- COUMARIN-MODIFIED ANDROGENS FOR THE TREATMENT OF PROSTATE CANCER
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Provided are androstane and dihydrotestosterone compounds functionalized with carbocyclic groups or heterocyclic groups that may be saturated or unsaturated. The compounds may be used in methods of inhibiting cell growth of malignant cells and/or hyperplastic cells and/or treating individuals having diseases associated with malignant cell growth (e.g., cancer, such as, for example, prostate cancer) and/or hyperplastic cell growth and/or molecular imaging of malignant cells and/or hyperplastic cells and/or inducing degradation of a target protein. Also provided are compositions.
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Paragraph 0115
(2020/11/12)
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- Formal synthesis of (+)-lactacystin from l-serine
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A formal, stereocontrolled synthesis of lactacystin has been completed from t-Bu-O-l-serine, providing the key intermediate 13, also useful for the generation of a range of C-9 analogues.
- Bulman Page, Philip C.,Goodyear, Ross L.,Chan, Yohan,Slawin, Alexandra M. Z.,Allin, Steven M.
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p. 30019 - 30032
(2019/10/01)
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- Preparation method for polyfluoromethylpyrazole compound, and intermediate of compound and preparation method thereof
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The invention discloses a preparation method for a polyfluoromethylpyrazole compound, and an intermediate of the compound and a preparation method thereof. The invention provides a preparation method for a compound 1 as defined in the specification. The preparation method comprises a step of subjecting a compound 2 as defined in the specification and methylhydrazine to a ring-closure reaction in an organic solvent so as to obtain the compound 1, wherein R is a C1-4 alkyl group, R is a methyl or ethyl group and x is 2 or 3. The preparation method provided by the invention uses cheap and easily available raw materials and is mild in reaction conditions, safe to operate, environment friendly, low in production cost, high in reaction conversion rate, low in the content of isomer in by-products, high in reaction yield and product purity and suitable for industrial production.
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Paragraph 0129; 0130; 0131
(2017/06/30)
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- MULTISTAGE PROCESS FOR PREPARING ALKALI METAL SALTS OF SPECIFIC 4-HYDROXY-2-OXO-2,5-DIHYDROFURAN-3-CARBOXYLIC ESTERS
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The present invention relates to a multi-stage method for preparing alkali metal salts of specific 4-hydroxy-2-oxo-2,5-dihydrofuran-3-carboxylic esters of the formula (I), in which M and R1 are as defined in the description, which proceeds from malonic ester and does not require isolation of intermediates.
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Paragraph 0070; 0071
(2015/08/04)
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- Pd-catalyzed decarboxylative cross-couplings of potassium malonate monoesters with aryl halides
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An efficient catalytic protocol for Pd-catalyzed decarboxylative cross-coupling of potassium malonate monoesters and derivatives with aryl bromides and chlorides are described. Because of its broad applicability, this new catalytic system provides an alternative method for the preparation of diverse aryl acetic acids and derivatives.
- Feng, Yi-Si,Wu, Wei,Xu, Zhong-Qiu,Li, Yan,Li, Ming,Xu, Hua-Jian
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supporting information; experimental part
p. 2113 - 2120
(2012/03/26)
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- Synthesis of α-Aryl nitriles through palladium-catalyzed decarboxylative coupling of cyanoacetate salts with aryl halides and triflates
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Worth its salt: The palladium-catalyzed decarboxylative coupling of the cyanoacetate salt as well as its mono- and disubstituted derivatives with aryl chlorides, bromides, and triflates is described (see scheme). This reaction is potentially useful for the preparation of a diverse array of α-aryl nitriles and has good functional group tolerance. S-Phos=2-(2,6- dimethoxybiphenyl)dicyclohexylphosphine), Xant-Phos=4,5-bis(diphenylphosphino)- 9,9-dimethylxanthene. Copyright
- Shang, Rui,Ji, Dong-Sheng,Chu, Ling,Fu, Yao,Liu, Lei
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supporting information; experimental part
p. 4470 - 4474
(2011/06/24)
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- Preparation of cilazapril intermediates
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The present application relates to cilazapril intermediates and processes for the preparation of cilazapril intermediates, including (S)-6,11-dioxo-1,2,3,4,6,11-hexahydro-pyridazino[1,2-b]naphthalazine-1-carboxylic acid and its salts.
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Page/Page column 8
(2010/09/05)
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- Discovery and structure-activity relationships of trisubstituted pyrimidines/pyridines as novel calcium-sensing receptor antagonists
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The trisubstituted pyrimidine 1 was identified through high-throughput screening as a novel calcium-sensing receptor (CaSR) antagonist. Small molecule CaSR antagonists and/or negative allosteric modulators have the potential to act as an anabolic agent for the treatment of osteoporosis. The investigation of structure-activity relationships around 1 resulted in the identification of 18c and 18d, which showed efficacy at promoting PTH release in vivo and exhibited improved potency and solubility over the original lead 1.
- Yang, Wu,Ruan, Zheming,Wang, Yufeng,Van Kirk, Katy,Zhengping, Ma.,Arey, Brian J.,Cooper, Christopher B.,Seethala, Ramakrishna,Feyen, Jean H. M.,Dickson Jr., John K.
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supporting information; experimental part
p. 1204 - 1208
(2009/12/25)
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- TRISUBSTITUTED HETEROAROMATIC COMPOUNDS AS CALCIUM SENSING RECEPTOR MODULATORS
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Trisubstituted heteroaromatic compounds having the structure Formula (I) are provided, wherein X is C or N; A and B are each independently CH or N, with the proviso that A and B cannot both be CH; R is Ar-L-; R is hydrogen or alkyl; or R and R can be joined together to form a 4- to 7-membered cycloheteroalkyl ring; R to R, Ar and L are as defined herein. A method for using these compounds to treat diseases associated with abnormal bone or mineral homeostasis is also provided.
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- Process for preparing potassium monoethyl malonate
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A process for preparing potassium monoethyl malonate by selective saponification of malonic acid diethyl ester with potassium hydroxide, in which the potassium hydroxide is added to the malonic acid diethyl ester, malonic acid diethyl ester and potassium hydroxide are used in a molar ratio of at least 1.5 and the potassium hydroxide is effectively distributed into the malonic acid diethyl ester.
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- Synthesis and decarboxylation of Δ2-cephem-4,4-dicarboxylic acids
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Penicillin V was converted in 14 steps into Δ2-cephems having hydrogen at C-3, hydrogen or methyl at C-2, and two methoxycarbonyl, two benzyloxycarbonyl, or one methoxycarbonyl and one benzyloxycarbonyl substituent at C-4. Deprotection of these Δ2-cephem-4,4-dicarboxylic acid esters by alkaline hydrolysis (in the case of methyl esters) or hydrogenolysis (in the case of benzyl esters) led in all cases to rapid decarboxylation of the Δ2-cephem-4,4-dicarboxylic acid or Δ2-cephem-4,4-dicarboxylic acid monoester. With hydrogen at C-2, hydrolysis of the dimethyl ester with 1 equiv of base produced a Δ2-cephem. With 2 equiv of base, and with all compounds having methyl at C-2, hydrolysis or hydrogenolysis afforded 4α-substituted-Δ2-cephems. In contrast, simpler benzyl or methyl acetamidomalonates could be deprotected without difficulty to afford stable malonic acids. Reasons for the differences in ease of decarboxylation were examined using semiempirical (AM1) and ab initio (3-21G) molecular orbital calculations. The decarboxylation barriers of unionized cephem or acetamido malonic acids were found to be high (35-40 kcal mol-1). Although the monoanion of acetamidomalonic acid retained a high barrier, the epimeric monoanions of a Δ2-cephem malonic acid decarboxylated with barriers of only 2 kcal mol-1.
- Wolfe,Ro,Kim,Shi
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p. 1238 - 1258
(2007/10/03)
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- THE SYNTHESIS OFβ-LACTONES AND β-LACTAMS FROM MALONATES AND MALONAMIDES
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The rhodium diacetate induced insertion reactions of some simple esters and amides of diazomalonic acid result in the formation of β-lactones and β-lactams.
- Box, Vernon G. S.,Marinovic, Nash,Yiannikouros, George P.
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p. 245 - 251
(2007/10/02)
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- Effect of Trace Impurities on a Bifurcation Structure in the Belousov-Zhabotinski Reaction and Preparation of High-Purity Malonic Acid
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We have found that impurities on the ppm level in malonic acid are sufficient to alter dramatically a sequence of bifurcations in the Belousov-Zhabotinskii (BZ) reaction.Samples of malonic acid from 15 vendors were tested, and each was found to contain one or more of the following impurities that effect the reaction dynamics: iron, paraformaldehyde, ethanol, methanol, ethyl ester, and methyl ester.We describe a straightforward procedure for purifying malonic acid.Reproducible bifurcation structures can only be observed with the highly purified malonic acid.Measurements with varying amounts of the above-mentioned impurities added to purified malonic acid show the striking effect of impurities on the dynamics of the BZ reaction.
- Noszticzius, Zoltan,McCormick, William D.,Swinney, Harry L.
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p. 5129 - 5134
(2007/10/02)
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