Discovery of a Potent and Selective PI3KÎ´ Inhibitor (<i>S</i>)-2,4-Diamino-6-((1-(7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4<i>H</i>-quinolizin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile with Improved Pharmacokinetic Profile and Superior Efficacy in Hematological Cancer Models.

Shukla, Manojkumar R; Patra, Sukanya; Verma, Mahip; Sadasivam, Gayathri; Jana, Nirmal; Mahangare, Sachin J; Vidhate, Prashant; Lagad, Dipak; Tarage, Anand; Cheemala, Murthy; Kulkarni, Chaitanya; Bhagwat, Shankar; Chaudhari, Vinod D; Sayyed, Majid; Pachpute, Vipul; Phadtare, Ramesh; Gole, Gopal; Phukan, Samiron; Sunkara, Brahmam; Samant, Charudatt; Shingare, Manisha; Naik, Aditya; Trivedi, Sneha; Marisetti, Ajit Kumar; Reddy, Madhusudhan; Gholve, Milind; Mahajan, Nilesh; Sabde, Sudeep; Patil, Vinod; Modi, Dipak; Mehta, Maneesh; Nigade, Prashant; Tamane, Kaustubh; Tota, Swati; Goyal, Hemant; Volam, Harish; Pawar, Shashikant; Ahirrao, Prajakta; Dinchhana, Lal; Mallurwar, Sadanand; Akarte, Atul; Bokare, Anand; Kanhere, Rupesh; Reddy, Neetinkumar; Koul, Sarita; Dandekar, Manoj; Singh, Minakshi; Bernstein, Peter R; Narasimham, Lakshmi; Bhonde, Mandar

Discovery of a Potent and Selective PI3KÎ´ Inhibitor (S)-2,4-Diamino-6-((1-(7-fluoro-1-(4-fluorophenyl)-4-oxo-3-phenyl-4H-quinolizin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile with Improved Pharmacokinetic Profile and Superior Efficacy in Hematological Cancer Models.

Shukla, Manojkumar R; Patra, Sukanya; Verma, Mahip; Sadasivam, Gayathri; Jana, Nirmal; Mahangare, Sachin J; Vidhate, Prashant; Lagad, Dipak; Tarage, Anand; Cheemala, Murthy; Kulkarni, Chaitanya; Bhagwat, Shankar; Chaudhari, Vinod D; Sayyed, Majid; Pachpute, Vipul; Phadtare, Ramesh; Gole, Gopal; Phukan, Samiron; Sunkara, Brahmam; Samant, Charudatt; Shingare, Manisha; Naik, Aditya; Trivedi, Sneha; Marisetti, Ajit Kumar; Reddy, Madhusudhan; Gholve, Milind; Mahajan, Nilesh; Sabde, Sudeep; Patil, Vinod; Modi, Dipak; Mehta, Maneesh; Nigade, Prashant; Tamane, Kaustubh; Tota, Swati; Goyal, Hemant; Volam, Harish; Pawar, Shashikant; Ahirrao, Prajakta; Dinchhana, Lal; Mallurwar, Sadanand; Akarte, Atul; Bokare, Anand; Kanhere, Rupesh; Reddy, Neetinkumar; Koul, Sarita; Dandekar, Manoj; Singh, Minakshi; Bernstein, Peter R; Narasimham, Lakshmi; Bhonde, Mandar.

Afiliação

Shukla MR; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Patra S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Verma M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Sadasivam G; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Jana N; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Mahangare SJ; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Vidhate P; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Lagad D; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Tarage A; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Cheemala M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Kulkarni C; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Bhagwat S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Chaudhari VD; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Sayyed M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Pachpute V; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Phadtare R; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Gole G; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Phukan S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Sunkara B; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Samant C; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Shingare M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Naik A; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Trivedi S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Marisetti AK; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Reddy M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Gholve M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Mahajan N; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Sabde S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Patil V; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Modi D; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Mehta M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Nigade P; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Tamane K; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Tota S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Goyal H; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Volam H; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Pawar S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Ahirrao P; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Dinchhana L; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Mallurwar S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Akarte A; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Bokare A; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Kanhere R; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Reddy N; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Koul S; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Dandekar M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Singh M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Bernstein PR; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Narasimham L; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.
Bhonde M; Novel Drug Discovery and Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47A, Village Nande, Taluka Mulshi, Pune 412115, India.

J Med Chem ; 63(23): 14700-14723, 2020 12 10.

Article em En | MEDLINE | ID: mdl-33297683

Assuntos

Antineoplásicos/uso terapêutico; Classe I de Fosfatidilinositol 3-Quinases/uso terapêutico; Neoplasias Hematológicas/tratamento farmacológico; Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico; Quinolizinas/uso terapêutico; Animais; Antineoplásicos/síntese química; Antineoplásicos/metabolismo; Antineoplásicos/farmacocinética; Linhagem Celular Tumoral; Classe I de Fosfatidilinositol 3-Quinases/síntese química; Classe I de Fosfatidilinositol 3-Quinases/metabolismo; Classe I de Fosfatidilinositol 3-Quinases/farmacocinética; Cães; Descoberta de Drogas; Feminino; Humanos; Masculino; Camundongos; Camundongos Endogâmicos BALB C; Camundongos Endogâmicos NOD; Camundongos SCID; Simulação de Acoplamento Molecular; Estrutura Molecular; Inibidores de Fosfoinositídeo-3 Quinase/síntese química; Inibidores de Fosfoinositídeo-3 Quinase/metabolismo; Inibidores de Fosfoinositídeo-3 Quinase/farmacocinética; Quinolizinas/síntese química; Quinolizinas/metabolismo; Quinolizinas/farmacocinética; Células RAW 264.7; Ratos Sprague-Dawley; Relação Estrutura-Atividade; Ensaios Antitumorais Modelo de Xenoenxerto

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Quinolizinas / Neoplasias Hematológicas / Classe I de Fosfatidilinositol 3-Quinases / Inibidores de Fosfoinositídeo-3 Quinase / Antineoplásicos Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article

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