The Experts below are selected from a list of 5586 Experts worldwide ranked by ideXlab platform
Naoki Miyata - One of the best experts on this subject based on the ideXlab platform.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Abstract Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis–trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.
Hidehiko Nakagawa - One of the best experts on this subject based on the ideXlab platform.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Abstract Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis–trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.
Syunsuke Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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melanin concentrating hormone receptor 1 antagonists lacking an Aliphatic Amine synthesis and structure activity relationships of novel 1 imidazo 1 2 a pyridin 6 yl pyridin 2 1h one derivatives
Journal of Medicinal Chemistry, 2016Co-Authors: Hideyuki Igawa, Masashi Takahashi, Keiko Kakegawa, Asato Kina, Minoru Ikoma, Jumpei Aida, Tsuneo Yasuma, Yayoi Kawata, Shuntaro Ashina, Syunsuke YamamotoAbstract:Aiming to discover melanin-concentrating hormone receptor 1 (MCHR1) antagonists with improved safety profiles, we hypothesized that the Aliphatic Amine employed in most antagonists reported to date could be removed if the bicyclic motif of the compound scaffold interacted with Asp123 and/or Tyr272 of MCHR1. We excluded Aliphatic Amines from our compound designs, with a cutoff value of pKa < 8, and explored Aliphatic Amine-free MCHR1 antagonists in a CNS-oriented chemical space limited by four descriptors (TPSA, ClogP, MW, and HBD count). Screening of novel bicyclic motifs with high intrinsic binding affinity for MCHR1 identified the imidazo[1,2-a]pyridine ring (represented in compounds 6a and 6b), and subsequent cyclization of the central Aliphatic amide linkage led to the discovery of a potent, orally bioavailable MCHR1 antagonist 4-[(4-chlorobenzyl)oxy]-1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)pyridin-2(1H)-one 10a. It exhibited low potential for hERG inhibition and phospholipidosis induction...
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Melanin-Concentrating Hormone Receptor 1 Antagonists Lacking an Aliphatic Amine: Synthesis and Structure–Activity Relationships of Novel 1‑(Imidazo[1,2‑a]pyridin-6-yl)pyridin-2(1H)‑one Derivatives
2016Co-Authors: Hideyuki Igawa, Masashi Takahashi, Keiko Kakegawa, Asato Kina, Minoru Ikoma, Jumpei Aida, Tsuneo Yasuma, Yayoi Kawata, Shuntaro Ashina, Syunsuke YamamotoAbstract:Aiming to discover melanin-concentrating hormone receptor 1 (MCHR1) antagonists with improved safety profiles, we hypothesized that the Aliphatic Amine employed in most antagonists reported to date could be removed if the bicyclic motif of the compound scaffold interacted with Asp123 and/or Tyr272 of MCHR1. We excluded Aliphatic Amines from our compound designs, with a cutoff value of pKa < 8, and explored Aliphatic Amine-free MCHR1 antagonists in a CNS-oriented chemical space limited by four descriptors (TPSA, ClogP, MW, and HBD count). Screening of novel bicyclic motifs with high intrinsic binding affinity for MCHR1 identified the imidazo[1,2-a]pyridine ring (represented in compounds 6a and 6b), and subsequent cyclization of the central Aliphatic amide linkage led to the discovery of a potent, orally bioavailable MCHR1 antagonist 4-[(4-chlorobenzyl)oxy]-1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)pyridin-2(1H)-one 10a. It exhibited low potential for hERG inhibition and phospholipidosis induction as well as sufficient brain concentration to exert antiobesity effects in diet-induced obese rats
Suguru Seike - One of the best experts on this subject based on the ideXlab platform.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Abstract Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis–trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.
Masatoshi Sugimoto - One of the best experts on this subject based on the ideXlab platform.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Abstract Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis–trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.
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peptidyl prolyl isomerase pin1 inhibitory activity of d glutamic and d aspartic acid derivatives bearing a cyclic Aliphatic Amine moiety
Bioorganic & Medicinal Chemistry Letters, 2015Co-Authors: Hidehiko Nakagawa, Suguru Seike, Masatoshi Sugimoto, Naoya Ieda, Mitsuyasu Kawaguchi, Takayoshi Suzuki, Naoki MiyataAbstract:Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic Aliphatic Amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl Amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity.