- NOVEL SALTS OF SELECTIVE ESTROGEN RECEPTOR DEGRADERS
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Provided herein are compounds, salts, crystalline forms, and pharmaceutical compositions that are related to Selective Estrogen Receptor Degraders, as well as methods of preparing the same. Also provided herein are methods of using the compounds, salts, crystalline forms, and pharmaceutical compositions for the treatment of diseases or disorders, such as breast cancer.
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Paragraph 0146
(2020/07/14)
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- Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors
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A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50–50.5 nM), hCA IX (KIs of 1.8–228.5 nM), and hCA XII (KIs of 3.5–96.2 nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure–activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates.
- Angapelly, Srinivas,Ramya, P.V. Sri,Angeli, Andrea,Del Prete, Sonia,Capasso, Clemente,Arifuddin, Mohammed,Supuran, Claudiu T.
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p. 5726 - 5732
(2017/10/09)
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- Telescopic one-pot condensation-hydroamination strategy for the synthesis of optically pure L-phenylalanines from benzaldehydes
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A chemo-enzymatic telescopic approach was designed for the synthesis of L-arylalanines in high yield and optical purity, starting from commercially available and inexpensive substituted benzaldehydes. The method exploits a chemical Knoevenagel–Doebner condensation (optimised to give complete conversions in a short reaction time, employing microwave irradiation) and a biocatalytic phenylalanine ammonia lyase mediated hydroamination (for the stereoselective addition of ammonia). The two reactions can be run sequentially in one pot, bringing together the advantages of chemical and biological catalysis. The preparative applicability was demonstrated with the synthesis of five L-dihalophenylalanines (71–84% yield, 98–99% ee) of relevance as molecular probes, for medicinal chemistry and for the synthesis of pharmaceutical ingredients.
- Parmeggiani, Fabio,Ahmed, Syed T.,Weise, Nicholas J.,Turner, Nicholas J.
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p. 7256 - 7262
(2016/10/26)
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- Design, synthesis and cytotoxic evaluation of novel imatinib amide derivatives that target Abl kinase
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Novel imatinib amide derivatives (a1-28, b1-9) were synthesized and evaluated for their biological activities. All compounds were characterized by 1H NMR, MS and elemental analysis. Among all the derivatives, compounds a4, a10, a21, b1 and b2 displayed the most significant ability of inhibiting K562 cell proliferation with the IC50 values of 0.67, 0.66, 0.65, 0.59 and 0.62 μM, respectively, indicating that these compounds were potent inhibitors of Bcr-Abl in leukemic K562 cells, comparable to the reference compound imatinib. Molecular docking study was performed to position compounds a21 and b1 into the active site of Abl to determine the probable binding modes
- Yao, Ri-Sheng,Guan, Qiu-Xiang,Lu, Xiao-Qin,Ruan, Ban-Feng
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- Autotaxin inhibitors
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The present invention relates to novel compounds that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in diseases and disorders mediated by autotaxin.
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Page/Page column
(2014/06/25)
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- PHARMACEUTICALLY ACTIVE BENZOXAZOLE, BENZTHIAZOLE AND BENZIMIDAZOLE ACID DERIVATIVES
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Compounds of formula (I): wherein R1, R2 and R3 are independently, hydrogen, halogen, CF3, OR6, NR7R8, NR8COR10, NR8SO2R10 or C1-6 alkyl optionally substituted by hydroxy, C1-6 alkoxy or NR7R8; R4 is NR8CONR8R9, NR8COR9, NR8SO2R9, or W-CONR8R9, where W is a bond, C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene; and R5 is Formula (A) methods for their synthesis, pharmaceutical compositions comprising them and their use in medicine, in particular for the treatment of cancer.
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- Indanylidenes. 2. Design and synthesis of (E)-2-(4-chloro-6-fluoro-1-indanylidene)-N-methylacetamide, a potent antiinflammatory and analgesic agent without centrally acting muscle relaxant activity
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Extension of the structure-activity relationship studies that led to the discovery of the nonsedating potent muscle relaxant, antiinflammatory, and analgesic agent (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 1, has given rise to (E)-2-(4-chloro-6-fluoro
- Musso, David L.,Orr, G. Faye,Cochran, Felicia R.,Kelley, James L.,Selph, Jeffrey L.,Rigdon, Greg C.,Cooper, Barrett R.,Jones, Michael L.
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p. 409 - 416
(2007/10/03)
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- Method for treating glaucoma
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Methods of using prostaglandin agonists for the reduction of intraocular pressure, and accordingly glaucoma.
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- Prevention of loss and restoration of bone mass by certain prostaglandin agonists
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Prostaglandin agonists of formula (I), in which, for example, A is a sulphonyl or acyl group, B is N or CH, M contains a ring and K and Q are linking groups, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits useful for the treatment of bone disorders including osteoporosis. STR1
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- DOPAMINE-BETA-HYDROXYLASE INHIBITORS
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Potent DBH inhibitors having the formula can be used to inhibit DBH activity in mammals.
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- Dopamine-β-hydroxylase inhibitors and use thereof
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The compounds of this invention are 1-phenylalkyl-2-mercaptotetrazole compounds which are dopamine-β-hydroxylase inhibitors.
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