- A novel and efficient asymmetric synthesis of anti-HIV drug maraviroc
-
A novel and efficient route to asymmetric synthesis of Maraviroc by using (S)-tert-butanesulfinamide as chiral auxiliary is described. Two interesting impurities of the process are isolated and identified. The synthesis was concise, mild, and easy to oper
- Zhu, Yijun,Li, Hongyan,Lin, Kuaile,Wang, Bing,Zhou, Weicheng
-
-
Read Online
- Palladium-Catalyzed Migratory Insertion of Carbenes and C-C Cleavage of Cycloalkanecarboxamides
-
A palladium catalyzed reaction of cycloalkanecarboxamides and diazomalonates or bis(phenylsulfonyl)diazomethane has been developed. The reaction proceeds via carbene migratory insertion and cascade C-C cleavage pathways. Cycloalkanecarboxamides with four to seven membered rings are applicable in the transformation. A series of ring opening products were prepared with moderate yields. The finding provides valuable clues for the development of new reactions involving carbene migratory insertion and the cleavage of unstrained C(sp3)-C(sp3) bonds.
- Zhang, Peng,Zeng, Jia,Pan, Ping,Zhang, Xue-Jing,Yan, Ming
-
supporting information
p. 536 - 541
(2022/01/20)
-
- Preparation method of
-
The preparation method comprises the following steps: taking a halogen-containing azide compound as a raw material in γ-position, carrying out a reaction, and preparing and a derivative thereof. The method is characterized in γ-position halogen-containing azide compound as a raw material and is subjected to reduction. A series of non-sequential reactions, such as hydrolysis, substitution, condensation, reductive amination, and the like. A target compound, that is, a Mahalanobis derivative, can be obtained. The preparation method has the advantages of mild reaction conditions, simplicity and convenience in operation, low cost, less side reaction, high product purity, simplicity and convenience in separation and purification and the like. The invention further provides the pulvernolol and derivatives thereof prepared by the method and application thereof.
- -
-
Paragraph 0070; 0075-0076; 0093; 0098-0099; 0116; 0121-0122
(2021/10/27)
-
- Decarboxylative Borylation of mCPBA-Activated Aliphatic Acids
-
A decarboxylative borylation of aliphatic acids for the synthesis of a variety of alkylboronates has been developed by mixing m-chloroperoxybenzoic acid (mCPBA)-activated fatty acids with bis(catecholato)diboron in N,N-dimethylformamide (DMF) at room temperature. A radical chain process is involved in the reaction which initiates from the B-B bond homolysis followed by the radical transfer from the boron atom to the carbon atom with subsequent decarboxylation and borylation.
- Wei, Dian,Liu, Tu-Ming,Zhou, Bo,Han, Bing
-
supporting information
p. 234 - 238
(2020/01/02)
-
- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
-
A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
-
supporting information
p. 5242 - 5247
(2020/02/28)
-
- A class of histone acetylase p300 inhibitors, and application thereof
-
The invention discloses a class of histone acetylase p300 inhibitors, and application thereof, and belongs to the technical field of medicinal chemistry. The invention discloses a compound representedby a formula (I), or a stereochemical isomer, a solvate or a pharmaceutically acceptable salt thereof. According to the invention, the compound can effectively inhibit the activity of histone acetylase p300 and can effectively inhibit the proliferation activity of various tumor cells; the compound is combined with a CDK4/6 inhibitor to play a synergistic role in inhibiting proliferation of tumorcells; and the compound has good application prospects in preparation of histone acetylase inhibitors, preparation of drugs for preventing and/or treating cancers, metabolic diseases, neurological diseases or inflammations, and combination of drugs.
- -
-
Paragraph 0576-0577; 0581-0583
(2020/06/17)
-
- Photochemical generation of acyl and carbamoyl radicals using a nucleophilic organic catalyst: Applications and mechanism thereof
-
We detail a strategy that uses a commercially available nucleophilic organic catalyst to generate acyl and carbamoyl radicals upon activation of the corresponding chlorides and anhydrides via a nucleophilic acyl substitution path. The resulting nucleophilic radicals are then intercepted by a variety of electron-poor olefins in a Giese-type addition process. The chemistry requires low-energy photons (blue LEDs) to activate acyl and carbamoyl radical precursors, which, due to their high reduction potential, are not readily prone to redox-based activation mechanisms. To elucidate the key mechanistic aspects of this catalytic photochemical radical generation strategy, we used a combination of transient absorption spectroscopy investigations, electrochemical studies, quantum yield measurements, and the characterization of key intermediates. We identified a variety of off-the-cycle intermediates that engage in a light-regulated equilibrium with reactive radicals. These regulated equilibriums cooperate to control the overall concentrations of the radicals, contributing to the efficiency of the overall catalytic process and facilitating the turnover of the catalyst. This journal is
- Balletti, Matteo,De Pedro Beato, Eduardo,Mazzarella, Daniele,Melchiorre, Paolo
-
p. 6312 - 6324
(2020/08/24)
-
- Asymmetric Mannich Reaction and Construction of Axially Chiral Sulfone-Containing Styrenes in One Pot from α-Amido Sulfones Based on the Waste-Reuse Strategy
-
A simultaneous asymmetric Mannich reaction and the construction of axially chiral sulfone-containing styrenes in one pot from α-amido sulfones based on the waste-reuse strategy was demonstrated. A series of chiral β-amino diesters and axially chiral sulfone-containing styrenes with various functional groups were synthesized in good to excellent yields and enantioselectivities under mild conditions. In addition, this protocol has been successfully applied to synthesize the anti-HIV drug Maraviroc and chiral trichloro derivatives.
- Li, Dongmei,Tan, Yu,Peng, Lei,Li, Shan,Zhang, Nan,Liu, Yidong,Yan, Hailong
-
p. 4959 - 4963
(2018/08/24)
-
- CATHEPSIN K INHIBITOR AND APPLICATION THEREOF
-
The invention relates to capthepsin K inhibitors and uses thereof, specifically relates to a class of compounds having the formula (I) which are used for treating or preventing cathepsin dependent diseases or conditions, specifically, wherein the cathepsin is capthepsin K. The compounds and compositions thereof can be used as bone resorption inhibitors for the treatment of associated diseases.
- -
-
Paragraph 0222
(2018/07/29)
-
- ANTIVIRAL COMPOUNDS
-
The present invention relates to novel compounds of general formula (I) wherein the groups X, and R1 to R4 have the meanings given in the description and claims, process for preparing these compounds and their use as for treating, preventing or ameliorating viral infections and their use for treating, preventing or ameliorating diseases which are associated with PLA2G16.
- -
-
Paragraph 0538
(2018/04/13)
-
- Visible Light-Mediated Decarboxylative Alkylation of Pharmaceutically Relevant Heterocycles
-
A net redox-neutral method for the decarboxylative alkylation of heteroarenes using photoredox catalysis is reported. Additionally, this method features the use of simple, commercially available carboxylic acid derivatives as alkylating agents, enabling the facile alkylation of a variety of biologically relevant heterocyclic scaffolds under mild conditions.
- Sun, Alexandra C.,McClain, Edward J.,Beatty, Joel W.,Stephenson, Corey R. J.
-
supporting information
p. 3487 - 3490
(2018/06/26)
-
- Photoinduced, Copper-Catalyzed Decarboxylative C-N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement
-
The Curtius rearrangement is a classic, powerful method for converting carboxylic acids into protected amines, but its widespread use is impeded by safety issues (the need to handle azides). We have developed an alternative to the Curtius rearrangement that employs a copper catalyst in combination with blue-LED irradiation to achieve the decarboxylative coupling of aliphatic carboxylic acid derivatives (specifically, readily available N-hydroxyphthalimide esters) to afford protected amines under mild conditions. This C-N bond-forming process is compatible with a wide array of functional groups, including an alcohol, aldehyde, epoxide, indole, nitroalkane, and sulfide. Control reactions and mechanistic studies are consistent with the hypothesis that copper species are engaged in both the photochemistry and the key bond-forming step, which occurs through out-of-cage coupling of an alkyl radical.
- Zhao, Wei,Wurz, Ryan P.,Peters, Jonas C.,Fu, Gregory C.
-
supporting information
p. 12153 - 12156
(2017/09/12)
-
- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
-
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
- -
-
Paragraph 0824
(2015/08/03)
-
- Simple sulfinate synthesis enables C-H trifluoromethylcyclopropanation
-
A simple method to convert readily available carboxylic acids into sulfinate salts by employing an interrupted Barton decarboxylation reaction is reported. A medicinally oriented panel of ten new sulfinate reagents was created using this method, including a key trifluoromethylcyclopropanation reagent, TFCS-Na. The reactivity of six of these salts towards C-H functionalization was field-tested using several different classes of heterocycles.
- Gianatassio, Ryan,Kawamura, Shuhei,Eprile, Cecil L,Foo, Klement,Ge, Jason,Baran, Phil S.,Burns, Aaron C.,Collins, Michael R.
-
supporting information
p. 9851 - 9855,5
(2014/10/15)
-
- IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
-
The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.
- -
-
Paragraph 00320
(2013/11/18)
-
- 1,2,4 -TRIAZOLES AS ALLOSTERIC MODULATORS OF MGLU5 RECEPTOR ACTIVITY FOR THE TREATMENT OF SCHIZOPHRENIA OF DEMENTIA
-
This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
- -
-
Page/Page column 89
(2013/06/27)
-
- SUBSTITUTED TRIAZOLES AND THEIR USE FOR TREATMENT AND/OR PREVENTION NEUROLOGICAL AND PSYCHIATRIC DISORDERS
-
This invention relates to compounds of formula (I), their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.
- -
-
Page/Page column 61
(2013/07/31)
-
- Asymmetric synthesis of maraviroc (UK-427,857)
-
The asymmetric synthesis of Maraviroc (UK-427,857), a chemochine receptor 5 (CCR-5) receptor antagonist, based on an expeditious organocatalytic enantioselective assembly of the chiral βamino aldehyde key fragment is presented. The reactions were performed on a gram-scale and allow for the rapid construction of new Maraviroc analogues.
- Zhao, Gui-Ling,Lin, Shuangzheng,Korotvicka, Ales,Deiana, Luca,Kullberg, Martin,Cordova, Armando
-
supporting information; experimental part
p. 2291 - 2298
(2010/12/20)
-
- Development of a bulk enabling route to maraviroc (UK-427,857), a CCR-5 receptor antagonist
-
A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1), is presented. Synthesis of the three key fragments, β-amino ester 3,4,4-difluorohexanecarboxylic acid (2), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation, and final scale-up of the developed route to 1.
- Haycock-Lewandowski, Sarah J.,Wilder, Alexander,Ahman, Jens
-
p. 1094 - 1103
(2013/01/03)
-
- PREPARATION AND UTILITY OF CCR5 INHIBITORS
-
Disclosed herein are substituted 8-azabicyclo[3.2.1]octane-based anti-infective agents of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 40
(2008/12/06)
-
- A PROCESS FOR PRODUCING [(4,4- DIF LUOROCYCLOHEXYL) METHYL] AMINE
-
A process for preparing a compound of formula I wherein R1 is H, C1-6alkyl, C2-6alkenyl, C1-6alkoxy, -OH, or amino; and n, m, and p are independently selected from 0, 1 and 2; which process comprises reacting a
- -
-
Page/Page column 10
(2008/06/13)
-
- INHIBITORS OF SERINE PALMITOYLTRANSFERASE
-
This invention provides compounds of the formula (I) useful in the inhibition or modulation of serine palmitoyl transferase and their use in methods of treatment or amelioration of type 2 diabetes, type 1 diabetes, insulin resistance, the effects of obesity, metabolic syndrome (sometimes referred to as Syndrome X), impaired glucose tolerance, Cushing's disease, cardiovascular disease, prothrombotic conditions, myocardial infarction, hypertension, congestive heart failure, cardiomyopathy, atherosclerosis, dyslipidemia, sepsis, liver damage, retinal degenerative disorders, cachexia, emphysema, hepatitis C infections, HIV infections and inflammatory disorders and useful in methods for raising HDL plasma levels in a mammal. The compounds of this invention can also be used to prevent damage or loss of pancreatic islet beta cells (such as in the case of pancreatic beta cell apoptosis, including those related to insulin-dependent diabetes mellitus).
- -
-
Page/Page column 39
(2008/12/07)
-
- Asymmetric allylboration of acyl imines catalyzed by chiral diols
-
Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of acyl imines. The reaction requires 15 mol % (S)-3,3′-Ph2-BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (75-94%) and high enantiomeric ratios (95:5-99.5:0.5) for aromatic and aliphatic imines. High diastereoselectivities (diastereomeric ratio > 98:2) and enantioselectivities (enantiomeric ratio > 98:2) are obtained in the reactions of acyl imines with crotyldiisopropoxyboranes. This asymmetric transformation is directly applied to the synthesis of Maraviroc, the selective CCR5 antagonist with potent activity against HIV-1 infection. Mechanistic investigations of the allylboration reaction including IR, NMR, and mass spectrometry studies indicate that acyclic boronates are activated by chiral diols via exchange of one of the boronate alkoxy groups with activation of the acyl imine via hydrogen bonding.
- Lou, Sha,Moquist, Philip N.,Schaus, Scott E.
-
p. 15398 - 15404
(2008/09/18)
-
- HETEROCYCLIC ANTIVIRAL COMPOUNDS
-
Chemokine receptor antagonists, in particular, 3,7-diazabicyclo [3.3.0] octane compounds according to formula (I) are antagonists of chemokine CCR5 receptors which are useful for treating or preventing an human immunodeficiency virus (HIV) infection, or treating AIDS or ARC. The invention further provides methods for treating diseases that are allieviated with CCR5 antagonists. The invention includes pharmaceutical compositions and methods of using the compounds for the treatment of these diseases. The invention further includes processes for the preparation of compounds according to formula (I).
- -
-
Page/Page column 138-139
(2010/02/15)
-
- Tropane derivatives useful in therapy
-
The present invention provides compounds of the formula: wherein R1 is C3-6 cycloalkyl optionally substituted by one or more fluorine atoms, or C1-6 alkyl optionally substituted by one or more fluorine atoms, or C3-6 cycloalkylmethyl optionally ring-substituted by one or more fluorine atoms; and R2 is phenyl optionally substituted by one or more fluorine atoms, to pharmaceutically acceptable salts and solvates thereof, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such compounds.
- -
-
-