations from aziridine and azetidine have been characterized by ESR spectriscopy following their generation in the solid state by γ irradiation of dilute solutions of the parent compounds in the CFCl3 maarix at 77 K.The ESR parameters of the azetidine radical cation are typical of those for nitrogen-centered amine radical cations such as Me2NH.+.On the other hand, the radical cation formed from aziridine has very different ESR parameters that compare closely to those for the isoelectronic C...C ring-opened form of the oxirane radical cation and the allyl radical.The radical cation formed from azetidine is therefore assigned a ring-closed structure with the unpaired electron in a 2pz orbital on nitrogen perpendicular to the ring plane, whereas the cation from aziridine is an allylic C...C ring-opened planar isomer with the unpaired electron in a nonbonding ? orbital centered mainly on the two end carbon atoms.The neutral 1-aziridinyl and 1-azetidinyl radicals have been detected as radical products following the γ-irradiation of the parent compounds in the CFCl2CF2Cl and CF3CCl3 matrices.In particular, the 1-azetidinyl radical is produced cleanly from the azetidine radical cation in the CFCl2CF2Cl matrix at ca. 100 K.
- Qin, Xue-Zhi,Williams, Ffrancon
-
-
Read Online
- Preparation of functionalized imidazolium salts under microwave irradiation
-
A direct alkylation of a substituted imidazole to prepare the corresponding functionalized ionic liquid has been developed in excellent yields under microwave irradiation. Copyright Taylor & Francis Group, LLC.
- Fu, Shih-Kang,Liu, Shiuh-Tzung
-
-
Read Online
- Living anionic polymerization of N-methacryloylazetidine: Anionic polymerizability of N,N-dialkylmethacrylamides
-
Anionic polymerization of a series of N,N-dialkylmethacrylamides such as TV-methacryloylazetidine (M4), N-methacryloylpyrrolidine (M5), and N-methacryloylpiperidine (M6) was carried out with diphenylmethyllithium (Ph2CHLi) or diphenylmethylpotassium (Ph2CHK) in the presence of LiCl or Et2Zn in THF to clarify the relationship between polymerizability and monomer structure. Poly(M4)s possessing predicted molecular weights and very narrow molecular weight distributions MwM n 2CHLi/LiCl or Ph2CHK/Et2Zn at -40 to 0 °C within 24 h. From the polymerizations of M4 at the various temperatures ranging from -40 to -20 °C, the apparent rate constant and the activation energy of the anionic polymerization were determined as follows: In kpap = -6.17 x 103/r+22.4 Lmol-1s-1 and 51 ± 5 kJ mol-1, respectively. Compared to the previous report on the anionic polymerization of N-methacryloyl-2-methylaziridine (M3), the polymerization rate of M4 was significantly slower and the activation energy was slightly larger, indicating the lower polymerizability of M4. The acryloyl counterpart, N-acryloylazetidine (A4), also underwent the anionic polymerization to afford the well-defined polymer quantitatively. The polymerizations of M5 gave the polymers in 30-77% yields but did not complete even after 1 week at 0 °C. By contrast, no polymer was obtained from the anionic polymerization system of M6 similar to the case of N.N-dimethylmethacrylamide (DMMA). From the experimental results, it was demonstrated that the polymerizability of a series of N,N-dialkylmethacrylamides with cyclic substituents decreased drastically with increasing the ring size from three to six (M3 > M4 > M5M6 = DMMA). The observed relative polymerizability was well correlated with the chemical shifts of vinyl β-carbons for monomers in the 13C NMR spectra. The NMR data suggested that the polymerizable M3 and M4 attained effective conjugation between C=C and C=O double bonds, while M5, M6, and DMMA had negligible conjugation effects.
- Suzuki, Takashi,Kusakabe, Jun-Ichi,Kitazawa, Keita,Nakagawa, Takeshi,Kawauchi, Susumu,Ishizone, Takashi
-
-
Read Online
- Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer
-
About 75% of breast cancers are estrogen receptor alpha (ER-α) positive, and women typically initially respond well to antihormonal therapies such as tamoxifen and aromatase inhibitors, but resistance often emerges. Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and shows some activity in patients who have progressed on antihormonal agents. However, fulvestrant must be administered by intramuscular injections that limit its efficacy. We describe the optimization of ER-α degradation efficacy of a chromene series of ER modulators resulting in highly potent and efficacious SERDs such as 14n. When examined in a xenograft model of tamoxifen-resistant breast cancer, 14n (ER-α degradation efficacy = 91%) demonstrated robust activity, while, despite superior oral exposure, 15g (ER-α degradation efficacy = 82%) was essentially inactive. This result suggests that optimizing ER-α degradation efficacy in the MCF-7 cell line leads to compounds with robust effects in models of tamoxifen-resistant breast cancer derived from an MCF-7 background.
- Nagasawa, Johnny,Govek, Steven,Kahraman, Mehmet,Lai, Andiliy,Bonnefous, Celine,Douglas, Karensa,Sensintaffar, John,Lu, Nhin,Lee, Kyoungjin,Aparicio, Anna,Kaufman, Josh,Qian, Jing,Shao, Gang,Prudente, Rene,Joseph, James D.,Darimont, Beatrice,Brigham, Daniel,Maheu, Kate,Heyman, Richard,Rix, Peter J.,Hager, Jeffrey H.,Smith, Nicholas D.
-
supporting information
p. 7917 - 7928
(2018/09/06)
-
- Synthesis of common-sized heterocyclic compounds by intramolecular cyclization over halide cluster catalysts
-
Five- to seven-membered common-sized heterocyclic compounds containing an oxygen, sulfur, or nitrogen were synthesized by the intramolecular condensation of α,ω-hydroxy, mercapto, or amino alkanes, respectively, over halide cluster complexes as a thermally stable molecular solid weak acid catalyst in the gas phase at temperatures ≥150 °C. From ω- mercapto and ω-amino alcohols, cyclic sulfides and amines were obtained, respectively. These unimolecular reactions are thermodynamically and kinetically favored.
- Nagashima, Sayoko,Sasaki, Tomoaki,Kamiguchi, Satoshi,Chihara, Teiji
-
supporting information
p. 764 - 766
(2015/06/22)
-
- Amino-alcohol cyclization: Selective synthesis of lactams and cyclic amines from amino-alcohols
-
By employing an amination catalyst, previously used in the direct synthesis of amines from alcohol with ammonia, n-amino-alcohols could be selectively cyclized to either the amide or the amine. By the addition of water, the amine could be produced as the major product whereas adding a sacrificial ketone as a hydrogen acceptor resulted in the amide as the major product. Without an additive a mixture of both the amine and the amide was observed. N-substituted amino-alcohols solely gave cyclic amines under these conditions. From 2-(n-alkanol) anilines the cyclic amines were produced, where the n-propanol derivative selectively formed quinoline as the major product.
- Pingen, Dennis,Vogt, Dieter
-
-
- Vapor-phase transport as a novel route to hyperbranched polyamine-oxide hybrid materials
-
A new method to prepare hyperbranched polyamine-oxide hybrid materials by means of a vapor-phase transport is developed. In this method, hybrid materials having hyperbranched amine polymers covalently bound to an oxide support are formed by exposing the oxide support to the vapor of small nitrogen-containing heterocyclic monomers, in contrast to the conventional liquid-phase method, in which the support is dispersed in an organic solution containing monomer species. The aziridine and azetidine monomers are polymerized on the surface of the oxide supports (i.e., silica and alumina), resulting in poly(ethylenimine) or poly(propylenimine) chains attached to the porous solid support. The results suggest that the hybrid materials can be prepared over a wide range of preparation conditions with organic contents comparable to or even higher than those obtained from the standard liquid-phase method. It is demonstrated that supports with more acidity result in the hybrid materials with higher organic content. Interestingly, the resulting supported polyamines have lower molecular weights than the previously reported materials prepared by the liquid-phase method. It is anticipated that the vapor-phase synthesis can be applied for the efficient introduction of polyamines into structural forms of supports such as fibers, membranes, and monoliths, for which the liquid-phase method may be inappropriate or inefficient.
- Chaikittisilp, Watcharop,Didas, Stephanie A.,Kim, Hyung-Ju,Jones, Christopher W.
-
p. 613 - 622
(2013/05/08)
-
- ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
-
Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.
- -
-
Page/Page column 113; 114
(2012/01/05)
-
- A concise synthesis of a novel insulin-like growth factor i receptor (IGF-IR) inhibitor
-
An efficient synthesis of a potent insulin-like growth factor I receptor (IGF-IR) inhibitor AEW541 (1) is described. The key step in the synthesis is the cis-selective reductive animation of cyclobutanone, which sets up the desired 1,3-stereochemistry of the cyclobutane ring. The amino group thus generated is used as a handle to build the pyrrolopyrimidine ring. The final step resulting in 1 is accomplished by alkylation of in situ generated mesylate with azetidine.
- Slade, Joel,Bajwa, Joginder,Liu, Hui,Parker, David,Vivelo, James,Chen, Guang-Pei,Calienni, John,Villhauer, Edwin,Prasad, Kapa,Repic, Oljan,Blacklock, Thomas J.
-
p. 825 - 835
(2012/12/30)
-
- ANTAGONISTS OF THE MGLU RECEPTOR AND USES THEREOF
-
The present invention discloses compounds of general formula (I) wherein X1-X4 and R1-R3 are as defined in the description. The present invention also discloses methods of treatment for pain, neurodegeneration and convulsive states in a host mammal in need thereof, and pharmaceutical compositions including those compounds.
- -
-
Page/Page column 51
(2008/06/13)
-
- Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use
-
The invention relates to compounds represented by the formula I and to prodrugs or metabolites thereof, or pharmaceutically acceptable salts or solvates of said compounds, said prodrugs, and said metabolites, wherein Z, Y, R11 and R14, R15, R16, and R17 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.
- -
-
-
- Oligomeric aminodiol-containing compounds, libraries thereof, and process of preparing the same
-
Oligomeric compounds comprising a plurality of aminodiol monomer subunits joined by linking groups are provided, as well as libraries of such compounds and processes for preparing the oligomeric compounds and libraries.
- -
-
-
- Cyclosporins
-
The present invention relates to novel cyclosporins, processes for their preparation, their use as pharmaceuticals and pharmaceutical compositions comprising them. The novel cyclosporins are represented by the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the letters A to L represent residues of amino acids.
- -
-
-
- Benzothiazole derivatives with activity as adenosine receptor ligands
-
The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
- -
-
-
- Scavenger assisted combinatorial process for preparing libraries of amides, carbamates and sulfonamides
-
This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
- -
-
-
- Efficient synthesis of azetidine through N-trityl- or N- dimethoxytritylazetidines starting from 3-amino-1-propanol or 3- halopropylamine hydrohalides
-
Efficient synthetic routes for the preparation of azetidine starting from commercially available 3-amino-1-propanol or 3-halopropylamine hydrohalides are reported. First, the appropriate N-trityl- or N-dimethoxytrityl protected tosyloxy- or halopropylamines were prepared. These precursors were then cyclized into the N-trityl- or N-dimethoxytritylazetidines. The N-protecting groups were removed in the presence of perchloric acid giving the hydrogen perchlorate salt of azetidine. The latter compound was transformed into its free base using a strong base under anhydrous conditions. The relatively expensive 4,4'-dimethoxytrityl chloride and less expensive trityl chloride used in these synthetic procedures were recycled in good yields. Azetidine hydrogenperchlorate can be used to prepare N-substituted azetidines without the need to isolate the free azetidine.
- Huszthy,Bradshaw,Krakowiak,Wang,Dalley
-
p. 1197 - 1207
(2007/10/02)
-
- A PRACTICAL SYNTHESIS OF AZETIDINE
-
A process for the preparation of kilogram quantities of distilled azetidine is described.
- Causey, David H.,Mays, Richard P.,Shamblee, Dwight A.,Lo, Young S.
-
p. 205 - 212
(2007/10/02)
-
- 2-azetidineacetic acid and certain of its congeners
-
2-Azetidinylacetic acid and certain of its congeners and use thereof for sterilizing the male parts of wheat plants.
- -
-
-
- Use of cyclic thiazines as microbiocides
-
Cyclic thiazines of the formula STR1 where the R's are hydrogen or a substituted group such as a hydrocarbon group, i.e., alkyl, etc. and N is a cyclic moiety, Z is S, STR2 and X is an anion, are prepared by reacting a cyclic secondary amine salt with a divinyl sulfur compound. These are illustrated by the reaction of piperidine hydrochloride with divinyl sulfone to yield STR3 These products have a wide variety of uses including their use as microbiocides, etc.
- -
-
-