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Jo Anne Saye - One of the best experts on this subject based on the ideXlab platform.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
Paul J Gilligan - One of the best experts on this subject based on the ideXlab platform.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
William E. Buhro - One of the best experts on this subject based on the ideXlab platform.
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Isolation of Amine Derivatives of (ZnSe)34 and (CdTe)34. Spectroscopic Comparisons of the (II–VI)13 and (II–VI)34 Magic-Size Nanoclusters
2019Co-Authors: Yang Zhou, Ruidong Jiang, Yuanyuan Wang, Henry W. Rohrs, Nigam P. Rath, William E. BuhroAbstract:The spectroscopically observed magic-size nanoclusters (ZnSe)34 and (CdTe)34 are isolated as amine derivatives. The nanoclusters [(ZnSe)34(n-octylamine)29±6(di-n-octylamine)5±4] and [(CdTe)34(n-octylamine)4±3(di-n-Pentylamine)13±3] are fully characterized by combustion-based elemental analysis, UV–visible spectroscopy, IR spectroscopy, and mass spectrometry. Amine derivatives of both (ZnSe)34 and (CdTe)34 are observed to convert to the corresponding (ZnSe)13 and (CdTe)13 derivatives, indicating that the former are kinetic products and the latter thermodynamic products, under the conditions employed. This conversion process is significantly inhibited in the presence of secondary amines. The isolation of the two new nanocluster derivatives adds to a total of nine of 12 possible isolated derivatives in the (II–VI)13 and (II–VI)34 families (II = Zn, Cd; VI = S, Se, Te), allowing comparisons of their properties. The members of these two families exhibit extensive spectroscopic homologies. In both the (II–VI)13 and (II–VI)34 families, linear relationships are established between the lowest-energy nanocluster electronic transition and the band gap of the corresponding bulk semiconductor phase
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The Magic-Size Nanocluster (CdSe)34 as a Low-Temperature Nucleant for Cadmium Selenide Nanocrystals; Room-Temperature Growth of Crystalline Quantum Platelets
2016Co-Authors: Yuanyuan Wang, Henry W. Rohrs, Ying Zhang, Fudong Wang, Jessica Hoy, Richard A Loomis, Daryl E. Giblin, William E. BuhroAbstract:ABSTRACT: Reaction of Cd(OAc)2·2H2O and selenourea in primary-amine/secondary-amine cosolvent mixtures affords crystalline CdSe quantum platelets at room temperature. Their crystallinity is established by X-ray diffraction analysis (XRD), high-resolution transmission electron microscopy (TEM), and their sharp extinction and photoluminescence spectra. Reaction monitoring establishes the magic-size nanocluster (CdSe)34 to be a key intermediate in the growth process, which converts to CdSe quantum platelets by first-order kinetics with no induction period. The results are interpreted to indicate that the critical crystal-nucleus size for CdSe under these conditions is in the range of (CdSe)34 to (CdSe)68. The nanocluster is obtained in isolated form as [(CdSe)34(n-octylamine)16(di-n-Pentylamine)2], which is proposed to function as crystal nuclei that may be stored in a bottle. We provide kinetic evidence that the metastable, magic-size (CdSe)34 nanocluster is near the critical-nucleus size for CdSe and supports the growth of wurtzite CdSe nanocrystal platelets at room temperature (20−25 °C). Typical conditions for th
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the magic size nanocluster cdse 34 as a low temperature nucleant for cadmium selenide nanocrystals room temperature growth of crystalline quantum platelets
Chemistry of Materials, 2014Co-Authors: Yuanyuan Wang, Henry W. Rohrs, Ying Zhang, Fudong Wang, Daryl Giblin, Jessica Hoy, Richard A Loomis, William E. BuhroAbstract:Reaction of Cd(OAc)2·2H2O and selenourea in primary-amine/secondary-amine cosolvent mixtures affords crystalline CdSe quantum platelets at room temperature. Their crystallinity is established by X-ray diffraction analysis (XRD), high-resolution transmission electron microscopy (TEM), and their sharp extinction and photoluminescence spectra. Reaction monitoring establishes the magic-size nanocluster (CdSe)34 to be a key intermediate in the growth process, which converts to CdSe quantum platelets by first-order kinetics with no induction period. The results are interpreted to indicate that the critical crystal-nucleus size for CdSe under these conditions is in the range of (CdSe)34 to (CdSe)68. The nanocluster is obtained in isolated form as [(CdSe)34(n-octylamine)16(di-n-Pentylamine)2], which is proposed to function as crystal nuclei that may be stored in a bottle.
Robert Zaczek - One of the best experts on this subject based on the ideXlab platform.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
Caryn Baldauf - One of the best experts on this subject based on the ideXlab platform.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.
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the discovery of 4 3 pentylamino 2 7 dimethyl 8 2 methyl 4 methoxyphenyl pyrazolo 1 5 a pyrimidine a corticotropin releasing factor hcrf1 antagonist
Bioorganic & Medicinal Chemistry, 2000Co-Authors: Paul J Gilligan, Caryn Baldauf, Anthony J Cocuzza, Dennis R Chidester, Robert Zaczek, Lawrence W Fitzgerald, John F Mcelroy, Mark A Smith, H S L Shen, Jo Anne SayeAbstract:Abstract Structure–activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki=1.0±0.2 nM (n=8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50=10.0±0.01 nM versus 10 nM r/hCRF, n=8); α-helical CRF(9-41) had weaker potency (IC50=286±63 nM, n=3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4±7.6 h, 0.49±0.08 L/kg/h and 23.0±4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax, t1/2 and bioavailability values were equal to 1260±290 nM, 0.75±0.25 h, 45.1±10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.