- Structure-activity relationships of novel piperazines as antagonists for the melanocortin-4 receptor
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During the investigation of antagonists for the MC4 receptor, we found that 10ab having a naphthyl group showed almost the same binding affinity for the MC4 receptor as that of the lead compound 1 with a benzoyl group. We also developed a new type of compounds, namely, bis-piperazines, and found that the bis-piperazines 10 exhibited a high affinity for the MC4 receptor. In particular, (-)-10bg exhibited the highest affinity for the MC4 receptor with an IC50 value of 8.13 nM. In this paper, we present the design, synthesis, and structure-activity relationships of the novel bis-piperazines as MC4 receptor antagonists.
- Nozawa, Dai,Okubo, Taketoshi,Ishii, Takaaki,Kakinuma, Hiroyuki,Chaki, Shigeyuki,Okuyama, Shigeru,Nakazato, Atsuro
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p. 1989 - 2005
(2007/10/03)
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- Synthesis of diphenylmethyl analogues and their affinity for the melanocortin-4 receptor and the serotonin transporter
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While examining antagonists of the melanocortin-4 receptor (MC4 receptor), we found that compound 12b, containing a diphenylmethyl moiety, had a relatively high affinity for the MC4 receptor. When diphenylmethyl analogues were further examined, compounds
- Nozawa, Dai,Okubo, Taketoshi,Ishii, Takaaki,Chaki, Shigeyuki,Okuyama, Shigeru,Nakazato, Atsuro
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p. 1044 - 1050
(2008/02/13)
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- PHARMACOLOGICAL CHAPERONES FOR TREATING OBESITY
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The invention relates to methods of enhancing normal melanocortin-4 receptor (MC4R) activity, and to enhancing activity of an MC4R having a mutation which affects protein folding and/or processing of the MC4R. The invention provides a method of treating an individual having a condition in which increased activity of an MC4R at the cell surface would be beneficial, for example in obesity, by administering an effective amount of a pharmacological chaperone for the MC4R. The invention provides MC4R pharmacological chaperones which enhance the activity of MC4R. The invention further provides a method of screening to identify pharmacological chaperones which enhance folding of an MC4R in the endoplasmic reticulum (ER), in order to enhance the activity of the MC4R at the cell surface.
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Page/Page column 5/18
(2008/06/13)
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- PIPERAZINE DERIVATIVE
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A piperazine derivative represented by the formula (1): ???wherein n is an integer of 1 to 8; R1 represents hydrogen or C1-10 alkyl; A represents CH or nitrogen; Ar1 represents phenyl or substituted phenyl; and Y represents a group represented by the formula Y1-Y2-Ar2 or Y3-Y4(Ar5)-Ar6 or a pharmaceutically acceptable salt of the derivative. The novel piperazine derivative has MC4 receptor antagonistic activity.
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- Structure-activity relationship of (1-Aryl-2-piperazinylethyl) piperazines: Antagonists for the AGRP/melanocortin receptor binding
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Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin action. In the hypothalamus, melanocortin peptide agonists act as satiety-inducing factors that mediate their action through the melanocortin-4 receptor (MC4R) whereas AGRP is a
- Arasasingham, Premilla N.,Fotsch, Christopher,Ouyang, Xiaohu,Norman, Mark H.,Kelly, Michael G.,Stark, Kevin L.,Karbon, Bill,Hale, Clarence,Baumgartner, James W.,Zambrano, Martha,Cheetham, Janet,Tamayo, Nuria A.
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- Remedial agent for anxiety neurosis or depression and piperazine derivative
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There are provided a therapeutic preparation for anxiety neurosis or depression which comprises a MC4 receptor antagonist as an effective ingredient; and a piperazine derivative represented by Formula [1]: [wherein Ar1 is a phenyl gr
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