- Synthesis process 2 - methyl -3 - methoxybenzoic acid
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The invention discloses a synthesis process of 2 - methyl -3 - methoxybenzoic acid, which comprises the following steps: (1) reducing hydrogenation reaction: taking 2 - methyl -3 - nitrobenzoic acid or 2 - methyl -3 - nitrobenzoate as raw materials and methanol as a solvent. The hydrogen is a hydrogen source, and palladium carbon or platinum carbon is used as a catalyst to prepare 3 - amino -2 - methyl benzoic acid or 3 - amino -2 - methyl benzoic acid methyl ester by hydrogenation reduction. (2) Diazotization and hydrolysis and esterification one-pot reaction: preparing and hydroxyl 3 - methyl benzoic acid methyl ester by carrying out diazotization and hydrolysis -2 - esterification reaction under the action of a reducing product as a raw material and methanol as a solvent and a diazotization reagent. (3) Methylation reaction: methyl benzoate serving 3 - hydroxyl -2 - is used as a raw material, dimethyl sulfate is used as a methylation reagent, and methyl benzoate is produced 3 - methoxy -2 - methyl benzoate in the presence of a base. (4) Hydrolysis Reaction: methyl 3 - methoxy -2 - methyl benzoate and base. Water is mixed, heated and hydrolyzed, the reaction is complete, the product precipitated by acid conditioning PH through 1-3, filtered, and dried to obtain 3 - methoxy -2 -methylbenzoic acid.
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- Preparation method of 6-chloro-2-methoxytoluene and synthesis process of methoxyfenozide
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The invention relates to the field of insecticides, in particular to a preparation method of 6-chloro-2-methoxytoluene and a synthesis process of methoxyfenozide. The preparation method of the 6-chloro-2-methoxytoluene comprises the following steps: in a solvent, mixing 2, 6-dichlorotoluene with sodium methoxide, and carrying out a substitution reaction to prepare a first reaction solution containing 3-chloro-2-sodium methylphenolate and the 6-chloro-2-methoxytoluene; and dropwise adding dimethyl sulfate into the first reaction solution, carrying out etherification reaction, removing 3-chloro-2-sodium methylphenolate to obtain a second reaction solution, and carrying out post-treatment to obtain the 6-chloro-2-methoxytoluene. The synthesis process of the methoxyfenozide comprises the following steps: preparing 3-methoxy-2-methyl benzoic acid by taking 6-chloro-2-methoxytoluene as an intermediate; using 3-methoxy-2-methyl benzoic acid and 3, 5-dimethyl benzoic acid as intermediates, and preparing to obtain the methoxyfenozide. According to the synthesis process disclosed by the invention, the yield and the purity of methoxyfenozide can be remarkably improved.
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- 2-methyl-3-methoxybenzoic acid and preparation method thereof
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The invention belongs to the field of compound synthesis, and discloses 2-methyl-3-methoxybenzoic acid and a preparation method thereof, wherein the 2-methyl-3-methoxybenzoic acid is prepared from thefollowing raw materials: 2-methyl-3-chloroanisole, methylbenzene, tetrahydrofuran, magnesium chips, an initiator and a carboxylating agent. According to the invention, the preparation method solves the problems of large pollution hazard, high cost and low yield in the existing 2-methyl-3-methoxybenzoic acid preparation method; and the yield of the intermediate 2-methyl-3-chloroanisole of 2-methyl-3-methoxybenzoic acid obtained in the preparation method can reach 90-91%, the yield of 2-methyl-3-methoxybenzoic acid prepared from 2-methyl-3-chloroanisole is about 88%, the reaction is easy to control, the pollution is small, and the cost is low.
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Paragraph 0034; 0036-0038; 0040-0043; 0044-0046; 0048-0050
(2020/05/01)
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- 2-methyl-3-methoxybenzoyl chloride synthesizing process
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The invention discloses a 2-methyl-3-methoxybenzoyl chloride synthesizing process. According to the present invention, low-cost o-xylene is used as a starting raw material, the product is synthesizedby using a conventional synthesis method comprising nitrification, esterification, reduction, diazotization, methylation, acyl chlorination and other steps, and the total yield is controlled at more than 65%; the esterification of the intermediate product improves the separation degree of the intermediate; the reaction solvent is added in the diazotization step, such that the process parameters are relatively easy to control, and the purity of the intermediate in the diazotization step is more than 96% so as to provide the guarantee for the quality of the subsequent product; and with the synthesis process, the product quality is stable and reliable, and the cost is low.
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- Preparation method of 2-methyl-3-methoxybenzoic acid
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The invention relates to a preparation method of 2-methyl-3-methoxybenzoic acid. The preparation method comprises the following specific steps: A, adding a proper amount of a sodium methoxide solution, 2,6-dichlorotoluene, dimethylformamide and cuprous salt into a reaction kettle; stirring and raising the temperature; controlling the temperature to 80 DEG C to 150 DEG C and reacting to obtain 2-methyl-3-chloroanisole; B, adding a proper amount of tetrahydrofuran and magnesium into the other reaction kettle; controlling the temperature to be 30 DEG C to 60 DEG C; adding a mixed solution of bromoethane and the 2-methyl-3-chloroanisole; after reacting for 20min to 40min, controlling the temperature to be 40 DEG C to 60 DEG C and dropwise adding the 2-methyl-3-chloroanisole; after dropwise adding, keeping heat and reacting for 1.5h to 2.5h; then cooling to -15 DEG C to -5 DEG C; adding dry ice by batches; controlling the temperature to be 0 DEG C to 20 DEG C, keeping the heat and reactingfor 2h to 4h; then recycling the tetrahydrofuran; adjusting the pH (Potential of Hydrogen) value to separate out white powder, namely the 2-methyl-3-methoxybenzoic acid. The preparation method of the2-methyl-3-methoxybenzoic acid, provided by the invention, is simple in route and high in yield.
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Paragraph 0021
(2018/03/24)
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- Synthesis method of 2-methyl-3-methoxybenzoic acid
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The invention relates to a synthesis method of 2-methyl-3-methoxybenzoic acid. The preparation method comprises the specific steps: A, adding a proper amount of a sodium methoxide solution, 2,6-dichlorotoluene, dimethylformamide and a cuprous salt into a reaction kettle, stirring to rise the temperature, controlling the temperature at 80 DEG C to 150 DEG C and carrying out a reaction, to obtain 2-methyl-3- chloroanisole; and B, adding a proper amount of butyl oxide and magnesium into another reaction kettle, controlling the temperature at 30 DEG C to 60 DEG C, adding a mixed liquid of bromoethane and 2-methyl-3-chlorobenzene, carrying out a reaction for 20 min-40 min, controlling the temperature at 40 DEG C to 60 DEG C, adding 2-methyl-3- chlorobenzene drop by drop, after drop-by-drop addition is finished, carrying out a heat preservation reaction for 1.5 h-2.5 h, then cooling to -15 DEG C to -5 DEG C, adding dry ice in batches, controlling the temperature at 0 DEG C to 20 DEG C, carrying out a heat preservation reaction for 2 h to 4 h, then recycling butyl oxide, adjusting the pH value, and separating out a white powder, namely 2-methyl-3-methoxybenzoic acid. The synthesis methodof the 2-methyl-3-methoxybenzoic acid is simple in route and high in yield.
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Paragraph 0018; 0019
(2018/03/25)
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- Preparation method for 2-methyl-3-methoxybenzoic acid and preparation method for intermediate thereof
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The invention discloses a preparation method for 2-methyl-3-methoxybenzoic acid and a preparation method for an intermediate thereof. The preparation method for the intermediate namely 2-methyl-3-chlorobenzoic acid comprises the following steps: introducing oxygen into a mixed solution of a C2-6 organic acid, a catalyst and 3-chloro-ortho-xylene, and carrying out a reaction, wherein the catalyst is a cobalt-manganese-bromine composite catalyst or a cobalt-bromine composite catalyst; the reaction temperature is 100 to 210 DEG C; the reaction pressure is 0.1 to 3 MPa; and the introduction time of the oxygen is 1 to 12 h. The preparation method provided by the invention uses 3-chloro-ortho-xylene as a starting material, has the advantages of simple and convenient process, short production period, high yield, clean production and reduced cost, and is applicable to industrial production.
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Paragraph 0040-0042; 0045; 0048
(2017/08/31)
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- First general, direct, and regioselective synthesis of substituted methoxybenzoic acids by ortho metalation
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(Chemical Equation Presented) New general methodology of value in aromatic chemistry based on ortho-metalation sites in o-, m-, and p-anisic acids (1-3) (Scheme 1) is described. The metalation can be selectively directed to either of the ortho positions by varying the base, metalation temperature, and exposure times. Metalation of o-anisic acid (1) with s-BuLi/TMEDA in THF at -78°C occurs exclusively in the position adjacente to the carboxylate. On the other hand, a reversal of regioselectivity is observed with n-BuLi/t-BuOK. With LTMP at 0°C, the two directors of m-anisic acid (2) function in concert to direct introduction of the metal between them while n-BuLi/t-BuOK removes preferentially the proton located ortho to the methoxy and para to the carboxylate (H-4). s-BuLi/TMEDA reacts with p-anisic acid (3) exclusively in the vicinity of the carboxylate. According to these methodologies, routes to very simple methoxybenzoic acids with a variety of functionalities that are not easily accessible by other means have been developed (Table 1).
- Nguyen, Thi-Huu,Chau, Nguyet Trang Thanh,Castanet, Anne-Sophie,Nguyen, Kim Phi Phung,Mortier, Jacques
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p. 3419 - 3429
(2008/02/03)
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- Toward a better understanding on the mechanism of ortholithiation. Tuning of selectivities in the metalation of meta-anisic acid by an appropriate choice of base
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(Chemical Equation Presented) If employed in THF at 0°C, LTMP metalates meta-anisic acid at the doubly activated position. In contrast, n-BuLi/t-BuOK deprotonates position C-4 preferentially at low temperature. Functionalization at C-6 requires protection of the C-2 site beforehand. As a result of these findings, a new mechanism is proposed for the heteroatom-directed ortholithiation of aromatic compounds.
- Nguyen, Thi-Huu,Chau, Nguyet Trang Thanh,Castanet, Anne-Sophie,Nguyen, Kim Phi Phung,Mortier, Jacques
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p. 2445 - 2448
(2007/10/03)
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- Preparation of 3-alkoxy-2-methylbenzoic acids
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The invention relates to an improved process for preparing 3-alkoxy-2-methylbenzoic acids by heating substituted naphthalenes in the presence of alkali metal hydroxides and subsequently alkylating.
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- Process for the preparation of 3-Alkoxy-2-methylbenzoic acids
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Preparation of 3-alkoxy-2-methyl-benzoic acid compounds (I) involves: (a) reacting a naphthalene compound with alkali metal hydroxide in presence of water; (b) partially neutralizing; (c) treating with an alkyl halide, alkyl sulfonate or alkyl sulfate and (d) acidifying. Preparation of 3-alkoxy-2-methyl-benzoic acids of formula (I) involves: (a) reacting a naphthalene derivative of formula (III) with alkali metal hydroxide in presence of water; (b) partially neutralizing the reaction mixture (optionally after adding water, removing insolubles and/or removing undesirable soluble components); (c) reacting the mixture with an alkyl halide of formula R1X (IVa), an alkyl sulfonate of formula R1-OSO2-R8 (IVb) or a dialkyl sulfate of formula R1OSO2OR1 (IVc); and (d) acidifying the mixture. R1 = 1-14C alkyl, 7-20C aralkyl, 13-20C diarylalkyl, A-OR2 or A-NR3R4; A = 1-4C alkylene; R2, R3, R4 = Me, Et or isopropyl; R5-R7 = H, OH, NH2 or SO3M; M = H, ammonium, alkali metal or 1 equivalent of alkaline earth metal; X = Cl, Br or I, and R8 = 1-4C alkyl, 1-4C perfluoroalkyl, phenyl or p-tolyl.
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- PROCESS FOR PRODUCING TOLUENE DERIVATIVES
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A toluene derivative of the general formula (2) wherein R denotes a fluorine atom, a chlorine atom, an alkoxy group, or an alkylthio group, and X denotes a halogen atom, is prepared by reacting metallic magnesium with a 2-chloro-6-substituted toluene derivative of the general formula (1) wherein R is as defined above, in an ethereal solvent in the presence of a lower alkyl bromide.
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- Process for synthesizing benzoic acids
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A nucleophilic substitution reaction on optionally substituted dihalobenzenes is carried out in the presence of an optional catalyst followed by formation of and subsequent carboxylation of a Grignard reaction intermediate. In particular the present invention provides a process leading to optionally substituted hydroxybenzoic, alkanoyloxybenzoic, formyloxybenzoic and alkoxybenzoic acids from 1-substituted 2,6-dihalobenzenes. The invention also provides a process for the direct formation of an acyl chloride from a Grignard reagent by quenching with phosgene.
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- Selective para metalation of unprotected 3-methoxy and 3,5-dimethoxy benzoic acids with n-butyl lithium-potassium tert-butoxide (LIC-KOR): Synthesis of 3,5-dimethoxy-4-methyl benzoic acid
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The potassium salt of 3-methoxy and 3,5-dimethoxy benzoic acids undergoes deprotonation at the position para to the carboxylate group selectively when treated with LIC-KOR in THF at -78°C and it has been extended to the synthesis of 3,5-dimethoxy-4-methyl benzoic acid. (C) 2000 Elsevier Science Ltd.
- Sinha, Surajit,Mandal, Bhubaneswar,Chandrasekaran, Srinivasan
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p. 3157 - 3160
(2007/10/03)
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- Relationships between structure and molting hormonal activity of tebufenozide, methoxyfenozide, and their analogs in cultured integument system of Chilo suppressalis Walker
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The molting hormonal activity of methoxyfenozide (RH-2485), tebufenozide (RH-5992), five analogs with various alkyl groups, and 18 acyl analogs was measured by using cultured integument of rice stem borers, Chilo suppressalis Walker. The hormonal activity of methoxyfenozide was remarkably high (EC50 = 1.1 x 10-9 M), being equivalent to that of tebufenozide (RH-5992). The hormonal activity of several tebufenozide analogs with varying alkyl groups such as CH3, n-C3H7, i-C3H7, n-C4H9 and n-C5H11 at the para-position of the benzene ring furthest from the tert-butyl group was lower than that of tebufenozide (alkyl group is C2H5). The activity decreased to varying degrees as a result of replacement of the 3,5-dimethylphenyl moiety of tebufenozide with either a phenyl, naphthyl, or cyclohexyl group. Both 1- and 2-naphthyl derivatives were very active (EC50 = 4.3 x 10-8 M and 3.2 x 10-8 M, respectively) without any significant difference between them. The activity of the 1-cyclohexenyl analog (EC50 = 1.0 x 10-7 M) was about 40x that of the corresponding 3-cyclohexenyl analog (EC50 = 4.4 x 10-6 M), but 1/100 that of tebufenozide. The activity varied parabolically with respect to the molecular hydrophobicity, and decreased with longer acyl moieties. Copyright (C) 2000 Elsevier Science Inc.
- Nakagawa, Yoshiaki,Hattori, Kazunari,Minakuchi, Chieka,Kugimiya, Soichi,Ueno, Tamio
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p. 117 - 123
(2007/10/03)
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- HIV protease inhibitors
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HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.
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- Insecticidal N'-substituted-N,N'-diacylhydrazines
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Insecticidal compounds having the formula N-(2-Ra -3-Rb -4-Rh -benzoyl)-N'-(2-Rc -3-Rd -4-Re -5-Rf -benzoyl)-N'-Rg -hydrazine wherein Ra is a halo or lower alkyl; R b is lower alkoxy, optionally substituted with halo (preferably fluoro); Rc is selected from hydrogen, halo, lower alkyl, lower alkoxy, lower alkoxy lower alkyl, and nitro; Rd, Re and Rf are each independently selected from hydrogen, bromo, chloro, fluoro, lower alkyl, lower alkoxy, and lower alkoxy lower alkyl; Rg is a (C4 -C6)alkyl; Rh is hydrogen, lower alkoxy, lower alkyl, or when taken together with Rb is methylenedioxy (--OCH2 O--), 1,2-ethylenedioxy (--OCH2 CH2 O--), 1,2-ethyleneoxy (--CH2 CH2 O--) or 1,3-propyleneoxy (--CH2 CH2 CH2 O--) wherein an oxo atom is located at the Rb position; and the substituents Rc and Rd, or Rd and Re, or Re and Rf when taken together can be methylenedioxy or 1,2-ethylenedioxy as well as compositions comprising an agronomically acceptable carrier and an insecticidally effective amount of such compounds; and methods of using such compounds and compositions. Also, methods for the production of the compounds and their intermediates, which methods comprise either admixing a 3-amino-2-(substituted)-benzoic acid, sodium nitrite and methanol under acidic conditions or admixing a 3,4-fused heterocyclic benzoic acid and an alkyl lithium reagent followed by subsequent reaction with an electrophilic reagent.
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- HIV protease inhibitors
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HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.
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- Intermediate and process for making
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The present invention provides novel HIV protease inhibitors, pharmaceutical formulations containing those compounds and methods of treating and/or preventing HIV infection and/or AIDS.
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- Directed lithiation of unprotected benzoic acids
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Benzoic acid gives the ortho-lithiated species 1 under standard conditions (s-BuLi-TMEDA-THF, -90 deg C).Reaction of 1 at -78 deg C with either methyl iodide, dimethyl disulfide, hexachloroethane, or 1,2-dibromotetrachloroethane gives the ortho-substituted product.Intramolecular competition between the carboxylic acid and methoxy, chloro, fluoro, or diethylamido functions in ortho- and -para-substituted benzoic acids establishes the carboxylic acid group to be of intermediate capacity in directing metallation.Complimentarity of directing effects is observed with the chloro and fluoro groups in the meta-substituted benzoic acid but not with the methoxy and trifluoromethyl groups.Electrophile introduction into meta- and para-lithiated benzoates occurs with equal efficacy and comparable scope.The 2,4-dihalogenobenzoic acids undergo hydrogen/metal exchange at the position flanked by both halogen substituents. 2,2-Difluoro-1,3-benzodioxole-4-carboxylic acid undergoes lithiation adjacent to the oxygen atom.By use of such methods, routes to benzoic acids contiguously tri- and tetra-substituted with a variety of functionalities have been developed.
- Bennetau, Bernard,Mortier, Jacques,Moyroud, Joel,Guesnet, Jean-Luc
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p. 1265 - 1272
(2007/10/02)
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- The Carboxylic Acid Group as an Effective Director of Ortho-Lithiation
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Treatment of PhCO2H in tetrahydrofuran with 2.2 equiv of a 1:1 sec-butyllithium/N,N,N',N'-tetramethyl-1,2-ethylenediamine complex at -90 deg C gave o-LiC6H4CO2Li, which was treated with electrophiles to give o-RC6H4CO2H (R = Me, SMe, Cl, Br) in good yields.
- Mortier, Jacques,Moyroud, Joeel,Bennetau, Bernard,Cain, Paul A.
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p. 4042 - 4044
(2007/10/02)
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- Synthesis, Tubulin Binding, Antineoplastic Evalutaion, and Structure-Activity Relationship of Oncodazole Analogues
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n an attempt to identify a soluble oncodazole analogue that could be easily formulated, a series of substituted oncodazoles was synthesized and evaluated for tubulin binding affinity, in vitro cyctotoxicity against cultured mouse B-16 cells, and ability to prolong lifespan at the maximally tolerated dose in the P388 mouse leukemia model.Biological evaluation of all the isomeric methyloncodazoles demonstrated the thiophene 4'-position to be the only site of significant bulk tolerance, although substitution of this position with polar or charged functional groups abolished biological activity.Simple esters of the 4'-carboxymethyloncodazole were shown to have enhanched antitumor activity and tubulin binding affinity relative to oncodazole.Despite a failure of this study to identify a water-soluble oncodazole with antitumor activity, the structure-activity relationship developed led to a derivative with enhanced activity in the P388 leukemia model and facilitated the preparation of a biologically active photolabile analogue.
- Kruse, Lawrence I.,Ladd, David L.,Harrsch, Peter B.,McCabe, Francis L.,Mong, Shau-Ming,et al.
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p. 409 - 417
(2007/10/02)
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- METALLATION OF RIGID 2-ARYL-1,3-DIOXANES
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Regioselective metallation and alkylation/acylation of 2-aryl-1,3-dioxanes was achieved in high yield.
- Campbell, Arthur L.,Khanna, Ish Kumar
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p. 3963 - 3966
(2007/10/02)
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