L'invention concerne un nouveau procede de preparation de certains derives de piperidine repr... more L'invention concerne un nouveau procede de preparation de certains derives de piperidine representes par les formules (i) et (II) dans lesquelles R1 represente hydrogene ou hydroxy R2 represente hydrogene; ou R1 et R2 pris ensemble forment une seconde liaison entre les atomes de carbone portant R1 et R2; n est un entier compris entre 1 et 5; R3 est -CH2OH, -COOHH ou COO alkyle dans lequel la fraction alkyle presente 1 a 6 atomes de carbone et est droite ou ramifiee; chaque A represente hydrogene ou hydroxy; ladite invention concerne egalement des sels acceptables pharmaceutiquement et des isomeres optiques individuels obtenus a partir desdits derives.
Cette invention concerne les composes macrocycliques indiques dans la description. Ces composes p... more Cette invention concerne les composes macrocycliques indiques dans la description. Ces composes peuvent etre utilises pour traiter l'infection par le virus de l'hepatite C.
A compound of the following formula: Formula ** ** wherein R1 is -H, -OH, C1-6 alkyl, C1-6 alkoxy... more A compound of the following formula: Formula ** ** wherein R1 is -H, -OH, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, heteroaryl, or -NH -ZR; wherein R is H, or a moiety selected from C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl, each of which is optionally mono-, di-, or tri-substituted halogen, nitro, cyano, amino, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, aryl, or heteroaryl; and Z is -C (O) -, -C (O) O-, -C (O) C (O) O-, -C (O) C (O) NH-, - C (O) NR'- , -OC (S) -, - C (S) NR'-, or -C (NH) O-, R 'is H, C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl ; R2 is H, or a moiety selected from C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl, each of which is optionally mono-, di-, or tri-substituted by halogen, nitro, cyano, amino, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, aryl, or heteroaryl; A is N or CH; U is -O-, -NH-, -NH (CO) -, -NHSO-, o...
The present invention is for a new process for preparing certain piperidine derivatives of formul... more The present invention is for a new process for preparing certain piperidine derivatives of formula (I) and (II) process wherein R1 represents hydrogen or hydroxy, R2 represents hydrogen; Or R1 and R2 taken together form a second bond between the carbon atoms SUPPORTING R1 and R2; N is an integer from 1 to 5; R3 is -CH2OH, -CH2OH, -COOH or -COOalkyl WHERE THE CENTRAL alkyl has 1 to 6 carbon atoms and is linear or branched; Each A is hydrogen or hydroxy. And pharmaceutically acceptable salts and isomers INDIVIDUAL OPTICAL them.
The Journal of pharmacology and experimental therapeutics, 1989
Castanospermine-glucosides (CS-glcs) are new compounds which have been evaluated as glycohydrolas... more Castanospermine-glucosides (CS-glcs) are new compounds which have been evaluated as glycohydrolase inhibitors in rats. 7-O-alpha-D-Glucopyranosyl-CS (7 alpha-glc-CS) and 8 alpha-glc-CS were potent sucrase inhibitors with IC50s of 40 and 30 nM, respectively. Their sucrase inhibition was poorly reversible. They were much weaker liver lysosomal alpha-glucosidase inhibitors with IC50s of 40,000 nM. 1 alpha-glc-CS and 8 beta-glc-CS were both weaker and less selective sucrase inhibitors. In vivo, 7 alpha-glc-CS and 8 alpha-glc-CS effectively reduced the glycemic response to an oral 2 g/kg sucrose load at doses less than or equal to 1 mg/kg. 8 alpha-glc-CS was effective when administered up to 4 hr before sucrose. The known glucohydrolase inhibitors 1-deoxynojirimycin and N-hydroxyethyl-1-deoxy-nojirimycin were also potent sucrase inhibitors (IC50s = 200 and 400 nM, respectively) but their sucrase inhibition was readily reversible in vitro and their in vivo duration of action was much shor...
3542 Poster Board III-479 Background The interaction between SDF-1 and its receptor, CXCR4, is re... more 3542 Poster Board III-479 Background The interaction between SDF-1 and its receptor, CXCR4, is responsible for retaining of stem cells in the bone marrow. CXCR4 antagonist disrupts the SDF-1/CXCR4 interaction and mobilizes CD34+ hematopoietic stem cells (CD34+ HSCs) and CD133+ endothelial progenitor cells (CD133+ EPCs) from bone marrow into circulation, which can be used as a source for stem cell transplantation and other potential clinical indications. TG-0054 is a novel CXCR4 antagonist. In vitro CXCR4 antagonistic activity and in vivo stem cell mobilization activity of TG-0054 were determined in this study. Materials and Methods In vitro pharmacological assays, including GTP-binding assay, calcium mobilization assay, and chemotaxis assays, were performed to assess the potency of TG-0054 as a CXCR4 antagonist. In addition, receptor-binding assays against a panel of human chemokine receptors as well as other 68 cellular receptors were screened to evaluate the specificity of TG-0054...
866 Background: Stem cells are retained in the bone marrow via the trophic effects of the binding... more 866 Background: Stem cells are retained in the bone marrow via the trophic effects of the binding of chemokine stromal cell-derived factor-1α (SDF-1α) to its receptor, CXC chemokine receptor 4 (CXCR4). TG-0054 inhibits SDF-1α/CXCR4 binding and therefore mobilizes stem cells into peripheral blood. Animal studies in mice showed rapid and effective mobilization of CD34+ hematopoietic stem cells (HSCs) and CD133+ endothelial progenitor cells (EPCs) into peripheral blood after TG-0054 administration. A Phase I study was conducted in healthy volunteers to assess safety, tolerability, pharmacokinetics (PK) and stem cell mobilization of TG-0054. Materials and Methods: This is a phase I, randomized, double-blind, placebo-controlled, single ascending dose study. In each cohort, 2 volunteers received placebo and 6 received 0.10, 0.14, 0.28, 0.56, 1.12, 2.24, 3.14, or 4.40 mg/kg of TG-0054 (dose was calculated based on TG-0054 free base) via 15 minutes single IV infusion. All subjects underwent...
L'invention concerne un nouveau procede de preparation de certains derives de piperidine repr... more L'invention concerne un nouveau procede de preparation de certains derives de piperidine representes par les formules (i) et (II) dans lesquelles R1 represente hydrogene ou hydroxy R2 represente hydrogene; ou R1 et R2 pris ensemble forment une seconde liaison entre les atomes de carbone portant R1 et R2; n est un entier compris entre 1 et 5; R3 est -CH2OH, -COOHH ou COO alkyle dans lequel la fraction alkyle presente 1 a 6 atomes de carbone et est droite ou ramifiee; chaque A represente hydrogene ou hydroxy; ladite invention concerne egalement des sels acceptables pharmaceutiquement et des isomeres optiques individuels obtenus a partir desdits derives.
Cette invention concerne les composes macrocycliques indiques dans la description. Ces composes p... more Cette invention concerne les composes macrocycliques indiques dans la description. Ces composes peuvent etre utilises pour traiter l'infection par le virus de l'hepatite C.
A compound of the following formula: Formula ** ** wherein R1 is -H, -OH, C1-6 alkyl, C1-6 alkoxy... more A compound of the following formula: Formula ** ** wherein R1 is -H, -OH, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, heteroaryl, or -NH -ZR; wherein R is H, or a moiety selected from C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl, each of which is optionally mono-, di-, or tri-substituted halogen, nitro, cyano, amino, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, aryl, or heteroaryl; and Z is -C (O) -, -C (O) O-, -C (O) C (O) O-, -C (O) C (O) NH-, - C (O) NR'- , -OC (S) -, - C (S) NR'-, or -C (NH) O-, R 'is H, C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl ; R2 is H, or a moiety selected from C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl, each of which is optionally mono-, di-, or tri-substituted by halogen, nitro, cyano, amino, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, aryl, or heteroaryl; A is N or CH; U is -O-, -NH-, -NH (CO) -, -NHSO-, o...
The present invention is for a new process for preparing certain piperidine derivatives of formul... more The present invention is for a new process for preparing certain piperidine derivatives of formula (I) and (II) process wherein R1 represents hydrogen or hydroxy, R2 represents hydrogen; Or R1 and R2 taken together form a second bond between the carbon atoms SUPPORTING R1 and R2; N is an integer from 1 to 5; R3 is -CH2OH, -CH2OH, -COOH or -COOalkyl WHERE THE CENTRAL alkyl has 1 to 6 carbon atoms and is linear or branched; Each A is hydrogen or hydroxy. And pharmaceutically acceptable salts and isomers INDIVIDUAL OPTICAL them.
The Journal of pharmacology and experimental therapeutics, 1989
Castanospermine-glucosides (CS-glcs) are new compounds which have been evaluated as glycohydrolas... more Castanospermine-glucosides (CS-glcs) are new compounds which have been evaluated as glycohydrolase inhibitors in rats. 7-O-alpha-D-Glucopyranosyl-CS (7 alpha-glc-CS) and 8 alpha-glc-CS were potent sucrase inhibitors with IC50s of 40 and 30 nM, respectively. Their sucrase inhibition was poorly reversible. They were much weaker liver lysosomal alpha-glucosidase inhibitors with IC50s of 40,000 nM. 1 alpha-glc-CS and 8 beta-glc-CS were both weaker and less selective sucrase inhibitors. In vivo, 7 alpha-glc-CS and 8 alpha-glc-CS effectively reduced the glycemic response to an oral 2 g/kg sucrose load at doses less than or equal to 1 mg/kg. 8 alpha-glc-CS was effective when administered up to 4 hr before sucrose. The known glucohydrolase inhibitors 1-deoxynojirimycin and N-hydroxyethyl-1-deoxy-nojirimycin were also potent sucrase inhibitors (IC50s = 200 and 400 nM, respectively) but their sucrase inhibition was readily reversible in vitro and their in vivo duration of action was much shor...
3542 Poster Board III-479 Background The interaction between SDF-1 and its receptor, CXCR4, is re... more 3542 Poster Board III-479 Background The interaction between SDF-1 and its receptor, CXCR4, is responsible for retaining of stem cells in the bone marrow. CXCR4 antagonist disrupts the SDF-1/CXCR4 interaction and mobilizes CD34+ hematopoietic stem cells (CD34+ HSCs) and CD133+ endothelial progenitor cells (CD133+ EPCs) from bone marrow into circulation, which can be used as a source for stem cell transplantation and other potential clinical indications. TG-0054 is a novel CXCR4 antagonist. In vitro CXCR4 antagonistic activity and in vivo stem cell mobilization activity of TG-0054 were determined in this study. Materials and Methods In vitro pharmacological assays, including GTP-binding assay, calcium mobilization assay, and chemotaxis assays, were performed to assess the potency of TG-0054 as a CXCR4 antagonist. In addition, receptor-binding assays against a panel of human chemokine receptors as well as other 68 cellular receptors were screened to evaluate the specificity of TG-0054...
866 Background: Stem cells are retained in the bone marrow via the trophic effects of the binding... more 866 Background: Stem cells are retained in the bone marrow via the trophic effects of the binding of chemokine stromal cell-derived factor-1α (SDF-1α) to its receptor, CXC chemokine receptor 4 (CXCR4). TG-0054 inhibits SDF-1α/CXCR4 binding and therefore mobilizes stem cells into peripheral blood. Animal studies in mice showed rapid and effective mobilization of CD34+ hematopoietic stem cells (HSCs) and CD133+ endothelial progenitor cells (EPCs) into peripheral blood after TG-0054 administration. A Phase I study was conducted in healthy volunteers to assess safety, tolerability, pharmacokinetics (PK) and stem cell mobilization of TG-0054. Materials and Methods: This is a phase I, randomized, double-blind, placebo-controlled, single ascending dose study. In each cohort, 2 volunteers received placebo and 6 received 0.10, 0.14, 0.28, 0.56, 1.12, 2.24, 3.14, or 4.40 mg/kg of TG-0054 (dose was calculated based on TG-0054 free base) via 15 minutes single IV infusion. All subjects underwent...
Uploads
Papers by Chi-Hsin King