- QUINUCLIDINONE ANALOGUES AS ANTICANCER AGENTS
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The disclosure includes compounds of Formula (I) and Formula(A) wherein R1, R2, R3, m, n, k, and L are defined herein. Also disclosed are methods for treating a neoplastic disease, autoimmune disease, or an inflammatory disorder with these compounds.
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Page/Page column 54-55
(2021/08/13)
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- Facile synthesis of 4-substituted-4-aminopiperidine derivatives, the key building block of piperazine-based CCR5 antagonists
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4-Substituted-4-aminopiperidine is an interesting structural motif found in a number of bioactive compounds. An efficient and convenient method for the synthesis of 4-differently substituted-4-aminopiperidine derivatives was described, employing isonipecotate as a starting material and Curtius rearrangement as a key step. The alkylation of isonipecotate could introduce various substituents at the 4-position of the piperidine ring. With this key building block, we are able to efficiently synthesize piperazino-piperidine based CCR5 antagonist in a highly convergent manner free of using toxic reagents such as diethylaluminum cyanide. The concise synthesis of a potent bioavailable CCR5 antagonist as HIV-1 entry inhibitor, Sch-350634 (1) was accomplished in excellent yield using N′-Boc-4-methyl-4-aminopiperidine 5a as a smart building block. The new methodology provides a facile and practical access to the piperazino-piperidine amide analogs as HIV-1 entry inhibitors.
- Jiang, Xiao-Hua,Song, Yan-Li,Long, Ya-Qiu
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p. 3675 - 3678
(2007/10/03)
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- Muscarinic M3 receptor antagonists with (2R)-2-[(1R)-3,3-Difluorocyclopentyl]-2-hydroxyphenylacetamide Structures. Part 2
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Optimization of the amine part of our original muscarinic M3 receptor antagonist 1 was performed to identify M3 receptor antagonists that are superior to 1. Compounds carrying a variety of diamine moieties without hydrophobic substituent on the nitrogen atom were screened against the binding affinity for the M3 receptor and the selectivity for M3 over the M1 and M2 receptors. This process led to a 4-aminopiperidinamide (2l) with a Ki value of 5.1 nM and with a selectivity of the M3 receptor that was 46-fold greater than that of the M2 receptor. Further derivatization of 2l by inserting a spacer group or by incorporating alkyl group(s) into the amine part resulted in the identification of an 4-(aminoethyl)piperidinamide 2l-b with a Ki value of 3.7 nM for the M3 receptor and a selectivity for the M3 receptor that was 170-fold greater than that of the M2 receptor.
- Ogino, Yoshio,Ohtake, Norikazu,Kobayashi, Kensuke,Kimura, Toshifumi,Fujikawa, Toru,Hasegawa, Takuro,Noguchi, Kazuhito,Mase, Toshiaki
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p. 2167 - 2172
(2007/10/03)
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