- First Total Synthesis of the Cytotoxic Carbazole Alkaloid Excavatine-A and Regioselective Annulation to Pyrano[2,3-a]carbazoles and [1,4]Oxazepino[2,3,4-jk]carbazoles
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We describe the first total synthesis of the cytotoxic carbazole alkaloid excavatine-A. The carbazole framework was constructed through double C–H bond activation of a diarylamine by using our palladium(II)-catalyzed oxidative cyclization. Treatment of th
- Brütting, Christian,Kataeva, Olga,Schmidt, Arndt W.,Kn?lker, Hans-Joachim
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- Structure-Based Optimization of 3-Phenyl-N-(2-(3-phenylureido)ethyl)thiophene-2-sulfonamide Derivatives as Selective Mcl-1 Inhibitors
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Selective Mcl-1 inhibitors may overcome the drug resistance caused by current anti-apoptotic Bcl-2 protein inhibitors in tumors with Mcl-1 overexpression. Based on previously discovered compounds with a 3-phenylthiophene-2-sulfonamide core moiety, in this work, we have obtained new compounds with improved binding affinity and/or selectivity under the guidance of structure-based design. The most potent compounds achieved sub-micromolar binding affinities to Mcl-1 (Ki～ 0.4 μM) and good cytotoxicity (IC5015N-heteronuclear single-quantum coherence NMR spectra suggested that these compounds bound to the BH3-binding groove on Mcl-1. Several cellular assays revealed that FWJ-D4 as well as its precursor FWJ-D5 effectively induced caspase-dependent apoptosis, and their target engagement at Mcl-1 was confirmed by co-immunoprecipitation experiments. Treatment with FWJ-D5 at 50 mg/kg every 2 days on an RS4;11 xenograft mouse model for 22 days led to 75% reduction in tumor volume without body weight loss.
- Li, Yan,Fan, Wenjie,Gong, Qineng,Tian, Jie,Zhou, Mi,Li, Qing,Uwituze, Laura B.,Zhang, Zhichao,Hong, Ran,Wang, Renxiao
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p. 10260 - 10285
(2021/07/26)
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- Synthesis of aspidodispermine via pericyclic framework reconstruction
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A divergent approach to the pyrroloquinoline scaffold as present in the class of Aspidosperma alkaloids was developed. As a case study, abundant and renewable nicotinic acid was transformed via pericyclic framework reconstruction into aspidodispermine, a unique member of pyrroloquinoline alkaloids. The sequence comprises a [2 + 2]-photocycloaddition, a Ramberg-B?cklund contraction, and a strain-promoted formal electrocyclic rearrangement of a bicyclo[2.2.0]hexene and is potentially extendable to pyrroloindole scaffolds as present in the ibophyllidine alkaloids.
- Reu?, Franziska,Heretsch, Philipp
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p. 3956 - 3959
(2020/05/19)
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- Dibenzothiophene Sulfoximine as an NH3 Surrogate in the Synthesis of Primary Amines by Copper-Catalyzed C?X and C?H Bond Amination
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Readily accessible dibenzothiophene sulfoximine is an NH3 surrogate allowing the preparation of free anilines by copper-catalyzed cross-coupling reactions with aryl iodides or amides followed by radical S?N bond cleavage. The one-pot/two-step r
- Li, Zhen,Yu, Hao,Bolm, Carsten
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supporting information
p. 9532 - 9535
(2017/08/01)
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- IMPROVED PROCESS FOR THE PREPARATION OF [3R,5R]-2-FLUOROPHENYL-β,δ- DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(2-HYDROXYPHENYLAMINO)- CARBONYL]-1H-PYRROLE-1-HEPTANOIC ACID, SODIUM SALT
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The present invention relates to an improved process for the preparation of [3R,5R]-2-fluorophenyl-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(2-hydroxyphenylamino)-carbonyl]-1H-pyrrole-1-heptanoic acid sodium salt compound of formula- 1 represented by the following structural formula:
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- Metal-Free Reduction of Aromatic and Aliphatic Nitro Compounds to Amines: A HSiCl3-Mediated Reaction of Wide General Applicability
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A new, mild, metal-free, HSiCl3-mediated reduction of both aromatic and aliphatic nitro groups to amines that is of wide general applicability, tolerant of many functional groups, and respectful of the stereochemical integrity of stereocenters is reported.
- Orlandi,Tosi,Bonsignore,Benaglia
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supporting information
p. 3941 - 3943
(2015/09/01)
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- PROCESS FOR THE REDUCTION OF NITRO DERIVATIVES TO AMINES
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Disclosed is a novel process for the reduction of nitro groups to amino derivatives, based on the use of trichlorosilane and an organic base, which is efficient from the chemical standpoint and of wide general applicability.
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Page/Page column 6; 7
(2014/03/26)
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- Synthesis of perspicamide A and related diverse analogues: Their bioevaluation as potent antileishmanial agents
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The first protocol for the synthesis of perspicamide A and related diverse analogues has been developed from economical and readily available starting materials. Furthermore, a few synthesized analogues, 24a, 24b, 24c, 24d, and 24l, exhibited potent activ
- Pandey, Anand Kumar,Sharma, Rashmi,Shivahare, Rahul,Arora, Ashish,Rastogi, Neeraj,Gupta, Suman,Chauhan, Prem M. S.
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p. 1534 - 1546
(2013/04/10)
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- Patterned recognition of amines and ammonium ions by a stimuli-responsive foldamer-based hexameric oligophenol host
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A stimuli-responsive hexameric oligophenol host undergoes amine-induced co-operative folding from a more fluorescent, more linear structure into less fluorescent, more curved or helically folded states, enabling easy identification and classification of the bound amine guests. The Royal Society of Chemistry 2013.
- Sun, Chang,Ren, Changliang,Wei, Yuchen,Qin, Bo,Zeng, Huaqiang
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supporting information
p. 5307 - 5309
(2013/06/27)
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- Synthesis of substituted 6H-benzo[c]chromenes: A palladium promoted ring closure of diazonium tetrafluoroborates
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A highly efficient palladium-catalysed phenyl diazonium tetrafluoroborate participation of C-H activation ring closure protocol has been developed. A series of 6H-benzo[c]chromenes have been synthesized by intramolecular cyclization of ortho diazonium sal
- Zhou, Jing,Huang, Liang-Zhu,Li, You-Qiang,Du, Zhen-Ting
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p. 7036 - 7039
(2013/01/15)
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- Syntheses and characterization of nimesulide derivatives for dual enzyme inhibitors of both cyclooxygenase-1/2 and 5-lipoxygenase
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Cyclooxygenase-1/2 (COX-1/2) and 5-lipoxygenase (5-LOX) are enzymes in two different pathways in the inflammatory process. In the present study, a variety of new nimesulide derivatives were synthesized through incorporation of a 5-LOX pharmacophore into nimesulide followed with some structural modifications, which were then characterized for dual enzyme inhibitors for these two types of enzymes. Their structure-activity relationships (SARs) were studied, and compound 20f was found to be an excellent dual enzyme inhibitor. Its binding conformation and interaction mode were studied with molecular docking experiments. Compound 20f could become a lead compound for further development for potential anti-inflammatory drugs.
- Li, Yue,Chen, Shu-Han,Ou, Tian-Miao,Tan, Jia-Heng,Li, Ding,Gu, Lian-Quan,Huang, Zhi-Shu
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experimental part
p. 2074 - 2083
(2011/05/05)
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- Total syntheses of Tardioxopiperazine A, Isoechinulin A, and Variecolorin C
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Chemical equations presented. First total syntheses of the isoechinulin-type alkaloids: Tardioxopiperazine A, Isoechinulin A, and Variecolorin C have been achieved from a common key intermediate 5, which was derived from a regiocontrolled Stille cross-coupling reaction of an allylindium reagent.
- Dai, Qipu,Xie, Xingang,Xu, Shiyan,Ma, Donghui,Tang, Shibing,She, Xuegong
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supporting information; experimental part
p. 2302 - 2305
(2011/06/26)
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- Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N-methyl- d -aspartate receptor
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The N-methyl- d-aspartate (NMDA) receptor as a type of ionotropic glutamatergic receptors is essential for physiological processes such as learning, memory and synaptic plasticity. A glutamate-induced overactivation of these receptors, accompanied by increased intracellular calcium concentration, causes cell injury and leads to a large number of acute or chronic neurological disorders, such as stroke, trauma, Parkinson's disease and Alzheimer's disease. In an attempt to visualise the glutamatergic neurotransmission in vivo with positron emission tomography, novel fluoroethoxy- and methoxy-substituted reference compounds based on the lead structure of a hydantoin-substituted indole-2-carboxylic acid were synthesised. The affinities towards the glycine binding site of the NMDA receptor showed Ki values between 322 and 11 nM and the lipophilicities ranged from logD values of 1.51 to 2.53. On the basis of these results, precursor compounds were synthesised containing a phenolic hydroxy moiety to obtain the radiolabelled ligands through an alkylation reaction. Radiosynthesis was achieved by labelling the precursor ethyl 4,6-dichloro-3-((3-(4-hydroxyphenyl)-2,4-dioxoimidazolidin-1-yl)methyl)- indole-2-carboxylate with 2-[18F]fluoroethyl tosylate or [ 11C]methyl iodide and subsequent cleavage of the ethyl ester moiety. This gave the final products in overall decay-corrected radiochemical yields of 5-7% and 6-9% and specific activities of 24-67 GBq/μmol and 8-26 GBq/μmol, respectively. Copyright
- Bauman,Piel,Hoehnemann,Krauss,Jansen,Solbach,Dannhardt,Roesch
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experimental part
p. 645 - 656
(2012/01/06)
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- Selective alkylation of aminophenols
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O-or N-Alkylated derivatives of aminophenols are important synthetic intermediates in organic synthesis. A series of aminophenols were selectively alkylated on their hydroxyl group in good yields via benzaldehyde protection of the amino group, subsequent alkylation, and hydrolysis; or on their amino group via imination and following reduction. ARKAT USA, Inc.
- Wang, Renchao,Xu, Jiaxi
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experimental part
p. 293 - 299
(2010/10/02)
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- Chemoselective reduction of azides catalyzed by molybdenum xanthate by using phenylsilane as the hydride source
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A chemoselective, neutral, and efficient strategy for the reduction of azides to corresponding amines catalyzed by dioxobis(N,N,-diethyldithiocarbamato) molybdenum complex (1, MoO2[S2CNEt2]2) in the presence of phenylsilane is discovered. This chemoselective reduction strategy tolerates a variety of reducible functional groups.
- Maddani, Mahagundappa R.,Moorthy, Saravana K.,Prabhu, Kandikere R.
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supporting information; experimental part
p. 329 - 333
(2010/03/01)
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- PROCESS FOR PRODUCING AROMATIC AMINE HAVING ARALKYLOXY OR HETEROARALKYLOXY GROUP
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There is provided a process for producing an aromatic amine compound having an aralkyloxy or heteroaralkyloxy group, in which an aromatic nitro compound having an aralkyloxy or heteroaralkyloxy group is reacted with hydrogen under mild conditions in accordance with a simple procedure while preventing the removal of aralkyl or heteroaralkyl group and keeping stable the other substituents on the aryl group or heteroaryl group so that the substituent does not take part in the reaction, to selectively reduce only the nitro group. The present invention is directed to a process for producing an aromatic amine compound which comprises reacting an aromatic nitro compound represented by the general formula (1): wherein Ar represents an aryl group or heteroaryl group which may have a substituent, and Z represents a divalent aromatic group which may have a substituent, with hydrogen in the presence of a metal catalyst to obtain an aromatic amine compound represented by the general formula (2): wherein Ar and Z have the meaning as defined above.
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Page/Page column 5
(2009/12/07)
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- SUBSTITUTED 5-CARBOXYAMIDE PYRAZOLES AND [1,2,4]TRIAZOLES AS ANTIVIRAL AGENTS
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The present invention provides compounds of formula I wherein X, Y, R1-R7 are as defined herein. Compositions containing these compounds, and methods for inhibiting HCV RNA-dependent RNA polymerase and treating hepatitis C and related disorders using thes
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Page/Page column 54-55
(2008/06/13)
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- HETEROCYCLYL COMPOUNDS
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Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein A, B, D, Z, R1, R2a , R2b, and Rx are as defined in the specification, a process for the preparation of such compounds, pharm
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Page/Page column 31
(2010/02/11)
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- Synthesis of 7-alkoxy/hydroxy-α-methyltryptamines
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A simple method for the preparation of 7-alkoxy/hydroxy-α -methyl-DL-tryptamines is reported. The key steps of the synthesis are the Japp-Klingemann coupling of 2-piperidone-3-carboxylic acid 3 with diazonium salts 4, the Fischer-type cyclization of hydrazones 5 to β-carboline derivatives 6 and their hydrolysis to title compounds 8.
- Dubash, Nauzer P.,Mangu, Naveen K.,Satyam, Apparao
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p. 1791 - 1799
(2007/10/03)
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- VLA-4 inhibitor compounds
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Compounds that selectively inhibit the binding of ligands to alpha4beta1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.
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- Synthesis of deuterium-labeled atorvastatin and its metabolites for use as internal standards in a LC/MS/MS method developed for quantitation of the drug and its metabolites in human serum
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D5-labeled isotopomers of atorvastatin, atorvastatin lactone and its hydroxy metabolites were synthesized as internal standards for use in a LC/MS/MS method developed for the simultaneous quantitative determination of atorvastatin and its hydroxy metabolites in human serum. d5-Atorvastatin and d5-atorvastatin lactone were prepared from d5-aniline whereas their corresponding hydroxy metabolites were synthesized using d5-benzaldehyde.
- Chen, Bang-Chi,Sundeen, Joseph E.,Guo, Peng,Bednarz, Mark S.,Hangeland, Jon J.,Ahmed, Syed Z.,Jemal, Mohammed
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p. 261 - 270
(2007/10/03)
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- Substituted aryl and heteroaryl compounds as E-type prostaglandin antagonists
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This invention relates to substituted and unsubstituted ???(aryl- and heteroaryl-) alkyl-, alkyloxy-, alkylthio-, oxo-, thio-, and alkylamino!- heteroaryl and aryl!- alkylamino-, aminoalkyl-, alkyloxy-, and alkylthio!- aryl and heteroaryl compounds of the formula STR1 and pharmaceutically acceptable salts thereof, which are useful as antagonists of the pain enhancing effects of E-type prostaglandins, to processes for the preparation of such compounds, to pharmaceutical compositions comprising such compounds, and to methods for treating pain comprising the administration of such compounds.
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- Certain indole derivatives useful as leukotriene antagonists
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A compound of the formula STR1 in which R1 is hydrogen, halo, C1-4 alkyl, C1-4 alkoxy, nitrile, optionally protected carboxy, optionally protected tetrazolyl, trihalomethyl, hydroxy-C1-4 alkyl, aldehydo, --CH2 Z, --CH=CH--Z or --CH2 CH2 Z where Z is optionally protected carboxy or optionally protected tetrazolyl; R2 is halo, nitrile, an optionally protected acid group or --CONR7 R8 where R7 and R8 are each hydrogen or C1-4 alkyl; R3 and R4 are each hydrogen, C1-4 alkyl, optionally substituted phenyl, or C1-4 alkyl substituted by --CONR7 R8 or an optionally protected acid group; R5 is STR2 where W is --CH=CH--, --CH=N--, --N=CH--, --O-- or --S--, R9 is hydrogen, halo, C1-4 alkyl, C1-4 alkoxy or trihalomethyl, and R10 is hydrogen, C1-4 alkyl, C2-6 alkenyl, C3-6 cycloalkyl or C1-4 alkyl-C3-6 cycloalkyl; R6 is hydrogen or C1-4 alkyl; X is --O--(CH2)n CR11 R12, --CR11 R12 --, --CR11 R12.(CH2)n.CR13 R14 -- or --CR11 =CR12 -- where R11, R12, R13 and R14 are each hydrogen or C1-4 alkyl, and n is 0, 1 or 2; and Y is --O--CR15 R16 --, --CR15 =CR16 -- or --CR15 R16.CR17 R18 -- where R15, R16, R17 and R18 are each hydrogen or C 1-4 alkyl; or a salt thereof. The compounds in unprotected form are active as leukotriene antagonists.
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- N-Benzyl-Indoles, processes for their preparation and pharmaceutical compositions containing them
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A compound of the formula in which R1 is hydrogen, halo, C??? alkyl, C??? alkoxy, nitrile, optionally protected carboxy, optionally protected tetrazolyl, trihalomethyl, hydroxy-C??? alkyl, aldehydo,-CH?Z,-CH=CH-Z or-CH?CH?Z where Z is optionally protected carboxy or optionally protected tetrazolyl; R2 is halo, nitrile, an optionally protected acid group or-CONR?R? where R? and R? are each hydrogen or C??? alkyl, R3 and R? are each hydrogen, C??? alkyl, optionally substituted phenyl, or C??? alkyl substituted by-CONR?R? or an optionally protected acid group; R? is where W is-CH=CH-,-CH=N-,-N=CH-,-O-or-S-, R? is hydrogen, halo, C??? alkyl, C? ?? alkoxy or trihalomethyl, and R1? is hydrogen, C? ?? alkyl, C??? alkenyl, C??? cycloalkyl or C??? alkyl-C??? cycloalkyl; R? is hydrogen or C??? alkyl; X is-O-(CH?)nCR11CR12-,-CR11R12-,-CR11R12.(CH?) n.CR13R1?-or-CR11=CR12-where R11, R12, R13 and R1? are each hydrogen or C??? alkyl, and n is 0, 1 or 2; and Y is-O-CR1?R1?-,-CR1?=CR1?-or-CR1? R1?.CR1?R1?-where R1?, R1?, R1? and R1? are each hydrogen or C??? alkyl; or a salt thereof. The compounds in unprotected form are active as leukotriene antagonists.
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- Pharmaceutical composition and method for treating cardiovascular diseases using substituted anilides and sulfonamides
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A novel pharmaceutical composition and method is disclosed for the treatment of cardiovascular diseases, e.g. myocardial ischemia and/or arrhythmia. The method and composition include an effective amount of a compound of the formula STR1 wherein X, Y, R, R1, A, A', m, n, p, p' and B are as defined herein.
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- Development of nonsteroidal antiandrogens: 4-Nitro-3-trifluoro-methyldiphenylamines
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For the development of new nonsteroidal antiandrogens a series of 4-nitro-3-trifluoromethyldiphenylamines was synthesized and compounds were tested for their affinities to steroid hormone receptors and for antiandrogenic activities. These compounds were synthesized by reacting 4-nitro-3-trifluoromethylphenylsulfocyanamide-sodium (4) with the corresponding aromatic amines to give the N-(4-nitro-3-trifluoromethylphenylsulfonyl)-N'-phenylguanidines. The crude products were then converted to the desired diphenylamines by Smiles rearrangement and hydrolysis. 2-Hydroxy-4'-nitro-3'-trifluoromethyldiphenylamine (13), which shows a relative binding affinity (RBA) to the androgen receptor (AR) of 6.5% of that of testosterone, exerts a higher affinity than hydroxyflutamide (RBA = 4.5). Shift of the hydroxy-function to position 3 or 4 as well as N-methylation caused a decrease in AR-affinity. Compounds exerting AR-affinity were tested for antiandrogenic activity. Compound 13 showed the best antiandrogenic effect, though less than the well-known antiandrogen flutamide.
- Humm,Schneider
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- SELECTIVE REDUCTION OF AROMATIC NITRO COMPOUNDS CONTAINING O- AND N-BENZYL GROUPS WITH HYDRAZINE AND RANEY NICKEL
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The selectivity in the catalytic reduction of aromatic nitro compounds containing O-benzyl, N-benzyl or chlorine with hydrazine and Raney nickel was studied.
- Yuste, Francisco,Saldana, Manuel,Walls, Fernando
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p. 147 - 148
(2007/10/02)
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