118488-08-7Relevant articles and documents
Direct reductive amination of ketones with ammonium salt catalysed by Cp*Ir(iii) complexes bearing an amidato ligand
Dai, Zengjin,Pan, Ying-Min,Wang, Shou-Guo,Yin, Qin,Zhang, Xumu
supporting information, p. 8934 - 8939 (2021/11/04)
A series of half-sandwich Ir(iii) complexes1-6bearing an amidato bidentate ligand were conveniently synthesized and applied to the catalytic Leuckart-Wallach reaction to produce racemic α-chiral primary amines. With 0.1 mol% of complex1, a broad range of ketones, including aryl ketones, dialkyl ketones, cyclic ketones, α-keto acids, α-keto esters and diketones, could be transformed to their corresponding primary amines with moderate to excellent yields (40%-95%). Asymmetric transformation was also attempted with chiral Ir complexes3-6, and 16% ee of the desired primary amine was obtained. Despite the unsatisfactory enantio-control achieved so far, the current exploration might stimulate more efforts towards the discovery of better chiral catalysts for this challenging but important transformation.
Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity
Wei, Binqing,Gunzner-Toste, Janet,Yao, Hui,Wang, Tao,Wang, Jing,Xu, Zijin,Chen, Jinhua,Wai, John,Nonomiya, Jim,Tsai, Siao Ping,Chuh, Josefa,Kozak, Katherine R.,Liu, Yichin,Yu, Shang-Fan,Lau, Jeff,Li, Guangmin,Phillips, Gail D.,Leipold, Doug,Kamath, Amrita,Su, Dian,Xu, Keyang,Eigenbrot, Charles,Steinbacher, Stefan,Ohri, Rachana,Raab, Helga,Staben, Leanna R.,Zhao, Guiling,Flygare, John A.,Pillow, Thomas H.,Verma, Vishal,Masterson, Luke A.,Howard, Philip W.,Safina, Brian
supporting information, p. 989 - 1000 (2018/01/01)
Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.
TETRAZOLE-SUBSTITUTED ARYLAMIDES AS P2X3 AND P2X2/3 ANTAGONISTS
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Paragraph 0661-0662, (2015/07/15)
Compounds of the formula I: or a pharmaceutically acceptable salt thereof, wherein, R1 is optionally substituted tetrazolyl, R2 is optionally substituted phenyl, optionally substituted pyridinyl or optionally substituted thienyl, and R3, R4, R5 and R6 are as defined herein. Also provided are methods of using the compounds for treating diseases associated with the P2X3 and/or a P2X2/3 receptor antagonist and methods of making the compounds.
PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF
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Page/Page column 80; 81, (2015/07/07)
This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
THIAZOLE AND OXAZOLE-SUBSTITUTED ARYLAMIDES AS P2X3 AND P2X2/3 ANTAGONISTS
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Page/Page column 38, (2012/02/03)
Compounds of the formula I: or a pharmaceutically acceptable salt thereof, wherein, R1 is a group of formula A or formula B, and X, R2, R3, R4, R5, R6, Ra and Rb are as defined herein. Also provided are methods of using the compounds for treating diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist and methods of making the subject compounds.
OXAZOLONE AND PYRROLIDINONE-SUBSTITUTED ARYLAMIDES AS P2X3 AND P2X2/3 ANTAGONISTS
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Page/Page column 24, (2010/12/31)
Compounds of the formula 1: or a pharmaceutically acceptable salt thereof, wherein, X, Y, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. Also disclosed are methods of using the compounds for treating diseases associated with P2X3 and/or a P2X2/3 receptor antagonists and methods of making the compounds.
INDOLE, INDAZOLE AND BENZIMIDAZOLE ARYLAMIDES AS P2X3 AND P2X2/3 ANTAGONISTS
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Page/Page column 20, (2010/12/31)
Compounds of the formula I: or a pharmaceutically acceptable salt thereof, wherein, X, Y, Z, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of using the compounds for treating diseases associated with P2X3 and/or a P2X2/3 receptor antagonists and methods of making the compounds.
Tetrazole-substituted arylamides as P2X3 and P2X2/3 antagonists
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Page/Page column 198, (2008/06/13)
Compounds of the formula I: or a pharmaceutically acceptable salt thereof, wherein, R1 is optionally substituted tetrazolyl, R2 is optionally substituted phenyl, optionally substituted pyridinyl or optionally substituted thienyl, and R3, R4, R5 and R6 are as defined herein. Also provided are methods of using the compounds for treating diseases associated with the P2X3 and/or a P2X2/3 receptor antagonist and methods of making the compounds.
THIAZOLE AND OXAZOLE-SUBSTITUTED ARYLAMIDES
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Page/Page column 61-62, (2008/12/05)
Compounds of the formula (I) or a pharmaceutically acceptable salt thereof, wherein: R1 is a group of formula A or formula B; and X, R2, R3, R4, R5, R6, Ra and Rb are as defined herein. Also provided are methods of using the compounds for treating diseases mediated by a P2X3 and/or a P2X2/3 receptor antagonist and methods of making the subject compounds.
Thienopyridines useful as cardiovascular agents
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, (2008/06/13)
The synthesis of thienopyridine derivatives is described. The novel thienopyridine derivatives are cardiotonic agents and renal vasodilating agents. The compounds are useful as cardiovascular agents.