- Compounds for treating spinal muscular atrophy
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Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy. In a specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN2 into mRNA that is transcribed from the SMN2 gene. In another specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 into mRNA that is transcribed from the SMN1 gene. In yet another embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 and SMN2 into mRNA that is transcribed from the SMN1 and SMN2 genes, respectively.
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Page/Page column 374
(2017/05/02)
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- Synthesis and biological activity evaluation of 1,2,3-thiadiazole derivatives as potential elicitors with highly systemic acquired resistance
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Elicitors provide a broad spectrum of systemic acquired resistance by altering the physical and physiological status of the host plants and, therefore, are among the most successful directions in modern pesticide development for plant protection. To develop a novel elicitor with highly systemic acquired resistance, two series of thiazole- and oxadiazole-containing thiadiazole derivatives were rationally designed and synthesized according to the principle of combination of bioactive substructures in this work. Their structures were characterized by 1H nuclear magnetic resonance (NMR), infrared (IR), high-resolution mass spectrometry (HRMS), or elemental analysis. Their potential systemic acquired resistance as an elicitor was also evaluated; bioassay results indicated that, among the 23 compounds synthesized, three compounds, 10a, 10d, and 12b, displayed better systemic acquired resistance than the positive control, tiadinil, a commercialized 1,2,3-thiadiazolebased elicitor. In addition, three other compounds, 10f, 12c, and 12j, exhibited a certain degree of fungus growth inhibition In vitro or In vivo. Our results demonstrated that, in combination of bioactive substructures is an interesting exploration for novel pesticide development, thiazole-and oxadiazole-containing thiadiazole derivatives are potential elicitors with good systemic acquired resistance.
- Fan, Zhijin,Shi, Zugui,Zhang, Haike,Liu, Xiufeng,Bao, Lili,Ma, Lin,Zuo, Xiang,Zheng, Qinxiang,Mi, Na
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experimental part
p. 4279 - 4286
(2010/06/16)
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- IMIDAZO (1, 2-A) PYRIDINE COMPOUNDS AS VEGF-R2 INHIBITORS
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The present invention provides compounds that are inhibitors of VEGF-R2 of the formula: (I) and methods of using these compounds.
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Page/Page column 23
(2008/06/13)
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- THIAZOLIMINE COMPOUND AND OXAZOLIMINE COMPOUND
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A compound represented by the formula (1): (wherein X represents sulfur or oxygen; R1 and R2 each represents a group represented by the formula -Y3-Z, etc.; Y3 represents a single bond or (un)substituted alkylene; Y1 and Y2 each represents (un)substituted alkylene; Z represents hydrogen, an (un)saturated monocyclic heterocyclic group, etc.; M represents carboxy, etc.; Q represents o-phenylene, etc.; and A represents an (un)saturated monocyclic hydrocarbon group, etc.), a prodrug thereof, or a pharmaceutically acceptable salt of either. They are compounds having chymase inhibitory activity and useful as a therapeutic agent for hypertension, cardiac failure, etc.
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Page/Page column 24
(2010/11/08)
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- Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer's disease
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High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC50 = ca. 320 nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved.
- Helal, Christopher J.,Sanner, Mark A.,Cooper, Christopher B.,Gant, Thomas,Adam, Mavis,Lucas, John C.,Kang, Zhijun,Kupchinsky, Stanley,Ahlijanian, Michael K.,Tate, Bonnie,Menniti, Frank S.,Kelly, Kristin,Peterson, Marcia
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p. 5521 - 5525
(2007/10/03)
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- 6-thienyl and 6-phenylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase
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Starting from the potent inhibitory effect of the previously described 2-methyl-6-(2-thienyl)imidazo[2,1-b]thiazole on mitochondrial complex I, we prepared a series of derivatives in order to study the effect of a different substitution at the positions 2, 5 and 6. The replacement of the thienyl group at position 6 with a phenyl group does not modify the biological behaviour of the lead compound, whereas the shift of the methyl group from position 2 to position 5 yields a compound devoid of inhibitory effects. In both the 6-thienyl and 6-phenyl series, the lengthening of the chain at position 2 has provided useful information to outline the structural determinants of the ubiquinone antagonist action in imidazothiazole derivatives.
- Andreani, Aldo,Rambaldi, Mirella,Leoni, Alberto,Morigi, Rita,Locatelli, Alessandra,Giorgi, Gianluca,Lenaz, Giorgio,Ghelli, Anna,Degli Esposti, Mauro
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p. 883 - 889
(2007/10/03)
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- 1-Oxo-1H-thiazolo[3,2-a]pyrimidine-2-carboxamides
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Antiallergy and antiulcer agents having the formula (I), STR1 and their pharmaceutically acceptable salts, wherein R1 and R2 taken separately are each hydrogen or lower alkyl; and R1 and R2 taken together are alkylene of 3-9 carbon atoms or phenylalkylene of 9-11 carbon atoms, with the proviso that the ring so formed is between 5- and 8-membered; acids of the formula (II), STR2 wherein R1 and R2 are as defined above and R3 is hydrogen, which are useful as intermediates for compounds of the formula (I), but in many instances also possess the same useful biological activity as do formula I compounds; and intermediates of the formula II wherein R1 and R2 are defined as above, and R3 is alkyl of 1 to 4 carbon atoms, carbalkoxy of 2 to 5 carbon atoms, carbophenoxy or carbobenzoxy, are also described.
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- Antiulcer thiazol-2-ylcarbamoyl-carboxylic acids, esters and amides
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This invention encompasses orally effective antiulcer agents of the formula STR1 wherein X is hydroxy, (C1 -C5)-alkoxy, phenoxy, benzyloxy, or --NH(CH2)n Y wherein n is an integer of value 2 to 4 and Y is di-(C1 -C3)-alkylamino, 1-pyrrolidinyl, 1-piperidinyl or 4-morpholinyl; R' and R" when taken together are (C3 -C8)-alkylene, with the proviso that the ring so formed is 5- to 8-membered; R' and R" when taken separately are each independently hydrogen, (C1 -C6)-alkyl or (C5 -C6)-cycloalkyl, with the proviso that when X is other than --NH(CH2)n Y, at least one of R' and R" is other than hydrogen; the pharmaceutically acceptable cationic salts thereof when X is hydroxyl, and the pharmaceutically acceptable anionic salts thereof when X is --NH(CH2)n Y.
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