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Kelly Chibale - One of the best experts on this subject based on the ideXlab platform.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
Chitalu C Musonda - One of the best experts on this subject based on the ideXlab platform.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
Vanessa Yardley - One of the best experts on this subject based on the ideXlab platform.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
Renata Carvalho C De Souza - One of the best experts on this subject based on the ideXlab platform.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
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application of multicomponent reactions to antimalarial drug discovery part 2 new antiplasmodial and antitrypanosomal 4 aminoquinoline gamma and delta lactams via a catch and release protocol
Bioorganic & Medicinal Chemistry, 2006Co-Authors: Chitalu C Musonda, Vanessa Yardley, Renata Carvalho C De Souza, Kelly ChibaleAbstract:A parallel synthesis of a new series of 4-aminoquinoline gamma- and Delta-Lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) of 0.096 microM, also inhibited recombinant falcipain-2 in vitro (IC(50)= 17.6 microM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED(50) of 1.44 microM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.
Tsutomu Takahashi - One of the best experts on this subject based on the ideXlab platform.
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cefozopran meropenem or imipenemecilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients a multicenter prospective randomized trial
2015Co-Authors: Takahiko Nakane, Kazuo Tamura, Masayuki Hino, Toshiharu Tamaki, Isao Yoshida, Toshihiro Fukushima, Youichi Tatsumi, Yasuaki Nakagawa, Kazuo Hatanaka, Tsutomu TakahashiAbstract:We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenemecilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenemecilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenemecilastatin patients compared with cefepime in the per-protocol population (delta ¼ 10%). The response rates for cefozopran, meropenem and imipenemecilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p ¼ 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenemecilastatin compared with cefepime were � 5.9% (95% confidence interval (CI): � 20.1 e8.4), � 0.7% (95% CI: � 14.6e13.3), and 5.7% (95% CI: � 8.1e19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3e5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count � 100 � 10 6 /L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3e5, p ¼ 0.006, and 76% versus 48% at day 7, p ¼ 0.002). Our results suggest that the effects of
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cefozopran meropenem or imipenem cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients a multicenter prospective randomized trial
Journal of Infection and Chemotherapy, 2015Co-Authors: Takahiko Nakane, Kazuo Tamura, Masayuki Hino, Toshiharu Tamaki, Isao Yoshida, Toshihiro Fukushima, Youichi Tatsumi, Yasuaki Nakagawa, Kazuo Hatanaka, Tsutomu TakahashiAbstract:We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤ 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462).