- Cyclopropyloxetanes. Reactions of 5-Oxaspirohexane with Hydrogen Halides
-
The title cyclopropyloxetane reacted with aqueous hydrogen chloride, bromide, and iodide to give mixtures of the corresponding 1-(halogenomethyl)-1-(hydroxymethyl)cyclopropane and 1-halogeno-1-(hydroxymethyl)cyclobutane.Keywords: Bicyclobutonium ion; Cyclopropyl carbinyl cation; Molecular rearrangement; Oxetane.
- Donnelly, John A.,Keegan, John R.
-
-
Read Online
- A Spiroalkylation Method for the Stereoselective Construction of α-Quaternary Carbons and Its Application to the Total Synthesis of (R)-Puraquinonic Acid
-
Cyclic α-quaternary carbon stereocenters were prepared from biselectrophillic substrates and an easily prepared chiral bicyclic sulfonyl lactam. This was achieved in two steps by spiroalkylation, employing biphasic reaction conditions with a phase-transfer catalyst, followed by reduction and alkylation with a series of alkyl halide electrophiles. The products of this method were isolated in good yields with with high levels of diastereoselectivity. This methodology was employed in the enantioselective total synthesis of (R)-puraquinonic acid (1) for a late-stage installation of the α-quaternary carbon stereocenter. This enabled the shortest synthesis of 1 to date, an eight-pot sequence providing an overall yield of 14%.
- Elmehriki, Adam A. H.,Gleason, James L.
-
supporting information
p. 9729 - 9733
(2019/12/02)
-
- Preparing method for 1,1-cyclopropyl dimethyl carbinol
-
The invention belongs to the technical field of drug synthesis and relates to a preparing method for 1,1-cyclopropyl dimethyl carbinol. Specifically, the preparing method for the 1,1-cyclopropyl dimethyl carbinol includes the following steps that firstly, under the participation of a catalyst A, a solvent A and an acid-binding agent, diethyl malonate and 1,2-dichloroethane are used for preparing 1,1-cyclopropyl dioctyl phthalate diethyl ester; and secondly, under the participation of a solvent B and a catalyst B, a reducing agent is used for reducing the 1,1-cyclopropyl dioctyl phthalate diethyl ester, and the target product 1,1-cyclopropyl dimethyl carbinol is obtained. Raw materials adopted in the preparing method are cheap, easy to obtain and free of toxins, the activity of the catalysts are high, the solvents can be recycled, and the cost is obviously reduced; and reaction conditions are moderate, the products are easy to separate, the three industrial wastes are little, and the environment-friendly chemical requirement is met. In addition, according to the preparing method, the yield of the target product can be obviously increased, and the total recovery can reach 88% through the two steps.
- -
-
Paragraph 0040; 0045; 0048; 0051; 0054
(2017/08/28)
-
- Structure-activity relationship study of β-oxidation resistant indole-based 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) receptor antagonists
-
5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is formed from 5S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) by the 5-lipoxygenase (5-LO) pathway under conditions associated with oxidative stress. 5-Oxo-ETE is an important pro-inflammatory mediator, which stimulates the migration of eosinophils via a selective G-protein coupled receptor, known as the OXE receptor (OXE-R). Previously, we designed and synthesized structural mimics of 5-oxo-ETE such as 1 using an indole scaffold. In the present work, we added various substituents at C-3 of this moiety to block potential β-oxidation of the 5-oxo-valerate side chain, and investigated the structure-activity relationships of the resulting novel β-oxidation-resistant antagonists. Cyclopropyl and cyclobutyl substituents were well tolerated in this position, but were less potent as the highly active 3S-methyl compound. It seems likely that 3-alkyl substituents can affect the conformation of the 5-oxovalerate side chain containing the critical keto and carboxyl groups, thereby affecting interaction with the OXE-receptor.
- Ye, Qiuji,Chourey, Shishir,Wang, Rui,Chintam, Nagendra Reddy,Gravel, Sylvie,Powell, William S.,Rokach, Joshua
-
supporting information
p. 4770 - 4776
(2017/09/27)
-
- Substituted 4-morpholine N-arylsulfonamides as γ-secretase inhibitors
-
The design, synthesis, SAR, and biological profile of a substituted 4-morpholine sulfonamide series of γ-secretase inhibitors (GSIs) were described. In several cases, the resulting series of GSIs reduced CYP liabilities and improved γ-secretase inhibition activity compared to our previous research series. Selected compounds demonstrated significant reduction of amyloid-β (Aβ) after acute oral dosing in a transgenic animal model of Alzheimer's disease (AD).
- Zhao, Zhiqiang,Pissarnitski, Dmitri A.,Josien, Hubert B.,Bara, Thomas A.,Clader, John W.,Li, Hongmei,McBriar, Mark D.,Rajagopalan, Murali,Xu, Ruo,Terracina, Giuseppe,Hyde, Lynn,Song, Lixin,Zhang, Lili,Parker, Eric M.,Osterman, Rebecca,Buevich, Alexei V.
-
-
- PYRROLOTRIAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrrolotriazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 51
(2016/09/26)
-
- PYRAZOLOPYRIMIDINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrazolopyrimidine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 76
(2016/09/26)
-
- THIENOPYRAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to thienopyrazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 41
(2016/09/26)
-
- PYRROLOPYRIDAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrrolopyridazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 44
(2016/09/26)
-
- BIARYL DERIVATIVES AS GPR120 AGONISTS
-
The present invention relates to biaryl derivatives of Formula 1, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The biaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in the liver or in muscle due to anti-inflammatory action in macrophages, lipocytes, etc., and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, obesity, non-alcoholic fatty liver, steatohepatitis, osteoporosis or inflammation.
- -
-
Paragraph 580; 581; 582
(2015/01/16)
-
- PREPARATION OF MONTELUKAST AND ITS SALTS
-
There is provided a process for the preparation of montelukast of the Formula (I).
- -
-
Page/Page column 34-35
(2008/12/05)
-
- NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
-
The invention relates to compounds of formula (I) wherein Ar, X, R1, R2, R3 and R4 are as defined herein and, pharmaceutical compositions thereof useful, either alone or in combination with other therapeutic agents as reverse transcriptase inhibitors against wild type and single or double mutant strains of HIV for the treatment or prophylaxis of HIV infection
- -
-
Page/Page column 93-94
(2008/06/13)
-
- 4-((PHENOXYALKYL)THIO)-PHENOXYACETIC ACIDS AND ANALOGS
-
The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR delta modulators to treat or inhibit the progression of, for example, dyslipidemia.
- -
-
Page/Page column 84-85
(2008/06/13)
-
- NUCLEOBASE PHOSPHONATE ANALOGS FOR ANTIVIRAL TREATMENT
-
The present invention provides novel compounds with activity against infectious viruses. The compounds of the invention may inhibit retroviral reverse transcriptases and thus inhibit the replication of the virus. They are useful for treating human patients infected with a human retrovirus, such as human immunodeficiency virus (strains of HIV-1 or HIV-2) or human T-cell leukemia viruses (HTLV-I or HTLV-II) which results in acquired immunodeficiency syndrome (AIDS) and/or related diseases. The present invention also relates generally to the accumulation or retention of therapeutic compounds inside cells. The invention is more particularly related to attaining high concentrations of active metabolite molecules in HIV infected cells. Intracellular targeting may be achieved by methods and compositions which allow accumulation or retention of biologically active agents inside cells. Such effective targeting may be applicable to a variety of therapeutic formulations and procedures.
- -
-
Page/Page column 106-107
(2008/06/13)
-
- NUCLEOSIDE PHOSPHONATE DERIVATIVES USEFUL IN THE TREATMENT OF HIV INFECTIONS
-
The present invention relates to a method of treating HIV infections by administering a nucleoside phosphonate derivative represented by formula (I).
- -
-
Page/Page column 51
(2008/06/13)
-
- Oxygenated esters of 4-lodo phenylamino benzhydroxamic acids
-
The present invention relates to oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof. The present invention also relates to crystaline forms of oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof.
- -
-
-
- Asymmetric total synthesis of (+)-aphanamol I based on the transition metal catalyzed [5 + 2] cycloaddition of allenes and vinylcyclopropanes
-
(equation presented) A concise asymmetric total synthesis of (+)-aphanamol I is described, based on the transition metal catalyzed [5 + 2] allenyl-vinylcyclopropane cycloaddition. The key cycloaddition precursor is convergently assembled from (R)-(+)-limonene and cyclopropane diester through a novel decarboxylative dehydration reaction. The metal-catalyzed [5 + 2] cycloaddition of this precursor proceeds with complete chemo, endo/exo, and diastereoselectivity in 93% yield, representing an effective general route to bicyclo[5.3.0]decane derivatives.
- Wender, Paul A.,Zhang, Lei
-
p. 2323 - 2325
(2007/10/03)
-
- Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists
-
Compounds having the formula I: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
- -
-
-
- SATURATED HYDROXYALKYLQUINOLINE ACIDS AS LEUKOTRIENE ANTAGONISTS
-
Compounds having the formula I: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
- -
-
-
- Thermolytic Rearrangements of 1,1-Cyclopropanedimethanol Disulfonates: Cyclopropylcarbinyl Cations Revisited
-
1,1-Cyclopropanedimethanol dimethanesulfonate (1a) and the corresponding ditosylate 1b underwent thermal rearrangement at 110-140 deg C after melting.Short reaction time resulted in the formation of mixtures containing 1-(sulfonyloxy)cyclobutanemethanol sulfonates 5a,b (major), starting material, and 2-methylene-1,4-butanediol disulfonates 6a,b.Longer reaction times afforded complete conversion to disulfonates 6a,b, isolated in 49 and 62 percent yield, respectively.These reactions are postulated to proceed via initial carbocation formation, presumably interconverting bicyclobutonium and cyclopropylcarbinyl cations, which exist as ion pairs in the melt.Crossover experiments with dimesylate 1a and ditosylate 1b offer support for the presence of ion pairs in the melt: internal return competed with external trapping of the intermediate cations.Reaction of 1a and 2-methylene-1,4-butanediol ditosylate (6b) gave a mixture in which 2-methylene-1,4-butanediol 1-mesylate 4-tosylate (8) predominated over the isomeric 4-mesylate 1-tosylate 7 by a 5:1 ratio.Crossover experiments with 6a and 6b indicated that partial allylic substitution was occurring for the open-chain products under the thermolysis conditions.Reaction of 1a with excess tetrabutylammonium tosylate at 114-15 deg C afforded mixed 1-(sulfonyloxy)cyclobutanemethanol sulfonates and 2-methylene-1,4-butanediol disulfonates formed competitively by internal return and tosylate interception.Acetolysis of 1a at 42-43 deg C afforded predominately products of internal return early on the reaction profile.Longer reaction times afforded predominately monoacetates while reactions run at 108-10 deg C afforded substantial amounts of diacetates.Acetolysis of 1-acetoxycyclobutanemethanol mesylate (12a) resulted in the substitution of the mesyloxy group with substantial rearrangement.
- Wade, Peter A.,Kondracki, Paul A.
-
p. 3140 - 3147
(2007/10/02)
-
- Polymers Containing Ring-Strain Energy. 1. New Monomers and Polymers Based on Cyclopropane, Norbornadiene, and Quadricyclane
-
The synthesis and polymerization chemistry of 1,1-bis(XCH2)cyclopropane was studied.Treatment of 1 with base in the presence of α,ω-dihalides did not produce a polyether.However, treatment of 4 with the bis(alkoxide) derived from hexanediol afforded a polyether of low molecular weight n=3000, PD=3>.A general method for alkylating norbornadiene in the 2-position was developed.Treatment of norbornadiene with tert-BuOK, tetramethylethylenediamine (TMEDA), n-BuLi, and tributylchlorostannane (in that order) afforded 2-(tributylstannyl)norbornadiene in excellent yield.On the other hand, carbon electrophiles required the generation of the 2-(lithiocyanocuprate) in order to effect clean alkylation.Treatment of 2-norbornadiene (8a) with RMgX in the presence of (dppp)NiCl2 afforded the cross-coupling products 2-(XCH2)-norbornadiene in high yield.Polymerization of 9 in THF initiated by n-BuLi resulted in an elastomeric polymer (12) n=18,000, PD=1.5>.Photolysis of 12 in the presence of (Ph3P)2CuBr converted the pendant norbornadiene to quadricyclane (13).Heating of the photoisomerized sample to 180 deg C caused an exothermic (by DSC) reaction which corresponded to 59percent of theory (using the value 26 kcal/mol: quadricyclane -> norbornadiene).
- Wright, Michael E.,Allred, Gary D.,Wardle, Robert B.,Cannizzo, Louis F.
-
p. 4122 - 4126
(2007/10/02)
-
- QUINOLINE-CONTAINING KETOACIDS AS LEUKOTRIENE ANTAGONISTS
-
Compounds having the formula I: STR1 are antagonists of the actions of leukotrienes. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection.
- -
-
-
- Fluorinated hydroxyalkylquinoline acids as leukotriene antagonists
-
Compounds having the formula I: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
- -
-
-
- Polynitro-substituted strained-ring compounds. 2. 1,2-Dinitrospiropentanes
-
trans-1,2-Dinitrospiropentane was prepared in 43% yield from 1,1-bis(nitromethyl)cyclopropane, best obtained by dry-phase ozonolysis of the corresponding diamine. The structure of trans-1,2-dinitrospiropentane was assigned on the basis of spectroscopic data, elemental analysis, and X-ray crystallographic data. The first pKa was determined to be 18.6-21.6 in DMSO solution with decomposition. Reaction of trans-1,2-dinitrospiropentane with sodium methoxide and iodine gave a mixture of iodinated spiropentanes, from which, cis- and trans-1,2-diiodo 1,2-dinitrospiropentane could be isolated in pure form. These diiodides were stable at room temperature but gave off iodine upon melting at 150-160°C. Treatment with sodium thiosulfate in aqueous DMSO solution gave back the deiodinated dinitro compound. trans-1,2-Dinitrospiropentane reacted with lithium diisopropylamide and benzaldehyde in THF to afford a bis(nitroaldol) product in 59% yield.
- Wade, Peter A.,Kondracki, Paul A.,Carroll, Patrick J.
-
p. 8807 - 8811
(2007/10/02)
-
- Insecticidal alkenes
-
A compound of formula: wherein X and Y are each selected from hydrogen and halogen, R1 and R2 are each lower alkyl of up to four carbon atoms, or together with the adjacent carbon atom form a cycloalkyl group of up to six carbon atoms, and R represents a phenoxy- or benzyl-substituted phenyl group which may optionally be substituted with fluorine. The compounds are useful for combating insect pests.
- -
-
-
- Insecticidal alkenes
-
Compounds of formula R3 --CH=CH--CR1 R2 --CH2 OCH2 R4 wherein R1 and R2 are H, alkyl or together form a cycloalkyl group with the adjacent carbon, R3 is a substituted phenyl group, R4 is an optionally substituted phenoxy phenyl group, and compositions containing them useful as insecticides, and compounds of formula HOCH2 --CR1 R2 --CH2 OCH2 R4 and OCH--CR1 R2 CH2 OCH2 R4, useful as intermediates therefor.
- -
-
-
- Insecticidal alkenes
-
Compounds of formula R3 --CH=CH--CR1 R2 --CH2 OCH2 R4 wherein R1 and R2 are H, alkyl or together form a cycloalkyl group with the adjacent carbon, R3 is a substituted phenyl group, R4 is an optionally subsituted phenoxy phenyl group, and compositions containing them useful as insecticides, and compounds of formula HOCH2 --CR1 R2 --CH2 OCH2 R4 and OCH--CR1 R2 CH2 OCH2 R4, useful as intermediates therefor.
- -
-
-
- STUDIES DIRECTED TOWARDS THE TOTAL SYNTHESIS OF MORPHINE ALKALOIDS
-
Application of metallated enamines to the synthesis of morphine related congeners is reported.A formal total synthesis of (+/-)-morphine has been completed.
- Evans, D. A.,Mitch, C. H.
-
p. 285 - 288
(2007/10/02)
-
- The Chemistry of 1,3-Glycol Derivatives. III. The Preparation of 1,1-Bis(1-hydroxyalkyl)cyclopropanes and Their Halogenation
-
By the reduction of 1,1-diacylcyclopropanes and their related compounds, several kinds of 1,1-bis(1-hydroxyalkyl)cyclopropanes have been prepared.Some of the stereoisomers were separated, and their configurations were determined by the NMR study of the 1,3-dioxanes prepared by the acetallization of the diols.The diols were subjected to halogenation.Although the reactions of meso- and dl-bis(1-hydroxyethyl)cyclopropanes with thionyl chloride and phosphorus pentachloride gave normal dichlorides, accompanied by slight skeletal rearrangements, the stereospecificities were rather low.With ZnCl2-HCl, the specificities were lost completely and large amounts of the homoallyl derivative were formed.The reaction mechanism is discussed.
- Itoh, Osamu,Kohmura, Yoshiro,Ichikawa, Yasunori,Umezu, Makoto,Okita, Tsutomu,Ichikawa, Katsuhiko
-
p. 146 - 153
(2007/10/02)
-
