- Synthesis of N-(2-guanidinoethyl)-tetrahydrothieno[3,2-c]azepine, N-(2- guanidinoethyl)-tetrahydro-2-benzazepine and N-(2-guanidinoethyl)-tetrahydro- 1-benzazepine as analogous to antihypertensive agent guanetidine
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N-(2-guanidinoethyl)-tetrahydrothieno[3,2-c]azepine 10a, N-(2- guanidinoethyl)-tetrahydro-2-benzazepine 10b and N-(2-guanidinoethyl)- tetrahydro-1-benzazepine 10c analogous of the antihypertensive agent Guanetidine were prepared by cyanomethylation of the corresponding azepines, reduction and subsequent guanilation of the resulting aminoethyl derivatives. These compounds were evaluated for antihypertensive activity in SHR rats but no significant activity was observed.
- Ravina,Ramos,Masaguer,Mera
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Read Online
- Continuous reductive amination of biomass-derived molecules over carbonized filter paper-supported FeNi alloy
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This paper reports the continuous reductive amination of different molecules, including biomass-related compounds, over carbon-supported FeNi nanoparticles obtained on the basis of inexpensive and abundant metal precursors and cellulose. A biorefinery case study for the preparation of pyrrolidones via acid-catalyzed hydrolysis of glucose followed by reductive amination of the obtained levulinic acid is described. Burn in the fire of filters: Continuous reductive amination of biomass-derivable molecules is achieved using a carbonized filter paper-supported FeNi catalyst in combination with EtOH, MeOH, and 2-methyl THF as green solvents. A biorefinery case study for the preparation of pyrrolidones using crude levulinic acid feeds is also investigated.
- Chieffi, Gianpaolo,Braun, Max,Esposito, Davide
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Read Online
- Two stepwise synthetic routes toward a hetero[4]rotaxane
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Heterorotaxanes have been emerging as an important class of mechanically interlocked molecules and have attracted much attention in recent years. Driven by the distinguishable host-guest interactions between crown ether macrocycles and ammonium with different sizes, a novel hetero[4]rotaxane was successfully prepared by employing the combination of copper-catalyzed "click" reaction and P(n-Bu)3-catalyzed esterification reaction as stoppering reactions. The hetero[4]rotaxane contains an interlocked species in which a dibenzo[24]crown-8 ring threaded by a dibenzylammonium-containing component with two benzo[21]crown-7 macrocycles at both ends to act as stoppers, and each of the two benzo[21]crown-7 rings is also threaded with a benzylalkylammonium unit to form the second interlocked species. The hetero[4]rotaxane was prepared through two different stepwise synthetic routes, and the complicated chemical structure of the hetero[4]rotaxane was well-characterized by 1H NMR spectroscopy and high-resolution electrospray ionization (HR-ESI) mass spectrometry. The investigation shows that the construction of complicated topological heterorotaxane can be achieved via distinct approaches with high efficiencies, which may provide a foundation for the construction of more sophisticated heterorotaxane systems or functional supermolecules.
- Luo, Qian-Fu,Zhu, Lan,Rao, Si-Jia,Li, Hong,Miao, Qi,Qu, Da-Hui
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Read Online
- NOVEL HISTONE METHYLTRANSFERASE INHIBITORS
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The present invention relates to novel compounds of formula (I) as defined herein. The compounds are inhibitors of histone methyltransferases of the seven-beta-strand family, in particular of KMT9.
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Page/Page column 30; 91-92
(2021/04/01)
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- An Alternative Approach to the Hydrated Imidazoline Ring Expansion (HIRE) of Diarene-Fused [1.4]Oxazepines
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A four-step approach to the “hydrated imidazoline ring expansion” (HIRE) is presented. In most cases, the ring expansion was the sole process. However, for the first time, an alternative course of the hydrated imidazoline evolution was discovered which gave N-aminoethyl derivatives. These can, in principle, be converted into the target HIRE products under sufficiently forcing conditions. The approach offers improved flexibility with respect to the peripheral substituents and is also applicable to the synthesis of eleven-membered lactams. We observed that the latter can exist in two stable isomeric forms due to lactam–amide bond isomerization. The latter finding further demonstrates the value of medium-sized rings as multiple-conformer probes for biological target interrogation.
- Grintsevich, Sergey,Sapegin, Alexander,Reutskaya, Elena,Peintner, Stefan,Erdélyi, Máté,Krasavin, Mikhail
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p. 5664 - 5676
(2020/07/21)
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- Cyclic Sulfamidite as Simultaneous Protecting Group for Amino Alcohols: Development of a Mild Deprotection Protocol Using Thiophenol
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This study describes the novel utility of cyclic sulfamidite as a simultaneous protecting group for 1,2- or 1,3-amino alcohols. An exceptionally mild and neutral condition for the removal of the cyclic sulfamidite was developed. The deprotection condition demonstrated a broad range of functional-group compatibility, including a substrate bearing a Z-enyne structure without any loss of double-bond stereochemistry.
- Sakata, Juri,Akita, Kazunari,Sato, Manabu,Shimomura, Masashi,Tokuyama, Hidetoshi
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p. 996 - 1000
(2020/11/03)
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- Iron-Catalyzed Anti-Markovnikov Hydroamination and Hydroamidation of Allylic Alcohols
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Hydroamination allows for the direct access to synthetically important amines. Controlling the selectivity of the reaction with efficient, widely applicable, and economic catalysts remains challenging, however. This paper reports an iron-catalyzed formal anti-Markovnikov hydroamination and hydroamidation of allylic alcohols, which yields γ-amino and γ-amido alcohols, respectively. Homoallylic alcohol is also feasible. The catalytic system, consisting of a pincer Fe-PNP complex (1-4 mol %), a weak base, and a nonpolar solvent, features exclusive anti-Markovnikov selectivity, broad substrate scope (>70 examples), and good functional group tolerance. The reaction could be performed at gram scale and applied to the synthesis of drug molecules and heterocyclic compounds. When chiral substrates are used, the stereochemistry and enantiomeric excess are retained. Further application of the chemistry is seen in the functionalization of amino acids, natural products, and existing drugs. Mechanistic studies suggest that the reaction proceeds via two cooperating catalytic cycles, with the iron complex catalyzing a dehydrogenation/hydrogenation process while the amine substrate acts as an organocatalyst for the Michael addition step.
- Ma, Wei,Zhang, Xiaohui,Fan, Juan,Liu, Yuxuan,Tang, Weijun,Xue, Dong,Li, Chaoqun,Xiao, Jianliang,Wang, Chao
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supporting information
p. 13506 - 13515
(2019/09/09)
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- Microwave-Assisted CuCl-Catalyzed Three-Component Reactions of Alkynes, Aldehydes, and Amino Alcohols
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A microwave (MW)-assisted three-component coupling of amino alcohols, aldehydes, and alkynes is developed under catalysis by CuCl. Compared with thermal conditions, MW irradiation greatly increases the reaction efficiency. The reactions of various primary N -alkyl/arylamino alcohols, aliphatic/aromatic aldehydes, and alkynes are systematically investigated, affording the desired products in moderate to good yields. Notably, acetylene is also an effective reactant under the current MW-assisted conditions.
- Chen, Ning,Li, Xiang,Xu, Jiaxi
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supporting information
p. 3336 - 3344
(2019/08/28)
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- [Co(TPP)]-Catalyzed Formation of Substituted Piperidines
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Radical cyclization via cobalt(III)-carbene radical intermediates is a powerful method for the synthesis of (hetero)cyclic structures. Building on the recently reported synthesis of five-membered N-heterocyclic pyrrolidines catalyzed by CoII porphyrins, the [Co(TPP)]-catalyzed formation of useful six-membered N-heterocyclic piperidines directly from linear aldehydes is presented herein. The piperidines were obtained in overall high yields, with linear alkenes being formed as side products in small amounts. A DFT study was performed to gain a deeper mechanistic understanding of the cobalt(II)-porphyrin-catalyzed formation of pyrrolidines, piperidines, and linear alkenes. The calculations showed that the alkenes are unlikely to be formed through an expected 1,2-hydrogen-atom transfer to the carbene carbon. Instead, the calculations were consistent with a pathway involving benzyl-radical formation followed by radical-rebound ring closure to form the piperidines. Competitive 1,5-hydrogen-atom transfer from the β-position to the benzyl radical explained the formation of linear alkenes as side products.
- Lankelma, Marianne,Olivares, Astrid M.,de Bruin, Bas
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p. 5658 - 5663
(2019/04/08)
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- Preparation method of 8-tert-butyl-1-ethyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepine-1,8(9H)-dicarboxylic acid ester
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The invention relates to a preparation method of 8-tert-butyl-1-ethyl-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepine-1,8(9H)-dicarboxylic acid ester. A purpose of the present invention is to mainly solvethe technical problem that no suitable industrial synthesis method exists at present. According to the present invention, the method comprises nine steps, the synthetic route is defined in the specification, and the obtained compound can be used as the useful intermediate or product for synthesizing a plurality of medicines.
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- Enantioselective Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C-H Alkylation
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Radical cyclization represents a powerful strategy for construction of ring structures. Traditional radical cyclization, which is based on radical addition as the key step, necessitates the use of unsaturated substrates. Guided by the concept of metalloradical catalysis, a different mode of radical cyclization that can employ saturated C-H substrates is demonstrated through the development of a Co(II)-based system for catalytic activation of aliphatic diazo compounds for enantioselective radical alkylation of various C(sp3)-H bonds. It allows for efficient construction of chiral pyrrolidines and other valuable 5-membered cyclic compounds. This alternative strategy of radical cyclization provides a new retrosynthetic paradigm to prepare five-membered cyclic molecules from readily available open-chain aldehydes through the union of C-H and C=O elements for C-C bond formation.
- Wang, Yong,Wen, Xin,Cui, Xin,Zhang, X. Peter
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p. 4792 - 4796
(2018/04/17)
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- Manganese catalyzed reductive amination of aldehydes using hydrogen as a reductant
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A one-pot two-step procedure was developed for the alkylation of amines via reductive amination of aldehydes using molecular dihydrogen as a reductant in the presence of a manganese pyridinyl-phosphine complex as a pre-catalyst. After the initial condensation step, the reduction of imines formed in situ is performed under mild conditions (50-100 °C) with 2 mol% of catalyst and 5 mol% of tBuOK under 50 bar of hydrogen. Excellent yields (>90%) were obtained for a large combination of aldehydes and amines (40 examples), including aliphatic aldehydes and amino-alcohols.
- Wei, Duo,Bruneau-Voisine, Antoine,Valyaev, Dmitry A.,Lugan, No?l,Sortais, Jean-Baptiste
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p. 4302 - 4305
(2018/05/03)
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- Acidic solvent-free removal of amine-protecting diphenylmethyl groups in the presence of camphorsulfonic acid
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We developed novel reaction conditions for the removal of the diphenylmethyl group, which is one of the most important protecting groups for amines. The reaction was promoted by adding one equivalent of camphorsulfonic acid in aqueous media, and no acidic
- Yamagiwa, Noriyuki,Okabe, Takayuki,Suto, Yutaka,Iwasaki, Genji
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p. 1456 - 1458
(2017/11/04)
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- Asymmetric Syntheses of (-)-ADMJ and (+)-ADANJ: 2-Deoxy-2-amino Analogues of (-)-1-Deoxymannojirimycin and (+)-1-Deoxyallonojirimycin
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The asymmetric syntheses of (-)-ADMJ and (+)-ADANJ, the 2-deoxy-2-amino analogues of (-)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin, are described herein. Methodology for the ring-closing iodoamination of bishomoallylic amines followed by in situ ring-expansion (via intramolecular ring-opening of the corresponding aziridinium intermediates with a tethered carbamate moiety) to give oxazolidin-2-ones was initially optimized on a model system. Subsequent application of this methodology to two enantiopure bishomoallylic amines (which were produced via aminohydroxylation of an α,β-unsaturated ester, partial reduction, and reaction of the corresponding aldehyde with vinylmagnesium bromide) also proceeded with concomitant N-debenzylation to afford the corresponding diastereoisomerically pure (>99:1 dr) oxazolidin-2-ones. Subsequent deprotection of these enantiopure templates gave (-)-ADMJ and (+)-ADANJ as single diastereoisomers in 16% and 24% overall yield, respectively.
- Davies, Stephen G.,Figuccia, Aude L. A.,Fletcher Paul, Ai M.,Roberts,Thomson, James E.
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p. 6481 - 6495
(2016/08/16)
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- Thiol activated prodrugs of sulfur dioxide (SO2) as MRSA inhibitors
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Drug resistant infections are becoming common worldwide and new strategies for drug development are necessary. Here, we report the synthesis and evaluation of 2,4-dinitrophenylsulfonamides, which are donors of sulfur dioxide (SO2), a reactive sulfur species, as methicillin-resistant Staphylococcus aureus (MRSA) inhibitors. N-(3-Methoxyphenyl)-2,4-dinitro-N-(prop-2-yn-1-yl)benzenesulfonamide (5e) was found to have excellent in vitro MRSA inhibitory potency. This compound is cell permeable and treatment of MRSA cells with 5e depleted intracellular thiols and enhanced oxidative species both results consistent with a mechanism involving thiol activation to produce SO2.
- Pardeshi, Kundansingh A.,Malwal, Satish R.,Banerjee, Ankita,Lahiri, Surobhi,Rangarajan, Radha,Chakrapani, Harinath
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p. 2694 - 2697
(2015/06/08)
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- The first asymmetric total synthesis of lycoposerramine-R
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The first asymmetric total synthesis of lycoposerramine-R, a Lycopodium alkaloid possessing a novel skeleton, was accomplished by a strategy featuring the stereoselective intramolecular aldol cyclization giving a cis-fused 5/6 bicyclic skeleton and a new method for the construction of the pyridone ring via the aza-Wittig reaction.
- Ishida, Hiroaki,Kimura, Shinya,Kogure, Noriyuki,Kitajima, Mariko,Takayama, Hiromitsu
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p. 7762 - 7771
(2015/07/15)
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- AGENTS FOR TREATING PAIN AND USES THEREOF
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This invention relates to: (a) compounds and salts thereof that, inter alia, treat pain; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Paragraph 0872
(2014/06/25)
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- Concise, stereodivergent and highly stereoselective synthesis of cis-and trans-2-substituted 3-hydroxypiperidines-development of a phosphite-driven cyclodehydration
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A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide.
- Huy, Peter H.,Westphal, Julia C.,Koskinen, Ari M.P.
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supporting information
p. 369 - 383
(2014/03/21)
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- Cyclization of nitroacetamide derivatives with a tethered phenyl ring in triflic acid
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N-(3-Hydroxypropyl)-2-nitro-N-(ω-phenylalkyl)acetami-des underwent intramolecular cyclization in triflic acid to afford the corresponding hydroxyimino six- to nine-membered benzofused lactams. The six-membered derivative slowly transformed into 2-(3-hydroxypropyl)isoquinolin-3-one. NMR spectroscopic analysis in situ provided information on the cationic species involved in the reaction, permitting a mechanism to be postulated. This reaction provides a novel and simple route to benzofused lactams.
- Fanté, Bamba,Soro, Yaya,Siaka, Sorho,Marrot, Jér?me,Coustard, Jean-Marie
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p. 969 - 974
(2014/05/06)
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- Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii
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The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasma gondii is reported. Using in vitro cultures of parasites in human fibroblasts, we determined that most of these compounds selectively disrupted Toxoplasma microtubules, and several displayed sub-micromolar potency against the parasite. The most potent compound was N1,N1-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3- benzenediamine (18b), which displayed an IC50 value of 36 nM against intracellular T. gondii. Based on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li, C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. Agents Chemother. 2010, 54, 1453], an antimitotic structure-activity relationship for dinitroanilines versus Toxoplasma is presented.
- Endeshaw, Molla M.,Li, Catherine,Leon, Jessica De,Yao, Ni,Latibeaudiere, Kirk,Premalatha, Kokku,Morrissette, Naomi,Werbovetz, Karl A.
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scheme or table
p. 5179 - 5183
(2010/10/03)
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- TRICYCLIC HETEROCYCLIC DERIVATIVES
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The present invention relates to a tricyclic heterocyclic derivative of Formula (I) wherein the variables are as defined in the specification. The present invention further relates to pharmaceutical compositions comprising these compounds and to their use in therapy, in particular for the treatment of serotonin-mediated disorders such as obesity, schizophrenia and cognitive dysfunction.
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Page/Page column 97
(2009/04/25)
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- Phenylpropanoic acid derivatives bearing a benzothiazole ring as PPARδ-selective agonists
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To find novel PPARδ-selective agonists, we designed and synthesized phenylpropanoic acid derivatives bearing 6-substituted benzothiazoles. Optimization of this series led to the identification of a potent and selective PPARδ agonist 17. Molecular modeling suggested that compound 17 occupies the Y-shaped pocket of PPARδ appropriately.
- Fujieda, Hiroki,Usui, Shinya,Suzuki, Takayoshi,Nakagawa, Hidehiko,Ogura, Michitaka,Makishima, Makoto,Miyata, Naoki
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p. 4351 - 4357
(2008/02/12)
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- Method of treating addiction or dependence using a ligand for a monoamine receptor or transporter
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One aspect of the present invention relates to a method of treating of drug addiction or drug dependence in a mammal, comprising the step of administering to a mammal in need thereof a therapuetically effective amount of a heterocyclic compound, e.g., a 3-substituted piperidine. In a preferred embodiment, the method of the present invention treats cocaine addiction or methamphetamine addiction.
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- FUSED BICYCLIC PYRIMIDINE DERIVATIVES
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A novel fused bicyclic pyrimidine derivative or a salt thereof that acts as a tachykinin receptor antagonist and, in particular, as an NK1 receptor antagonist is represented by the following general formula (1): wherein the rings A and B are each a benzene ring having 1 to 3 substituents (any adjacent two of which may be bound to one another to form a ring); the ring C is a nitrogen-containing ring; m is 1 or 2; and n is 2 or 3.
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- Solution-phase parallel synthesis of substituted 1,2-ethyl and 1,3-propyl diamines
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A solution-phase synthesis for the preparation of substituted 1,2-ethyl and 1,3-propyl diamines has been developed for the purpose of producing diverse lead generation libraries with a minimal scaffold. Crude products were obtained in high purity and further purified through mass guided preparative HPLC.
- Dagan, Ido D.,Lowden, Christopher T.
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p. 7575 - 7577
(2007/10/03)
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- Ligands for monoamine receptors and transporters, and methods of use thereof
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One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.
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- Heterocyclic analgesic compounds and methods of use thereof
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One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including opiate receptors, other G-protein-coupled receptors, and ion channels. An additional aspect of the present invention relates to the use of the novel heterocyclic compounds as analgesics.
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- Heterocyclic analgesic compounds and methods of use thereof
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One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including opiate receptors, other G-protein-coupled receptors, and ion channels. An additional aspect of the present invention relates to the use of the novel heterocyclic compounds as analgesics.
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- Heterocyclic analgesic compounds and methods of use thereof
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One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including opiate receptors, other G-protein-coupled receptors, and ion channels. An additional aspect of the present invention relates to the use of the novel heterocyclic compounds as analgesics.
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- Convenient methods for the hydrolysis of oxazolidinones to vicinal aminoalcohols
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We have developed two convenient methods for hydrolysis of 2-oxazolidinones to the corresponding vicinal aminoalcohols. N-Substituted oxazolidinones can be readily hydrolyzed using Dowex 1×8-100 resin. N-Unsubstituted oxazolidinones cannot be hydrolyzed using Dowex resins but are effectively hydrolyzed using polymer supported ethylenediamine.
- Katz, Steven J,Bergmeier, Stephen C
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p. 557 - 559
(2007/10/03)
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- Pyrimidinone-1,3-oxathiolane derivatives with antiviral activity
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Compounds of formula (I) wherein Ra and Rb the same or different, are hydrogen atoms, acyl groups deriving from a lower carboxylic acid or chains of formula (a) useful as reverse transcriptase inhibitors antiviral activity are described.
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- Compounds having a plurality of nitrogenous substitutents
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Novel compounds having the formula: STR1wherein the constituent variables are defined herein. The compounds are constructed to include a central aromatic, aliphatic, or heterocyclic ring system. Attached to the central ring system are two linear groups having nitrogenous moieties that are derivatized with chemical functional groups. The ring system can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring, that may also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the these compounds. In accordance with certain embodiments of the invention, libraries of such compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the libraries.
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS
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Novel compounds having the formula: STR1 wherein the constituent variables are defined herein. The compounds are constructed to include a central aromatic, aliphatic, or heterocyclic ring system. Attached to the central ring system are two linear groups having nitrogenous moieties that are derivatized with chemical functional groups. The ring system can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring, that may also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the these compounds. In accordance with certain embodiments of the invention, libraries of such compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the libraries.
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- Nitrogenous macrocyclic compounds
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PCT No. PCT/US96/04215 Sec. 371 Date Sep. 19, 1997 Sec. 102(e) Date Sep. 19, 1997 PCT Filed Mar. 27, 1996 PCT Pub. No. WO96/30377 PCT Pub. Date Oct. 3, 1996Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring system. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.
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- New anti-HIV derivatives: Synthesis and antiviral evaluation
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A small focused library of 18 compounds incorporating the motif 1,3-(N,N'-dibenzyl)diamino-2-propanol has been synthesized, using adapted synthetic methodologies. These series of compounds were evaluated for their in vitro anti-HIV activity on infected MT4 cells (syncytium formation observation). Some of the new synthesized compounds show potent anti-HIV activities. EC50 values for compounds (31, 40, 34, 37 and 46Scheme 3(i) Na2SO4, CH2Cl2, rt; (ii) NaBH4, EtOH, 0°C; (iii) Boc2O, CH2Cl2, 0°C; (iv) DMSO, TFAA, Et3N, CH2Cl2, -60°C; (v) TFA, CH2Cl2, rt; (vi) BOP, RCOOH, Et3N, CH2Cl2, rt.) range from 0.1 to 1μM. In order to determine at which level these new derivatives interfere with the HIV replicative cycle, inhibition assays on recombinant HIV protease and HIV integrase have been performed. None of the compounds were found active on these two enzymatic targets. Experiments are in progress in order to identify their biological target within the HIV replicative cycle. Copyright (C) 2000 Elsevier Science Ltd.
- De Michelis,Rocheblave,Priem,Chermann,Kraus
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p. 1253 - 1262
(2007/10/03)
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- An efficient and stereoselective construction of the core structure of the manzamines via an intramolecular Michael reaction
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A strategically functionalized tricyclic subunit of the manzamines was efficiently synthesized with complete stereochemical control using a combination of an intramolecular Michael reaction of a pyroglutamic acid derivative and a hydrogenation.
- Brands,DiMichele
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p. 1677 - 1680
(2007/10/03)
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- Solution-phase synthesis of novel linear oxyamine combinatorial libraries with antibacterial activity
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Use of solution phase combinatorial library synthesis led to the discovery of several oxyaminecontaining antibacterial compounds. Solution-phase simultaneous addition of meta-substituted benzyl bromides and 'fix-last' combinatorial strategies were used to prepare libraries. Additional structure-activity relationship studies were conducted by reductive cleavage of the oxyamine moiety and led to loss of antibacterial activity. Several single compounds were designed and synthesized on the basis of library screening results and were shown to have antibacterial activity.
- Kung, Pei-Pei,Bharadwaj, Ramesh,Fraser, Allister S.,Cook, Daniel R.,Kawasaki, Andrew M.,Cook, P. Dan
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p. 1846 - 1852
(2007/10/03)
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- Enantioselective synthesis of 1,2-, 1,3- and 1,4- aminoalcohols by the addition of dialkylzincs to 1,2-, 1,3- and 1,4- aminoaldehydes
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Chiral 1,3- and 1,4- aminoalcohols were prepared by the addition of functionalized dialkylzincs to 1,3-aliphatic and 1,4-unsaturated aminoaldehydes with good to excellent enantioselectivity. Syn- or anti-1,2- aminoalcohols are stereoselectively obtained by asymmetric addition of dialkylzincs to α-aminoaldehydes depending on the choice of the chiral catalyst. A chelate controlled addition is observed if less than stoichiometric amounts of Ti(Oi-Pr)4 are used.
- Lutz, Christian,Lutz, Volker,Knochel, Paul
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p. 6385 - 6402
(2007/10/03)
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- Triazinines: Synthesis and proteolytic decomposition of a new class of cyclic triazenes
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The reaction of 1-azido-3-chloropropane with various Grignard reagents and subsequent treatment with anhydrous isopropylamine results in the formation of the corresponding azimine. If the initial magnesium-triazene complex if first hydrolyzed with Dowex resin and then concentrated, the resultant linear triazene begins self-catalyzed cyclization to form the six- membered-ring triazenes as the major product, with HCl as the byproduct. Addition of an amine, at reduced temperature, allows for the neutralization of the byproduct, HC1, which would otherwise react with the linear triazene and the cyclic six-membered-ring triazene to form hydrolysis products. We have assigned the trivial name of triazinines to this new class of cyclic triazenes. The hydrolytic decomposition of these compounds in mixed acetonitrile-aqueous buffers predominantly forms 3-(alkylamino)-1-propanol and lesser amounts of the rearranged alcohol 1-(alkylamino)-2-propanol and N- alkyl-2-propenamine. The rate of hydrolysis of 1-alkyltriazinines is approximately equal to that of the analogous 1,3,3-trialkyltriazenes, about three times slower than that of the analogous 1-alkyltriazolines, and varies in the order ethyl > butyl > 3,3-diethoxypropyl > benzyl. As was true for other triazenes, the mechanism of the decomposition was found to be specific acid-catalyzed (A1), involving rapid reversible protonation followed by rate- limiting formation of a 3-(alkylamino)propyldiazonium ion. The slopes of the log k(obs) versus pH plots were near -1.0 The solvent deuterium isotope effect, k(H)2O/k(D)2O, was in all cases 1.0 and ranges from 0.82 for 1- benzyltriazinine to 0.89 for 1-ethyltriazinine. The activation parameters of the proteolytic decomposition of a series, 1-ethyltriazinine, 1- ethyltriazoline, 1,3,3-triethyltriazene, and 1-ethyl-3-methyltriazene, had similar values for ΔH(+) (+9 → 12 kcal/mol) and ΔS(+) (+7 → 15 eu), respectively.
- Schmidt,Schmidt, Brigitte F.,Snyder,Snyder, Emily J.,Carroll,Carroll, Robin M.,Farnsworth,Farnsworth, David W.,Michejda,Michejda, Christopher J.,Smith R.H.,Smith Jr., Richard H.
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p. 8660 - 8665
(2007/10/03)
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- Regiochemistry of mercury(II) oxide oxidation of unsymmetrical N,N-disubstituted hydroxylamines
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Mercury(II) oxide oxidation of N,N-disubstituted hydroxylamines with the α and α' carbon atoms containing one and two hydrogen atoms, respectively, gave aldonitrones in a highly regioselective manner. Removal of the α proton is involved in the rate determining step as shown by primary kinetic isotope effect.
- Ali, Sk. Asrof,Hashmi, S. M. Azhar,Siddiqui, Mohammad N.,Wazeer, Mohammed I. M.
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p. 14917 - 14928
(2007/10/03)
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- N-t-butoxycarbonyl protection of primary and secondary amines in the hydroboration reaction: Synthesis of amino alcohols
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The use of the BOC group as a protecting group in the hydroboration of aminoalkenes is described. The isolated yields of amino alcohols via the hydroboration-oxidation sequence are excellent.
- Kabalka,Li,Pace
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p. 2135 - 2143
(2007/10/02)
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- Selective O-benzylation of aminoalkanols
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A simple and one-step method has been developed for selective O-benzylation of aminoalkanols. Study of steric effects shows the best selectivity in adjacent 1°-OH vs 2°-CHNH2 and decreased selectivity in 2°-OH vs 1°-CH2NH2 and non adjacent aminoalkanol.
- Hu,Cassady
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p. 907 - 913
(2007/10/02)
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- A One-pot Synthesis of Nitrohydroxylated Pyrrolidine and Piperidine Ring Sytems by Tandem Michael-Henry Reaction
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Nitrohydroxylated pyrrolidine and piperidine ring systems are coveniently obtained through a one-pot procedure involving sequential Michael-Henry reaction between nitroethylene and a nitrogen nucleophile incorporating a suitably placed precursor for the generation either reductively or oxidatively of an aldehyde group which is directly trapped in the subsequent nitroaldolization step.
- Barco, Achille,Benetti, Simonetta,Risi, Carmela De,Pollini, Gian P.,Romagnoli, Romeo,Zanirato, Vinicio
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p. 9293 - 9296
(2007/10/02)
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- A new approach to the synthesis of N-arylakyl aminoalcohols
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N-arylmethyl substituted aminoalcohols were prepared by enantioselective reductive amination of different aromatic and heteroaromatic aldehydes using aminoalcohols and NaBH3CN as a catalyst. The reaction of optically active aminoalcohols afforded optically pure products.
- Leskovsek,Urleb
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p. 1415 - 1424
(2007/10/02)
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- SIMPLE SYNTHESIS OF 3-(N-ALKYLAMINO)-1-PROPANOLS
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Various 3-(N-alkylamino)-1-propanols were obtained by the lithium aluminum hydride reduction of the products of the reaction of 3-amino-1-propanol with carbonyl compounds.This method for the synthesis of aminopropanols is applicable in the case of optimal electrophilicity of the carbonyl component.
- Artyushin, O. I.,Petrovskii, P. V.,Mastryukova, T. A.,Kabachnik, M. I.
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p. 1911 - 1913
(2007/10/02)
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- Substituted benzamide derivatives, for enhancing gastrointestinal motility
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Compounds of the formula: STR1 wherein R is hydrogen, alkoxycarbonyl, benzyloxycarbonyl, heteroarylalkyl, phenylalkenyl, or --T--(Y)p --R6 (wherein T is single bond or alkylene, Y is oxygen, sulfur or carbonyl, R6 is phenyl, substituted phenyl, naphthyl, or diphenylmethyl, and p is 0 or 1, provided that when T is single bond, p is 0); R1 is halogen, hydroxy, alkoxy, cycloalkyloxy, alkenyloxy, alkynyloxy, alkoxy interrupted by oxygen or carbonyl, alkylthio, amino, monosubstituted amino, or a substituted alkoxy; R2 is hydrogen; R3 is hydrogen, halogen, amino, alkylamino, dialkylamino, alkanoylamino, or nitro; R4 is hydrogen, halogen, nitro, sulfamoyl, alkylsulfamoyl, or dialkylsulfamoyl; or any two adjacent groups of the R1, R2, R3 and R4 may combine to form alkylenedioxy, and the remaining two groups are each hydrogen; R5 is hydrogen or alkyl; X is alkylene; m and n are each 1 or 2; provided that at least one of the groups R2, R3 and R4 is other than hydrogen, and acid addition salts, quaternary ammonium salts and N-oxide derivatives thereof, processes for preparation thereof, and pharmaceutical composition containing the same. Said compounds, salts and N-oxide derivatives thereof show excellent gastrointestinal motility enhancing activity.
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- HYDROBORATION OF UNSATURATED AMINES VIII A CONVENIENT SYNTHESIS OF AMINO-3 PROPANOL-1
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A new route with increased yield and stereoselectivity is reported for the synthesis of amino-3 propanols-1.It involved a hydroboration-oxidation reaction using bora- 9 bicyclo nonane.The amino group was protected by a phosphorylated grouping giving rise to novel and potentially useful phosphorylated reagents.
- Benmaarouf-Khallaayoun, Z.,Baboulene, M.,Speziale, V.,Lattes, A.
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p. 233 - 242
(2007/10/02)
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- Preparation of Azetidines from 1,3-Aminopropanols
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The preparation of 1,3-amino alcohols by the reduction of azetidin-2-ones with diborane is described.New methods for the cyclisation of the aminopropanols to the corresponding azetidines are reported; these methods centre on the use of a modified Mitsunobu reaction.
- Sammes, Peter G.,Smith, Steven
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p. 2415 - 2420
(2007/10/02)
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- On the Synthesis of Azetidines from 3-Hydroxypropylamines
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New methods are described for preparing azetidines from 3-hydroxypropylamines involving the use of triphenylphosphine and diethyl azodicarboxylate and related reagents.
- Sammes, Peter G.,Smith, Steven
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p. 682 - 684
(2007/10/02)
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