- PYRROLIDINE-PYRAZOLES AS PYRUVATE KINASE ACTIVATORS
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The subject matter described herein is directed to pyruvate kinase activating compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds and methods of administering the compounds for the treatment of diseases associated with PKR and/or PKM2, such as pyruvate kinase deficiency, sickle cell disease, and beta-thalassemia.
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- PYRROLOPYRROLE COMPOSITIONS AS PYRUVATE KINASE (PKR) ACTIVATORS
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The disclosure relates to modulating pyruvate kinase and provides novel chemical compounds of formula (I) useful as activators of PKR, as well as various uses of these compounds. PKR activating compounds are useful in the treatment of diseases and disorders associated with PKR and/or PKM2, such as pyruvate kinase deficiency (PKD), sickle cell disease (SCD), and thalassemia.
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Paragraph 00191-00194
(2018/10/19)
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- N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
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Compounds of structural formula I are modulators of the androgen receptor (AR) in a tissue selective manner. These compounds are useful in the enhancement of weakened muscle tone and the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including osteoporosis, osteopenia, glucocorticoid-induced osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, postmenopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, obesity, aplastic anemia and other hematopoietic disorders, inflammatory arthritis and joint repair, HIV-wasting, prostate cancer, benign prostatic hyperplasia (BPH), abdominal adiposity, metabolic syndrome, type II diabetes, cancer cachexia, Alzheimer's disease, muscular dystrophies, cognitive decline, sexual dysfunction, sleep apnea, depression, premature ovarian failure, and autoimmune disease, alone or in combination with other active agents.
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Page/Page column 39
(2008/06/13)
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- KETENE BIS(TRIMETHYLSILYL) ACETALS. CROSS-ALDOL TYPE CONDENSATION REACTIONS WITH ALDEHYDES AND SCHIFF BASES
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Condensation of the title acetals with aldehydes and Schiff bases in the presence of titanium tetrachloride is reported for the first time.It leads to β-hydroxyacids and to β-lactams via a cross-aldol type reaction, with good yields.
- Dubois, Jacqes-Emile,Axiotis, Georges
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p. 2143 - 2146
(2007/10/02)
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- ERYTHROSELECTIVITY IN ADDITION OF γ-SUBSTITUTED ALLYLSILANES TO ALDEHYDES IN THE PRESENCE OF TITANIUM CHLORIDE
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(E)-Crotyltrimethylsilane and (E)-cinnamyltrimethylsilane were allowed to react with aldehydes (RCHO: t-Bu, i-Pr, Et, Me) in the presence of titanium chloride to give erythro homoallyl alcohols with over 93percent selectivity.Lower erythroselectivity was observed in the reaction of (Z)-allylsilanes.
- Hayashi, Tamio,Kabeta, Keiji,Hamachi,Itaru,Kumada, Makoto
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p. 2865 - 2868
(2007/10/02)
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- Stereochemistry of the Addition of Carboxylic Acid Dianions to Aldehydes under Kinetic and Thermodynamic Control - Synthesis and Configurational Assignment of 2,3-Disubstituted threo- and erythro-3-Hydroxycarboxylic Acids
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Under kinetically controlled conditions (-50 deg C, 10 min) the carboxylic dianions 2 add to aldehydes 3 to give the threo/erythro-adducts 4/5 (Scheme 1); the threo-selectivity markedly increases with the bulkiness of the substituents of 2 or 3 and decreases with the charge/radius ratio of the counter-ions of 2.From these results a syn-transition state with a HOMO-LUMO ineraction between 2 and 3 is derived (Scheme 3).For appropriate substituents a far higher threo-selectivity is observed under thermodynamically (22-50 deg C, 1-3 days) than under kinetically controlled conditions.We describe the isolation of the hydroxy acids 6 and 7, which are formed from 4 and 5 on acidic hydrolysis, and show how their configurations can be unambiguously assigned on the basis of 1H-NMR data.
- Mulzer, Johann,Zippel, Matthias,Bruentrup, Gisela,Segner, Johannes,Finke, Juergen
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p. 1108 - 1134
(2007/10/02)
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