Mary Didiuk - Academia.edu (original) (raw)
Papers by Mary Didiuk
Current Organic Chemistry, 1998
: A large variety of metal-based chiral complexes have been developed in the past twenty five yea... more : A large variety of metal-based chiral complexes have been developed in the past twenty five years that allow for the effective catalytic resolution of an impressive range of racemic compounds. After the initial discovery of Ti-catalyzed kinetic resolution of allylic alcohols by Sharpless and coworkers in the early eighties, a number of other transformations have emerged that may be used for catalytic resolution. Amongst them are the Ru-catalyzed hydrogenation, the Zr-catalyzed carbomagnesation, the Mn-catalyzed epoxidation, the Co-catalyzed epoxide hydrolysis, and the Ti-catalyzed reduction of C=N and C=0 bonds. Most recently, the Mo-catalyzed ring-closing metathesis has been utilized to catalytically resolve organic molecules in an efficient manner. This article provides a brief overview of these and other major developments in metal-catalyzed kinetic resolution; strengths and weaknesses of various methods are discussed, and different protocols that afford identical or similar optically pure or enriched compounds are compared. Where possible, the available mechanistic paradigms that affords a rationale as to the observed stereochemical outcomes are provided.
La presente invention concerne de nouveaux derives de pyrido[4,3-D]pyrimidin-4(3H)-one, et leurs ... more La presente invention concerne de nouveaux derives de pyrido[4,3-D]pyrimidin-4(3H)-one, et leurs sels pharmaceutiquement acceptables, de formule structurelle I, les variables R1, R2, R3, R4 et R5 etant telles qu'elles sont decrites dans la presente invention. L'invention concerne egalement des compositions pharmaceutiques contenant les composes de formule I ainsi que des procedes de traitement utilisant lesdits composes de formule I pour traiter une maladie ou un trouble caracterise par une homeostase anormale osseuse ou minerale, notamment l'hypoparathyroidisme, l'osteoporose, l'osteopenie, la parodontopathie, la maladie de Paget, une fracture osseuse, l'osteoarthrite, la polyarthrite rhumatoide, et l'hypercalcemie humorale maligne.
Journal of the American Chemical Society, 1995
Zirconocene-catalyzed carbomagnesation reactions of cyclic ethers 4 and 7 with n-PrMgC1 and n-BuM... more Zirconocene-catalyzed carbomagnesation reactions of cyclic ethers 4 and 7 with n-PrMgC1 and n-BuMgC1 afford homoallylic and bishomoallylic alcohols 5, 8, 9, and 11 in-40% yield and exceptional levels of enantioselectivity and regiocontrol. Where n-BuMgC1 is used as the alkylating agent, high levels of diastereochemical control are also observed (cf. 9 vs 10 in entries 4 and 5 of Table 1). Studies reported herein underline a number of important mechanistic issues: (i) Although zirconocene-alkene complexes 3 exist as a mixture of diastereomers in solution (syn and anti), it is only one of the isomers which reacts to afford the observed products. (ii) Whereas insertion of an alkene substrate into the unsymmetric complexes 3 and 18 proceeds with low levels of regioselectivity at 22 "C, at 70 "C high levels of regiocontrol are observed (cf. intermediacy of 20 vs 24 in Scheme 4). In this context, various mechanistic experiments shed light on factors that may be responsible for the observed temperature effect. (iii) Unusual modes of preference for the regioselectivity in p-hydride abstraction of intermediate dialkylzirconocene are reported; these observations may be accounted for through consideration of the steric effects imposed by the cyclohexyl groups of the chiral ligand and the stereoelectronic requirements of the elimination reaction.
Chemistry & Biodiversity, 2009
Bioorganic & Medicinal Chemistry Letters, 2013
![Research paper thumbnail of Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists](https://attachments.academia-assets.com/101808126/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry Letters, 2009
Bioorganic & Medicinal Chemistry Letters, 2013
Glucokinase activators are a class of experimental agents under investigation as a therapy for Ty... more Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor-acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor-acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor-acceptor motifs may find utility in other glucokinase activator series or beyond.
The present invention relates to a novel pyrido [4,3-d] pyrimidin-4 (3H) -one derivative of formu... more The present invention relates to a novel pyrido [4,3-d] pyrimidin-4 (3H) -one derivative of formula (I) as defined in claim 1 and a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are as described herein]. In addition, pharmaceutical compositions comprising a compound of formula (I), and diseases or disorders characterized by abnormal bone or mineral homeostasis (eg, parathyroidism, osteoporosis, osteopenia, periodontal disease, Paget's disease, fractures, osteoarthritis, rheumatoid arthritis) And humoral hypercalcemia caused by malignant tumors).
Current Organic Chemistry, 1998
: A large variety of metal-based chiral complexes have been developed in the past twenty five yea... more : A large variety of metal-based chiral complexes have been developed in the past twenty five years that allow for the effective catalytic resolution of an impressive range of racemic compounds. After the initial discovery of Ti-catalyzed kinetic resolution of allylic alcohols by Sharpless and coworkers in the early eighties, a number of other transformations have emerged that may be used for catalytic resolution. Amongst them are the Ru-catalyzed hydrogenation, the Zr-catalyzed carbomagnesation, the Mn-catalyzed epoxidation, the Co-catalyzed epoxide hydrolysis, and the Ti-catalyzed reduction of C=N and C=0 bonds. Most recently, the Mo-catalyzed ring-closing metathesis has been utilized to catalytically resolve organic molecules in an efficient manner. This article provides a brief overview of these and other major developments in metal-catalyzed kinetic resolution; strengths and weaknesses of various methods are discussed, and different protocols that afford identical or similar optically pure or enriched compounds are compared. Where possible, the available mechanistic paradigms that affords a rationale as to the observed stereochemical outcomes are provided.
La presente invention concerne de nouveaux derives de pyrido[4,3-D]pyrimidin-4(3H)-one, et leurs ... more La presente invention concerne de nouveaux derives de pyrido[4,3-D]pyrimidin-4(3H)-one, et leurs sels pharmaceutiquement acceptables, de formule structurelle I, les variables R1, R2, R3, R4 et R5 etant telles qu'elles sont decrites dans la presente invention. L'invention concerne egalement des compositions pharmaceutiques contenant les composes de formule I ainsi que des procedes de traitement utilisant lesdits composes de formule I pour traiter une maladie ou un trouble caracterise par une homeostase anormale osseuse ou minerale, notamment l'hypoparathyroidisme, l'osteoporose, l'osteopenie, la parodontopathie, la maladie de Paget, une fracture osseuse, l'osteoarthrite, la polyarthrite rhumatoide, et l'hypercalcemie humorale maligne.
Journal of the American Chemical Society, 1995
Zirconocene-catalyzed carbomagnesation reactions of cyclic ethers 4 and 7 with n-PrMgC1 and n-BuM... more Zirconocene-catalyzed carbomagnesation reactions of cyclic ethers 4 and 7 with n-PrMgC1 and n-BuMgC1 afford homoallylic and bishomoallylic alcohols 5, 8, 9, and 11 in-40% yield and exceptional levels of enantioselectivity and regiocontrol. Where n-BuMgC1 is used as the alkylating agent, high levels of diastereochemical control are also observed (cf. 9 vs 10 in entries 4 and 5 of Table 1). Studies reported herein underline a number of important mechanistic issues: (i) Although zirconocene-alkene complexes 3 exist as a mixture of diastereomers in solution (syn and anti), it is only one of the isomers which reacts to afford the observed products. (ii) Whereas insertion of an alkene substrate into the unsymmetric complexes 3 and 18 proceeds with low levels of regioselectivity at 22 "C, at 70 "C high levels of regiocontrol are observed (cf. intermediacy of 20 vs 24 in Scheme 4). In this context, various mechanistic experiments shed light on factors that may be responsible for the observed temperature effect. (iii) Unusual modes of preference for the regioselectivity in p-hydride abstraction of intermediate dialkylzirconocene are reported; these observations may be accounted for through consideration of the steric effects imposed by the cyclohexyl groups of the chiral ligand and the stereoelectronic requirements of the elimination reaction.
Chemistry & Biodiversity, 2009
Bioorganic & Medicinal Chemistry Letters, 2013
Bioorganic & Medicinal Chemistry Letters, 2009
Bioorganic & Medicinal Chemistry Letters, 2013
Glucokinase activators are a class of experimental agents under investigation as a therapy for Ty... more Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor-acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor-acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor-acceptor motifs may find utility in other glucokinase activator series or beyond.
The present invention relates to a novel pyrido [4,3-d] pyrimidin-4 (3H) -one derivative of formu... more The present invention relates to a novel pyrido [4,3-d] pyrimidin-4 (3H) -one derivative of formula (I) as defined in claim 1 and a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are as described herein]. In addition, pharmaceutical compositions comprising a compound of formula (I), and diseases or disorders characterized by abnormal bone or mineral homeostasis (eg, parathyroidism, osteoporosis, osteopenia, periodontal disease, Paget's disease, fractures, osteoarthritis, rheumatoid arthritis) And humoral hypercalcemia caused by malignant tumors).