Identification of 4-amino-2-cyclohexylaminoquinazolines as metabolically stable melanin-concentrating hormone receptor 1 antagonists

Kanuma, Kosuke; Omodera, Katsunori; Nishiguchi, Mariko; Funakoshi, Takeo; Chaki, Shigeyuki; Nagase, Yukihiro; Iida, Ikuo; Yamaguchi, Junichi; Semple, Graeme; Tran, Thuy-Anh; Sekiguchi, Yoshinori

doi:10.1016/j.bmc.2005.12.052

Cited by 32 publications

(15 citation statements)

References 31 publications

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“…A large proportion of compounds being developed are substituted with fluorine or trifluoromethyl, beneficial effects of which were revealed through lead optimization experiments [48,49,50]. Examples are given in Fig.…”

Section: Melanin-concentrating Hormone (Mch) Receptor Antagonists As mentioning

confidence: 99%

Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules

Kirk

2006

Journal of Fluorine Chemistry

848

264

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Section: Melanin-concentrating Hormone (Mch) Receptor Antagonists As mentioning

confidence: 99%

Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules

Kirk

2006

Journal of Fluorine Chemistry

848

264

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“…The initial analog 2,4-dichloroquinazoline (3) was synthesized from 2-nitrobenzoic acid according to the reported literature [13][14][15][16][17][18]. The structure of compound 3 was confirmed by 1 H NMR and 13 C NMR (SI Fig S1-S2) spectrometric analysis.…”

Section: Results and Discussion Chemistrymentioning

confidence: 99%

“…The resulting precipitate was filtered off and washed with 50 mL water, and dried to give 2,4-dichloroquinazoline (3) to be used in the next step without further purification [16]. …”

Section: Synthesis Of 24-dichloroquinazoline (3)mentioning

confidence: 99%

Discovery of new coumarin substituted quinazolines as potential bioactive agents

Patel¹,

Raval

2015

Res Chem Intermed

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In view of the biological importance of some important pharmacophores such as quinazoline, coumarin, and benzothiazole, we frame these moieties in a single molecular scaffold to be screened in vitro for their antimicrobial activity. The newly synthesized analogs have been examined for their in vitro biological efficacy against two Gram-positive bacteria, three Gram-negative bacteria, two fungi, and for antimycobacterial activity against M. tuberculosis H 37 Rv. The bioassay results revealed that the majority of final analogs exhibited potential bio efficacies with the remarkable level of MICs comparable to control drugs. The new synthesized compounds were characterized by FT-IR, 1 H NMR, 13 C NMR, and MS analysis.

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“…In general, they suggest that the presence of small polar group in the antagonists capable of binding Gln5. 42 and/or Gln6.55 appears to be important for their activity as MCH-R1 antagonist. 71 Vasudevan et al discovered quinoline scaffold for the development of MCH-R1 antagonists, they reported a compound derived from 2-amino-8-alkoxy quinolines, denominated A-224940 ( Figure 23) with an IC 50 of 91 nM.…”

Section: Figure 16 Compounds 16 and 17mentioning

confidence: 97%

“…Interestingly, they established the following conclusions: a) the biphenyl group binds in an aromatic cage formed by residues of phenylalanine and tyrosine; b) the basic amine is involved in an ionic interaction with Asp3.32; c) the flexibility of the chain joining the two former scaffolds must be enough to allow a good binding of both them; d) the hydroxyl group and the urea hydrogen atom present are predicted to bind residue Gln5. 42. In general, they suggest that the presence of small polar group in the antagonists capable of binding Gln5.…”

Section: Figure 16 Compounds 16 and 17mentioning

confidence: 99%

MCH-R1 Antagonists as Potential Anti-obesity Drugs. Design Strategies and Structure-activity Relationship

Rivera¹,

Moreno²,

Bocanegra-García³

2013

Revista Virtual De Química

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Resumo:A obesidade é uma doença crônica que é caracterizada por um acúmulo de excesso de tecido adiposo. Atualmente, existem alguns medicamentos seguros e eficazes para o tratamento farmacológico da obesidade. Portanto, torna-se necessário o desenvolvimento de novas drogas. Na última década, o alvo mais promissor para a obesidade foi o hormônio concentrador de melanina. Com isso, diversas indústrias farmacêuticas desenvolveram peptídeos e pequenas moléculas como antagonistas MCH-R1, mas estes compostos apresentaram problemas como afinidade para o canal hERG e perfil farmacocinético pobre. Neste artigo, fizemos uma breve revisão da concepção da estratégia mais relevante e relações da estrutura-atividade no desenvolvimento de carboxamida, ureias, quinolina e derivados quinazolina como antagonistas MCH-R1. Palavras-chave:Antagonistas; hormônio concentrador de melanina; obesidade. AbstractObesity is a chronic disease that is characterized by an accumulation of excess adipose tissue. Actually, there are few safe and effective drugs for pharmacological treatment of obesity. Therefore, it becomes necessary the development of new drugs. In the last decade, the most promising target for obesity was melanin-concentrating hormone. Thereat, diverse pharmaceutical companies developed peptides and small molecules as MCH-R1 antagonists, but, these compounds had problems as affinity for hERG channel and poor pharmacokinetic profile. In this manuscript, we made a brief review of the most relevant strategy design and structure-activity relationships in the development of carboxamide, ureas, quinoline, and quinazoline derivatives as MCH-R1 antagonists.

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Identification of 4-amino-2-cyclohexylaminoquinazolines as metabolically stable melanin-concentrating hormone receptor 1 antagonists

Cited by 32 publications

References 31 publications

Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules

Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules

Discovery of new coumarin substituted quinazolines as potential bioactive agents

MCH-R1 Antagonists as Potential Anti-obesity Drugs. Design Strategies and Structure-activity Relationship

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