- Photoinduced Acetylation of Anilines under Aqueous and Catalyst-Free Conditions
-
A green and efficient visible-light induced functionalization of anilines under mild conditions has been reported. Utilizing nontoxic, cost-effective, and water-soluble diacetyl as photosensitizer and acetylating reagent, and water as the solvent, a variety of anilines were converted into the corresponding aryl ketones, iodides, and bromides. With advantages of environmentally friendly conditions, simple operation, broad substrate scope, and functional group tolerance, this reaction represents a valuable method in organic synthesis.
- Yang, Yu-Ming,Yan, Wei,Hu, Han-Wei,Luo, Yimin,Tang, Zhen-Yu,Luo, Zhuangzhu
-
p. 12344 - 12353
(2021/09/02)
-
- Transition-Metal-Free and Base-Promoted Carbon-Heteroatom Bond Formation via C-N Cleavage of Benzyl Ammonium Salts
-
A facile and general method for constructing carbon-heteroatom (C-P, C-O, C-S, and C-N) bonds via C-N cleavage of benzyl ammonium salts under transition-metal-free conditions was reported. The combination of t-BuOK and 18-crown-6 enabled a wide range of substituted benzyl ammonium salts to couple readily with different kinds of heteroatom nucleophiles, i.e. hydrogen phosphoryl compounds, alcohols, thiols, and amines. Good functional group tolerance was demonstrated. The scale-up reaction and one-pot synthesis were also successfully performed.
- Liu, Long,Tang, Yuanyuan,Wang, Kunyu,Huang, Tianzeng,Chen, Tieqiao
-
p. 4159 - 4170
(2021/03/09)
-
- Optimization of ether and aniline based inhibitors of lactate dehydrogenase
-
Lactate dehydrogenase (LDH) is a critical enzyme in the glycolytic metabolism pathway that is used by many tumor cells. Inhibitors of LDH may be expected to inhibit the metabolic processes in cancer cells and thus selectively delay or inhibit growth in transformed versus normal cells. We have previously disclosed a pyrazole-based series of potent LDH inhibitors with long residence times on the enzyme. Here, we report the elaboration of a new subseries of LDH inhibitors based on those leads. These new compounds potently inhibit both LDHA and LDHB enzymes, and inhibit lactate production in cancer cell lines.
- Christov, Plamen P.,Kim, Kwangho,Jana, Somnath,Romaine, Ian M.,Rai, Ganesha,Mott, Bryan T.,Allweil, Alexander A.,Lamers, Alexander,Brimacombe, Kyle R.,Urban, Daniel J.,Lee, Tobie D.,Hu, Xin,Lukacs, Christine M.,Davies, Douglas R.,Jadhav, Ajit,Hall, Matthew D.,Green, Neal,Moore, William J.,Stott, Gordon M.,Flint, Andrew J.,Maloney, David J.,Sulikowski, Gary A.,Waterson, Alex G.
-
supporting information
(2021/04/12)
-
- Chromium-Salen Complex/Nitroxyl Radical Cooperative Catalysis: A Combination for Aerobic Intramolecular Dearomative Coupling of Phenols
-
We describe an aerobic intramolecular dearomative coupling reaction of tethered phenols using a catalytic system consisting of a chromium-salen (Cr-salen) complex combined with a nitroxyl radical. This novel catalytic system enables formation of various spirocyclic dienone products including those unable to be accessed by previously reported methods efficiently under mild reaction conditions.
- Nagasawa, Shota,Fujiki, Shogo,Sasano, Yusuke,Iwabuchi, Yoshiharu
-
p. 6952 - 6968
(2021/05/29)
-
- ANTIVIRAL 1,3-DI-OXO-INDENE COMPOUNDS
-
The invention provides compounds of Formula (I): as described herein, along with pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and methods to use these compounds, salts and compositions for treating viral infections.
- -
-
Paragraph 0401
(2021/10/22)
-
- Design, synthesis, biological evaluation and inhibition mechanism of 3-/4-alkoxy phenylethylidenethiosemicarbazides as new, potent and safe tyrosinase inhibitors
-
Tyrosinase plays important roles in many different disease related processes, and the development of its inhibitors is particularly important in biotechnology. In this study, thirty-nine 3-/4-alkoxyphenylethyli-denethiosemicarbazides were synthesized as novel tyrosinase inhibitors based on structure-based molecular design. Our experimental results demonstrated that thirty-one of them possess remarkable tyrosinase inhibitory activities with IC50 value below 1μM, and 5a, 6e, 6g and 6t did not display any toxicity to 293T cell line at the concentration of 1000μmol/L. According to the inhibitory activities, several compounds were selected for detail investigation on the structure–activity relationships (SARs), mechanisms of enzyme inhibition, inhibitory kinetics and cytotoxicity. In particular, the interaction between the selected inhibitors and the active center of tyrosinase was considered and discussed in detail based on their structural characteristics. Taken together, the results presented here demonstrated that the newly designed compounds are promising candidates for the treatment of tyrosinase-related disorders and further development of them may have significant contribution in biomedical science.
- Liao, Bing,Mai, Yuliang,Shi, Huahong,Song, Senchuan,Wang, Fei
-
p. 369 - 379
(2020/05/14)
-
- Method for removing acyl group in diazo of aryl diazonium salt
-
The invention provides a method for removing an acyl group in diazo of an aryl diazonium salt. The method is characterized in that the aryl diazonium salt and its derivative and an ortho-dicarbonyl compound undergo an illumination reaction to obtain a corresponding arylacyl product. The method has the advantages of high yield of the product, no metal involvement, and simple process.
- -
-
Paragraph 0052; 0062-0064; 0087
(2019/02/13)
-
- HETEROCYCLIC INHIBITORS OF MCT4
-
Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula I: Methods of inhibition MCT4 activity in a human or animal subject are also provided.
- -
-
Paragraph 0509
(2018/06/30)
-
- Stereoselective Metal-Free Reduction of Chiral Imines in Batch and Flow Mode: A Convenient Strategy for the Synthesis of Chiral Active Pharmaceutical Ingredients
-
The convenient, metal-free reduction of imines that contain an inexpensive and removable chiral auxiliary allowed for the synthesis of the immediate precursors of chiral active pharmaceutical ingredients (APIs). This protocol was carried out under batch and flow conditions to give the correspoding products in high yields with almost complete stereocontrol. In the presence of trichlorosilane, an inexpensive and nontoxic reducing agent, and an achiral Lewis base such as N,N-dimethylformamide, the formal syntheses of Rivastgmine, calcimimetic NPS R-568, and a Rho kinases inhibitor were successfully accomplished. For the first time, both the diastereoselective imine reduction and the auxiliary removal were efficiently performed in a micro- or mesoreactor under continuous-flow conditions, which paved the way towards the development of a practical process for the syntheses of industrially relevant, biologically active, enantiopure N-alkylamines.
- Brenna, Davide,Benaglia, Maurizio,Porta, Riccardo,Fernandes, Silvia,Burke, Anthony J.
-
supporting information
p. 39 - 44
(2017/01/14)
-
- Acetophenone derivatives: Novel and potent small molecule inhibitors of monoamine oxidase B
-
Two series of acetophenone derivatives have been designed, synthesized and evaluated for human monoamine oxidase A and B inhibitory activity in vitro. Most of the tested compounds acted preferentially on MAO-B with IC50 values in the nanomolar range and weak or no inhibition of MAO-A. In particular, compounds 1j (IC50 = 12.9 nM) and 2e (IC50 = 11.7 nM) were the most potent MAO-B inhibitors being 2.76- and 2.99-fold more active than selegiline. In addition, the structure-activity relationships for MAO-B inhibition indicated that substituents at C3 and C4 of the acetophenone moiety, particularly with the halogen substituted benzyloxy, were more favorable for MAO-B inhibition. Molecular docking and kinetic studies have been carried out to explain the binding modes of MAO-B with the acetophenone derivatives. Furthermore, the representative compounds 1j and 2e showed low neurotoxicity in SH-SY5Y cells. It may be concluded that the acetophenone derivatives could be used to develop promising lead compounds for treating neurodegenerative diseases.
- Wang, Zhi-Min,Li, Xue-Mei,Xu, Wei,Li, Fan,Wang, Jin,Kong, Ling-Yi,Wang, Xiao-Bing
-
p. 2146 - 2157
(2015/12/11)
-
- METABOTROPIC GLUTAMATE RECEPTOR NEGATIVE ALLOSTERIC MODULATORS (NAMS) AND USES THEREOF
-
Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions.
- -
-
Paragraph 00470
(2016/01/01)
-
- Metal-free trifluoromethylation of aromatic and heteroaromatic aldehydes and ketones
-
The ability to convert simple and common substrates into fluoroalkyl derivatives under mild conditions remains an important goal for medicinal and agricultural chemists. One representative example of a desirable transformation involves the conversion of aromatic and heteroaromatic ketones and aldehydes into aryl and heteroaryl β,β,β-trifluoroethylarenes and -heteroarenes. The traditional approach for this net transformation involves stoichiometric metals and/or multistep reaction sequences that consume excessive time, material, and labor resources while providing low yields of products. To complement these traditional strategies, we report a one-pot metal-free decarboxylative procedure for accessing β,β,β- trifluoroethylarenes and -heteroarenes from readily available ketones and aldehydes. This method features several benefits, including ease of operation, readily available reagents, mild reaction conditions, high functional-group compatibility, and scalability.
- Qiao, Yupu,Si, Tuda,Yang, Ming-Hsiu,Altman, Ryan A.
-
p. 7122 - 7131
(2014/08/18)
-
- Natural Products as Sources of New Fungicides (I): Synthesis and Antifungal Activity of Acetophenone Derivatives Against Phytopathogenic Fungi
-
Several series of 45 acetophenone derivatives bearing various alkyl or benzyl substituents were conveniently synthesized and their structures characterized by 1H and 13C NMR spectroscopy, HRMS and single-crystal X-ray analysis. Their in vitro antifungal activities against a panel of phytopathogenic fungi were evaluated by mycelial growth rate assay. Of them, 12 derivatives (e.g., 3a-c, 4c and 4e) exhibited more potent antifungal effects on some phytopathogens than a commercial fungicide hymexazol as positive control. In particular, compound 3b with IC50 values of 10-19μg/mL was found to be the most active in this series and might be a potential lead structure for further optimization. The preliminary structure-activity relationship (SAR) studies of a series of acetophenones are also discussed. A series of acetophenone derivatives have been synthesized and tested for their antifungal activities. Of them 12 derivatives exhibited more potent antifungal effects on some phytopathogens than a positive control hymexazol. Especially, compound 3b (IC50=10-19μg/mL) was found to be the most active and might be a potential lead structure. The SAR of these acetophenones is also discussed.
- Ma, Ya-Tuan,Fan, Hua-Fang,Gao, Yu-Qi,Li, He,Zhang, An-Ling,Gao, Jin-Ming
-
p. 545 - 552
(2013/06/05)
-
- Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1)
-
According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of β-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A-and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC50=0.27 μM).
- Ma, Lei,Yang, Zhengyi,Li, Chenjing,Zhu, Zhiyuan,Shen, Xu,Hu, Lihong
-
experimental part
p. 643 - 648
(2012/04/10)
-
- Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues
-
Based on our pharmacophore model of the aryl diketoacids (ADKs), we designed and prepared a series of novel ADK analogues, which showed potent inhibitory activities against the NS5B polymerase in the submicromolar range. Pharmacophore-guided docking study revealed that the antiviral activities of the ADKs are highly dependent upon the aryl linker as well as the size and position of the aromatic substituent. It is of another importance that, unlike previously reported ADKs, three ADK analogues synthesized in this study effectively blocked Hepatitis C Virus (HCV) replication in the replicon systems.
- Kim, Jinyoung,Kim, Ki-Sun,Lee, Hyo Seon,Park, Kwang-Su,Park, Sun Young,Kang, Seock-Yong,Lee, Soo Jae,Park, Hyung Soon,Kim, Dong-Eun,Chong, Youhoon
-
body text
p. 4661 - 4665
(2009/04/08)
-
- Asymmetric synthesis of (S)-(-)-N-acetylcolchinol via Ullmann biaryl coupling
-
A modified Ziegler Ullmann coupling process has been developed as the key step in an effective synthesis of (S)-(-)-N-acetylcolchinol, analogues of which are selective vascular targeting agents with potential importance in cancer chemotherapy. Asymmetric induction is achieved by enamide hydrogenation using FerroTANE catalysts.
- Broady, Simon D.,Golden, Michael D.,Leonard, John,Muir, James C.,Maudet, Mickael
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p. 4627 - 4630
(2008/02/06)
-
- 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)
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- PESTICIDAL SUBSTITUTED PHENYLETHERS
-
The invention relates to the use of phenylether derivatives of formula (I), to compositions thereof for the control of pests, including arthropods and helminths.
- -
-
Page/Page column 42; 43
(2008/06/13)
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- CHEMICAL PROCESSES AND INTERMEDIATES
-
The present invention provides a process for the formation of an enamide (III) wherein each R is independently selected from (1-6C)alkyl, benzyl and C(O)(1-6C)alkyl, or two RO groups together form a (1-4C)alkylenedioxy group, comprising the steps of reductive acylation of an oxime of formula (IX) wherein each R is independently selected from (1-6C)alkyl, benzyl and C(O)(1-6C)alkyl, or two RO groups together form a (1-4C)alkylenedioxy group, and the hydroxy group may optionally be protected by a hydroxy protecting group; and thereafter if necessary, removal of any protecting groups. Intermediates to the enamide (III) and methods for their preparation are also described.
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Page/Page column 37
(2008/06/13)
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- CHEMICAL PROCESSES FOR THE PREPARATION OF A COLCHINOL DERIVATIVE AND INTERMEDIATES
-
A process for the preparation of a colchinol derivative of the Formula (I): wherein each R, which may be the same or different, is selected from (1-6C)alkyl, benzyl and C(O)(1-6C)alkyl, or two RO groups together form a (1-4C)alkylenedioxy group and Ac is acetyl, by reduction of the corresponding enamide of formula (II): Colchinol derivatives with high enantiomeric purity are obtained by hydrogenation in the presence of a transition metal catalyst, particularly a catalyst selected from a rhodium complex, a ruthenium complex or an iridium complex. Novel compounds of formula (II'): wherein each R, which may be the same or different, is selected from (1-6C)alkyl, benzyl and C(O)(1-6C)alkyl, or two RO groups together form a (1-4C)alkylenedioxy group, and P is hydrogen or a suitable hydroxy protecting group are also described.
- -
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Page/Page column 35
(2008/06/13)
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- Design and syntheses of novel phthalazin-1(2H)-one derivatives as acetohydroxyacid synthase inhibitors
-
A series of 2-substituted-8-(4,6-dimethoxypyrimidin-2-yloxy)-4- methylphthalazin-1-one derivatives, 7a-7w, were designed via an ortho-substituent cyclization strategy to discover a new herbicidal lead structure. These compounds were synthesized by a seven-step route using 3-hydroxy-acetophenone as a starting material. Determination of the K i values against wild-type A. thaliana acetohydroxyacid synthase (AHAS) (EC 4.1.3.18) indicated that some of the compounds displayed good enzyme inhibition activity comparable to that of KIH-6127. The further preliminary bioassay data on weeds showed that the synthesized compounds exhibited typical injury symptoms of AHAS-inhibiting herbicides, and some of them showed broad-spectrum and high herbicidal activities in postemergence treatments against Echinochloa crusgalli, Digitaria sanguinalis, Setaria viridis, Brassica juncea, Amaranthus retroflexus, and Chenopodium album at an application rate of 150 g ai/ha. To our knowledge, this is the first report of methylphthalazin-1- one derivatives as AHAS inhibitors.
- Li, Yuan-Xiang,Luo, Yan-Ping,Xi, Zhen,Niu, Congwei,He, Yan-Zhen,Yang, Guang-Fu
-
p. 9135 - 9139
(2008/02/02)
-
- Synthesis and anticancer activity of benzyloxybenzaldehyde derivatives against HL-60 cells
-
A series of benzyloxybenzaldehyde derivatives were prepared and tested against the HL-60 cell line for anticancer activity. Preliminary structure-activity relationships were established. It was discovered that 2-(benzyloxy)benzaldehyde (17), 2-(benzyloxy)-4-methoxybenzaldehyde (26), 2-(benzyloxy)-5-methoxybenzaldehyde (27), 2-(benzyloxy)-5-chlorobenzaldehyde (28), 2-[(3-methoxybenzyl)oxy]benzaldehyde (29), 2-[(2-chlorobenzyl)oxy] benzaldehyde (30), and 2-[(4-chlorobenzyl)oxy]benzaldehyde (31) exhibited significant activity at 1-10 μM. Among them, compound 29 was the most potent one. The morphological assessment and DNA fragmentation analysis indicated that these compounds arrested cell cycle progression at G2/M phase and induced cell apoptosis. They resulted in the loss of mitochondrial membrane potential after 12 h of treatment.
- Lin, Chin-Fen,Yang, Jai-Sing,Chang, Chiung-Yun,Kuo, Sheng-Chu,Lee, Miau-Rong,Huang, Li-Jiau
-
p. 1537 - 1544
(2007/10/03)
-
- INDENE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF
-
The inventive indene derivatives of formula (I) are capable of selectively modulating the activities of peroxisome proliferator activated receptors (PPARs), causing no adverse side effects, and thus, they are useful for the treatment and prevention of disorders modulated by PPARs, i.e., metabolic syndromes such as diabetes, obesity, arteriosclerosis, hyperlipidemia, hyperinsulinism and hypertension, inflammatory diseases such as osteoporosis, liver cirrhosis and asthma, and cancer.
- -
-
Page/Page column 45
(2010/02/14)
-
- Tryptamine-based human β3-adrenergic receptor agonists. Part 3: Improved oral bioavailability via modification of the sulfonamide moiety
-
The continued SAR investigation of tryptamine-based human β3-adrenergic receptor (AR) agonists is reported. Prior efforts resulted in the identification of 2 as a potent β3-AR agonist. Further modification of the left side arylsulfonamide portion in 2 provided compounds with good cell permeability, which have potent agonistic activity for β3-AR. Cinnamylamine analog 16i exhibited an excellent agonistic profile in vitro and good oral bioavailability in rats.
- Sawa, Masaaki,Mizuno, Kazuhiro,Harada, Hiroshi,Tateishi, Hirotaka,Arai, Yukiyo,Suzuki, Shinya,Oue, Mayumi,Tsujiuchi, Hiroshi,Furutani, Yasuji,Kato, Shiro
-
p. 1061 - 1064
(2007/10/03)
-
- Efficient methods for the preparation of alkyl-aryl and symmetrical or unsymmetrical dialkyl ethers between alcohols and phenols or two alcohols by oxidation-reduction condensation
-
Oxidation-reduction condensation via alkoxydiphenylphosphines (diphenylphosphinite esters) (1), generated in situ from chlorodiphenylphosphine (2) and alcohols, 2,6-dimethyl-1,4-benzoquinone (3), and phenols proceeds smoothly to afford alkyl-aryl ethers in good to high yields under neutral conditions. In a similar fashion, a new and efficient method for the preparation of symmetrical or unsymmetrical dialkyl ethers in good to high yields is established via tetrafluoro-1,4-benzoquinone (fluoranil) (4), alcohols, and 1 formed in situ from nBuLi-treated alcohols and 2. This method is applicable also to the etherification of chiral secondary or tertiary alcohols with retention or inversion of configurations. The inverted ethers are afforded by treating chiral alkoxydiphenylphosphines and achiral alcohols, while the reaction of achiral alkoxydiphenylphosphines and chiral alcohols forms retained ethers.
- Shintou, Taichi,Mukaiyama, Teruaki
-
p. 7359 - 7367
(2007/10/03)
-
- Design and synthesis of oxadiazolidinediones as inhibitors of plasminogen activator inhibitor-1
-
A novel series of PAI-1 inhibitors containing an oxadiazolidinedione moiety were identified by high through-put screening. Optimization of substituents by parallel synthesis and the iterative design toward understanding structure-activity relationship to improve potency are described.
- Gopalsamy, Ariamala,Kincaid, Scott L.,Ellingboe, John W.,Groeling, Thomas M.,Antrilli, Thomas M.,Krishnamurthy, Girija,Aulabaugh, Ann,Friedrichs, Gregory S.,Crandall, David L.
-
p. 3477 - 3480
(2007/10/03)
-
- 2,4,6-TRISUBSTITUTED PYRIMIDINES AS PHOSPHOTIDYLINOSITOL (PI) 3-KINASE INHIBITORS AND THEIR USE IN THE TREATMENT OF CANCER
-
Compounds having formula I are provided where the variables have the values described herein. (I). Pharmaceutical formulations include the compounds or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and combinations with other agents. A method of treating a patient comprises administering a pharmaceutical formulation according to the invention to a patient in need thereof.
- -
-
-
- Discovery of α,γ-Diketo Acids as Potent Selective and Reversible Inhibitors of Hepatitis C Virus NS5b RNA-Dependent RNA Polymerase
-
α,γ-Diketo acids (DKA) were discovered from screening as selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. The diketo acid moiety proved essential for activity, while substitution on the γ position was necessary for selectivity and potency. Optimization led to the identification of a DKA inhibitor of NS5b polymerase with IC50 = 45 nM, one of the most potent HCV NS5b polymerase inhibitors reported.
- Summa, Vincenzo,Petrocchi, Alessia,Pace, Paola,Matassa, Victor G.,De Francesco, Raffaele,Altamura, Sergio,Tomei, Licia,Koch, Uwe,Neuner, Philippe
-
-
- Regioselectivity in the syntheses of enantiopure 2-benzopyrans through intramolecular cyclization of tethered lactaldehydes. Conformations of the products
-
Using titanium tetraisopropoxide, the enantiopure tethered lactaldehyde (α′S,2S)-2-(3′-hydroxy-α′-methyl-benzyloxy) propanal (6) is cyclized with complete regio- and diastereoselectivity ortho to the phenolic hydroxyl group to give (1S,3S,4R)-3,4-dihydro-1,3,-dimethyl-2-benzopyran-4,5-diol (7). Similar cyclization of the epimeric (α′R,2S)-lactaldehyde (25) yields solely the corresponding (1R,3S,4R)-4,5-diol (34). The 4,5-diacetate (26), but not (35), undergoes conformational inversion of the heterocyclic ring through significant 4,5-peri interactions between the adjacent acetoxy substituents. Spontaneous cyclizations of the corresponding phenoxide ions of the lactaldehydes (6) and (25), generated by fluoride from their silyl ethers, led to the related 4,7-diols with high regioselectivity through ring-closure para to the aromatic oxygen.
- Aggarwal, Rachna,Birkbeck, Anthony A.,Giles, Robin G.F.,Green, Ivan R.,Gruchlik, Yolanta,Oosthuizen, Francois J.
-
p. 489 - 498
(2007/10/03)
-
- Synthesis of 2-phenylbenzofuran derivatives as testosterone 5α- reductase inhibitor
-
A series of 2-phenylbenzofuran derivatives with a carbamoyl, alkylamino, or alkyloxy group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5α-reductase inhibitory activities in vitro. Against rat enzyme, the carbamoyl derivatives had more potent inhibitory activities than the alkylamino or alkyloxy derivatives, and the 6-carbamoyl derivatives tended to be more potent than the 5-carbamoyl derivatives. Against human enzyme, the 6-substituted derivatives had more potent inhibitory activities than the 5-substituted derivatives. The 6-carbamoyl and 6-alkylamino derivatives tended to show stronger inhibitory activities against human type 1 enzyme than against type 2 enzyme, but they were not largely selective.
- Ishibashi, Koki,Nakajima, Katsuyoshi,Sugioka, Yuki,Sugiyama, Mitsuo,Hamada, Takakazu,Horikoshi, Hiroyoshi,Nishi, Takahide
-
p. 226 - 240
(2007/10/03)
-
- Endothelin receptor antagonists
-
Novel indane and indene derivatives are described which are endothelin receptor antagonists.
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-
-
- Studies of the New Herbicide KIH-6127. Part I. Novel Synthesis of Methyl 6-Acetylsalicylate as a Key Synthetic Intermediate for the Preparation of 6-Acetyl Pyrimidin-2-yl Salicylates and Analogues
-
A novel synthesis of methyl 6-acetylsalicylate as a key synthetic intermediate for methyl 2-[(4,6-dimethoxypyrimidin-2-yl)oxy]-6-[1-(methoxyimino)ethyl]benzoate (KIH-6127) was studied, and directed at 6-substituted pyrimidin-2-yl salicylate herbicides and their analogues. Three synthetic approaches were successful: a modification of the Sandmeyer reaction of 6-acetylanthranilate (Method A), a direct ring-opening reaction of 3-methylphthalide using potassium permanganate, and magnesium nitrate (Method B), and a regioselective ortholithiation of the protected 3-hydroxyacetophenone (Method C). These methods were applicable for the synthesis of various 6-acyl salicylates.
- Tamaru, Masatoshi,Saito, Yoshihiro
-
p. 125 - 130
(2007/10/03)
-
- Efficient asymmetric hydrogenation of α-amino ketone derivatives. A highly enantioselective synthesis of phenylephrine, levamisole, carnitine and propranolol
-
The complexes of pyrrolidine bisphosphine ligands (CPMs) with rhodium (I) were found to be efficient catalysts for asymmetric hydrogenation of α-amino ketone hydrochloride derivatives. Utilizing this methodology, we have developed efficient asymmetric syntheses of the optically active β-amino alcohols, phenylephrine, levamisole, carnitine and propranolol.
- Sukuraba,Takahashi,Takeda,Achiwa
-
p. 738 - 747
(2007/10/02)
-
- A practical synthesis of 6-acetylsalicylic acid methyl ester
-
A new and efficient synthesis of the title compound is reported. The method includes a regioselective ortho-lithiation step in none polar solvents at an ambient temperature and the overall yield for 5 steps is more than 70% from a commercially available 3-hydroxyacetophenone.
- Tamaru,Umezu,Maejima,Kageyama,Kimura
-
p. 2749 - 2756
(2007/10/02)
-
- Conformationally Constrained Analogues of Anatoxin. Chirospecific Synthesis of s-Trans Carbonyl Ring-Fused Analogues
-
Anatoxin is the most potent agonist known for the nicotinic acetylcholine receptor (nAChR).Although it possesses a semirigid structure, it can adopt four distinctly different conformations.Further conformationally constrained analogues of anatoxin should help to refine and discriminate among the current models for activation of this receptor.This report describes three s-trans ring-fused analogues which have been synthesized starting from D-glutamic acid and 3-hydroxyacetophenone.All of them have in common a 3-oxo-13-azatricyclo2,7>tridecane structure.They represent the first fully constrained analogues of anatoxin and are designed to serve as probes of the bioactive conformation of anatoxin at the acetylcholine nicotinic receptor site.
- Hernandez, Andres,Rapoport, Henry
-
p. 1058 - 1066
(2007/10/02)
-
- Substituted 1-[3-(heteroarylmethoxy)phenyl]alkanols and related compounds in the treatment of asthma
-
Substituted 1-[3-(heteroarylmethoxy)phenyl]-alkanols and related compounds which, by inhibiting 5-lipoxygenase enzyme and/or blocking leukotriene receptors, are useful in the prevention or treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction, stroke and related disease states in mammals; pharmaceutical compositions thereof; and a method of treatment therewith.
- -
-
-
- Oxygen Isosteric Derivatives of 3-(3-Hydroxyphenyl)-N-n-propylpiperidine
-
Some substituted 3-phenylmorpholines (10a-e,j,k) and 3-thienylmorpholines (10f,g), isosteres of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP), were prepared and submitted to binding assays on D-2 dopaminergic and 5-HT1 and 5-HT2 serotonergic receptors, in comparison with 3-PPP and its analogue 3a,b.The results show the loss of D-2 affinity for all morpholines, while a certain activity was still observable for piperidine derivatives.Regarding the serotonergic affinity, only chloro and methoxy derivatives (10a-d) were moderately active on the 5-HT1A receptor, either when the substituent was in the C-2 or C-3 position, whereas no tested compounds showed affinity toward the 5-HT2 receptor.
- Perrone, Roberto,Berardi, Francesco,Leopoldo, Marcello,Tortorella, Vincenzo,Lograno, Marcello D.,et al.
-
p. 3045 - 3049
(2007/10/02)
-
- Formal Synthesis of the Antitumour Antibiotic CC-1065
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A formal total synthesis of the potent antitumour antibiotic CC-1065 (1) is described; both the cyclopropapyrroloindole (2) and the 'dimeric' pyrroloindole (3) are synthesized by routes involving vinyl azide chemistry.The cyclopropapyrroloindole (2) is prepared from 5-benzyloxy-2-bromoacetophenone (Schemes 3-5), the key steps being the formation of both indoles by decomposition of the azides (9) and (13).The dimer (3) is prepared by coupling the monomeric pyrroloindoles (25) and (27), followed by functional group transformations (Scheme 7).
- Bolton, Richard E.,Moody, Christopher J.,Pass, Martin,Rees, Charles W.,Tojo, Gabriel
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p. 2491 - 2500
(2007/10/02)
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- Phenylethanolamine derivatives and acid addition salts thereof for enhancing the growth rate of meat-producing animals and improving the efficiency of feed utilization thereby
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There is provided a method for enhancing the growth rate of meat-producing animals and/or improving the efficiency of feed utilization thereby, which involves, orally or parenterally, administering to said animals a growth-enhancing amount of a phenylethane compound or the acid addition salt thereof.
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- Phenylethanolamine derivatives and acid addition salts thereof for the depression of fat deposition in warm blooded animals
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There is provided a method for increasing lean meat deposition and/or improving lean meat to fat ratio in poultry, domestic pets, sheep, swine, rabbits, goats and cattle by administering, orally or parenterally, to said animals an effective amount of a phenylethane derivative or acid salt thereof.
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- Intermediates for making 1-(3-benzyloxyphenyl)-1,1-dimethylheptane
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Process for making 1-(3-benzyloxyphenyl)-1,1-dimethylheptane, a valuable intermediate for the preparation of analgesic agents, which comprises benzylation of 3-hydroxyacetophenone to produce 3-benzyloxyacetophenone which is converted to 1-(3-benzyloxyphenyl)-1-methylheptan-1-ol via Grignard reaction with n-hexylmagnesium bromide; chlorination of said heptanol by reaction with hydrogen chloride followed by methylation of the thus-produced 1-(3-benzyloxyphenyl)-1-chloro-1-methylheptane with trimethylaluminum.
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