Novel nicotinamide analog as inhibitor of nicotinamide N-methyltransferase.

Ruf, Sven; Hallur, Mahanandeesha Siddappa; Anchan, Nisha K; Swamy, Indu N; Murugesan, Karthikai Raj; Sarkar, Sayantani; Narasimhulu, Lokesh Kananti; Putta, V P Rama Kishore; Shaik, Shama; Chandrasekar, Devaraj Venkatapura; Mane, Vishal Subhash; Kadnur, Sanjay Venkatachalapathi; Suresh, Juluri; Bhamidipati, Ravi Kanth; Singh, Manvi; Burri, Raghunadha Reddy; Kristam, Rajendra; Schreuder, Herman; Czech, Joerg; Rudolph, Christine; Marker, Alexander; Langer, Thomas; Mullangi, Ramesh; Yura, Takeshi; Gosu, Ramachandraiah; Kannt, Aimo; Dhakshinamoorthy, Saravanakumar; Rajagopal, Sridharan

Ruf, Sven; Hallur, Mahanandeesha Siddappa; Anchan, Nisha K; Swamy, Indu N; Murugesan, Karthikai Raj; Sarkar, Sayantani; Narasimhulu, Lokesh Kananti; Putta, V P Rama Kishore; Shaik, Shama; Chandrasekar, Devaraj Venkatapura; Mane, Vishal Subhash; Kadnur, Sanjay Venkatachalapathi; Suresh, Juluri; Bhamidipati, Ravi Kanth; Singh, Manvi; Burri, Raghunadha Reddy; Kristam, Rajendra; Schreuder, Herman; Czech, Joerg; Rudolph, Christine; Marker, Alexander; Langer, Thomas; Mullangi, Ramesh; Yura, Takeshi; Gosu, Ramachandraiah; Kannt, Aimo; Dhakshinamoorthy, Saravanakumar; Rajagopal, Sridharan.

Afiliação

Ruf S; Integrated Drug Discovery, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany. Electronic address: Sven.Ruf@sanofi.com.
Hallur MS; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Anchan NK; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Swamy IN; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Murugesan KR; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Sarkar S; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Narasimhulu LK; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Putta VPRK; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Shaik S; Department of Discovery Biology, Jubilant Biosys Ltd, Bangalore 560022, India; Department of Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore 560022, India.
Chandrasekar DV; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore 560022, India.
Mane VS; Department of Discovery Biology, Jubilant Biosys Ltd, Bangalore 560022, India; Department of Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore 560022, India.
Kadnur SV; Department of Discovery Biology, Jubilant Biosys Ltd, Bangalore 560022, India; Department of Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore 560022, India.
Suresh J; Department of Discovery Biology, Jubilant Biosys Ltd, Bangalore 560022, India; Department of Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore 560022, India.
Bhamidipati RK; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore 560022, India.
Singh M; Department of Computational Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Burri RR; Department of Computational Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Kristam R; Department of Computational Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Schreuder H; Integrated Drug Discovery, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
Czech J; Integrated Drug Discovery, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
Rudolph C; Integrated Drug Discovery, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
Marker A; R&D Drug Metabolism & Pharmacokinetics, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
Langer T; Biologics Research, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
Mullangi R; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore 560022, India.
Yura T; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India.
Gosu R; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore 560022, India.
Kannt A; R&D Diabetes, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany; Institute of Experimental Pharmacology, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany.
Dhakshinamoorthy S; Department of Discovery Biology, Jubilant Biosys Ltd, Bangalore 560022, India; Department of Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Bangalore 560022, India.
Rajagopal S; Department of Medicinal Chemistry, Jubilant Biosys Ltd, Bangalore 560022, India. Electronic address: sridharan_rajagopal@jubilantbiosys.com.

Bioorg Med Chem Lett ; 28(5): 922-925, 2018 03 01.

Article em En | MEDLINE | ID: mdl-29433927

ABSTRACT

ABSTRACT

Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by â¼80% at 2â¯h when dosed in mice orally at 50â¯mg/kg.

Assuntos

Inibidores Enzimáticos/farmacologia; Niacinamida/farmacologia; Nicotinamida N-Metiltransferase/antagonistas & inibidores; Relação Dose-Resposta a Droga; Inibidores Enzimáticos/síntese química; Inibidores Enzimáticos/química; Humanos; Estrutura Molecular; Niacinamida/síntese química; Niacinamida/química; Nicotinamida N-Metiltransferase/metabolismo; Relação Estrutura-Atividade

Palavras-chave

Diabetes; Methyl-nicotinamide (MNA); Ncotinamide; Nicotinamide N-methyltransferase (NNMT); Obesity

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Niacinamida / Inibidores Enzimáticos / Nicotinamida N-Metiltransferase Limite: Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2018 Tipo de documento: Article

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