- CALICHEAMICIN DERIVATIVES AND ANTIBODY DRUG CONJUGATES THEREOF
-
The present invention is directed to novel calicheamicin derivatives useful as payloads in antibody-drug-conjugates (ADC's), and to payload-linker compounds and ADC compounds comprising the same; to pharmaceutical compositions comprising the same and to methods for using the same to treat pathological conditions such as cancer.
- -
-
Page/Page column 192
(2018/08/20)
-
- Selective reaction of benzyl alcohols with HI gas: Iodination, reduction, and indane ring formations
-
Reactions of benzyl alcohols with HI in solvent-free conditions were examined. Three types of reactions (iodination, reduction, and ring formation) occurred depending on the degree of crowding around the benzyl position and the benzylic stabilization of substrates. Results also showed that the ring formation to give indanes proceeded efficiently when HI was used, and that compounds with electron-rich aromatic rings gave indane derivatives in good yields.
- Matsumoto, Shoji,Naito, Masafumi,Oseki, Takehisa,Akazome, Motohiro,Otani, Yasuhiko
-
p. 7254 - 7259
(2017/11/24)
-
- ARYL AND HETEROARYL ETHER COMPOUNDS AS ROR GAMMA MODULATORS
-
The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein Ring A, Ring B, R, R2, R3, n, and p are as defined herein, which are active as modulators of retinoid-related orpha
- -
-
Page/Page column 47; 48; 49; 54; 55
(2015/11/09)
-
- Improved preparative route toward 3-arylcyclopropenes
-
A convenient preparative protocol for the synthesis of various 3-arylcyclopropenes in a multigram scale is disclosed. Optimization of the reaction conditions and isolation procedures allowed for significant improvement of the chemical yields of these strained products. The described protocol was used for efficient preparation of a series of 3-methyl-3-arylcyclopropenes possessing different substituents in the aromatic ring. The effect of substitution in the aryl group on the stability of 3-arylcyclopropenes, as well as the corresponding precursors, is discussed.
- Sherrill, William M.,Kim, Ryan,Rubin, Michael
-
p. 8610 - 8617
(2008/12/21)
-
- Kinetics and mechanism of acid catalysed hydration of α- methylstyrenes
-
Twelve para-substituted α-methylstyrenes with substituents H, CH 3, CF3, CH3O, CH3S, F, Cl, Br, CH3CO, CH3SO2, CN a NO2 were synthesised; additionally, the acid catalysed hydration kinetics of these compounds were measured in sulfuric acid in a concentration range c from 0.017 to 9.58 mol l-1, at 25.0°C. The observed rate constants obtained were used to construct the kinetic acidity function and calculate the catalytic rate constants. Based on the evaluation of the acidity function kinetic dependence on acid medium concentration, and the substituent effects of acid catalysed hydration of α-methylstyrenes on the catalytic rate constants, the mechanism of acid catalysed hydration was verified. The mechanism involves the addition of a proton to the double bond of α-methylstyrene in the rate-limiting reaction step denoted as A-SE2. No evident difference was found between the effects of the acid medium on the acid catalysed hydration of styrenes and α-methylstyrenes, which indicates very similar activity coefficients of the reactants, and of the transition state of both substrates. The substituent effects evaluation shows that the rate-limiting step of the reaction consists in the addition of a proton to the substrate. The carbocation formation in the transition state of this reaction step proceeds roughly half-way compared with the extent of the carbocation formation by cumyl chloride hydrolysis. The obtained carbocation is in particular stabilised by the substituents with +M effect, while the influence of the substituents with -M and I effects is significantly smaller.
- Pytela, Oldrich,Trlida, Bronislav
-
p. 1025 - 1036
(2008/09/19)
-
- Photooxidation of aryl alkanes by a decatungstate/triethylsilane system in the presence of molecular oxygen
-
Decatungstate photocatalyzes the oxidation of aryl alkanes to the corresponding tertiary hydroperoxides and alcohols, in the presence of molecular oxygen. The addition of triethylsilane to the reaction mixture substantially increases the proportion of hydroperoxide formed.
- Lykakis, Ioannis N.,Orfanopoulos, Michael
-
p. 7645 - 7649
(2007/10/03)
-
- Spectral properties and absolute rate constants for β-scission of ring-substituted cumyloxyl radicals. A laser flash photolysis study
-
A laser flash photolysis study of the spectral properties and β-scission reactions of a series of ring-substituted cumyloxyl radicals has been carried out. All cumyloxyl radicals display a broad absorption band in the visible region of the spectrum, which decays on the microsecond time scale, leading to a strong increase in absorption in the UV region of the spectrum, which is attributed to the corresponding acetophenone formed after β-scission of the cumyloxyl radicals. The position of the visible absorption band is red-shifted by the presence of electron-donating ring substituents, while a blue-shift is observed in the presence of electron-withdrawing ring substituents, suggesting that + R ring substituents promote charge separation in the excited cumyloxyl radical through stabilization of the partial positive charge on the aromatic ring of an incipient radical zwitterion. Along this line, an excellent Hammett-type correlation between the experimentally measured energies at the visible absorption maxima of the cumyloxyl radicals and σ+ substituent constants is obtained. A red-shift is also observed on going from MeCN to MeCN/H2O for all cumyloxyl radicals, pointing toward a specific effect of water. The ring substitution does not influence to a significant extent the rate constants for β-scission of the cumyloxyl radicals, which varies between 7.1 × 105 and 1.1 × 106 s-1, a result that suggests that cumyloxyl radical β-scission is not governed by the stability of the resulting acetophenone. Finally, κβ increases on going from MeCN to the more polar MeCN/H2O 1:1 for all cumyloxyl radicals, an observation that reflects the increased stabilization of the transition state for β-scission through increased solvation of the incipient acetophenone product.
- Baciocchi, Enrico,Bietti, Massimo,Salamone, Michela,Steenken, Steen
-
p. 2266 - 2270
(2007/10/03)
-
- Phenyl spiroethercycloalkyl tachykinin receptor antagonists
-
The present invention is directed to certain novel compounds represented by structural formula I: STR1 or a pharmaceutically acceptable salt thereof, wherein R 3, R 6, R 7, R 8, R 11, R 12, R 13, m, n and the dashed lines are defined herein. The invention is also concerned with pharmaceutical formulations comprising these novel compounds as active ingredients and the use of the novel compounds and their formulations in the treatment of certain disorders. The compounds of this invention are tachykinin receptor antagonists and are useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis.
- -
-
-
- Substituted 6-azaandrostenones
-
The present invention relates to certain substituted 17β-substituted carbonyl-6-azaandrost-4-en-3-ones of formula (I), wherein R1 and R2 i) are independently hydrogen or lower alkyl and the bond between the carbons bearing R1/s
- -
-
-
- Metal cation-exchanged montmorillonite(Mn+-mont)-catalysed carbonyl-ene reactions
-
Metal cation-exchanged montmorillonite (Mn+-mont) works in acetonitrile at 80°C as a Lewis acid catalyst for the intermolecular carbonyl-ene reaction of α-methylstyrenes with paraformaldehyde to give the corresponding homoallylic alcohols, Zr4+-mont being the most effective of the many Mn+-mont catalysts examined. Similarly, the catalyst is also useful for the highly stereoselective intramolecular cyclization of citronellals to afford isopulegols, the reaction being much faster. Regeneration of the catalyst is confirmed for Zr4+-mont, which can be effectively recycled at least five times.
- Tateiwa, Jun-Ichi,Kimura, Akihiro,Takasuka, Masaaki,Uemura, Sakae
-
p. 2169 - 2174
(2007/10/03)
-
- Radical ions in photochemistry. Carbon-carbon bond cleavage of radical cations in solution: Theory and application
-
The cleavage of radical cations of two series of alkanes, 1,1,2-triaryl- and 1,1,2,2-tetraarylalkanes, generated by photoinduced single electron transfer in acetonitrile-methanol, occurs with formation of radical and carbocation fragments. The radical cations of some unsymmetrically substituted alkanes cleave to give all four of the possible products, two hydrocarbons emanating from the radicals and two methyl ethers from the carbocations, in proportion to the oxidation potentials of the two possible radical fragments. There is an excellent linear correlation between the logarithm of the observed ratio of products and that calculated from the reported electrochemically determined oxidation potentials (r = 0.998, 5 points). The proportionality constant (1.27) for this relationship is close to unity which indicates that the product ratio is determined by the relative rates of cleavage in the two possible modes or by equilibration of the radicals and carbocations before separation of the geminate radical carbocation pair and not by equilibration upon reencounter of freely solvated radical and carbocation fragments. The effect of temperature on the relative oxidation potentials of the radicals studied is small and can be neglected when radicals of the same order (i.e., both secondary or both tertiary) and of similar size are compared. The ratio of products obtained upon cleavage of the radical cation at 25 °C can be used to determined standard oxidation potentials of radicals. The oxidation potential of the diphenylmethyl radical (0.350 V vs SCE) has been accepted as the primary standard and the (4-methyl-phenyl)phenylmethyl (0.265 V) and bis(4-methylphenyl)methyl (0.188 V) radicals are established as secondary standards against which the oxidation potentials of other radicals can be measured. Oxidation potentials of several 4-substituted cumyl radicals have been determined by this photochemical method. There is a good (r = 0.987, 5 points) linear correlation between the measured oxidation potentials and the σ+ substituent constants. The reaction constant is appropriately negative and large (p = -6).
- Popielarz,Arnold
-
p. 3068 - 3082
(2007/10/02)
-