Category: 82-73-5

Xu, Guowei; Yang, Yaqing; Yang, Yanming; Song, Gao; Li, Shanshan; Zhang, Jiajun; Yang, Weimin; Wang, Liang-Liang; Weng, Zhiying; Zuo, Zhili published the artcile< The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation>, Safety of 4-Bromoisobenzofuran-1,3-dione, the main research area is adenylate cyclase agonist virtual screening cyclic adenosine monophosphate IL6; Adenylate cyclase; Agonist; Cyclic adenosine monophosphate; Interleukin-6; Virtual screening.

Adenylate cyclases (ACs), play a critical role in the conversion of ATP (ATP) into the second messenger cyclic adenosine monophosphate (cAMP). Studies have indicated that adenylyl cyclase type 2 (AC2) is potential drug target for many diseases, however, up to now, there is no AC2-selective agonist reported. In this research, docking-based virtual screening with the combination of cell-based biol. assays have been performed for discovering novel potent and selective AC2 agonists. Virtual screening disclosed a novel hit compound 8 as an AC2 agonist with EC50 value of 8.10μM on recombinant human hAC2 + HEK293 cells. The SAR (structure activity relationship) based on the derivatives of compound 8 was further explored on recombinant AC2 cells and compound 73 was found to be the most active agonist with the EC50 of 90 nM, which is 160-fold more potent than the reported agonist Forskolin and could selectively activate AC2 to inhibit the expression of Interleukin-6. The discovery of a new class of AC2-selective agonists would provide a novel chem. probe to study the physiol. function of AC2.

European Journal of Medicinal Chemistry published new progress about Drug screening (docking-based virtual screening). 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Safety of 4-Bromoisobenzofuran-1,3-dione.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Eberson, L.; Welinder, H. published the artcile< Cyclic anhydrides. III. Equilibrium constants for the acid-anhydride equilibrium in aqueous solutions of certain vicinal diacids>, Safety of 4-Bromoisobenzofuran-1,3-dione, the main research area is cyclic anhydrides equilibrium constant; acid anhydride equilibrium; vicinal diacids anhydrides equilibrium; succinic acid anhydrides equilibrium; alicyclic acid anhydrides equilibrium; maleic acid anhydrides equilibrium; phthalic acid anhydrides equilibrium.

Equilibrium constant were measured for the equilibrium diacid ⇌ anhydride + H2O in aqueous solutions of a number of vicinal diacids, chosen to correspond to relatively stable or very stable anhydrides. Such acids include di-, tri-, and tetraalkylsuccinic acids, certain alicyclic diacids, dialkylmaleic acids, and some alkyl-substituted phthalic acids. In all cases, the driving force for formation of a stable anhydride is relief of steric strain in the anhydride as compared to the corresponding diacid. Diisopropylmaleic anhydride was prepared as a new compound Low–melting 2,3-diethyl-2,3-dimethylsuccinic acid was shown to possess the dl-configuration by resolution.

Journal of the American Chemical Society published new progress about Anhydrides Role: PRP (Properties). 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Safety of 4-Bromoisobenzofuran-1,3-dione.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Bricelj, Alesa; Dora Ng, Yuen Lam; Ferber, Dominic; Kuchta, Robert; Muller, Sina; Monschke, Marius; Wagner, Karl G.; Kronke, Jan; Sosic, Izidor; Gutschow, Michael; Steinebach, Christian published the artcile< Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands>, Application of C8H3BrO3, the main research area is PROTAC CRBN stability neosubstrate cereblon linker degradation.

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.

ACS Medicinal Chemistry Letters published new progress about Cereblons Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Application of C8H3BrO3.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Dewar, Michael J. S.; Poesche, Werner H. published the artcile< New heteroaromatic compounds. XVIII. Boron-containing analogs of benz[a]anthracene>, Name: 4-Bromoisobenzofuran-1,3-dione, the main research area is .

The amines, 2,3-Ph(H2N)C10H6 (I) and 2-(2-H2NC6H4)C10H7 (II) on treatment with BCl3 and a catalytic amount of AlCl3 in boiling xylene gave the corresponding chloroborazarobenz[a]anthracenes (III, R = Cl) (IV) and (V, R = Cl) (VI). NaNO2 (55 ml., 2M) in concentrated H2SO4 stirred below 25° with addition of 18.8 g. 3,2-O2N(H2N)C10H6 in 670 ml. AcOH (boiled and cooled rapidly to 20°) and the mixture kept 15 min., added with stirring to 38 g. CuBr in 200 ml. 48% HBr and kept overnight, and diluted with H2O yielded 54% 3,2-Br(O2N)C10H6, m. 79-80°. The compound (20.8 g.) and 55 g. PhI stirred 36 hrs. at 110° with 31.8 g. Cu bronze yielded 74% 3,2-Ph(O2N)C10H6 (VII), m. 96.0-6.8° (MeOH). VII (6.0 g.) and 0.2 g. 10% Pd-C in 230 ml. boiling alc. treated gradually with 20 ml. N2H4.H2O and kept 1 hr. yielded quant. I, m. 82.7-3.5° (90% MeOH). I (10 g.) in 160 ml. dry xylene added (N atm.) slowly to 7.0 g. BCl3 in 45 ml. ice-cold xylene and the mixture treated with 0.2 g. AlCl3, the mixture heated to 140° in 4 hrs. and the temperature maintained 16 hrs., cooled and taken up in 750 ml. 2:1 Et2O-C6H6, the H2O-washed and dried (MgSO4) solution evaporated on a steam bath and the residue taken up in 500 ml. hot MeOH, the solution concentrated and kept at -15°, the product recovered from hot MeOH and the purified material (4.2 g.) recrystallized using an efficient dry box gave III (R = OMe) (VIII), m. 159° (evacuated capillary). The mother liquors gave 0.85 g. III (R = 1/2 O), C32H22B2N2O, m. 322°. VIII (1.3 g.) in 40 ml. dry Et2O stirred (H2O-free atm.) at 0° with addition of 12.5 ml. 0.6M MeMgBr and the mixture stirred 24 hrs. with rise of temperature to 20, the filtered solution evaporated and the residue sublimed at 150°/0.005 mm. gave III (R = Me) (VIIIa), m. 160.0-1.3° (petr. ether, b. 60-8°). LiAlH4 (1.35 millimoles) added to 3.86 millimoles VIII in 40 ml. dry Et2O and the mixture refluxed 2 hrs. with 0.45 millimole AlCl3 gave 5,6-borazarobenz[a]anthracene (III, R = H) (IX), m. 139° (decomposition). Cu bronze (46.5 g.), 65.0 g. 2-IC10H7, and 56.0 g. 1,2-Br(O2N)C6H4 stirred 40 hrs. at 110° gave 60% 2-(o-O2NC6H4)C10H7 (X), m. 101° (MeOH). X (9.0 g.) in 450 ml. alc. hydrogenated at 20° and 30 lb./in.2 with 0.3 g. 10% Pd-C and the filtered solution concentrated gave 6.0g. II, m. 95-7°. X (32 g.) and 1.0 g. 10% Pd-C refluxed 1 hr. in 1400 ml. alc. with gradual addition of 45 ml. N2H4.H2C and the filtered solution concentrated gave 22 g. II. II (22.0 g.) in 350 ml. dry xylene added slowly with stirring to 13.0 g. BCl3 in 100 ml. ice-cold xylene and the mixture heated 4 hrs. at 140° with 0.5 g. AlCl3 and stirred 16 hrs. at 140° gave 10.4 g. V (R = 1/2 O) (XI), m. 261-4°, recrystallized from PhMe(C) to give an analytical sample, m. 275.5°. Further concentration of the mother liquors gave a 2nd crop of XI (4.8 g., m. 264-5°), and evaporation of the filtrate yielded 8.6 g. residue (XII), m. 225-47°. The ether XI (12.7 g.) taken up in 500 ml. hot absolute MeOH and concentrated to 350 ml., cooled and the product (10.5 g., m. 174-6°) recrystallized from MeOH (C) gave V (R = OMe) (XIII), m. 183-4° (evacuated capillary). The filtrate evaporated and the residue combined with XII, the mixture recrystallized from absolute MeOH to give 4.80 g. XIII, and the filtrate evaporated in vacuo gave a dark brown oil with an ultraviolet spectrum identical with that of XIII and containing no other bands. XIII (2.6 g.) stirred at 20° in 100 ml. dry Et2O with dropwise addition of 15 ml. M MeMgBr in Et2O and the mixture stirred 2 hrs., the filtered solution diluted with moist Et2O and shaken with H2O, the organic layer dried over CaCl2 and evaporated yielded 87% product, m. 136-40°, sublimed at 120°/0.1 mm. to give V (R = Me) (XIV), m. 141-3°. XIII (1.00 g.) stirred at 0° in 30 ml. dry Et2O with gradual addition of 1.00 millimole LiAlH4 (standardized Et2O solution) and the mixture refluxed 2 hrs. with 0.04 g. AlCl3, the filtered solution evaporated and the residue sublimed at 120°/0.005 mm. gave 65% V (R = H) (XV), m. 136.5-7.0° (decomposition). XIII (2.0 g.) in 20 ml. hot AcOH treated with 10 ml. concentrated HCl and the mixture cooled quickly to 5°, diazotized with 0.60 g. NaNO2 in a min. of H2O and kept 2 hrs., added with stirring to 300 ml. boiling H2O and the mixture boiled 30 min., kept overnight and the precipitate recrystallized twice from PhMe(C) gave 64% 6-hydroxy-6,5-boroxarobenz[a]-anthracene (XVI), m. 279.5-81.0°. The cyclization of II to V rather than to a borazachrysene illustrated very clearly the large steric requirements of the Friedel-Crafts reaction. The charge transfer spectra of the complexes formed by III and V with tetracyanoethylene (XVII) were determined in CHCl3. No difficulty was encountered with the Me or MeO derivatives, VIII, VIIIa, XIII, or XIV, all of which gave stable colorations with XVII, but the parent compounds, IX and XV, reacted rapidly with the acceptor. XV in CHCl3 and XVII in CHCl3 initially gave a green mixture rapidly changing to violet before fading and forming a white precipitate The ultraviolet spectrum of the final colorless solution was identical with that of XIII, suggesting that EtOH in the CHCl3 was forming V (R = OEt) and precipitating (NC)2CHCH(CN)2. The wave lengths of the charge transfer spectra of XVII complexes are given (compound and wave lengths of charge transfer band in A given): IX, 614; VIII, 627; VIIIa, 620; XV, 690, 477; XIII, 701, 500; XIV, 704, 486. The π-electron distribution in these compounds is probably too uneven for first-order perturbation theory to be applicable. The ultra violet spectra of IX and XV in methylcyclohexane and alc.-free CHCl3, and of VIII, XIII, VIIIa, and XIV in CHCl3 were tabulated with the spectrum of benz[a]anthracene (XVIII) in methylcyclohexane listed for comparison. The estimated band maximum (mμ of π-π transitions in methyl cyclohexane for XVIII, IX, and XV were tabulated. The spectra of IX and XV are very similar to that of XVIII, the main difference being an increase in intensity of the α-bands in the hetero aromatics, in accordance with theory.

Journal of the American Chemical Society published new progress about Entropy. 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Name: 4-Bromoisobenzofuran-1,3-dione.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

D′Addio, Adriano; Malincik, Juraj; Fuhr, Olaf; Fenske, Dieter; Haussinger, Daniel; Mayor, Marcel published the artcile< Gelander Molecules with Orthogonal Joints: Synthesis of Macrocyclic Dimers>, Quality Control of 82-73-5, the main research area is carbazole thiophene macrocycle preparation conformation helicity CD; Geländer molecules; atropisomer; helical chirality; heteroarenes; macrocyclization.

Orthogonal joints, understood as connections with an angle of 90°, were introduced in the design of the “”Gelander”” model compounds 1 and 2. The banister, consisting of a conjugated carbazole dimer linked by either 1,3-butadiyne (2) or a single thiophene (1), wraps around an axis composed of a phthalimide dimer due to the dimensional mismatch of both subunits, which are interconnected by phenylene rungs. The “”Gelander”” structure was assembled from a monomer comprising the 1,4-diaminobenzene rung with one amino substituent as part of a 4-bromo phthalimide subunit forming the orthogonal junction to the axis, and the other as part of a masked 2-ethynyl carbazole as orthogonal joint to the banister. The macrocycle was obtained by two sequential homocoupling steps. A first dimerization by a reductive homocoupling assembled the axis, while an oxidative acetylene coupling served as ring-closing reaction. The formed butadiyne was further derivatized to a thiophene, rendering all carbons of the model compound sp2 hybridized. Both helical structures were fully characterized and chirally resolved. Assignment of the enantiomers was achieved by simulation of chiroptical properties and enantiopure synthesis.

Chemistry – A European Journal published new progress about Chirality. 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Quality Control of 82-73-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Karle, Isabella L.; Flippen-Anderson, Judith L.; Chiang, Joseph F.; Lowrey, Alfred H. published the artcile< The conformations of five tetra- and pentamethoxylated phenyl derivatives: Weberine analogs and polymethoprims>, HPLC of Formula: 82-73-5, the main research area is mol structure weberine analog polymethoprim; conformation weberine analog polymethoprim; tetramethoprim structure; pentamethoprim structure; methoxyisoquinoline structure.

The conformations of methoxy groups on Ph rings when there are 4 or more adjacent methoxy groups were established. In 3 of the compounds studied, the Me C atoms are placed alternately above and below the plane of the aryl group in a regular fashion, while in 2 very similar compounds there are unexpected irregularities in the rotations about the CPh-O bonds and consequent crowding of adjacent methoxy groups. Relative potential energy profiles calculated by the MM2 program for the rotation about CPh-O bonds in the free mols. do not provide any clues for the irregularities. The unexpected methoxy conformations appear to result from packing interactions. 5,6,7,8-Tetramethoxy-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (1-methylweberine.HCl) is orthorhombic, space group Pbca, with a 10.262(4), b 17.865(4), and c 18.127(4) Å, d.(calculated) = 1.270 for Z = 8; R = 6.8% for 2009 reflections. 2-(2,3,4,5-Tetramethoxyphenyl)ethylamine hydrochloride is monoclinic, space group P21/a, with a 10.646(8), b 7.623(6), c 18.862(10) Å, and β 104.47(6)°; d.(calculated) = 1.244 for Z = 4; R = 7.7% for 1105 reflections. 5,6,7,8-Tetramethoxy-1-methylisoquinoline hydrochloride is triclinic, space group P1̅, with a 9.298(4), b 9.679(4), c 9.664(4) Å, α 80.77(3), β 63.44(3), and γ 70.36(3)°; d.(calculated) = 1.359 for Z = 2; R = 4.9% for 1787 reflections. 2,4-Diamino-5-(2,3,4,5-tetramethoxybenzyl)pyrimidine (tetramethoprim) is monoclinic, space group P21/n, with a 12.335(10), b 11.828(10), c 12.511(10) Å, and β 119.00(6)°; d.(calculated) = 1.33 for Z = 4; R = 10.3% for 1075 reflections. 2,4-Diamino-5-(2,3,4,5,6-pentamethoxybenzyl)pyrimidine (pentamethoprim) is triclinic, space group P1̅, with a 6.016(4), b 8.319(5), c 18.613(10) Å, α 82.73(5), β 83.58(5), and γ 89.29(5)°; d.(calculated) = 1.267 for Z = 2; R = 8.6% for 1531 reflections. Rotations about the 2 bonds linking the aryl groups are similar in pentamethoprim and trimethoprim but quite different from tetramethoprim. Relative potential energies for both conformations are similar. Only trimethoprim exhibits potent antifolate activity.

Acta Crystallographica, Section B: Structural Science published new progress about Crystal structure. 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, HPLC of Formula: 82-73-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Menzel, Karsten; Dimichele, Lisa; Mills, Paul; Frantz, Doug E.; Nelson, Todd D.; Kress, Michael H. published the artcile< Regioselective halogen-metal exchange reaction of 3-substituted 1,2-dibromo arenes: the synthesis of 2-substituted 5-bromobenzoic acids>, Formula: C8H3BrO3, the main research area is substituted dibromoarene isopropylmagnesium chloride regioselective halogen metal exchange; bromoarene substituted preparation; bromobenzoic acid substituted preparation; regioselective halogen metal exchange reagent isopropylmagnesium chloride.

Regioselective halogen-metal exchange reactions using isopropylmagnesium chloride were carried out on 3-substituted 1,2-dibromo arenes, e.g., I. When the 3-substituent was either electron-withdrawing and/or possessed lone pair electrons that enabled chelation of isopropylmagnesium chloride, a high regioselectivity for the halogen-metal exchange adjacent to the 3-substituents resulted.

Synlett published new progress about Aromatic carboxylic acids Role: SPN (Synthetic Preparation), PREP (Preparation) (bromo-). 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Formula: C8H3BrO3.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Ariano, R. published the artcile< Determining the proportion of cement in finished concrete>, Synthetic Route of 82-73-5, the main research area is .

The methods of Kriege (cf. C. A. 25, 4680) and Florentin (cf. C. A. 21, 3440) consist in solubilizing the SiO2 of the cement (which is present as Ca silicates) by treating with HCl and then determining it by the usual methods. In Scheibe’s method (cf. C. A. 29, 8273.5) the coarse aggregate is eliminated, the residue (sand and cement) is pulverized and the portions soluble and insoluble in HCl are determined after calcination; it is assumed arbitrarily that the sum of the loss on ignition and the insoluble matter in the cement = 3%. It is then easy to calculate the amount of cement. None of these methods gives reliable results, and the same is true of indirect methods based only on the finished concrete and on samples of the sand and gravel entering into its composition There always remains a certain degree of uncertainty if the complete composition of the cement and the loss on ignition are not known. It should be noted that in all cases where the concrete itself is analyzed, the results give the composition of the finished concrete, and not that of the original mix. For the water also, it is possible to establish only the quantity which is actually combined in the concrete.

Chimie et Industrie (Paris) published new progress about Cement. 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Synthetic Route of 82-73-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Herrero, C. Alvarez published the artcile< Vitamin C. The effect of deproteinizing agents on its reductive power>, HPLC of Formula: 82-73-5, the main research area is .

Direct determinations of blood vitamin C by the method of Berend and Fischer (C.A. 31, 7970.8) are compared with determinations by the method of Farmer and Abt (C.A. 30, 8273.5) in which 5% HPO3, 10% Cl3CCO2H, or 15% sulfosalicylic acid were used for the precipitation of protein. The deproteinizing agents caused 25-40% loss of vitamin C, but HPO3 stabilized also the vitamin C which otherwise decompose quickly.

Medicina Colonial published new progress about Blood. 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, HPLC of Formula: 82-73-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Parthan, Anju; Kruse, Morgan; Yurgin, Nicole; Huang, Joice; Viswanathan, Hema N; Taylor, Douglas published the artcile< Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US.>, Synthetic Route of 82-73-5, the main research area is .

BACKGROUND: In the US, 26 % of women aged ≥65 years, and over 50 % of women aged ≥85 years are affected with postmenopausal osteoporosis (PMO). Each year, the total direct health care costs are estimated to be $US12-18 billion. OBJECTIVE: The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal osteoporotic women from a US third-party payer perspective was evaluated. METHODS: A lifetime cohort Markov model was developed with seven health states: ‘well’, hip fracture, vertebral fracture, ‘other’ osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Relative fracture risk reductions, background fracture risks, mortality rates, treatment-specific persistence rate, utilities, and medical and drug costs were derived using published sources. Expected costs and quality-adjusted life years (QALYs) were estimated for generic alendronate, denosumab, branded risedronate, and branded ibandronate in the overall PMO population and high-risk subgroups: (a) ≥2 of the following risks: >70 years of age, bone mineral density (BMD) T score less than or equal to -3.0, and prevalent vertebral fracture; and (b) ≥75 years of age. Costs and QALYs were discounted at 3 % annually, and all costs were inflated to 2012 US dollars. Sensitivity analyses were conducted by varying parameters e.g., efficacies of interventions, costs, utilities, and the medication persistence ratio. RESULTS: In the overall PMO population, total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were $US64,400, $US67,400, $US67,600 and $US69,200, respectively. Total QALYs were 8.2804, 8.3155, 8.2735 and 8.2691, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus generic alendronate was $US85,100/QALY. Risedronate and ibandronate were dominated by denosumab. In the high-risk subgroup (a), total costs for alendronate, denosumab, risedronate and ibandronate were $US70,400, $US70,800, $US74,000 and $US76,900, respectively. Total QALYs were 7.2006, 7.2497, 7.1969 and 7.1841, respectively. Denosumab had an ICER of $US7,900/QALY versus generic alendronate and dominated all other strategies. Denosumab dominated all strategies in women aged ≥75 years. Base-case results between denosumab and generic alendronate were most sensitive to the relative risk of hip fracture for both drugs and the cost of denosumab. CONCLUSION: In each PMO population examined, denosumab represented good value for money compared with branded bisphosphonates. Furthermore, denosumab was either cost effective or dominant compared with generic alendronate in the high-risk subgroups.

Applied health economics and health policy published new progress about 82-73-5. 82-73-5 belongs to class bromides-buliding-blocks, and the molecular formula is C8H3BrO3, Synthetic Route of 82-73-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary