- A novel chimeric amine dehydrogenase shows altered substrate specificity compared to its parent enzymes
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We created a novel chimeric amine dehydrogenase (AmDH) via domain shuffling of two parent AmDHs ('L- and F-AmDH'), which in turn had been generated from leucine and phenylalanine DH, respectively. Unlike the parent proteins, the chimeric AmDH ('cFL-AmDH') catalyzes the amination of acetophenone to (R)-methylbenzylamine and adamantylmethylketone to adamantylethylamine.
- Bommarius, Bettina R.,Schürmann, Martin,Bommarius, Andreas S.
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Read Online
- Preparation de cations chiraux (η5-cyclopentadienyl fer η6-arene)+ comportant une fonction oxime ou cetone en α du ligande arene, reduction electrochimique en amine ou en alcool optiquement actifs
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Treatment of the species formed by deprotonation of the (η5-cyclopentadienylη6-tetraliniron) cation with the chiral alkyl nitrite (menthyl nitrite) yields the optically active (η5-cyclopentadienyl-η6-α-tetralono
- Rudulier, M. Le,Moinet, C.
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Read Online
- Palladium/Lewis Acid Co-catalyzed Divergent Asymmetric Ring-Opening Reactions of Azabenzonorbornadienes with Alcohols
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By fine tuning the combinations of chiral palladium catalysts and Lewis acids, both the additional and reductive asymmetric ring-opening reactions of azabenzonorbornadienes with alcohols were accomplished with good chemoselectivity, regioselectivity, and enantioselectivity. It was proven that the reductive ring-opening products were generated through a transfer-hydrogenation process with alcohols as hydrogen source.
- Yang, Fan,Chen, Jingchao,Xu, Jianbin,Ma, Fujie,Zhou, Yongyun,Shinde, Madhuri Vikas,Fan, Baomin
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Read Online
- Direct reductive amination of ketones with ammonium salt catalysed by Cp*Ir(iii) complexes bearing an amidato ligand
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A series of half-sandwich Ir(iii) complexes1-6bearing an amidato bidentate ligand were conveniently synthesized and applied to the catalytic Leuckart-Wallach reaction to produce racemic α-chiral primary amines. With 0.1 mol% of complex1, a broad range of ketones, including aryl ketones, dialkyl ketones, cyclic ketones, α-keto acids, α-keto esters and diketones, could be transformed to their corresponding primary amines with moderate to excellent yields (40%-95%). Asymmetric transformation was also attempted with chiral Ir complexes3-6, and 16% ee of the desired primary amine was obtained. Despite the unsatisfactory enantio-control achieved so far, the current exploration might stimulate more efforts towards the discovery of better chiral catalysts for this challenging but important transformation.
- Dai, Zengjin,Pan, Ying-Min,Wang, Shou-Guo,Yin, Qin,Zhang, Xumu
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supporting information
p. 8934 - 8939
(2021/11/04)
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- Air Stable Iridium Catalysts for Direct Reductive Amination of Ketones
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Half-sandwich iridium complexes bearing bidentate urea-phosphorus ligands were found to catalyze the direct reductive amination of aromatic and aliphatic ketones under mild conditions at 0.5 mol % loading with high selectivity towards primary amines. One of the complexes was found to be active in both the Leuckart–Wallach (NH4CO2H) type reaction as well as in the hydrogenative (H2/NH4AcO) reductive amination. The protocol with ammonium formate does not require an inert atmosphere, dry solvents, as well as additives and in contrast to previous reports takes place in hexafluoroisopropanol (HFIP) instead of methanol. Applying NH4CO2D or D2 resulted in a high degree of deuterium incorporation into the primary amine α-position.
- Polishchuk, Iuliia,Sklyaruk, Jan,Lebedev, Yury,Rueping, Magnus
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supporting information
p. 5919 - 5922
(2021/03/08)
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- Rh(III)-catalyzed synthesis of isoquinolines using the N-Cl bond of N-chloroimines as an internal oxidant
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The Rh(III)-catalyzed coupling of N-chloroimines with alkynes for the efficient synthesis of isoquinolines is reported. This represents the first use of the N-Cl bond of N-chloroimines as an internal oxidant for construction of the isoquinoline skeleton. The synthesis features atom and step economy, a green solvent (EtOH), mild reaction conditions, and a broad substrate scope.
- Chu, Benfa,Fang, Lili,Guo, Shan,Qi, Bing,Shi, Pengfei,Wang, Qi,Zhu, Jin
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supporting information
(2020/03/10)
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- CXCR2 ANTAGONIST
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A compound as a CXCR2 antagonist and an application thereof in preparing a drug as a CXCR2 antagonist. In particular, the present invention relates to a compound represented by formula (II) or an isomer or pharmaceutically acceptable salt thereof.
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Paragraph 0088-0089; 0092; 0113-0115
(2020/11/23)
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- Reductive amination of ketonic compounds catalyzed by Cp*Ir(III) complexes bearing a picolinamidato ligand
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Cp*Ir complexes bearing a 2-picolinamide moiety serve as effective catalysts for the direct reductive amination of ketonic compounds to give primary amines under transfer hydrogenation conditions using ammonium formate as both the nitrogen and hydrogen source. The clean and operationally simple transformation proceeds with a substrate to catalyst molar ratio (S/C) of up to 20,000 at relatively low temperature and exhibits excellent chemoselectivity toward primary amines.
- Tanaka, Kouichi,Miki, Takashi,Murata, Kunihiko,Yamaguchi, Ayumi,Kayaki, Yoshihito,Kuwata, Shigeki,Ikariya, Takao,Watanabe, Masahito
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p. 10962 - 10977
(2019/09/03)
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- Rapid and Quantitative Profiling of Substrate Specificity of ω-Transaminases for Ketones
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ω-Transaminases (ω-TAs) have gained growing attention owing to their capability for asymmetric synthesis of chiral amines from ketones. Reliable high-throughput activity assay of ω-TAs is essential in carrying out extensive substrate profiling and establishing a robust screening platform. Here we report spectrophotometric and colorimetric methods enabling rapid quantitation of ω-TA activities toward ketones in a 96-well microplate format. The assay methods employ benzylamine, a reactive amino donor for ω-TAs, as a cosubstrate and exploit aldehyde dehydrogenase (ALDH) as a reporter enzyme, leading to formation of benzaldehyde detectable by ALDH owing to concomitant NADH generation. Spectrophotometric substrate profiling of two wild-type ω-TAs of opposite stereoselectivity was carried out at 340 nm with 22 ketones, revealing subtle differences in substrate specificities that were consistent with docking simulation results obtained with cognate amines. Colorimetric readout for naked eye detection of the ω-TA activity was also demonstrated by supplementing the assay mixture with color-developing reagents whose color reaction could be quantified at 580 nm. The colorimetric assay was applied to substrate profiling of an engineered ω-TA for 24 ketones, leading to rapid identification of reactive ketones. The ALDH-based assay is expected to be promising for high-throughput screening of enzyme collections and mutant libraries to fish out the best ω-TA candidate as well as to tailor enzyme properties for efficient amination of a target ketone.
- Han, Sang-Woo,Shin, Jong-Shik
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p. 3287 - 3295
(2019/06/21)
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- N-Alkylation of Aqueous Ammonia with Alcohols Leading to Primary Amines Catalyzed by Water-Soluble N-Heterocyclic Carbene Complexes of Iridium
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A new catalytic system for the N-monoalkylation of aqueous ammonia with a variety of alcohols was developed. Water-soluble dicationic complexes of iridium bearing N-heterocyclic carbene and diammine ligands exhibited high catalytic activity for this type of reaction on the basis of hydrogen-transfer processes without generating harmful or wasteful byproducts. Various primary amines were efficiently synthesized by using safe, inexpensive, and easily handled aqueous ammonia as a nitrogen source. For example, the reaction of 1-(4-methylphenyl)ethanol with aqueous ammonia in the presence of a water-soluble N-heterocyclic carbene complex of iridium at 150 °C for 40 h gave 1-(4-methylphenyl)ethylamine in 83 % yield.
- Fujita, Ken-Ichi,Furukawa, Shohichi,Morishima, Namino,Shimizu, Mineyuki,Yamaguchi, Ryohei
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p. 1993 - 1997
(2018/03/13)
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- Selective Catalytic Hydrogenation of Arenols by a Well-Defined Complex of Ruthenium and Phosphorus-Nitrogen PN3-Pincer Ligand Containing a Phenanthroline Backbone
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Selective catalytic hydrogenation of aromatic compounds is extremely challenging using transition-metal catalysts. Hydrogenation of arenols to substituted tetrahydronaphthols or cyclohexanols has been reported only with heterogeneous catalysts. Herein, we demonstrate the selective hydrogenation of arenols to the corresponding tetrahydronaphthols or cyclohexanols catalyzed by a phenanthroline-based PN3-ruthenium pincer catalyst.
- Li, Huaifeng,Wang, Yuan,Lai, Zhiping,Huang, Kuo-Wei
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p. 4446 - 4450
(2017/07/24)
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- B(C6F5)3-Catalyzed Reduction of Aromatic and Aliphatic Nitro Groups with Hydrosilanes
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A transition-metal-free method for the hydrosilane reduction of aromatic and aliphatic nitro compounds to the corresponding amines is reported. Et3SiH is found to be the optimal reductant in this B(C6F5)3-catalyzed deoxygenation. The functional-group tolerance is, however, moderate.
- Porwal, Digvijay,Oestreich, Martin
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supporting information
p. 3307 - 3309
(2016/07/23)
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- SYNTHESIS OF AMIDES AND AMINES FROM ALDEHYDES OR KETONES BY HETEROGENEOUS METAL CATALYSIS
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This invention concerns the first mild and efficient synthesis of primary amines and amides from aldehydes or ketones using a heterogeneous metal catalystand amine donor. The initial heterogeneous metal- catalyzed reaction between the carbonyl and the amine donor components is followed up with the addition of a suitable acylating agent component in one-pot. Hence, the present invention provides a novel catalytic one-pot three-component synthesis of amides. Moreover, the integration of enzyme catalysis allows for eco-friendly one-pot co-catalytic synthesis ofamides from aldehyde and ketone substrates, respectively. The process can be applied to the co-catalytic one-pot three-component synthesis of capsaicin and its analogues from vanillin or vanillyl alcohol. It can also be applied for asymmetric synthesis. In the present invention, a novel co-catalytic reductive amination/dynamic kinetic resolution (dkr) relay sequence for the asymmetric synthesis of optically active amides from ketones is disclosed. Moreover, implementation of a catalytic reductive amination/kinetic resolution (kr) relay sequence produces the corresponding optically active amide product and optical active primary amine product with the opposite stereochemistry from the starting ketones.
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Page/Page column 22
(2016/07/05)
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- Integrated Heterogeneous Metal/Enzymatic Multiple Relay Catalysis for Eco-Friendly and Asymmetric Synthesis
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Organic synthesis is in general performed using stepwise transformations where isolation and purification of key intermediates is often required prior to further reactions. Herein we disclose the concept of integrated heterogeneous metal/enzymatic multiple relay catalysis for eco-friendly and asymmetric synthesis of valuable molecules (e.g., amines and amides) in one-pot using a combination of heterogeneous metal and enzyme catalysts. Here reagents, catalysts, and different conditions can be introduced throughout the one-pot procedure involving multistep catalytic tandem operations. Several novel cocatalytic relay sequences (reductive amination/amidation, aerobic oxidation/reductive amination/amidation, reductive amination/kinetic resolution and reductive amination/dynamic kinetic resolution) were developed. They were next applied to the direct synthesis of various biologically and optically active amines or amides in one-pot from simple aldehydes, ketones, or alcohols, respectively.
- Palo-Nieto, Carlos,Afewerki, Samson,Anderson, Mattias,Tai, Cheuk-Wai,Berglund, Per,Córdova, Armando
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p. 3932 - 3940
(2016/07/06)
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- A Single Lipase-Catalysed One-Pot Protocol Combining Aminolysis Resolution and Aza-Michael Addition: An Easy and Efficient Way to Synthesise β-Amino Acid Esters
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A novel one-pot protocol combining aza-Michael addition and aminolysis resolution was developed to obtain chiral β-amino acid esters with lipase B from Candida antarctica (CAL-B) as the only catalyst. This method is conducted under mild reaction conditions and is very easy to handle. After a series of detailed optimization studies, ten racemic aromatic or aliphatic amines were subjected to this one-pot procedure, and twelve chiral β-amino acid esters and ten chiral amides were successfully synthesised with excellent ee values in theoretical yields. Scaled-up procedures also worked without apparent reduction in reaction rate or enantioselectivity, which makes this method suitable for large-scale production of chiral β-amino acid esters. A one-pot protocol for simultaneous synthesis of chiral β-amino acid esters and amides was developed by combining single lipase B from Candida antarctica (CAL-B) catalysed aza-Michael addition and aminolysis resolution. This method requires mild reaction conditions and is very easy to handle. Chiral β-amino acid esters and chiral amides were obtained with excellent ee values and in theoretical yields.
- Xu, Fan,Wu, Qiongsi,Chen, Xiaoyang,Lin, Xianfu,Wu, Qi
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supporting information
p. 5393 - 5401
(2015/08/24)
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- CATALYST COMPOUNDS
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The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formulas: where ring B is either itself polycyclic, or ring B together with R is polycyclic. The catalysts of the invention are particularly effective in reductive amination procedures 10 which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
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Paragraph 0314; 0321
(2015/03/28)
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- Primary amines by transfer hydrogenative reductive amination of ketones by using cyclometalated IrIII catalysts
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Cyclometalated iridium complexes are found to be versatile catalysts for the direct reductive amination (DRA) of carbonyls to give primary amines under transfer-hydrogenation conditions with ammonium formate as both the nitrogen and hydrogen source. These complexes are easy to synthesise and their ligands can be easily tuned. The activity and chemoselectivity of the catalyst towards primary amines is excellent, with a substrate to catalyst ratio (S/C) of 1000 being feasible. Both aromatic and aliphatic primary amines were obtained in high yields. Moreover, a first example of homogeneously catalysed transfer-hydrogenative DRA has been realised for β-keto ethers, leading to the corresponding β-amino ethers. In addition, non-natural α-amino acids could also be obtained in excellent yields with this method. Reduce the work! A broad range of ketones have been successfully aminated to afford primary amines under transfer-hydrogenation conditions by using ammonium formate as the amine source and 0.1 mol % of a cyclometalated IrIII catalyst (see scheme). Copyright
- Talwar, Dinesh,Salguero, Noemi Poyatos,Robertson, Craig M.,Xiao, Jianliang
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supporting information
p. 245 - 252
(2014/01/17)
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- Efficient racemization of 1-phenylethylamine and its derivatives
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We report on simple and efficient procedure for the racemization of 1-phenylethylamine and its derivatives. In the presence of trichloroisocyanuric acid, N-chloroimine derivative is formed as the intermediates, with subsequent hydrogenation catalyzed by Pd-C leading to the racemic product.
- Xiong, Xiaoxia,Xu, Xinliang,Zhou, Yifeng,Weng, Chenchen
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p. 2402 - 2405
(2014/03/21)
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- CATALYST COMPOUNDS
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The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formulas: where ring B is either itself polycyclic, or ring B together with R is polycyclic. The catalysts of the invention are particularly effective in reductive amination procedures 10 which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
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Paragraph 00163; 00170
(2013/11/05)
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- Quenched skeletal Ni as the effective catalyst for selective partial hydrogenation of polycyclic aromatic hydrocarbons
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Quenched skeletal Ni is an active and selective catalyst for selective partial hydrogenation of polycyclic aromatic hydrocarbons (PAHs). The molecular structure of PAHs significantly dominate the hydrogenation process and furthermore, the distribution of hydrogenated products.
- Liu, Chengyun,Rong, Zeming,Sun, Zhuohua,Wang, Yong,Du, Wenqiang,Wang, Yue,Lu, Lianhai
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p. 23984 - 23988
(2013/11/19)
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- Reductive amination of ketones: Novel one-step transfer hydrogenations in batch and continuous-flow mode
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Various ketones were efficiently transformed into the corresponding amines using ammonium formate in the presence of Zn dust or 10% Pd/C. The low-cost Zn dust method proved to be effective in amine formation from carbonyl groups at the benzylic side-chain position of aromatic systems, whereas 10% Pd/C was an efficient catalyst in the reductive aminations of carbonyl groups non-conjugated with any π-system. The 10% Pd/C-catalyzed reductions were performed more effectively in a continuous-flow X-Cube reactor than in the batch system.
- Falus, Péter,Boros, Zoltán,Hornyánszky, Gábor,Nagy, József,Darvas, Ferenc,ürge, László,Poppe, László
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supporting information; experimental part
p. 1310 - 1312
(2011/03/22)
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- A versatile catalyst for reductive animation by transfer hydrogenation
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An iridium catalyst enables the reductive amination of carbonyl groups with unprecedented substrate scope, selectivity, and activity using formic acid as the hydrogen source (see scheme) The catalyst system provides significant improvement over commonly used boron hydrides.
- Wang, Chao,Pettman, Alan,Basca, John,Xiao, Jianliang
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supporting information; experimental part
p. 7548 - 7552
(2010/12/19)
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- Fast racemisation of chiral amines and alcohols by using cationic half-sandwich ruthena- and iridacycle catalysts
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The lipase-catalysed resolution of alcohols and amines yields only 50% of the desired enantiopure product. However, addition of a racemisation catalyst leads to 100% yield in what is called a dynamic kinetic resolution (DKR). There is a need for new racemisation catalysts that are fast and compatible with the conditions of the enzymatic reaction. We show that cationic half-sandwich ruthena- and iridacycle complexes are highly active and efficient in the racemisation of chiral alcohols and amines. Upon activation with base, these complexes are able to selectively racemise alcohols, whereas the non-activated complexes are selective catalysts for the racemisation of amines. We have applied the iridacycles in the DKR of racemic β-chloroalcohols to produce chiral epoxides in a biphasic system in good yields and high ee (ee = enantiomeric excess).
- Jerphagnon, Thomas,Gayet, Arnaud J.A.,Berthiol, Florian,Ritleng, Vincent,Mrsic, Natasa,Meetsma, Auke,Pfeffer, Michel,Minnaard, Adriaan J.,Feringa, Ben L.,De Vries, Johannes G.
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scheme or table
p. 12780 - 12790
(2010/06/16)
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- Asymmetric synthesis of optically pure pharmacologically relevant amines employing ω-transaminases
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Various ω-transaminases were tested for the synthesis of enantiomerically pure amines from the corresponding ketones employing D- or L-alanine as amino donor and lactate dehydrogenase to remove the side-product pyruvate to shift the unfavourable reaction equilibrium to the product side. Both enantiomers, (R)- and (S)-amines, could be prepared with up to 99% ee and >99% conversions within 24 h at 50 mM substrate concentration. The activity and stereoselectivity of the amination reaction depended on the ω-transaminase and substrate employed; furthermore the co-solvent significantly influenced both the stereoselectivity and activity of the transaminases. Best results were obtained by employing ATA-117 to obtain the (R)-enantiomer and ATA-113 or ATA-103 to access the (S)-enantiomer with 15% v v-1 DMSO.
- Koszelewski, Dominik,Lavandera, Ivan,Clay, Dorina,Rozzell, David,Kroutil, Wolfgang
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scheme or table
p. 2761 - 2766
(2009/10/06)
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- Heterogeneous raney nickel and cobalt catalysts for racemization and dynamic kinetic resolution of amines
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Raney metals were studied as heterogeneous catalysts for racemization and dynamic kinetic resolution (DKR) of chiral amines, as an alternative to metals like palladium or ruthenium. Both Raney nickel and cobalt were able to selectively racemize various chiral amines with high selectivity. In the racemization of benzylic primary amines, the minor formation of side products, e.g., secondary amines, can be suppressed by varying the hydrogen pressure. In the racemization of aliphatic amines over Raney catalysts, the selectivity is very high, with the enantiomeric amine as the sole product. DKR of racemic aliphatic amines can be performed with immobilized Candida antarctica lipase B and Raney nickel in one pot; for 2-hexylamine, a yield of 95% of the acetylated amide was achieved, with 97% ee. Attention is devoted to the compatibility of the enzyme and the metal catalyst during the DKR. For benzylic primary amines, a two-pot process is proposed in which the liquid is alternatingly shuttled between two vessels containing the solid racemization catalyst and the biocatalyst. After 4 such cycles, the amide of (R)-1-phenylethylamine was obtained with 94% yield and more than 90% ee.
- Parvulescu, Andrei N.,Jacobs, Pierre A.,De Vos, Dirk E.
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scheme or table
p. 113 - 121
(2009/04/16)
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- Facile rearrangement of O-silylated oximes on reduction with boron trifluoride/borane
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Aromatic O-triisopropylsilyl ketoximes were efficiently rearranged to cyclic and acyclic aniline derivatives on reduction with BF3- ethearate /borane. The bulk of the substituents on the silicon atom, the size of the aliphatic ring, and the presence of alkoxy substituents on the aryl group all play an important role in the aniline.
- Ortiz-Marciales, Margarita,Rivera, Luis D.,De Jesus, Melvin,Espinosa, Sandraliz,Benjamin, Josue A.,Casanova, Orlando E.,Figueroa, Irving G.,Rodriguez, Sheila,Correa, Wilbert
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p. 10132 - 10134
(2007/10/03)
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- Synthesis of tetrahydronaphthyl thioureas as potent appetite suppressants
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A series of thiourea derivatives (7-23, 25-27) of 1- aminotetrahydronaphthalene (4) and 1-amino-2-hydroxytetrahydronaphthalene (5) were synthesized in single pot in 48-90% yield and evaluated for their anorexigenic activity. Among them compounds 10, 14, 15, 16 and 22 exhibited significant anorexigenic activity without any antidepressant effect and provided a new structural lead for appetite suppressants.
- Bhandari, Kalpana,Srivastava, Shipra,Shankar, Girija
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p. 4189 - 4196
(2007/10/03)
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- Synthesis of enantiomerically pure amino-substituted fused bicyclic rings
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This invention describes various processes for synthesis and resolution of racemic amino-substituted fused bicyclic ring systems. One process utilizes selective hydrogenation of an amino-substituted fused bicyclic aromatic ring system. An alternative process prepares the racemic amino-substituted fused bicyclic ring system via nitrosation. In addition, the present invention describes the enzymatic resolution of a racemic mixture to produce the (R)- and (S)-forms of amino-substituted fused bicyclic rings as well as a racemization process to recycle the unpreferred enantioner. Further provided by this invention is an asymmetric synthesis of the (R)- or (S)-enantiomer of primary amino-substituted fused bicyclic ring systems.
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- 2-aminopyridine derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
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- Process for producing optically active amine
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A novel process for producing an optically active amine is provided. The optically active amine is adapted for use as an intermediate in synthesizing physiologically active compounds such as pharmaceuticals and agricultural chemicals, as a functional material such as a liquid crystal, and as a starting material in synthesizing fine chemicals. The process comprises the step of reacting an imine with a hydride reagent in the presence of an optically active metal compound and an alcohol compound and/or carboxylic acid compound.
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- N-aralkylaminotetralins as ligands for the neuropeptide Y Y5 receptor
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β-Aminotetralin derivatives of the formula: which are ligands for the neuropeptide Y Y5 (NPY5) receptor, methods of preparation and pharmaceutical compositions containing a β-aminotetralin derivative as the active ingredient are described. The 62 -aminotetralins are useful in the treatment of disorders and diseases associated with NPY receptor subtype Y5.
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- DOPAMINE D-3 AND SEROTONIN (5-HT1A) RECEPTOR LIGANDS AND IMAGING AGENTS
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Tetralin derivatives, such as 7-hydroxy-2-(N-n-propyl-N-3 '-iodo-2'-propenyl)-amino]tetralin and 8-hydroxy-2-(N-n-propyl-N-3 '-iodo-2'-propenyl)amino-tetralin, are disclosed which have affinity and specificity for dopamine D-3 and/or serotonin 5-HT 1A receptors.
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- Inhibitors of acyl CoA:cholesterol acyltransferase
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Conformational restriction of previously disclosed acyclic diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4- Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 μM in an in vitro rat hepatic microsomal ACAT assay, ED50 = 0.72 mg/kg/day in cholesterol-fed hamsters).
- Vaccaro, Wayne,Amore, Cindy,Berger, Joel,Burrier, Robert,Clader, John,Davis, Harry,Domalski, Martin,Fevig, Tom,Salisbury, Brian,Sher, Rosy
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p. 1704 - 1719
(2007/10/03)
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- AMINO ACID DERIVATIVES CYCLIZED AT THE C-TERMINAL
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Novel α-substituted Trp dipeptoid derivatives cyclized at the C-terminal useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with or use of nicotine, diazepam, alcohol, cocaine, caffeine, or opioids. The compounds of the invention are also useful in treating and/or preventing panic attacks. Also disclosed are pharmaceutical compositions and methods of treatment using the compounds as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the compounds in diagnostic compositions.
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- Aryloxypropanolaminotetralins, a process for their preparation and pharmaceutical compositions containing them
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Aryloxypropanolaminotetralins with beta-antagonist activity of the formula STR1 wherein R is hydrogen, hydroxy or methoxy and Ar is an optionally substituted aromatic or heteroaromatic group, in optically active or inactive form as well as their acid addition salts are described.A process for their preparation and pharmaceutical compositions containing the compounds of formula (i) or their pharmaceutically acceptable acid addition salts, are also described.
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- Stereoisomers of Allenic Amines as Inactivators of Monoamine Oxidase Type B. Stereochemical Probes of the Active Site
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The kinetics of inactivation of mitochondrial monoamine oxidase type B (MAO-B) by a series of 18 stereoisomers of tertiary α-allenic amines have been investigated in detail.The chirality of the allene group in N-methyl-N-aralkylpenta-2,3-dienamines was found to have a profound effect on the inactivation rate, with the (R)-allenes being up to 200-fold more potent than their (S)-allenic counterparts.The ability of (S)-allenes to inactivate MAO was severely compromised by the presence of N-phenethyl or N-α-substituted-aralkyl substituents.The opposing chiralities in both the allene and aralkyl groups of (R,R)- and (S,S)-N-methyl-N-(1,2,3,4-tetrahydro-1-naphthyl)-penta-2,3-dieneamine resulted in a difference of more than 3 oredrs of magnitude in inactivation rates.The stereoselectivity of MAO-B was examined further with a series of reversible aralkylamine inhibitors; thus (R)-1,2,3,4-tetrahydro-1-naphthylamine was determined to be 150-fold more potent than its enantiomer.
- Smith, Roger A.,White, Robert L.,Krantz, Allen
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p. 1558 - 1566
(2007/10/02)
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