ChemInform Abstract: Chemical Stability of a Prostacyclin Analogue Due to the Absence of Intramolecular Catalysis.

Bergman, N.-A.; Halvarsson, Torbjörn

doi:10.1002/chin.198842188

Cited by 3 publications

(3 citation statements)

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“…Thus, it was demonstrated that polymer chains grafted from nanoparticles by SI-ATRP were effective for preparing transparent bulk hybrids with improved refractive indices. With this procedure, phosphorus coupling agents (CPMP and IDP) can form stable M−O−P bonds with various inorganic oxides, 42 and ATRP can be applicable to a variety of polymers. The present strategy is therefore applicable to many inorganic−organic hybrids.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Preparation of Transparent Bulk TiO₂/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO₂ Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization

Maeda

Fujita

Idota

et al. 2016

ACS Appl. Mater. Interfaces

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Transparent TiO/PMMA hybrids with a thickness of 5 mm and improved refractive indices were prepared by in situ polymerization of methyl methacrylate (MMA) in the presence of TiO nanoparticles bearing poly(methyl methacrylate) (PMMA) chains grown using surface-initiated atom transfer radical polymerization (SI-ATRP), and the effect of the chain length of modified PMMA on the dispersibility of modified TiO nanoparticles in the bulk hybrids was investigated. The surfaces of TiO nanoparticles were modified with both m-(chloromethyl)phenylmethanoyloxymethylphosphonic acid bearing a terminal ATRP initiator and isodecyl phosphate with a high affinity for common organic solvents, leading to sufficient dispersibility of the surface-modified particles in toluene. Subsequently, SI-ATRP of MMA was achieved from the modified surfaces of the TiO nanoparticles without aggregation of the nanoparticles in toluene. The molecular weights of the PMMA chains cleaved from the modified TiO nanoparticles increased with increases in the prolonging of the polymerization period, and these exhibited a narrow distribution, indicating chain growth controlled by SI-ATRP. The nanoparticles bearing PMMA chains were well-dispersed in MMA regardless of the polymerization period. Bulk PMMA hybrids containing modified TiO nanoparticles with a thickness of 5 mm were prepared by in situ polymerization of the MMA dispersion. The transparency of the hybrids depended significantly on the chain length of the modified PMMA on the nanoparticles, because the modified PMMA of low molecular weight induced aggregation of the TiO nanoparticles during the in situ polymerization process. The refractive indices of the bulk hybrids could be controlled by adjusting the TiO content and could be increased up to 1.566 for 6.3 vol % TiO content (1.492 for pristine PMMA).

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Section: ■ Results and Discussionmentioning

confidence: 99%

Preparation of Transparent Bulk TiO₂/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO₂ Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization

Maeda

Fujita

Idota

et al. 2016

ACS Appl. Mater. Interfaces

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“…Out of these series of analogues, [(5Z, 13E, 9a, 1 la, 15S)-2,3,4-trinor-1,5-inter-m-phenylene-6,9-epoxy-11,15-dihydroxy-15-cyclohexyl-16,17,18,19,20-pentanor]-prosta-5,13-dienoic acid, sodium salt (CG 4203; taprostene sodium-hereafter referred to as taprostene) ( Fig. 1) yielded substantial prostacyclin activity as well as chemical and metabolic stability (10,25,34).…”

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confidence: 99%

Taprostene Sodium

Schneider

Friderichs

Kögel

et al. 1993

Cardiovascular Drug Reviews

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In 1976 Vane, Moncada, Gryglewski, and Bunting discovered that "an enzyme isolated from arteries transforms prostaglandin peroxides to an unstable substance that inhibits platelet aggregation" (58). This endothelium-derived compound, later named prostacyclin (PGI,), turned out to be the strongest inhibitor of platelet aggregation described to date. It was further characterized as a potent vasorelaxant agent in vitro (14,22) and in vivo (3). The unique pharmacological profile of prostacyclin very soon raised many hopes as to its therapeutic potential. Prostacyclin has been tested clinically in extracorporeal circulation, cardiopulmonary bypass, peripheral arterial disease, ischemic stroke, pulmonary hypertension, congestive heart failure, and coronary artery disease (91). Further clinical development of prostacyclin was hampered, however, by its chemical and metabolic instability.To overcome these shortcomings of natural prostacyclin, many attempts have been made to synthesize analogues with improved stability. Analogues with the common feature of a replacement of C1-C4 of prostacyclin by a carboxyphenylene residue and substitutions at or near C,, to achieve resistance against 15-hydroxyprostaglandin dehydrogenase have been described (25). Out of these series of analogues, [(5Z, 13E, 9a, 1 la, 15S)-2,3,4-trinor-1,5-inter-m-phenylene-6,9-epoxy-11,15-dihydroxy-15-cyclohexyl-16,17,18,19,20-pentanor]-prosta-5,13-dienoic acid, sodium salt (CG 4203; taprostene sodium-hereafter referred to as taprostene) (Fig. 1) yielded substantial prostacyclin activity as well as chemical and metabolic stability (10,25,34). PHARMACOLOGY Inhibition of Platelet ActivityIn hemostasis and thrombosis, activated platelets change shape, adhere to the site of the injury on a vessel wall, aggregate, and produce procoagulant activity. Inhibition of

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“…thesized to obtain a PG12 analog with maximal metabolic stability ( Fig. 1) (3,7). To achieve stability, a 2,3,4,-trinor-1,5-inter-rn-phylene analog was designed.…”

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Taprostene (CG‐4203)

Lefer

Darius

1989

Cardiovascular Drug Reviews

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The first reports on prostacyclin (PG12), an autocoid released from the vascular endothelium, was published in 1976 (36). Thereafter, major research interest was focused on this interesting substance. The reasons were the unique properties of PG12, being able to relax vascular smooth muscle and to inhibit platelet aggregation at nanomolar concentrations (37). Later on, additional properties of PG12 were discovered, including inhibition of platelet mitogen release (60) and cytoprotective effects (2 1) useful in myocardial ischemia (22). The successful chemical synthesis of PG12 made sufficient quantities of the substance available to allow investigations of its pharmacologic effects in a variety of experimental models and in initial clinical trials.During this early phase of prostacyclin research, its chemical and metabolic instability was recognized as being a major shortcoming in terms of its becoming a clinically important drug (10). The half-life of PG12 at physiologic pH is about 3 min, and chemical stability occurred only at alkaline pH values (i.e., above pH 9). In vivo, the chemical and metabolic instability of the substance led to rapid inactivation by 15-OH-prostaglandin dehydrogenase and other hydrolytic enzymes. Therefore, it became evident very early that only chemically stable PG12 analogs would be useful as clinically relevant drugs (4 1). Chemically stable analogs of PGIz might additionally offer the chance of manipulating some of the pharmacologic properties of the compound to select for certain properties, including platelet inhibition, vasodilation, or inhibition of mitogen release. Additionally, selective chemically stable analogs offer the opportunity of decreasing the incidence of unwanted side effects, which were evident during the first clinical trials with PGIp (i.e., anxiety and headaches).Several chemically stable analogs of PGIz have been synthesized and studied by experimental and clinical pharmacologists. The present review will focus on the pharmacologic properties and clinical effects of taprostene (CG 4203), a compound syn-

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ChemInform Abstract: Chemical Stability of a Prostacyclin Analogue Due to the Absence of Intramolecular Catalysis.

Cited by 3 publications

References 1 publication

Preparation of Transparent Bulk TiO₂/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO₂ Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization

Preparation of Transparent Bulk TiO₂/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO₂ Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization

Taprostene Sodium

Taprostene (CG‐4203)

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ChemInform Abstract: Chemical Stability of a Prostacyclin Analogue Due to the Absence of Intramolecular Catalysis.

Cited by 3 publications

References 1 publication

Preparation of Transparent Bulk TiO2/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO2 Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization

Preparation of Transparent Bulk TiO2/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO2 Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization

Taprostene Sodium

Taprostene (CG‐4203)

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Product

Resources

About

Preparation of Transparent Bulk TiO₂/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO₂ Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization

Preparation of Transparent Bulk TiO₂/PMMA Hybrids with Improved Refractive Indices via an in Situ Polymerization Process Using TiO₂ Nanoparticles Bearing PMMA Chains Grown by Surface-Initiated Atom Transfer Radical Polymerization