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example-0 | 10335724 | [
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" Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis. PURPOSE: To assess the value of serial determinations of antineutrophil cytoplasmic autoantibodies (ANCA) for monitoring disease activity in patients with systemic vasculitis. PATIENTS AND METHODS: Forty-three patients with histologically proven vasculitis (21 with Wegener's granulomatosis, 17 with microscopic polyangiitis, and 5 with renal-limited vasculitis) were studied for a median follow-up of 22 months. Disease activity was prospectively assessed and quantified by the Birmingham Vasculitis Activity Score. A total of 347 sera were analyzed for ANCA determination. RESULTS: Relapses occurred in 23 (54%) of 43 patients. Diagnostic category (Wegener's granulomatosis vs micropolyangiitis and renal-limited vasculitis), severity of initial symptoms (mean vasculitis activity score, mean number of organs involved), and ANCA pattern [cytoplasmic-ANCA (c-ANCA) vs perinuclear-ANCA (p-ANCA)] did not significantly differ between relapsers and nonrelapsers. Lung involvement was more frequent at onset among relapsers [16 of 23 ( ) vs 6 of ( ); P = 0.02]. Relapses were slightly, but not significantly, more frequent in patients with Wegener's granulomatosis or a c-ANCA pattern. The percentage of relapsers was greater in patients with persistently positive ANCA than in patients with negative or decreasing ANCA titers (86% vs , P = 0.0001). However, the predictive value of an increase in ANCA titers for the occurrence of a subsequent relapse was only 28% (4 of 14) for c-ANCA, 12% (2 of 17) for anti-proteinase 3-ANCA, and 43% (6 of 14) for anti-myeloperoxidase-ANCA. An increase in ANCA occurred before or during relapse in 33% ( of ) of cases for c-ANCA/anti-proteinase 3 antibodies, and 73% (11 of 15) of cases for anti-myeloperoxidase antibodies. CONCLUSION: The persistence of ANCA positivity is strongly associated with relapses. However, an increase in ANCA titers has a poor value for the early prediction of a subsequent relapse and should not be used as a sole parameter for therapeutic intervention. In addition, our results suggest that serial anti-myeloperoxidase determination may be useful as a prognostic marker in patients who are p-ANCA positive."
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example-1 | 9719587 | [
{
"id": "passage-1",
"type": "abstract",
"text": [
"The synthesis of a range of 3-hydroxy-4(1H)-pyridinones with potential for the chelation of iron(III) is described. The pKa values of respective ligands and the stability constants of their iron(III) complexes are presented. The distribution coefficient values of a range of 48hydroxypyridinones and their corresponding iron(III) complexes between 1-octanol and MOPS buffer (pH 7.4) are reported. The range of log Dcomplex values covers 7 orders of magnitude. The results suggest the existence of a biphasic relationship between the distribution coefficient values of the chelator and the correspondingiron (III) complexes. For ligands with a log Dligand = -1, a linear relationship exists with a value of the slope 2.53, whereas with ligands with a log Dligand < -1, a linear relationship exists with a slope of 0.49. The reduced slope for the more hydrophilic molecules of the series offers some advantage for this type of hydroxypyridinone as the distribution coefficients for such complexes do not change so rapidly with increasing ligand hydrophilicity. The ability of selected 3-hydroxypyridinones to facilitate the excretion of iron in bile was investigated in non-iron-overloaded, bile duct-cannulated rats and in a [59Fe]ferritin-loaded rat model. Both systems compare the ability of chelators to remove iron from the liver, the prime target organ in thalassemia. The N-(hydroxyalkyl)-3-hydroxypyridin-4-ones are demonstrated to be orally active under the in vivo conditions adopted. Thus both 1-(hydroxyalkyl)- and 1-(carboxyalkyl)pyridinones are able to remove iron from the liver. Although 1-(carboxyalkyl)hydroxypyridinones are active, they do not demonstrate any clear advantage over Deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one). Indeed 1-(hydroxyalkyl)hydroxypyridinones which are known to be rapidly converted to 1-(carboxyalkyl)hydroxypyridinones are also marginally superior to Deferiprone. In contrast, 2-ethyl-1-(2'-hydroxyethyl)-3-hydroxypyridin-4-one, which is not metabolized to the corresponding (carboxyalkyl)hydroxypyridinone, was found to be superior to Deferiprone and therefore deserves further consideration as an orally active iron chelator with potential for the treatment of ironoverload associated with transfusion-dependent thalassemia."
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example-2 | 3625710 | [
{
"id": "passage-2",
"type": "abstract",
"text": [
"A series of analogues of the analgesic dipeptide derivative H-Lys-Trp(NPS)-OMe has been designed to determine the influence of the (2-nitrophenyl)sulfenyl (NPS) moiety on the activity. The syntheses and antinociceptive effects of these analogues of general formulaH -Lys-Trp(R)-OMe [R = phenylsulfenyl (PS) (9); R = (2-carbomethyoxyphenyl)sulfenyl (CmPS) ( ); R = (4-nitrophenyl)sulfenyl (pNPS) (11); R = (2,4-dinitrophenyl)sulfenyl (DNPS) (12); R = [2-(acetylamino)-2-carbomethoxyethyl]sulfenyl (AacCmES) (13); R = [2-(acetylamino)phenyl]sulfenyl (AacPS) (17); R = tert-butylsulfenyl (t-BuS) (23); R = (2-carbomethoxyethyl)sulfenyl (CmES) (24)] are described. Reaction of Z-Lys(Z)-Trp-OMe (3) with PS-, CmPS-, pNPS-, DNPS-, and AacCmES-Cl afforded the corresponding 2-(sulfenyl)tryptophan derivatives, which on treatment with boron-tris(trifluoroacetate)/trifluoroacetic acid or trimethylsilyl iodide in acetonitrile (Me3SiI/CH3CN) provided 9-13, respectively. Sulfenylation of 3 with NPS-Cl gave Z-Lys(Z)-Trp(NPS)-OMe, which, on catalytic hydrogenation of the nitro group using Pd/C followed by acetylation of the resulting amino function and removal of the protecting Z groups, gave 17. Condensation of 2-(tert-butylsulfenyl)- and 2-[(2-carbomethoxyethyl)sulfenyl]tryptophan methyl ester, obtained by reaction of methyl 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxyla te with the corresponding thiol, with Z-Lys(Z)-OSu afforded Z-Lys(Z)-Trp(t-BuS)-OMe and Z-Lys(Z)-Trp(CmES)-OMe, which on treatment with Me3SiI/CH3CN provided 23 and 24, respectively. Intracerebroventricular administration of elicited a naloxone-reversible antinociceptive effect in mice similar to that of H-Lys-Trp(NPS)-OMe. No analgesia was however found with the phenylsulfenyl or acyclic sulfenyl substituted dipeptides 9, 11, and 17 or 13, 23, and 24. The Trp(DNPS)-containing analogue was neurotoxic. Structure-activity studies indicate that the role of the NPS and CmPS moietiescould be related to the adoption of a preferential active conformation."
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"CmPS"
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"offsets": [
[
1970,
1974
]
],
"normalized": []
},
{
"id": "entity-2-51",
"type": "MODIFIER",
"text": [
"moieties"
],
"offsets": [
[
1975,
1983
]
],
"normalized": []
}
] | [] | [] | [] |
example-3 | 2153828 | [
{
"id": "passage-3",
"type": "abstract",
"text": [
"A series of substituted 1,4-dihydronaphthoquinones, hydroindoloquinones, benzofuran-4,7-dihydroquinones, and benzothiophene-4,7-dihydroquinones were synthesized and evaluated for inhibitory activity against 5-lipoxygenase. These compounds were found to be active in vitro for LTC4/D4 inhibition with the potencies (IC50's) ranging from 0.2 to 85 microM. Active 1,4-dihydronaphthoquinone acetates (IC50 less than microM) were evaluated in an ex vivo LTB4 inhibition assay. The acetates of 1,4-dihydronaphthoquinones containing the alkyl substituent(s) (2-n-butyl, 11, and 2,3-diethyl, 15) exhibited the best activity in LTC4/D4 inhibition (IC50 = 0.2-0.4 microM, in vitro) as well as in LTB4 inhibition ( inhibition)."
],
"offsets": [
[
0,
725
]
]
}
] | [
{
"id": "entity-3-0",
"type": "IUPAC",
"text": [
"1,4-dihydronaphthoquinones"
],
"offsets": [
[
24,
50
]
],
"normalized": []
},
{
"id": "entity-3-1",
"type": "TRIVIAL",
"text": [
"hydroindoloquinones"
],
"offsets": [
[
52,
71
]
],
"normalized": []
},
{
"id": "entity-3-2",
"type": "IUPAC",
"text": [
"benzofuran-4,7-dihydroquinones"
],
"offsets": [
[
73,
103
]
],
"normalized": []
},
{
"id": "entity-3-3",
"type": "IUPAC",
"text": [
"benzothiophene-4,7-dihydroquinones"
],
"offsets": [
[
109,
143
]
],
"normalized": []
},
{
"id": "entity-3-4",
"type": "IUPAC",
"text": [
"1,4-dihydronaphthoquinone acetates"
],
"offsets": [
[
361,
395
]
],
"normalized": []
},
{
"id": "entity-3-5",
"type": "FAMILY",
"text": [
"acetates"
],
"offsets": [
[
479,
487
]
],
"normalized": []
},
{
"id": "entity-3-6",
"type": "IUPAC",
"text": [
"1,4-dihydronaphthoquinones"
],
"offsets": [
[
491,
517
]
],
"normalized": []
},
{
"id": "entity-3-7",
"type": "PARTIUPAC",
"text": [
"alkyl"
],
"offsets": [
[
533,
538
]
],
"normalized": []
},
{
"id": "entity-3-8",
"type": "MODIFIER",
"text": [
"substituent(s)"
],
"offsets": [
[
539,
553
]
],
"normalized": []
},
{
"id": "entity-3-9",
"type": "PARTIUPAC",
"text": [
"2-n-butyl"
],
"offsets": [
[
555,
564
]
],
"normalized": []
},
{
"id": "entity-3-10",
"type": "PARTIUPAC",
"text": [
"2,3-diethyl"
],
"offsets": [
[
574,
585
]
],
"normalized": []
}
] | [] | [] | [] |
example-4 | 8817480 | [
{
"id": "passage-4",
"type": "abstract",
"text": [
" The regulation of total creatine content in a myoblast cell line. Total cellular creatine content is an important bioenergetic parameter in skeletal muscle. To understand its regulation we investigated creatine transport and accumulation in the G8 cultured skeletal myoblast line. Like other cell types, these contain a creatine transporter, whose activity, measured using a radiolabelling technique, was saturable (Km = +/- 25 microM) and largely dependent on extracellular [Na+]. To study sustained influences on steady state creatine concentration we measured total cellular creatine content using a fluorimetric method in 48 h incubations. We found that the total cellular creatine content was relatively independent of extracellular creatine concentration, consistent with high affinity sodium-dependent uptake balanced by slow passive efflux. Accordingly, in creatine-free incubations net creatine efflux was slow (5 +/- 1% of basal creatine content per day over 6 days), while creatine content in 48 h incubations was reduced by 28 +/- 13% of control by the Na+, K(+)-ATPase inhibitor ouabain. Creatine accumulation after 48 h was stimulated by treatment with the mixed alpha- and beta-adrenergic agonist noradrenaline, the beta-adrenergic agonist isoproterenol, the beta 2-agonist clenbuterol and the cAMP analogue N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate, but was unaffected by the alpha 1 adrenergic agonist methoxamine. The noradrenaline enhancement of creatine accumulation at 48 h was inhibited by the mixed alpha- and beta-antagonist labetalol and by the beta-antagonist propranolol, but was unaffected by the alpha 2 antagonist phentolamine; greater inhibition was caused by the beta 2 antagonist butoxamine than the beta 1 antagonist atenolol. Creatine accumulation at 48 h was increased to +/- 6% of control by insulin and by +/- 13% by IGF-I (both at 3 nM). Creatine accumulation at 48 h was also increased to +/- of control by 3,3',5-triiodothyronine (at microM) and to +/- 35% of control by amylin ( nM). As 3,3', 5-triiodothyronine, amylin and isoproterenol all stimulate the Na+, K(+)-ATPase, we suggest that they stimulate Na(+)-creatine cotransport indirectly by increasing the transmembrane [Na+] concentration gradient and membrane potential."
],
"offsets": [
[
0,
2320
]
]
}
] | [
{
"id": "entity-4-0",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
33,
41
]
],
"normalized": []
},
{
"id": "entity-4-1",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
91,
99
]
],
"normalized": []
},
{
"id": "entity-4-2",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
212,
220
]
],
"normalized": []
},
{
"id": "entity-4-3",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
542,
550
]
],
"normalized": []
},
{
"id": "entity-4-4",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
592,
600
]
],
"normalized": []
},
{
"id": "entity-4-5",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
691,
699
]
],
"normalized": []
},
{
"id": "entity-4-6",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
752,
760
]
],
"normalized": []
},
{
"id": "entity-4-7",
"type": "TRIVIAL",
"text": [
"sodium"
],
"offsets": [
[
806,
812
]
],
"normalized": []
},
{
"id": "entity-4-8",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
879,
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]
],
"normalized": []
},
{
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"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
909,
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]
],
"normalized": []
},
{
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"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
953,
961
]
],
"normalized": []
},
{
"id": "entity-4-11",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
998,
1006
]
],
"normalized": []
},
{
"id": "entity-4-12",
"type": "TRIVIAL",
"text": [
"ouabain"
],
"offsets": [
[
1106,
1113
]
],
"normalized": []
},
{
"id": "entity-4-13",
"type": "TRIVIAL",
"text": [
"Creatine"
],
"offsets": [
[
1115,
1123
]
],
"normalized": []
},
{
"id": "entity-4-14",
"type": "TRIVIAL",
"text": [
"noradrenaline"
],
"offsets": [
[
1226,
1239
]
],
"normalized": []
},
{
"id": "entity-4-15",
"type": "TRIVIAL",
"text": [
"isoproterenol"
],
"offsets": [
[
1269,
1282
]
],
"normalized": []
},
{
"id": "entity-4-16",
"type": "TRIVIAL",
"text": [
"clenbuterol"
],
"offsets": [
[
1303,
1314
]
],
"normalized": []
},
{
"id": "entity-4-17",
"type": "TRIVIAL",
"text": [
"cAMP"
],
"offsets": [
[
1323,
1327
]
],
"normalized": []
},
{
"id": "entity-4-18",
"type": "MODIFIER",
"text": [
"analogue"
],
"offsets": [
[
1328,
1336
]
],
"normalized": []
},
{
"id": "entity-4-19",
"type": "IUPAC",
"text": [
"N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate"
],
"offsets": [
[
1337,
1390
]
],
"normalized": []
},
{
"id": "entity-4-20",
"type": "TRIVIAL",
"text": [
"methoxamine"
],
"offsets": [
[
1445,
1456
]
],
"normalized": []
},
{
"id": "entity-4-21",
"type": "TRIVIAL",
"text": [
"noradrenaline"
],
"offsets": [
[
1462,
1475
]
],
"normalized": []
},
{
"id": "entity-4-22",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
1491,
1499
]
],
"normalized": []
},
{
"id": "entity-4-23",
"type": "TRIVIAL",
"text": [
"labetalol"
],
"offsets": [
[
1575,
1584
]
],
"normalized": []
},
{
"id": "entity-4-24",
"type": "TRIVIAL",
"text": [
"propranolol"
],
"offsets": [
[
1612,
1623
]
],
"normalized": []
},
{
"id": "entity-4-25",
"type": "TRIVIAL",
"text": [
"phentolamine"
],
"offsets": [
[
1670,
1682
]
],
"normalized": []
},
{
"id": "entity-4-26",
"type": "TRIVIAL",
"text": [
"butoxamine"
],
"offsets": [
[
1739,
1749
]
],
"normalized": []
},
{
"id": "entity-4-27",
"type": "TRIVIAL",
"text": [
"atenolol"
],
"offsets": [
[
1777,
1785
]
],
"normalized": []
},
{
"id": "entity-4-28",
"type": "TRIVIAL",
"text": [
"Creatine"
],
"offsets": [
[
1787,
1795
]
],
"normalized": []
},
{
"id": "entity-4-29",
"type": "TRIVIAL",
"text": [
"Creatine"
],
"offsets": [
[
1911,
1919
]
],
"normalized": []
},
{
"id": "entity-4-30",
"type": "IUPAC",
"text": [
"3,3',5-triiodothyronine"
],
"offsets": [
[
1989,
2012
]
],
"normalized": []
},
{
"id": "entity-4-31",
"type": "TRIVIAL",
"text": [
"amylin"
],
"offsets": [
[
2061,
2067
]
],
"normalized": []
},
{
"id": "entity-4-32",
"type": "IUPAC",
"text": [
"3,3', 5-triiodothyronine"
],
"offsets": [
[
2080,
2104
]
],
"normalized": []
},
{
"id": "entity-4-33",
"type": "TRIVIAL",
"text": [
"amylin"
],
"offsets": [
[
2106,
2112
]
],
"normalized": []
},
{
"id": "entity-4-34",
"type": "TRIVIAL",
"text": [
"isoproterenol"
],
"offsets": [
[
2117,
2130
]
],
"normalized": []
},
{
"id": "entity-4-35",
"type": "SUM",
"text": [
"Na(+)"
],
"offsets": [
[
2198,
2203
]
],
"normalized": []
},
{
"id": "entity-4-36",
"type": "TRIVIAL",
"text": [
"creatine"
],
"offsets": [
[
2204,
2212
]
],
"normalized": []
},
{
"id": "entity-4-37",
"type": "SUM",
"text": [
"Na+"
],
"offsets": [
[
2269,
2272
]
],
"normalized": []
}
] | [] | [] | [] |
example-5 | 12742193 | [
{
"id": "passage-5",
"type": "abstract",
"text": [
"12742193 Attenuation of cerebral vasospasm in rabbits using clonidine hydrochloride, a central adrenergic agonist. The aim of this study was to assess, firstly, if exclusion of central noradrenergic areas in the hypothalamus and brain stem with the central sympathetic blocker clonidine hydrochloride could prevent the development of chronic vasospasm following experimental subarachnoid haemorrhage in rabbits and, secondly, if, parallel with the effect on cerebral arteries, changes in dopamine beta-hydroxylase concentration in the hypothalamus and brain stem could also be detected.Experimental subarachnoid haemorrhage, in concentrations of 1 ml of autologous arterial blood/1 kg of body weight was carried out on 18 New Zealand rabbits. Histological specimens were obtained by the method of perfusion fixation after the rabbits were sacrificed on day 8 after subarachnoid haemorrhage. The spastic effect of experimentally induced subarachnoid haemorrhage was determined by assessing the intensity of corrugation of the intima of the rabbit basilar artery by the previously developed method of corrugation coefficient and computer image analysis. The concentration and localization of dopamine beta-hydroxylase in noradrenaline-containing neurons was immunohistochemically assessed (semiquantitatively as 0, 1 and 2) with anti-dopamine beta-hydroxylase, at precisely defined sites of the hypothalamus and brain stem of the same rabbit.The results revealed less corrugated and smoother intima in the basilar artery and significantly lower dopamine beta-hydroxylase concentration in the control group of rabbits with sham subarachnoid haemorrhage and without any additional interventions (mean corrugation coefficient=1.123+/-0.024, P=0.35 x (-3); mean dopamine beta-hydroxylase=0.350+/-0.071, P=0.22 x (-3)), and smoother intima in the basilar artery with significantly lower concentration of dopamine beta-hydroxylase in the clonidine group (rabbits with subarachnoid haemorrhage and central alpha(2)-blocker clonidine hydrochloride at a daily dose of 0.03 mg/kg of body weight for 8 days; mean corrugation coefficient=1.177+/-0.058, P=1.7 x (-3); mean dopamine beta-hydroxylase=0.583+/-0.175, P=1.1 x (-3)). In comparison, the haemorrhage only group (rabbits with subarachnoid haemorrhage and without medication; mean corrugation coefficient=1.370+/-0.101; mean dopamine beta-hydroxylase=1.214+/-0.313) displayed intensive corrugation of the intima of the basilar artery and a significantly more intensive accumulation of dopamine beta-hydroxylase than did the control group and the clonidine group.The results of this study demonstrated that the central alpha(2)-blocker clonidine hydrochlorideeffectively prevents vasospasm, and diminishes the concentration of cerebral dopamine beta-hydroxylase in the hypothalamus and brain stem after experimental subarachnoid haemorrhage in rabbits."
],
"offsets": [
[
0,
2905
]
]
}
] | [
{
"id": "entity-5-0",
"type": "IUPAC",
"text": [
"clonidine hydrochloride"
],
"offsets": [
[
61,
84
]
],
"normalized": []
},
{
"id": "entity-5-1",
"type": "IUPAC",
"text": [
"clonidine hydrochloride"
],
"offsets": [
[
279,
302
]
],
"normalized": []
},
{
"id": "entity-5-2",
"type": "TRIVIAL",
"text": [
"noradrenaline"
],
"offsets": [
[
1221,
1234
]
],
"normalized": []
},
{
"id": "entity-5-3",
"type": "TRIVIAL",
"text": [
"clonidine"
],
"offsets": [
[
1936,
1945
]
],
"normalized": []
},
{
"id": "entity-5-4",
"type": "MODIFIER",
"text": [
"group"
],
"offsets": [
[
1946,
1951
]
],
"normalized": []
},
{
"id": "entity-5-5",
"type": "IUPAC",
"text": [
"clonidine hydrochloride"
],
"offsets": [
[
2020,
2043
]
],
"normalized": []
},
{
"id": "entity-5-6",
"type": "TRIVIAL",
"text": [
"dopamine"
],
"offsets": [
[
2166,
2174
]
],
"normalized": []
},
{
"id": "entity-5-7",
"type": "IUPAC",
"text": [
"clonidine hydrochloride"
],
"offsets": [
[
2688,
2711
]
],
"normalized": []
}
] | [] | [] | [] |
example-6 | 16682228 | [
{
"id": "passage-6",
"type": "abstract",
"text": [
"16682228 Heterologous expression of lipoprotein-associated phospholipase A2 in different expression systems. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a key enzyme involved in atherosclerosis, and has been considered as a new target for drug discovery. The major difficulty for high-throughput screening of Lp-PLA(2) inhibitors and for functional studies was their fast and efficient production. Purification of native Lp-PLA(2) from human plasma was complicated and produced a very low yield. We herein examined the feasibility of expressing and purifying recombinant Lp-PLA(2) in different heterologous expression systems. The fusion Lp-PLA(2) was expressed at high levels and exhibited strong enzyme activity in insect cell-baculovirus expression system. The functional enzyme could also be produced in Pichia pastoris. The inclusion of a Kozak sequence increased greatly the expression level of recombinant Lp-PLA(2) in insect cells, but had little effect on the expression of recombinant Lp-PLA(2) in P. pastoris and Escherichia coli. P. pastoris-produced Lp-PLA(2) could be purified rapidly and conveniently through a one-step procedure, while baculovirus-produced Lp-PLA(2) could be efficiently purified through a two-step procedure. This ability to readily produce recombinant Lp-PLA(2) could provide a screening model for Lp-PLA(2) inhibitors and will facilitate further studies on this enzyme."
],
"offsets": [
[
0,
1420
]
]
}
] | [] | [] | [] | [] |
example-7 | 10639285 | [
{
"id": "passage-7",
"type": "abstract",
"text": [
"A series of 2-(diethylamino)thieno1,3?xazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno2,3-d1,3?xazin-4-ones bearing various substituents at positions 5 and 6. Both thieno2,3-d and thieno3,2-d fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-1benzothieno2,3-d1,3?xazin-4-one, exhibited a K(i) value of 5.8 nM. 2-(Diethylamino)thieno1, 3?xazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophenereplacement accounts for an enhanced stability of the acyl-enzyme intermediates."
],
"offsets": [
[
0,
998
]
]
}
] | [
{
"id": "entity-7-0",
"type": "IUPAC",
"text": [
"2-(diethylamino)thieno1,3?xazin-4-ones"
],
"offsets": [
[
12,
50
]
],
"normalized": []
},
{
"id": "entity-7-1",
"type": "TRIVIAL",
"text": [
"thiophene"
],
"offsets": [
[
164,
173
]
],
"normalized": []
},
{
"id": "entity-7-2",
"type": "IUPAC",
"text": [
"ethyl 2-aminothiophene-3-carboxylates"
],
"offsets": [
[
215,
252
]
],
"normalized": []
},
{
"id": "entity-7-3",
"type": "IUPAC",
"text": [
"thieno2,3-d1,3?xazin-4-ones"
],
"offsets": [
[
317,
344
]
],
"normalized": []
},
{
"id": "entity-7-4",
"type": "PARTIUPAC",
"text": [
"thieno2,3-d"
],
"offsets": [
[
401,
412
]
],
"normalized": []
},
{
"id": "entity-7-5",
"type": "PARTIUPAC",
"text": [
"thieno3,2-d"
],
"offsets": [
[
417,
428
]
],
"normalized": []
},
{
"id": "entity-7-6",
"type": "IUPAC",
"text": [
"oxazin-4-ones"
],
"offsets": [
[
435,
448
]
],
"normalized": []
},
{
"id": "entity-7-7",
"type": "IUPAC",
"text": [
"2-(diethylamino)-4H-1benzothieno2,3-d1,3?xazin-4-one"
],
"offsets": [
[
645,
697
]
],
"normalized": []
},
{
"id": "entity-7-8",
"type": "IUPAC",
"text": [
"2-(Diethylamino)thieno1, 3?xazin-4-ones"
],
"offsets": [
[
733,
772
]
],
"normalized": []
},
{
"id": "entity-7-9",
"type": "IUPAC",
"text": [
"4H-3,1-benzoxazin-4-ones"
],
"offsets": [
[
860,
884
]
],
"normalized": []
},
{
"id": "entity-7-10",
"type": "IUPAC",
"text": [
"benzene-thiophene"
],
"offsets": [
[
900,
917
]
],
"normalized": []
}
] | [] | [] | [] |
example-8 | 17371003 | [
{
"id": "passage-8",
"type": "abstract",
"text": [
"Structure-activity relationships have been investigated for inhibition of DNA-dependent protein kinase (DNA-PK) and ATM kinase by a series of pyran-2-ones, pyran-4-ones, thiopyran-4-ones, and pyridin-4-ones. A wide range of IC50 values were observed for pyranones and thiopyranones substituted at the 6-position, with the 3- and 5-positions proving intolerant to substitution. Related pyran-2-ones, pyran-4-ones, and thiopyran-4-ones showed similar IC50 values against DNA-PK, whereas the pyridin-4-one system proved, in general, ineffective at inhibiting DNA-PK. Extended libraries exploring the 6-position of 2-morpholino-pyran-4-ones and 2-morpholino-thiopyrano-4-ones identified the first highly potent and selective ATM inhibitor 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (151C; ATM; IC50 = 13 nM) and revealed constrained SARs for ATM inhibition compared with DNA-PK. One of the most potent DNA-PK inhibitors identified, 2-(4-methoxyphenyl)-6-(morpholin-4-yl)pyran-4-one (16; DNA-PK; IC50 = nM) effectively sensitized HeLa cells to the topoisomerase II inhibitor etoposidein vitro."
],
"offsets": [
[
0,
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]
}
] | [
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"id": "entity-8-0",
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],
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170,
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},
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"id": "entity-8-3",
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"offsets": [
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192,
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],
"normalized": []
},
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"id": "entity-8-4",
"type": "FAMILY",
"text": [
"pyranones"
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254,
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],
"normalized": []
},
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"id": "entity-8-5",
"type": "FAMILY",
"text": [
"thiopyranones"
],
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268,
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},
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"id": "entity-8-9",
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],
"offsets": [
[
489,
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]
],
"normalized": []
},
{
"id": "entity-8-10",
"type": "IUPAC",
"text": [
"2-morpholino-pyran-4-ones"
],
"offsets": [
[
611,
636
]
],
"normalized": []
},
{
"id": "entity-8-11",
"type": "IUPAC",
"text": [
"2-morpholino-thiopyrano-4-ones"
],
"offsets": [
[
641,
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]
],
"normalized": []
},
{
"id": "entity-8-12",
"type": "IUPAC",
"text": [
"2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one"
],
"offsets": [
[
735,
781
]
],
"normalized": []
},
{
"id": "entity-8-13",
"type": "IUPAC",
"text": [
"2-(4-methoxyphenyl)-6-(morpholin-4-yl)pyran-4-one"
],
"offsets": [
[
932,
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]
],
"normalized": []
},
{
"id": "entity-8-14",
"type": "TRIVIAL",
"text": [
"etoposide"
],
"offsets": [
[
1078,
1087
]
],
"normalized": []
}
] | [] | [] | [] |
example-9 | 6780324 | [
{
"id": "passage-9",
"type": "abstract",
"text": [
" Differential effects of luteinizing hormone-releasing hormone on follicle-stimulating hormone-dependent responses in rat granulosa cells and Sertoli cells in vitro. The abilities of LHRH and a potent LHRH agonist ([D-Ser-(But),6, des-Gly-NH210]LHRH ethylamide) inhibit FSH responses by rat granulosa cells and Sertoli cells in vitro have been compared. Granulosa cells isolated from 22- or 25-day-old diethylstilbestrol-primed rats and cultured under defined conditions for 48 h with NIH-FSH-S13 ( ng/ml) or cholera toxin (0.1 microgram/ml) showed increased aromatase activity, as determined by the release of 3H2O from [1 beta-3H]testosterone. LHRH ( (-7) M) or th agonist ( (-8) M) added simultaneously with FSH or cholera toxin inhibited the effects on the release of 3H2O without influencing the protein content of the cell cultures. A smaller stimulation of 3H2O production occurred with (Bu)2cAMP (1.0 mM) plus 3-isobutyl-l-methylxanthine (0.1 mM), and this was partially suppressed in the presence of LHRH or the agonist. Parallel studies with Sertoli cells from 15- or -day-old rats demonstrated that culture under appropriate conditions with FSH, cholera toxin, or (Bu)2cAMP (0.5 mM) for 24 h caused an increase in cellular aromatase activity and enhanced secretion into the medium of plasminogen activator. However, no inhibition by LHRH ( (-7) or (-9) M) or the agonist ( (-6) or (-8) M) occurred when the peptides were added either simultaneously or 24 h before the stimulatory agent. Similarly, Sertoli cells from 11-day-old rats treated daily with LHRH agonist for 5 days in culture, showed no inhibition of aromatase activity after a 4-h stimulation with FSH or (Bu)2cAMP. FSH dose-response curves (0-300 ng/ml) for aromatase activity were shown to be similar after 5 days of culture with or without (-8) M LHRH agonist, indicating that the LHRH did not cause a shift in the sensitivity to FSH. The lack of inhibition was seen in Sertoli cell cultures maintained at 37 or 32 C. The enzyme digestion method used to isolated Sertoli cells was not responsible for the lack of effects of LHRH, since cell cultures prepared without the aid of proteolytic enzymes showed similar FSH stimulation of aromatase activity in the presence or absence of (-8) M agonist. Further, there was no evidence of degradation of the LHRH agonist when incubated with Sertoli cell cultures. From these studies, we conclude that 1) granulosa cells and Sertoli cells from immature rats differ in their responses to LHRH, and 2) the immature Sertoli cell is an unlikely target for a direct inhibiting influence of LHRH on spermatogenesis."
],
"offsets": [
[
0,
2652
]
]
}
] | [
{
"id": "entity-9-0",
"type": "",
"text": [
"[D-Ser-(But),6, des-Gly-NH210]LHRH ethylamide"
],
"offsets": [
[
224,
269
]
],
"normalized": []
},
{
"id": "entity-9-1",
"type": "TRIVIAL",
"text": [
"diethylstilbestrol"
],
"offsets": [
[
411,
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]
],
"normalized": []
},
{
"id": "entity-9-2",
"type": "TRIVIALVAR",
"text": [
"NIH-FSH-S13"
],
"offsets": [
[
494,
505
]
],
"normalized": []
},
{
"id": "entity-9-3",
"type": "TRIVIAL",
"text": [
"cholera toxin"
],
"offsets": [
[
521,
534
]
],
"normalized": []
},
{
"id": "entity-9-4",
"type": "IUPAC",
"text": [
"[1 beta-3H]testosterone"
],
"offsets": [
[
633,
656
]
],
"normalized": []
},
{
"id": "entity-9-5",
"type": "TRIVIAL",
"text": [
"cholera toxin"
],
"offsets": [
[
732,
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]
],
"normalized": []
},
{
"id": "entity-9-6",
"type": "SUM",
"text": [
"3H2O"
],
"offsets": [
[
786,
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]
],
"normalized": []
},
{
"id": "entity-9-7",
"type": "SUM",
"text": [
"3H2O"
],
"offsets": [
[
878,
882
]
],
"normalized": []
},
{
"id": "entity-9-8",
"type": "IUPAC",
"text": [
"(Bu)2cAMP"
],
"offsets": [
[
908,
917
]
],
"normalized": []
},
{
"id": "entity-9-9",
"type": "IUPAC",
"text": [
"3-isobutyl-l-methylxanthine"
],
"offsets": [
[
932,
959
]
],
"normalized": []
},
{
"id": "entity-9-10",
"type": "TRIVIAL",
"text": [
"cholera toxin"
],
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[
1173,
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]
],
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},
{
"id": "entity-9-11",
"type": "IUPAC",
"text": [
"(Bu)2cAMP"
],
"offsets": [
[
1191,
1200
]
],
"normalized": []
},
{
"id": "entity-9-12",
"type": "IUPAC",
"text": [
"(Bu)2cAMP"
],
"offsets": [
[
1700,
1709
]
],
"normalized": []
}
] | [] | [] | [] |
example-10 | 12672235 | [
{
"id": "passage-10",
"type": "abstract",
"text": [
"We have previously described (RS)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid (4-AHCP) as a highly effective agonist at non-N-methyl-d-aspartate (non-NMDA) glutamate (Glu) receptors in vivo, which is more potent than (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) but inactive at NMDA receptors. However, 4-AHCP was found to be much weaker than AMPA as an inhibitor of [(3)H]AMPA binding and to have limited effect in a [(3)H]kainic acid binding assay using rat cortical membranes. To shed light on the mechanism(s) underlying this quite enigmatic pharmacological profile of 4-AHCP, we have now developed a synthesis of (S)-4-AHCP (6) and (R)-4-AHCP (7). At cloned metabotropic Glu receptors mGluR1alpha (group I), mGluR2 (group II), and mGluR4a (group III), neither 6 nor 7 showed significant agonist or antagonist effects. The stereoisomer 6, but not 7, activated cloned AMPA receptor subunits GluR1o, GluR3o, and GluR4o with EC( ) values in the range 4.5-15 microM and the coexpressed kainate-preferring subunits GluR6 + KA2 (EC( ) = 6.4 microM). Compound 6, but not 7, proved to be a very potent agonist (EC( ) = 0.13 microM) at the kainate-preferring GluR5 subunit, equipotent with (S)-2-amino-3-(5-tert-butyl-3-hydroxyisothiazol-4-yl)propionic acid [(S)-Thio-ATPA, 4] and almost 4 times more potent than (S)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionic acid [(S)-ATPA, 3]. Compound 6 thus represents a new structural class of GluR5 agonists. Molecular modeling and docking to a crystal structure of the extracellular binding domain of the AMPAsubunit GluR2 has enabled identification of the probable active conformation and binding mode of 6. We are able to rationalize the observed selectivities by comparing the docking of 4 and 6 to subtype constructs, i.e., a crystal structure of the extracellular binding domain of GluR2 and a homology model of GluR5."
],
"offsets": [
[
0,
1936
]
]
}
] | [
{
"id": "entity-10-0",
"type": "IUPAC",
"text": [
"(RS)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid"
],
"offsets": [
[
29,
111
]
],
"normalized": []
},
{
"id": "entity-10-1",
"type": "ABBREVIATION",
"text": [
"4-AHCP"
],
"offsets": [
[
113,
119
]
],
"normalized": []
},
{
"id": "entity-10-2",
"type": "IUPAC",
"text": [
"(RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid"
],
"offsets": [
[
251,
313
]
],
"normalized": []
},
{
"id": "entity-10-3",
"type": "ABBREVIATION",
"text": [
"AMPA"
],
"offsets": [
[
315,
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]
],
"normalized": []
},
{
"id": "entity-10-4",
"type": "ABBREVIATION",
"text": [
"4-AHCP"
],
"offsets": [
[
362,
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]
],
"normalized": []
},
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"id": "entity-10-5",
"type": "ABBREVIATION",
"text": [
"AMPA"
],
"offsets": [
[
402,
406
]
],
"normalized": []
},
{
"id": "entity-10-6",
"type": "IUPAC",
"text": [
"[(3)H]AMPA"
],
"offsets": [
[
426,
436
]
],
"normalized": []
},
{
"id": "entity-10-7",
"type": "IUPAC",
"text": [
"[(3)H]kainic acid"
],
"offsets": [
[
477,
494
]
],
"normalized": []
},
{
"id": "entity-10-8",
"type": "ABBREVIATION",
"text": [
"4-AHCP"
],
"offsets": [
[
632,
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]
],
"normalized": []
},
{
"id": "entity-10-9",
"type": "ABBREVIATION",
"text": [
"(S)-4-AHCP"
],
"offsets": [
[
677,
687
]
],
"normalized": []
},
{
"id": "entity-10-10",
"type": "ABBREVIATION",
"text": [
"(R)-4-AHCP"
],
"offsets": [
[
696,
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]
],
"normalized": []
},
{
"id": "entity-10-11",
"type": "TRIVIAL",
"text": [
"kainate"
],
"offsets": [
[
1046,
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]
],
"normalized": []
},
{
"id": "entity-10-12",
"type": "TRIVIAL",
"text": [
"kainate"
],
"offsets": [
[
1197,
1204
]
],
"normalized": []
},
{
"id": "entity-10-13",
"type": "IUPAC",
"text": [
"(S)-2-amino-3-(5-tert-butyl-3-hydroxyisothiazol-4-yl)propionic acid"
],
"offsets": [
[
1247,
1314
]
],
"normalized": []
},
{
"id": "entity-10-14",
"type": "ABBREVIATION",
"text": [
"(S)-Thio-ATPA"
],
"offsets": [
[
1316,
1329
]
],
"normalized": []
},
{
"id": "entity-10-15",
"type": "IUPAC",
"text": [
"(S)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionic acid"
],
"offsets": [
[
1370,
1435
]
],
"normalized": []
},
{
"id": "entity-10-16",
"type": "ABBREVIATION",
"text": [
"(S)-ATPA"
],
"offsets": [
[
1437,
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]
],
"normalized": []
},
{
"id": "entity-10-17",
"type": "ABBREVIATION",
"text": [
"AMPA"
],
"offsets": [
[
1617,
1621
]
],
"normalized": []
}
] | [] | [] | [] |
example-11 | 7205876 | [
{
"id": "passage-11",
"type": "abstract",
"text": [
"The synthesis of aminoaceto-2',6'-xylidides substituted on the amide nitrogen with 2-(diethylamino)ethyl, 2-aminoethyl, 2-hydroxyethyl, and 2-ethoxyethyl groups is described. The 2-aminoethyl derivatives were prepared by treatment of N-(2-phthalimidoethyl)-2',6'-xylidine with chloroacetyl chloride, followed by treatment with either potassium phthalmide or diethylamine. Hydrazinolysis of the phthalimides liberated the free amines. The remaining target compounds were produced by alkylation of lidocaine or of 2-phthalimidoaceto-2',6'-xylidide with the appropriate halide and sodium hydride, followed by hydrazinolysis where necessary. All target compounds were evaluated for antiarrhythmic efficacy against chloroform-induced ventricular tachycardia, as well as for acute CNS toxicity in mice. Most of the target compounds were more potent than the corresponding secondary amides and had improved therapeutic margins toward CNS toxicity. The diamines N-(2-aminoethyl)-2-aminoaceto-2',6'-xylidide (13) and N-(2-aminoethyl)--2-(diethylamino)aceto-2',6'-xylidide( 29) are especially promising in this respect. Several compounds were tested as spinal anesthetics."
],
"offsets": [
[
0,
1162
]
]
}
] | [
{
"id": "entity-11-0",
"type": "IUPAC",
"text": [
"aminoaceto-2',6'-xylidides"
],
"offsets": [
[
17,
43
]
],
"normalized": []
},
{
"id": "entity-11-1",
"type": "MODIFIER",
"text": [
"substituted"
],
"offsets": [
[
44,
55
]
],
"normalized": []
},
{
"id": "entity-11-2",
"type": "FAMILY",
"text": [
"amide"
],
"offsets": [
[
63,
68
]
],
"normalized": []
},
{
"id": "entity-11-3",
"type": "TRIVIAL",
"text": [
"nitrogen"
],
"offsets": [
[
69,
77
]
],
"normalized": []
},
{
"id": "entity-11-4",
"type": "PARTIUPAC",
"text": [
"2-(diethylamino)ethyl"
],
"offsets": [
[
83,
104
]
],
"normalized": []
},
{
"id": "entity-11-5",
"type": "PARTIUPAC",
"text": [
"2-aminoethyl"
],
"offsets": [
[
106,
118
]
],
"normalized": []
},
{
"id": "entity-11-6",
"type": "PARTIUPAC",
"text": [
"2-hydroxyethyl"
],
"offsets": [
[
120,
134
]
],
"normalized": []
},
{
"id": "entity-11-7",
"type": "PARTIUPAC",
"text": [
"2-ethoxyethyl"
],
"offsets": [
[
140,
153
]
],
"normalized": []
},
{
"id": "entity-11-8",
"type": "MODIFIER",
"text": [
"groups"
],
"offsets": [
[
154,
160
]
],
"normalized": []
},
{
"id": "entity-11-9",
"type": "PARTIUPAC",
"text": [
"2-aminoethyl"
],
"offsets": [
[
179,
191
]
],
"normalized": []
},
{
"id": "entity-11-10",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
192,
203
]
],
"normalized": []
},
{
"id": "entity-11-11",
"type": "IUPAC",
"text": [
"N-(2-phthalimidoethyl)-2',6'-xylidine"
],
"offsets": [
[
234,
271
]
],
"normalized": []
},
{
"id": "entity-11-12",
"type": "IUPAC",
"text": [
"chloroacetyl chloride"
],
"offsets": [
[
277,
298
]
],
"normalized": []
},
{
"id": "entity-11-13",
"type": "IUPAC",
"text": [
"potassium phthalmide"
],
"offsets": [
[
334,
354
]
],
"normalized": []
},
{
"id": "entity-11-14",
"type": "TRIVIAL",
"text": [
"diethylamine"
],
"offsets": [
[
358,
370
]
],
"normalized": []
},
{
"id": "entity-11-15",
"type": "FAMILY",
"text": [
"phthalimides"
],
"offsets": [
[
394,
406
]
],
"normalized": []
},
{
"id": "entity-11-16",
"type": "FAMILY",
"text": [
"amines"
],
"offsets": [
[
426,
432
]
],
"normalized": []
},
{
"id": "entity-11-17",
"type": "TRIVIAL",
"text": [
"lidocaine"
],
"offsets": [
[
496,
505
]
],
"normalized": []
},
{
"id": "entity-11-18",
"type": "IUPAC",
"text": [
"2-phthalimidoaceto-2',6'-xylidide"
],
"offsets": [
[
512,
545
]
],
"normalized": []
},
{
"id": "entity-11-19",
"type": "PARTIUPAC",
"text": [
"halide"
],
"offsets": [
[
567,
573
]
],
"normalized": []
},
{
"id": "entity-11-20",
"type": "IUPAC",
"text": [
"sodium hydride"
],
"offsets": [
[
578,
592
]
],
"normalized": []
},
{
"id": "entity-11-21",
"type": "TRIVIAL",
"text": [
"chloroform"
],
"offsets": [
[
710,
720
]
],
"normalized": []
},
{
"id": "entity-11-22",
"type": "IUPAC",
"text": [
"N-(2-aminoethyl)-2-aminoaceto-2',6'-xylidide"
],
"offsets": [
[
954,
998
]
],
"normalized": []
},
{
"id": "entity-11-23",
"type": "IUPAC",
"text": [
"N-(2-aminoethyl)--2-(diethylamino)aceto-2',6'-xylidide"
],
"offsets": [
[
1008,
1062
]
],
"normalized": []
}
] | [] | [] | [] |
example-12 | 2104934 | [
{
"id": "passage-12",
"type": "abstract",
"text": [
"Some novel 6-fluoro-7-substituted-1,4-dihydro-4-oxoquinoline-3-carboxylic acids have been prepared. At the N-1 position \"standard\" substitution was employed with the ethyl, cyclopropyl, and p-fluorophenyl groups being used. At C-7 the introduction of some novel piperazines was made. Most notably, 2-(fluoromethyl)piperazine ( ) and hexahydro-6-fluoro-1H-1,4-diazepine (16, fluorohomopiperazine) at the quinolone C-7 position produced products with similar in vitro antibacterial activity as the ciprofloxacin reference. The in vivo efficacy of 1-cyclopropyl-6-fluoro-7-[3-(fluoromethyl)piperazinyl]-1,4-dihydro-4- oxoquinoline-3-carboxylic acid ( ) was excellent with better oral absorption than ciprofloxacin( 2)."
],
"offsets": [
[
0,
717
]
]
}
] | [
{
"id": "entity-12-0",
"type": "IUPAC",
"text": [
"6-fluoro-7-substituted-1,4-dihydro-4-oxoquinoline-3-carboxylic acids"
],
"offsets": [
[
11,
79
]
],
"normalized": []
},
{
"id": "entity-12-1",
"type": "PARTIUPAC",
"text": [
"ethyl"
],
"offsets": [
[
166,
171
]
],
"normalized": []
},
{
"id": "entity-12-2",
"type": "PARTIUPAC",
"text": [
"cyclopropyl"
],
"offsets": [
[
173,
184
]
],
"normalized": []
},
{
"id": "entity-12-3",
"type": "PARTIUPAC",
"text": [
"p-fluorophenyl"
],
"offsets": [
[
190,
204
]
],
"normalized": []
},
{
"id": "entity-12-4",
"type": "MODIFIER",
"text": [
"groups"
],
"offsets": [
[
205,
211
]
],
"normalized": []
},
{
"id": "entity-12-5",
"type": "FAMILY",
"text": [
"piperazines"
],
"offsets": [
[
262,
273
]
],
"normalized": []
},
{
"id": "entity-12-6",
"type": "IUPAC",
"text": [
"2-(fluoromethyl)piperazine"
],
"offsets": [
[
298,
324
]
],
"normalized": []
},
{
"id": "entity-12-7",
"type": "IUPAC",
"text": [
"hexahydro-6-fluoro-1H-1,4-diazepine"
],
"offsets": [
[
334,
369
]
],
"normalized": []
},
{
"id": "entity-12-8",
"type": "TRIVIAL",
"text": [
"fluorohomopiperazine"
],
"offsets": [
[
375,
395
]
],
"normalized": []
},
{
"id": "entity-12-9",
"type": "TRIVIAL",
"text": [
"quinolone"
],
"offsets": [
[
404,
413
]
],
"normalized": []
},
{
"id": "entity-12-10",
"type": "TRIVIAL",
"text": [
"ciprofloxacin"
],
"offsets": [
[
497,
510
]
],
"normalized": []
},
{
"id": "entity-12-11",
"type": "IUPAC",
"text": [
"1-cyclopropyl-6-fluoro-7-[3-(fluoromethyl)piperazinyl]-1,4-dihydro-4- oxoquinoline-3-carboxylic acid"
],
"offsets": [
[
546,
646
]
],
"normalized": []
},
{
"id": "entity-12-12",
"type": "TRIVIAL",
"text": [
"ciprofloxacin"
],
"offsets": [
[
699,
712
]
],
"normalized": []
}
] | [] | [] | [] |
example-13 | 2329575 | [
{
"id": "passage-13",
"type": "abstract",
"text": [
"The thermal Fischer indolization of hydrazones resulting from 4-hydrazino-5-methyl-1H-pyridin-2-one and various beta- and alpha-tetralones led to 4-methyl-6,7-dihydro-2H,5H-pyrido[4,3- b]benzo[e]indol-1-ones and 4-methyl-11-dihydro-2H,5H-pyrido[4,3- b]benzo[g]indol-1-ones, respectively. After aromatization, these compounds were transformed by phosphorus oxychloride, giving 1-chloro-4-methyl-5H-pyrido[4,3- b]benzo[e]- and -benzo[g]indoles which were substituted by [(dialkylamino)alkyl]amines. The resulting 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido- [4,3-b]benzo[e]- and -benzo[g]indoles, as well ashydroxy derivatives obtained by demethylation of methoxylated compounds with hydrobromic acid, were tested for antitumor activity in vitro (leukemic and solid tumor cells) and in vivo on various experimental tumor models using the standard NCI protocols. 1-[[3-(Dialkylamino)propyl]-amino]-4-methyl-9-hydroxy-5H-pyrido[4,3- b]benzo[e]indolesappeared as a promising new class of antineoplastic agents."
],
"offsets": [
[
0,
1013
]
]
}
] | [
{
"id": "entity-13-0",
"type": "FAMILY",
"text": [
"hydrazones"
],
"offsets": [
[
36,
46
]
],
"normalized": []
},
{
"id": "entity-13-1",
"type": "IUPAC",
"text": [
"4-hydrazino-5-methyl-1H-pyridin-2-one"
],
"offsets": [
[
62,
99
]
],
"normalized": []
},
{
"id": "entity-13-2",
"type": "PARTIUPAC",
"text": [
"beta-"
],
"offsets": [
[
112,
117
]
],
"normalized": []
},
{
"id": "entity-13-3",
"type": "IUPAC",
"text": [
"alpha-tetralones"
],
"offsets": [
[
122,
138
]
],
"normalized": []
},
{
"id": "entity-13-4",
"type": "IUPAC",
"text": [
"4-methyl-6,7-dihydro-2H,5H-pyrido[4,3- b]benzo[e]indol-1-ones"
],
"offsets": [
[
146,
207
]
],
"normalized": []
},
{
"id": "entity-13-5",
"type": "IUPAC",
"text": [
"4-methyl-11-dihydro-2H,5H-pyrido[4,3- b]benzo[g]indol-1-ones"
],
"offsets": [
[
212,
272
]
],
"normalized": []
},
{
"id": "entity-13-6",
"type": "IUPAC",
"text": [
"phosphorus oxychloride"
],
"offsets": [
[
345,
367
]
],
"normalized": []
},
{
"id": "entity-13-7",
"type": "PARTIUPAC",
"text": [
"1-chloro-4-methyl-5H-pyrido[4,3- b]benzo[e]-"
],
"offsets": [
[
376,
420
]
],
"normalized": []
},
{
"id": "entity-13-8",
"type": "PARTIUPAC",
"text": [
"-benzo[g]indoles"
],
"offsets": [
[
425,
441
]
],
"normalized": []
},
{
"id": "entity-13-9",
"type": "IUPAC",
"text": [
"[(dialkylamino)alkyl]amines"
],
"offsets": [
[
468,
495
]
],
"normalized": []
},
{
"id": "entity-13-10",
"type": "PARTIUPAC",
"text": [
"1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido- [4,3-b]benzo[e]-"
],
"offsets": [
[
511,
578
]
],
"normalized": []
},
{
"id": "entity-13-11",
"type": "PARTIUPAC",
"text": [
"-benzo[g]indoles"
],
"offsets": [
[
583,
599
]
],
"normalized": []
},
{
"id": "entity-13-12",
"type": "PARTIUPAC",
"text": [
" hydroxy"
],
"offsets": [
[
611,
619
]
],
"normalized": []
},
{
"id": "entity-13-13",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
620,
631
]
],
"normalized": []
},
{
"id": "entity-13-14",
"type": "IUPAC",
"text": [
"hydrobromic acid"
],
"offsets": [
[
689,
705
]
],
"normalized": []
},
{
"id": "entity-13-15",
"type": "IUPAC",
"text": [
"1-[[3-(Dialkylamino)propyl]-amino]-4-methyl-9-hydroxy-5H-pyrido[4,3- b]benzo[e]indoles"
],
"offsets": [
[
867,
953
]
],
"normalized": []
}
] | [] | [] | [] |
example-14 | 596853 | [
{
"id": "passage-14",
"type": "abstract",
"text": [
"596853 [Synthesis and properties of carminomycinone derivatives] The possibility of chemical modification of carminomycinone-aglycone (II) of carminomicin, a side product in the antibiotic production was studied. The methyl group C-14 was functionilized by introducing the bromine atom and performing a number of exchange reactions with the bromine atom. It was found that under definite conditions (1. 1 equiv. Br2in dioxane, degrees, 24 hours) carminomycinone (II) was subjected to selective bromination into the side acetyl group with formation of 14-bromcarminomycinone (III). On interaction with anhydrous potassium acetate 14-bromcarminomycinone (III) yield 14-acetoxycarminomycinone (IV). In its turn the latter compound (IV) easily hydrolized to 14-oxycarminomycinone (V) in treatment with aqueous alkali or acid. 14-oxycarminomycinone (V) was also prepared with a high yield ( per cent) by direct alkaline hydrolysis of 14-bromcarminomycinone (III) in treatment with 0.1N solution of sodium carbonate in a mixture of dioxane and water. The structure of 14-substituted derivatives of carminomycinone was proved by analytical and spectral data and confirmed by their transformation. Thus, according to the data of mass-spectrometry 14-oxycarminomycinone (V) had a molecular weight of c. u. In treatment with an excess of acetic anhydride in pyridine it formed a hexa-acetyl derivative, i.e. 4, 6, 7, 9, 11, 14-hexa-acetyl-14-oxycarminomycinone (VI). The aglycones (III-V) prepared by us may serve a starting material in chemical synthesis, as well as biosynthesis of semi-synthetic preparations of the carminomycin series."
],
"offsets": [
[
0,
1640
]
]
}
] | [
{
"id": "entity-14-0",
"type": "TRIVIAL",
"text": [
"carminomycinone"
],
"offsets": [
[
37,
52
]
],
"normalized": []
},
{
"id": "entity-14-1",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
53,
64
]
],
"normalized": []
},
{
"id": "entity-14-2",
"type": "TRIVIAL",
"text": [
"carminomycinone-aglycone"
],
"offsets": [
[
111,
135
]
],
"normalized": []
},
{
"id": "entity-14-3",
"type": "TRIVIAL",
"text": [
"carminomicin"
],
"offsets": [
[
144,
156
]
],
"normalized": []
},
{
"id": "entity-14-4",
"type": "PARTIUPAC",
"text": [
"methyl"
],
"offsets": [
[
219,
225
]
],
"normalized": []
},
{
"id": "entity-14-5",
"type": "MODIFIER",
"text": [
"group"
],
"offsets": [
[
226,
231
]
],
"normalized": []
},
{
"id": "entity-14-6",
"type": "SUM",
"text": [
"C-14"
],
"offsets": [
[
232,
236
]
],
"normalized": []
},
{
"id": "entity-14-7",
"type": "TRIVIAL",
"text": [
"bromine"
],
"offsets": [
[
275,
282
]
],
"normalized": []
},
{
"id": "entity-14-8",
"type": "MODIFIER",
"text": [
"atom"
],
"offsets": [
[
283,
287
]
],
"normalized": []
},
{
"id": "entity-14-9",
"type": "TRIVIAL",
"text": [
"bromine"
],
"offsets": [
[
343,
350
]
],
"normalized": []
},
{
"id": "entity-14-10",
"type": "MODIFIER",
"text": [
"atom"
],
"offsets": [
[
351,
355
]
],
"normalized": []
},
{
"id": "entity-14-11",
"type": "SUM",
"text": [
"Br2"
],
"offsets": [
[
414,
417
]
],
"normalized": []
},
{
"id": "entity-14-12",
"type": "TRIVIAL",
"text": [
"dioxane"
],
"offsets": [
[
420,
427
]
],
"normalized": []
},
{
"id": "entity-14-13",
"type": "TRIVIAL",
"text": [
"carminomycinone"
],
"offsets": [
[
451,
466
]
],
"normalized": []
},
{
"id": "entity-14-14",
"type": "TRIVIAL",
"text": [
"acetyl"
],
"offsets": [
[
525,
531
]
],
"normalized": []
},
{
"id": "entity-14-15",
"type": "MODIFIER",
"text": [
"group"
],
"offsets": [
[
532,
537
]
],
"normalized": []
},
{
"id": "entity-14-16",
"type": "IUPAC",
"text": [
"14-bromcarminomycinone"
],
"offsets": [
[
556,
578
]
],
"normalized": []
},
{
"id": "entity-14-17",
"type": "IUPAC",
"text": [
"potassium acetate 14-bromcarminomycinone"
],
"offsets": [
[
616,
656
]
],
"normalized": []
},
{
"id": "entity-14-18",
"type": "IUPAC",
"text": [
"14-acetoxycarminomycinone"
],
"offsets": [
[
669,
694
]
],
"normalized": []
},
{
"id": "entity-14-19",
"type": "IUPAC",
"text": [
"14-oxycarminomycinone"
],
"offsets": [
[
759,
780
]
],
"normalized": []
},
{
"id": "entity-14-20",
"type": "IUPAC",
"text": [
"14-oxycarminomycinone"
],
"offsets": [
[
827,
848
]
],
"normalized": []
},
{
"id": "entity-14-21",
"type": "IUPAC",
"text": [
"14-bromcarminomycinone"
],
"offsets": [
[
936,
958
]
],
"normalized": []
},
{
"id": "entity-14-22",
"type": "IUPAC",
"text": [
"sodium carbonate"
],
"offsets": [
[
1000,
1016
]
],
"normalized": []
},
{
"id": "entity-14-23",
"type": "TRIVIAL",
"text": [
"dioxane"
],
"offsets": [
[
1033,
1040
]
],
"normalized": []
},
{
"id": "entity-14-24",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
1084,
1095
]
],
"normalized": []
},
{
"id": "entity-14-25",
"type": "TRIVIAL",
"text": [
"carminomycinone"
],
"offsets": [
[
1099,
1114
]
],
"normalized": []
},
{
"id": "entity-14-26",
"type": "IUPAC",
"text": [
"14-oxycarminomycinone"
],
"offsets": [
[
1246,
1267
]
],
"normalized": []
},
{
"id": "entity-14-27",
"type": "IUPAC",
"text": [
"acetic anhydride"
],
"offsets": [
[
1339,
1355
]
],
"normalized": []
},
{
"id": "entity-14-28",
"type": "TRIVIAL",
"text": [
"pyridine"
],
"offsets": [
[
1359,
1367
]
],
"normalized": []
},
{
"id": "entity-14-29",
"type": "IUPAC",
"text": [
"hexa-acetyl"
],
"offsets": [
[
1380,
1391
]
],
"normalized": []
},
{
"id": "entity-14-30",
"type": "MODIFIER",
"text": [
"derivative"
],
"offsets": [
[
1392,
1402
]
],
"normalized": []
},
{
"id": "entity-14-31",
"type": "IUPAC",
"text": [
"4, 6, 7, 9, 11, 14-hexa-acetyl-14-oxycarminomycinone"
],
"offsets": [
[
1409,
1461
]
],
"normalized": []
},
{
"id": "entity-14-32",
"type": "FAMILY",
"text": [
"aglycones"
],
"offsets": [
[
1472,
1481
]
],
"normalized": []
},
{
"id": "entity-14-33",
"type": "TRIVIAL",
"text": [
"carminomycin"
],
"offsets": [
[
1620,
1632
]
],
"normalized": []
},
{
"id": "entity-14-34",
"type": "MODIFIER",
"text": [
"series"
],
"offsets": [
[
1633,
1639
]
],
"normalized": []
}
] | [] | [] | [] |
example-15 | 7040662 | [
{
"id": "passage-15",
"type": "abstract",
"text": [
"Adenosine 5'-triphosphate (ATP) derivatives of the types N6-R-ATP [R = (CH2)nNHCOCH2I, (CH2)nNHCO-(CH2)mNHCOCH2I, or (CH2)nCON(Me)(CH2)mN(Me)CO(CH2)nNHCOCH2I], N6-Me-N6-R-ATP [R = (CH2)nN-(Me)CO(CH2)mNHCOCH2I], and 8-R-ATP [R = NM(CH2)nNHCOCH2I] with 5--19 spacer atoms between N6 or C-8 and iodine have been evaluated as potential exo-ATP-site-directed reagents for phosphokinases. Substrate and inhibitor properties indicated that the compounds possessed affinity for the ATP sites of the muscle (M), kidney (K), and liver (L) isozymes of rat pyruvate kinase (PK), of E. coli thymidine kinase (TK), and of yeast hexokinase (HK) and rat KH I, II, and III isozymes. Tests for time-dependent loss of enzyme activity (inactivation) were performed under conditions in which a large proportion of each phosphokinase was present as an enzyme-inhibitor complex. No ATP-site-directed inactivations resulted when the M, L, or K isozymes of PK were exposed for 8 h, 22 degrees C, to 5 mM levels of 18 ATP derivatives or 6 analogous ADP derivatives or when yeast HK or rat KH I, II, or III was exposed for 6 h, 22 degrees C, to 5 mM levels of 28 ATP derivatives. Escherichia coli TK was inactivated by 6 of 25 ATP derivatives tested at mM, 6 h, 0 degrees C; inactivation was slowed by MgATP in the case of N6-CH3-N6-R-ATP [R = (CH2)4N(CH3)CO(CH2)5NHCOCH2I]. Only 1% of 298 enzyme-inhibitor combinations exhibited ATP-site-directed inactivation, signifying that few suitably positioned and sufficiently reactive nucleophilic groups were present near the enzymic ATPsites . Studies have now shown that exo-active-site-directed reagents can act as isozyme- or species-selective enzyme inhibitors. The present survey indicates that in many cases such reagents may be difficult of access when data are not available regarding structural or physicochemical features of the target enzyme adjacent to its catalytic site."
],
"offsets": [
[
0,
1905
]
]
}
] | [
{
"id": "entity-15-0",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
27,
30
]
],
"normalized": []
},
{
"id": "entity-15-1",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
32,
43
]
],
"normalized": []
},
{
"id": "entity-15-2",
"type": "ABBREVIATION",
"text": [
"N6-R-ATP"
],
"offsets": [
[
57,
65
]
],
"normalized": []
},
{
"id": "entity-15-3",
"type": "SUM",
"text": [
"(CH2)nNHCOCH2I"
],
"offsets": [
[
71,
85
]
],
"normalized": []
},
{
"id": "entity-15-4",
"type": "SUM",
"text": [
"(CH2)nNHCO-(CH2)mNHCOCH2I"
],
"offsets": [
[
87,
112
]
],
"normalized": []
},
{
"id": "entity-15-5",
"type": "SUM",
"text": [
"(CH2)nCON(Me)(CH2)mN(Me)CO(CH2)nNHCOCH2I"
],
"offsets": [
[
117,
157
]
],
"normalized": []
},
{
"id": "entity-15-6",
"type": "ABBREVIATION",
"text": [
"N6-Me-N6-R-ATP"
],
"offsets": [
[
160,
174
]
],
"normalized": []
},
{
"id": "entity-15-7",
"type": "SUM",
"text": [
"(CH2)nN-(Me)CO(CH2)mNHCOCH2I"
],
"offsets": [
[
180,
208
]
],
"normalized": []
},
{
"id": "entity-15-8",
"type": "ABBREVIATION",
"text": [
"8-R-ATP"
],
"offsets": [
[
215,
222
]
],
"normalized": []
},
{
"id": "entity-15-9",
"type": "SUM",
"text": [
"NM(CH2)nNHCOCH2I"
],
"offsets": [
[
228,
244
]
],
"normalized": []
},
{
"id": "entity-15-10",
"type": "TRIVIAL",
"text": [
"iodine"
],
"offsets": [
[
292,
298
]
],
"normalized": []
},
{
"id": "entity-15-11",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
336,
339
]
],
"normalized": []
},
{
"id": "entity-15-12",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
474,
477
]
],
"normalized": []
},
{
"id": "entity-15-13",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
859,
862
]
],
"normalized": []
},
{
"id": "entity-15-14",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
992,
995
]
],
"normalized": []
},
{
"id": "entity-15-15",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
996,
1007
]
],
"normalized": []
},
{
"id": "entity-15-16",
"type": "ABBREVIATION",
"text": [
"ADP"
],
"offsets": [
[
1023,
1026
]
],
"normalized": []
},
{
"id": "entity-15-17",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
1027,
1038
]
],
"normalized": []
},
{
"id": "entity-15-18",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
1136,
1139
]
],
"normalized": []
},
{
"id": "entity-15-19",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
1140,
1151
]
],
"normalized": []
},
{
"id": "entity-15-20",
"type": "ABBREVIATION",
"text": [
"MgATP"
],
"offsets": [
[
1278,
1283
]
],
"normalized": []
},
{
"id": "entity-15-21",
"type": "ABBREVIATION",
"text": [
"N6-CH3-N6-R-ATP"
],
"offsets": [
[
1299,
1314
]
],
"normalized": []
},
{
"id": "entity-15-22",
"type": "SUM",
"text": [
"(CH2)4N(CH3)CO(CH2)5NHCOCH2I"
],
"offsets": [
[
1320,
1348
]
],
"normalized": []
},
{
"id": "entity-15-23",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
1406,
1409
]
],
"normalized": []
},
{
"id": "entity-15-24",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
1554,
1557
]
],
"normalized": []
}
] | [] | [] | [] |
example-16 | 2944474 | [
{
"id": "passage-16",
"type": "abstract",
"text": [
"2944474 Effect of recombinant human fibroblast interferon and mezerein on growth, differentiation, immune interferon binding and tumor associated antigen expression in human melanoma cells. The combination of recombinant human fibroblast interferon (INF-delta) and the antileukemic compound mezerein (MEZ) results in a synergistic suppression in the growth of human melanoma cells and a concomitant increase in melanin synthesis. In the present study we have further analyzed this synergistic interaction and have also evaluated the effect of IFN-delta and MEZ, alone and in combination, on recombinant human gamma interferon (IFN-gamma) binding and Class I HLA and melanoma associated antigen (MAA) expression in the HO-1 human melanoma cell line. Single cell clones isolated from the HO-1 cell line varied in their sensitivity to the antiproliferative effects of IFN-delta and MEZ. With all twelve clones, however, the combination of IFN-delta plus MEZ was more growth inhibitory than either agent used alone, even in HO-1 subclones displaying relative resistance to IFN-delta. By continuous growth in gradually increasing concentrations of IFN-delta, a variant population of HO-1 cells, HO-1 delta R-D, was generated which was more resistant to the antigrowth effects of IFN-delta than the original HO-1 parental cell line. In the IFN delta R-D cell line the combination of IFN-delta plus MEZ synergistically suppressed growth. Exposure of HO-1 cells to units/ml IFN-delta or ng/ml MEZ for 96 hr resulted in no change or an increase in the binding of labelled IFN-gamma to surface receptors, whereas the combination of IFN-delta plus MEZ increased IFN-gamma binding 2-to-4-fold in HO-1 cells. This increase was the result of an increase in the number of receptors on treated cells coupled with a protection against a decrease in receptors observed for confluent untreated cells. Changes in IFN-gamma binding resulting from treatment with IFN-delta plus MEZ were not associated with alterations in the binding affinity of INF-gamma to its receptor. Changes were also observed in the expression of HLA Class I antigens and MAAs following treatment of HO-1 cells with IFN-delta, MEZ or IFN-delta plus MEZ. IFN-delta and MEZincreased the expression of HLA Class I antigens a 96 kd MAA defined by MoAb CL203, a kd MAA defined by MoAb 376.96 and a 115 kd MAA defined by MoAb 345.134 but decreased the expression of a high molecular weight-melanoma associated antigen (HMW-MAA) defined by MoAb 325.28S.(ABSTRACT TRUNCATED AT WORDS)"
],
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"MEZ"
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"MEZ"
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"MEZ"
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"type": "ABBREVIATION",
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"MEZ"
],
"offsets": [
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2230,
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]
],
"normalized": []
}
] | [] | [] | [] |
example-17 | 16033265 | [
{
"id": "passage-17",
"type": "abstract",
"text": [
"Degarelix (FE200486, Ac-d-2Nal(1)-d-4Cpa(2)-d-3Pal(3)-Ser(4)-4Aph(l-Hor)(5)-d-4Aph(Cbm)(6)-Leu(7)-ILys(8)-Pro(9)-d-Ala( )-NH(2)) is a potent and very long acting antagonist of gonadotropin-releasing hormone (GnRH) after subcutaneous administration in mammals including humans. Analogues of degarelix were synthesized, characterized, and screened for the antagonism of GnRH-induced response in a reporter gene assay in HEK-293 cells expressing the human GnRH receptor. The duration of action was also determined in the castrated male rat assay to measure the extent (efficacy and duration of action) of inhibition of luteinizing hormone (LH) release. Structurally, this series of analogues has novel substitutions at positions 3, 7, and 8 and N(alpha)-methylation at positions 6, 7, and 8 in the structure of degarelix. These substitutions were designed to probe the spatial limitations of the receptor's cavity and to map the steric and ionic boundaries. Some functional groups were introduced that were hypothesized to influence the phamacokinetic properties of the analogues such as bioavailability, solubility, intra- or intermolecular hydrogen bond forming capacity, and ability to bind carrier proteins. Substitutions at positions 3 ([N(beta)-(2-pyridyl-methyl)d-Dap(3)]degarelix, IC( ) = 2.71 nM) (5), 7 ([Pra(7)]degarelix, IC( ) = 2.11 nM) (16), and 8 ([N(delta)-(IGly)Orn(8)]degarelix, IC( ) = 1.38 nM) ( ) and N-methylation ([N(alpha)-methyl-Leu(7)]degarelix, IC( ) = 1.47 nM) (32) yielded analogues that were equipotent to degarelix (2) in vitro (IC( ) = 1.64 nM) but shorter acting in vivo. Out of the 33 novel analogues tested for the duration of action in this series, two analogues ([N(epsilon)-cyclohexyl-Lys(8)]degarelix, IC( ) = 1.50 nM) (23) and ([N(beta)-(IbetaAla)Dap(8)]degarelix, IC( ) = 1.98 nM) (26) had antagonist potencies and duration of action similar to that of azaline B {inhibited LH (> ) release for >72 h after sc injection to castrated male rats at a standard dose of mug/rat in 5% mannitol}. Under similar conditions analogues ([N(gamma)-(IGly)Dab(8)]degarelix, IC( ) = 1.56 nM) (21) and ([IOrn(8)]degarelix, IC( ) = 1.72 nM) (18) had a longer duration of action {inhibited LH (>96 h) release} than azaline B; however they were shorter acting than degarelix. Hydrophilicity of these analogues, a potential measure of their ability to be formulated for sustained release, was determined using RP-HPLC at neutral pH yielding analogues with shorter as well as longer retention times. No correlation was found between retention times and antagonist potency or duration of action."
],
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0,
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"text": [
"Ac-d-2Nal(1)-d-4Cpa(2)-d-3Pal(3)-Ser(4)-4Aph(l-Hor)(5)-d-4Aph(Cbm)(6)-Leu(7)-ILys(8)-Pro(9)-d-Ala(10)-NH(2)"
],
"offsets": [
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21,
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]
],
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{
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"degarelix"
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]
],
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{
"id": "entity-17-3",
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"degarelix"
],
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[
809,
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]
],
"normalized": []
},
{
"id": "entity-17-4",
"type": "IUPAC",
"text": [
"[N(beta)-(2-pyridyl-methyl)d-Dap(3)]degarelix"
],
"offsets": [
[
1240,
1285
]
],
"normalized": []
},
{
"id": "entity-17-5",
"type": "TRIVIAL",
"text": [
"[Pra(7)]degarelix"
],
"offsets": [
[
1313,
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]
],
"normalized": []
},
{
"id": "entity-17-6",
"type": "IUPAC",
"text": [
"[N(delta)-(IGly)Orn(8)]degarelix"
],
"offsets": [
[
1363,
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]
],
"normalized": []
},
{
"id": "entity-17-7",
"type": "IUPAC",
"text": [
"[N(alpha)-methyl-Leu(7)]degarelix"
],
"offsets": [
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1439,
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]
],
"normalized": []
},
{
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],
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1539,
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],
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},
{
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"type": "IUPAC",
"text": [
"[N(epsilon)-cyclohexyl-Lys(8)]degarelix"
],
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1704,
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]
],
"normalized": []
},
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"[N(beta)-(IbetaAla)Dap(8)]degarelix"
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1773,
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],
"normalized": []
},
{
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"azaline B"
],
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1900,
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]
],
"normalized": []
},
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"type": "IUPAC",
"text": [
"[N(gamma)-(IGly)Dab(8)]degarelix"
],
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]
],
"normalized": []
},
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"type": "IUPAC",
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"[IOrn(8)]degarelix"
],
"offsets": [
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]
],
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},
{
"id": "entity-17-14",
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],
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"text": [
"degarelix"
],
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2308,
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],
"normalized": []
}
] | [] | [] | [] |
example-18 | 16329601 | [
{
"id": "passage-18",
"type": "abstract",
"text": [
" [Method of determination of biogenic amines in wines by high-performance liquid chromatography with fluorescence detector and ultraviolet detector] OBJECTIVE: A pre-column derivation reversed-phase high-performance liquid chromatography method was developed for the determination of biogenic amines (tryptamine, phenylethyamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine) in wines with fluorescecse detector (FLD) and ultraviolet detector (UVD). METHODS: Liqiud-liqiud extraction (LLE) was used to clean up wine samples with chloroform/butanol prior to derivatization with dansyl chloride, biogenic amines were separated using gradient elution. Mobile phase A was methanol and mobile phase B was water with the flow rate 1.5 ml/min. The column used was a CAPCELL PAK C18 MG (4.6 mm I.D. x mm, 5 microm) and gradient elution at constant column tempereture with degrees C under fluorescence detector with Ex and Em , The method and ultraviolet detector with 254nm. 1,7-Diaminoheptane was used as the internal standard (IS). RESULTS: was linear for the amines studied at concentration ranging from 0.05 to 25 mg/L, except for spermidine and spermine, which ranging from 0.05 to 15 mg/L. The average recoveries ranged from 79.2% to 127.5% for all amines, The RSDs were less than . With this method, 5 wine samples were determined, the results were favorable. CONCLUTION: method can be applied for determination of biogenic amines in wines."
],
"offsets": [
[
0,
1495
]
]
}
] | [
{
"id": "entity-18-0",
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"text": [
"amines"
],
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[
47,
53
]
],
"normalized": []
},
{
"id": "entity-18-1",
"type": "TRIVIAL",
"text": [
"tryptamine"
],
"offsets": [
[
311,
321
]
],
"normalized": []
},
{
"id": "entity-18-2",
"type": "TRIVIAL",
"text": [
"phenylethyamine"
],
"offsets": [
[
323,
338
]
],
"normalized": []
},
{
"id": "entity-18-3",
"type": "TRIVIAL",
"text": [
"putrescine"
],
"offsets": [
[
340,
350
]
],
"normalized": []
},
{
"id": "entity-18-4",
"type": "TRIVIAL",
"text": [
"cadaverine"
],
"offsets": [
[
352,
362
]
],
"normalized": []
},
{
"id": "entity-18-5",
"type": "TRIVIAL",
"text": [
"histamine"
],
"offsets": [
[
364,
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]
],
"normalized": []
},
{
"id": "entity-18-6",
"type": "TRIVIAL",
"text": [
"tyramine"
],
"offsets": [
[
375,
383
]
],
"normalized": []
},
{
"id": "entity-18-7",
"type": "TRIVIAL",
"text": [
"spermidine"
],
"offsets": [
[
385,
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]
],
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"id": "entity-18-8",
"type": "TRIVIAL",
"text": [
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401,
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"normalized": []
},
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"text": [
"chloroform"
],
"offsets": [
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564,
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]
],
"normalized": []
},
{
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"text": [
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],
"offsets": [
[
575,
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]
],
"normalized": []
},
{
"id": "entity-18-11",
"type": "IUPAC",
"text": [
"dansyl chloride"
],
"offsets": [
[
612,
627
]
],
"normalized": []
},
{
"id": "entity-18-12",
"type": "IUPAC",
"text": [
"1,7-Diaminoheptane"
],
"offsets": [
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1020,
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]
],
"normalized": []
},
{
"id": "entity-18-13",
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],
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"type": "TRIVIAL",
"text": [
"spermine"
],
"offsets": [
[
1195,
1203
]
],
"normalized": []
}
] | [] | [] | [] |
example-19 | 3656362 | [
{
"id": "passage-19",
"type": "abstract",
"text": [
"The isomeric 4-(3-chloro-4-hydroxyphenyl)- and 4-(4-chloro-3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinolines, the N-methyl derivative of the 4-(4-chloro-3-hydroxyphenyl) isomer, and 4-(3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline were synthesized and evaluated for dopamine D-1 antagonist activity. The 4-(3-chloro-4-hydroxyphenyl) and the 4-(3-hydroxyphenyl) isomer possessed similar potencies as D-1 antagonists. Introduction of the N-methyl group enhanced potency about twofold. The \"pharmacophore\" for selective dopamine D-1 antagonist activity appears to be a tertiary 2-(3-hydroxyphenyl)-2-phenethylamine."
],
"offsets": [
[
0,
613
]
]
}
] | [
{
"id": "entity-19-0",
"type": "PARTIUPAC",
"text": [
"4-(3-chloro-4-hydroxyphenyl)-"
],
"offsets": [
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13,
42
]
],
"normalized": []
},
{
"id": "entity-19-1",
"type": "IUPAC",
"text": [
"4-(4-chloro-3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinolines"
],
"offsets": [
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47,
107
]
],
"normalized": []
},
{
"id": "entity-19-2",
"type": "PARTIUPAC",
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],
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113,
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],
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},
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"id": "entity-19-3",
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"derivative"
],
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122,
132
]
],
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},
{
"id": "entity-19-4",
"type": "IUPAC",
"text": [
"4-(4-chloro-3-hydroxyphenyl)"
],
"offsets": [
[
140,
168
]
],
"normalized": []
},
{
"id": "entity-19-5",
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"text": [
"isomer"
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169,
175
]
],
"normalized": []
},
{
"id": "entity-19-6",
"type": "IUPAC",
"text": [
"4-(3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline"
],
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181,
231
]
],
"normalized": []
},
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"id": "entity-19-7",
"type": "IUPAC",
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"4-(3-chloro-4-hydroxyphenyl)"
],
"offsets": [
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305,
333
]
],
"normalized": []
},
{
"id": "entity-19-8",
"type": "IUPAC",
"text": [
"4-(3-hydroxyphenyl)"
],
"offsets": [
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342,
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],
"normalized": []
},
{
"id": "entity-19-9",
"type": "MODIFIER",
"text": [
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362,
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]
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},
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"id": "entity-19-10",
"type": "PARTIUPAC",
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437,
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"id": "entity-19-11",
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446,
451
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],
"normalized": []
},
{
"id": "entity-19-12",
"type": "IUPAC",
"text": [
"2-(3-hydroxyphenyl)-2-phenethylamine"
],
"offsets": [
[
576,
612
]
],
"normalized": []
}
] | [] | [] | [] |
example-20 | 14998335 | [
{
"id": "passage-20",
"type": "abstract",
"text": [
"In a continuing effort to design small-molecule inhibitors of dihydrofolate reductase (DHFR) that combine the enzyme-binding selectivity of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine (trimethoprim, TMP) with the potency of 2,4-diamino-5-methyl-6-(2',5'-dimethoxybenzyl)pyrido[2,3-d]pyrimidine (piritrexim, PTX), seven previously undescribed 2,4-diamino-5-[2'-methoxy-5'-(substituted benzyl)]pyrimidines were synthesized in which the substituent at the 5'-position was a carboxyphenyl group linked to the benzyl moiety by a bridge of two or four atoms in length. The new analogues were all obtained from 2,4-diamino-5-(5'-iodo-2'-methoxybenzyl)pyrimidine via a Sonogashira reaction, followed, where appropriate, by catalytic hydrogenation. The new analogues were tested as inhibitors of DHFR from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), and Mycobacterium avium (Ma), three life-threatening pathogens often found in AIDS patients and individuals whose immune system is impaired as a result of treatment with immunosuppressive chemotherapy or radiation. The selectivity index (SI) of each compound was obtained by dividing its inhibitory concentration (IC( )) against Pc, Tg, or Ma DHFR by its IC( ) against rat DHFR. 2,4-Diamino-[2'-methoxy-5'-(3-carboxyphenyl)ethynylbenzyl]pyrimidine (28), with an IC( ) of 23 nM and an SI of 28 in the Pc DHFR assay, had about the same potency as PTX and was times more potent than TMP. As an inhibitor of Tg DHFR, 28 had an IC( ) of 5.5 nM ( -fold lower than that of TMP and similar to that of PTX) and an SI value of (2-fold better than TMP and vastly superior to PTX). Against Ma DHFR, 28 had IC( ) and SI values of 1.5 nM and , respectively, compared with nM and for TMP. Although it had 2.5-fold lower potency than 28 against Ma DHFR (IC( ) = 3.7 nM) and was substantially weaker against Pc and Tg DHFR, 2,4-diamino-[2'-methoxy-5'-(4-carboxyphenyl)ethynylbenzyl]pyrimidine (29), with the carboxy group at the para rather than the meta position, displayed -fold selectivity against the Ma enzyme and was the most selective 2,4-diamino-5-(5'-substituted benzyl)pyrimidineinhibitor of this enzyme we have encountered to date. Additional bioassay data for these compounds are also reported."
],
"offsets": [
[
0,
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]
}
] | [
{
"id": "entity-20-0",
"type": "IUPAC",
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"2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine"
],
"offsets": [
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140,
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]
],
"normalized": []
},
{
"id": "entity-20-1",
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193,
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]
],
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},
{
"id": "entity-20-2",
"type": "ABBREVIATION",
"text": [
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],
"offsets": [
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207,
210
]
],
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},
{
"id": "entity-20-3",
"type": "IUPAC",
"text": [
"2,4-diamino-5-methyl-6-(2',5'-dimethoxybenzyl)pyrido[2,3-d]pyrimidine"
],
"offsets": [
[
232,
301
]
],
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},
{
"id": "entity-20-4",
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],
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303,
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],
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},
{
"id": "entity-20-5",
"type": "ABBREVIATION",
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"PTX"
],
"offsets": [
[
315,
318
]
],
"normalized": []
},
{
"id": "entity-20-6",
"type": "IUPAC",
"text": [
"2,4-diamino-5-[2'-methoxy-5'-(substituted benzyl)]pyrimidines"
],
"offsets": [
[
350,
411
]
],
"normalized": []
},
{
"id": "entity-20-7",
"type": "PARTIUPAC",
"text": [
"carboxyphenyl"
],
"offsets": [
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479,
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]
],
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},
{
"id": "entity-20-8",
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},
{
"id": "entity-20-9",
"type": "PARTIUPAC",
"text": [
"benzyl"
],
"offsets": [
[
513,
519
]
],
"normalized": []
},
{
"id": "entity-20-10",
"type": "MODIFIER",
"text": [
"moiety"
],
"offsets": [
[
520,
526
]
],
"normalized": []
},
{
"id": "entity-20-11",
"type": "IUPAC",
"text": [
"2,4-diamino-5-(5'-iodo-2'-methoxybenzyl)pyrimidine"
],
"offsets": [
[
612,
662
]
],
"normalized": []
},
{
"id": "entity-20-12",
"type": "IUPAC",
"text": [
"2,4-Diamino-[2'-methoxy-5'-(3-carboxyphenyl)ethynylbenzyl]pyrimidine"
],
"offsets": [
[
1241,
1309
]
],
"normalized": []
},
{
"id": "entity-20-13",
"type": "ABBREVIATION",
"text": [
"PTX"
],
"offsets": [
[
1408,
1411
]
],
"normalized": []
},
{
"id": "entity-20-14",
"type": "ABBREVIATION",
"text": [
"TMP"
],
"offsets": [
[
1447,
1450
]
],
"normalized": []
},
{
"id": "entity-20-15",
"type": "ABBREVIATION",
"text": [
"TMP"
],
"offsets": [
[
1536,
1539
]
],
"normalized": []
},
{
"id": "entity-20-16",
"type": "ABBREVIATION",
"text": [
"PTX"
],
"offsets": [
[
1563,
1566
]
],
"normalized": []
},
{
"id": "entity-20-17",
"type": "ABBREVIATION",
"text": [
"TMP"
],
"offsets": [
[
1611,
1614
]
],
"normalized": []
},
{
"id": "entity-20-18",
"type": "ABBREVIATION",
"text": [
"PTX"
],
"offsets": [
[
1638,
1641
]
],
"normalized": []
},
{
"id": "entity-20-19",
"type": "ABBREVIATION",
"text": [
"TMP"
],
"offsets": [
[
1755,
1758
]
],
"normalized": []
},
{
"id": "entity-20-20",
"type": "IUPAC",
"text": [
"2,4-diamino-[2'-methoxy-5'-(4-carboxyphenyl)ethynylbenzyl]pyrimidine"
],
"offsets": [
[
1894,
1962
]
],
"normalized": []
},
{
"id": "entity-20-21",
"type": "TRIVIAL",
"text": [
"carboxy"
],
"offsets": [
[
1978,
1985
]
],
"normalized": []
},
{
"id": "entity-20-22",
"type": "MODIFIER",
"text": [
"group"
],
"offsets": [
[
1986,
1991
]
],
"normalized": []
},
{
"id": "entity-20-23",
"type": "IUPAC",
"text": [
"2,4-diamino-5-(5'-substituted benzyl)pyrimidine"
],
"offsets": [
[
2116,
2163
]
],
"normalized": []
}
] | [] | [] | [] |
example-21 | 9120816 | [
{
"id": "passage-21",
"type": "abstract",
"text": [
" Parenteral hydroxypropyl cyclodextrins: intravenous and intracerebral administration of lipophiles. Hydroxypropyl cyclodextrins are nontoxic carbohydrate derivatives of moderate molecular weight ( Da) which form water-soluble complexes with many lipophiles. The fate of hydroxypropyl beta-cyclodextrin alone and in complex with testosterone or cholesterol injected intravenously or intracerebrally into rats was followed. More than of intravenously administered hydroxypropyl beta-cyclodextrin was cleared into urine in 4 h, as previously described (Monbaliu, J.; Van Beijsterveld, L.; Meuldermans, W.; Szathmary, S.; Haykants, J. Abstracts, 5th International Symposium on Cyclodextrins, Paris, ; Abstract 65). After the injection of steroids in complex with hydroxypropyl beta-cyclodextrin into the tail vein of rats, the steroid component was released from the complex, before it reached the kidneys; the release occurred mainly into the proteins and lipoproteins of serum. Hydroxypropyl beta-cyclodextrins injected alone into the brain were cleared within less than 24 h, presumably via the flow of interstitial and cerebrospinal fluids, and eventually were excreted in urine. Testosterone, incorporated in a hydroxypropyl beta-cyclodextrin complex, after intracerebral injection was cleared from the brain even more rapidly than hydroxypropyl beta-cyclodextrin, presumably by crossing the blood-brain barrier and later removal to the liver by the specific carrier proteins in serum. Complexed cholesterol, in a similar experiment, was largely retained in the brain and its distribution there was uneven and remained that way for at least 3 days. It is clear that lipophilic agents, after their incorporation into hydroxypropyl beta-cyclodextrin complexes and subsequent in vivo administration, are rapidly released and exchanged into the plasma. In absence of plasma they enter tissues surrounding the injection site and thus are also promptly transferred into the organism's lipid systems. The manner in which different lipophilic agents are transported in vivo appears not to be greatly affected by their previous complexation; rather hydroxypropyl cyclodextrinsjust enable their entry in a larger amount and in an exchangeable, nonaggregated form."
],
"offsets": [
[
0,
2282
]
]
}
] | [
{
"id": "entity-21-0",
"type": "IUPAC",
"text": [
"hydroxypropyl cyclodextrins"
],
"offsets": [
[
20,
47
]
],
"normalized": []
},
{
"id": "entity-21-1",
"type": "IUPAC",
"text": [
"Hydroxypropyl cyclodextrins"
],
"offsets": [
[
110,
137
]
],
"normalized": []
},
{
"id": "entity-21-2",
"type": "FAMILY",
"text": [
"carbohydrate"
],
"offsets": [
[
151,
163
]
],
"normalized": []
},
{
"id": "entity-21-3",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
164,
175
]
],
"normalized": []
},
{
"id": "entity-21-4",
"type": "IUPAC",
"text": [
"hydroxypropyl beta-cyclodextrin"
],
"offsets": [
[
289,
320
]
],
"normalized": []
},
{
"id": "entity-21-5",
"type": "TRIVIAL",
"text": [
"testosterone"
],
"offsets": [
[
347,
359
]
],
"normalized": []
},
{
"id": "entity-21-6",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
"offsets": [
[
363,
374
]
],
"normalized": []
},
{
"id": "entity-21-7",
"type": "IUPAC",
"text": [
"hydroxypropyl beta-cyclodextrin"
],
"offsets": [
[
485,
516
]
],
"normalized": []
},
{
"id": "entity-21-8",
"type": "TRIVIAL",
"text": [
"Cyclodextrins"
],
"offsets": [
[
696,
709
]
],
"normalized": []
},
{
"id": "entity-21-9",
"type": "IUPAC",
"text": [
"hydroxypropyl beta-cyclodextrin"
],
"offsets": [
[
786,
817
]
],
"normalized": []
},
{
"id": "entity-21-10",
"type": "IUPAC",
"text": [
"Hydroxypropyl beta-cyclodextrins"
],
"offsets": [
[
1003,
1035
]
],
"normalized": []
},
{
"id": "entity-21-11",
"type": "TRIVIAL",
"text": [
"Testosterone"
],
"offsets": [
[
1207,
1219
]
],
"normalized": []
},
{
"id": "entity-21-12",
"type": "IUPAC",
"text": [
"hydroxypropyl beta-cyclodextrin"
],
"offsets": [
[
1239,
1270
]
],
"normalized": []
},
{
"id": "entity-21-13",
"type": "MODIFIER",
"text": [
"complex"
],
"offsets": [
[
1271,
1278
]
],
"normalized": []
},
{
"id": "entity-21-14",
"type": "IUPAC",
"text": [
"hydroxypropyl beta-cyclodextrin"
],
"offsets": [
[
1360,
1391
]
],
"normalized": []
},
{
"id": "entity-21-15",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
"offsets": [
[
1524,
1535
]
],
"normalized": []
},
{
"id": "entity-21-16",
"type": "IUPAC",
"text": [
"hydroxypropyl beta-cyclodextrin"
],
"offsets": [
[
1744,
1775
]
],
"normalized": []
},
{
"id": "entity-21-17",
"type": "MODIFIER",
"text": [
"complexes"
],
"offsets": [
[
1776,
1785
]
],
"normalized": []
},
{
"id": "entity-21-18",
"type": "FAMILY",
"text": [
"lipid"
],
"offsets": [
[
2007,
2012
]
],
"normalized": []
},
{
"id": "entity-21-19",
"type": "IUPAC",
"text": [
"hydroxypropyl cyclodextrins"
],
"offsets": [
[
2168,
2195
]
],
"normalized": []
}
] | [] | [] | [] |
example-22 | 6264792 | [
{
"id": "passage-22",
"type": "abstract",
"text": [
"6264792 Inhibition of renin secretion by intrarenal alpha-adrenoceptor blockade. This study was designed to determine whether renal alpha-adrenoceptors can mediate tonic neural stimulation of renin secretion. The effect of alpha-adrenoceptor blockade by phenoxybenzamine (POB) or prazosin on renin secretion rate (RSR) was studied in pentobarbital-anesthetized dogs in which renal perfusion pressure was held constant with an adjustable aortic clamp. POB alone ( micrograms.kg-1.min-1 iv) did not change arterial plasma renin activity (PRA). However, when beta-adrenoceptors were blocked by intravenous propranolol, intravenous POB infusion ( micrograms.kg-1.min-1) decreased PRA and RSR to 48 +/- 8 and 21 +/- 9% of previous levels within min. This effect was abolished by acute bilateral renal denervation. Direct intrarenal POB infusion ( or 3.3 micrograms.kg-1.min-1) decreased RSR, whereas intravenous POB (3.3 micrograms.kg-1.min-1) had no effect on either RSR or PRA in propranolol-pretreated dogs. Prazosin (1 microgram.kg-1.min-1 iv) also significantly decreased PRA. These data indicate that when beta-adrenoceptors are blocked by propranolol, tonic neural stimulation of renin secretion is mediated by renal alpha-adrenoceptors."
],
"offsets": [
[
0,
1252
]
]
}
] | [
{
"id": "entity-22-0",
"type": "TRIVIAL",
"text": [
"phenoxybenzamine"
],
"offsets": [
[
256,
272
]
],
"normalized": []
},
{
"id": "entity-22-1",
"type": "ABBREVIATION",
"text": [
"POB"
],
"offsets": [
[
274,
277
]
],
"normalized": []
},
{
"id": "entity-22-2",
"type": "TRIVIAL",
"text": [
"prazosin"
],
"offsets": [
[
282,
290
]
],
"normalized": []
},
{
"id": "entity-22-3",
"type": "TRIVIAL",
"text": [
"pentobarbital"
],
"offsets": [
[
336,
349
]
],
"normalized": []
},
{
"id": "entity-22-4",
"type": "ABBREVIATION",
"text": [
"POB"
],
"offsets": [
[
453,
456
]
],
"normalized": []
},
{
"id": "entity-22-5",
"type": "TRIVIAL",
"text": [
"propranolol"
],
"offsets": [
[
608,
619
]
],
"normalized": []
},
{
"id": "entity-22-6",
"type": "ABBREVIATION",
"text": [
"POB"
],
"offsets": [
[
633,
636
]
],
"normalized": []
},
{
"id": "entity-22-7",
"type": "ABBREVIATION",
"text": [
"POB"
],
"offsets": [
[
838,
841
]
],
"normalized": []
},
{
"id": "entity-22-8",
"type": "ABBREVIATION",
"text": [
"POB"
],
"offsets": [
[
920,
923
]
],
"normalized": []
},
{
"id": "entity-22-9",
"type": "TRIVIAL",
"text": [
"propranolol"
],
"offsets": [
[
990,
1001
]
],
"normalized": []
},
{
"id": "entity-22-10",
"type": "TRIVIAL",
"text": [
"Prazosin"
],
"offsets": [
[
1019,
1027
]
],
"normalized": []
},
{
"id": "entity-22-11",
"type": "TRIVIAL",
"text": [
"propranolol"
],
"offsets": [
[
1154,
1165
]
],
"normalized": []
}
] | [] | [] | [] |
example-23 | 5808825 | [
{
"id": "passage-23",
"type": "abstract",
"text": [
" Metabolism of D- and L-glyceraldehyde in adipose tissue: a stereochemical probe for glycerokinase activity. Distributions of (14)C have been determined in free glycerol, in glycerol from triglycerides, in glucose from glycogen, and in lactate after incubation of d-glyceraldehyde-3-(14)C andl -glyceraldehyde-3-(14)C with rat adipose tissue. The distributions are interpreted in terms of presently accepted possible reactions for the initial metabolism of glyceraldehyde. Formation of glycerol-1-(14)C fromd -glyceraldehyde-3-(14)C indicates that in adipose tissue glyceraldehyde is reduced to glycerol. Incorporation of (14)C from d-glyceraldehyde-3-(14)C into carbon 3 of the glycerol of triglyceride indicates thatd -glyceraldehyde is either phosphorylated or oxidized to d-glyceric acid, or both, in its initial metabolism. Incorporation of (14)C froml -glyceraldehyde-3-(14)C into carbon 3 of glycerol indicates that l-glyceraldehyde is reduced to glycerol, which is phosphorylated and (or) converted to d-glyceric acid via l-glyceric acid. Some (14)C from l-glyceraldehyde-3-(14)C is incorporated into carbon 1 of glycerol of triglycerides and carbon 4 of glycogen; the explanation for this incorporation is uncertain."
],
"offsets": [
[
0,
1234
]
]
}
] | [
{
"id": "entity-23-0",
"type": "IUPAC",
"text": [
"D-"
],
"offsets": [
[
23,
25
]
],
"normalized": []
},
{
"id": "entity-23-1",
"type": "IUPAC",
"text": [
"L-glyceraldehyde"
],
"offsets": [
[
30,
46
]
],
"normalized": []
},
{
"id": "entity-23-2",
"type": "SUM",
"text": [
"(14)C"
],
"offsets": [
[
135,
140
]
],
"normalized": []
},
{
"id": "entity-23-3",
"type": "TRIVIAL",
"text": [
"glycerol"
],
"offsets": [
[
170,
178
]
],
"normalized": []
},
{
"id": "entity-23-4",
"type": "TRIVIAL",
"text": [
"glycerol"
],
"offsets": [
[
183,
191
]
],
"normalized": []
},
{
"id": "entity-23-5",
"type": "FAMILY",
"text": [
"triglycerides"
],
"offsets": [
[
197,
210
]
],
"normalized": []
},
{
"id": "entity-23-6",
"type": "TRIVIAL",
"text": [
"glucose"
],
"offsets": [
[
215,
222
]
],
"normalized": []
},
{
"id": "entity-23-7",
"type": "TRIVIAL",
"text": [
"glycogen"
],
"offsets": [
[
228,
236
]
],
"normalized": []
},
{
"id": "entity-23-8",
"type": "IUPAC",
"text": [
"d-glyceraldehyde-3-(14)C"
],
"offsets": [
[
273,
297
]
],
"normalized": []
},
{
"id": "entity-23-9",
"type": "IUPAC",
"text": [
" l-glyceraldehyde-3-(14)C"
],
"offsets": [
[
301,
326
]
],
"normalized": []
},
{
"id": "entity-23-10",
"type": "TRIVIAL",
"text": [
"glyceraldehyde"
],
"offsets": [
[
466,
480
]
],
"normalized": []
},
{
"id": "entity-23-11",
"type": "IUPAC",
"text": [
"glycerol-1-(14)C"
],
"offsets": [
[
495,
511
]
],
"normalized": []
},
{
"id": "entity-23-12",
"type": "IUPAC",
"text": [
" d-glyceraldehyde-3-(14)C"
],
"offsets": [
[
516,
541
]
],
"normalized": []
},
{
"id": "entity-23-13",
"type": "TRIVIAL",
"text": [
"glyceraldehyde"
],
"offsets": [
[
575,
589
]
],
"normalized": []
},
{
"id": "entity-23-14",
"type": "TRIVIAL",
"text": [
"glycerol"
],
"offsets": [
[
604,
612
]
],
"normalized": []
},
{
"id": "entity-23-15",
"type": "SUM",
"text": [
"(14)C"
],
"offsets": [
[
631,
636
]
],
"normalized": []
},
{
"id": "entity-23-16",
"type": "IUPAC",
"text": [
"d-glyceraldehyde-3-(14)C"
],
"offsets": [
[
642,
666
]
],
"normalized": []
},
{
"id": "entity-23-17",
"type": "TRIVIAL",
"text": [
"carbon"
],
"offsets": [
[
672,
678
]
],
"normalized": []
},
{
"id": "entity-23-18",
"type": "TRIVIAL",
"text": [
"glycerol"
],
"offsets": [
[
688,
696
]
],
"normalized": []
},
{
"id": "entity-23-19",
"type": "FAMILY",
"text": [
"triglyceride"
],
"offsets": [
[
700,
712
]
],
"normalized": []
},
{
"id": "entity-23-20",
"type": "IUPAC",
"text": [
" d-glyceraldehyde"
],
"offsets": [
[
727,
744
]
],
"normalized": []
},
{
"id": "entity-23-21",
"type": "IUPAC",
"text": [
"d-glyceric acid"
],
"offsets": [
[
785,
800
]
],
"normalized": []
},
{
"id": "entity-23-22",
"type": "SUM",
"text": [
"(14)C"
],
"offsets": [
[
855,
860
]
],
"normalized": []
},
{
"id": "entity-23-23",
"type": "IUPAC",
"text": [
" l-glyceraldehyde-3-(14)C"
],
"offsets": [
[
865,
890
]
],
"normalized": []
},
{
"id": "entity-23-24",
"type": "TRIVIAL",
"text": [
"carbon"
],
"offsets": [
[
896,
902
]
],
"normalized": []
},
{
"id": "entity-23-25",
"type": "TRIVIAL",
"text": [
"glycerol"
],
"offsets": [
[
908,
916
]
],
"normalized": []
},
{
"id": "entity-23-26",
"type": "IUPAC",
"text": [
"l-glyceraldehyde"
],
"offsets": [
[
932,
948
]
],
"normalized": []
},
{
"id": "entity-23-27",
"type": "TRIVIAL",
"text": [
"glycerol"
],
"offsets": [
[
963,
971
]
],
"normalized": []
},
{
"id": "entity-23-28",
"type": "IUPAC",
"text": [
"d-glyceric acid"
],
"offsets": [
[
1019,
1034
]
],
"normalized": []
},
{
"id": "entity-23-29",
"type": "IUPAC",
"text": [
"l-glyceric acid"
],
"offsets": [
[
1039,
1054
]
],
"normalized": []
},
{
"id": "entity-23-30",
"type": "SUM",
"text": [
"(14)C"
],
"offsets": [
[
1061,
1066
]
],
"normalized": []
},
{
"id": "entity-23-31",
"type": "IUPAC",
"text": [
"l-glyceraldehyde-3-(14)C"
],
"offsets": [
[
1072,
1096
]
],
"normalized": []
},
{
"id": "entity-23-32",
"type": "TRIVIAL",
"text": [
"carbon"
],
"offsets": [
[
1118,
1124
]
],
"normalized": []
},
{
"id": "entity-23-33",
"type": "TRIVIAL",
"text": [
"glycerol"
],
"offsets": [
[
1130,
1138
]
],
"normalized": []
},
{
"id": "entity-23-34",
"type": "FAMILY",
"text": [
"triglycerides"
],
"offsets": [
[
1142,
1155
]
],
"normalized": []
},
{
"id": "entity-23-35",
"type": "TRIVIAL",
"text": [
"carbon"
],
"offsets": [
[
1160,
1166
]
],
"normalized": []
},
{
"id": "entity-23-36",
"type": "TRIVIAL",
"text": [
"glycogen"
],
"offsets": [
[
1172,
1180
]
],
"normalized": []
}
] | [] | [] | [] |
example-24 | 12553880 | [
{
"id": "passage-24",
"type": "abstract",
"text": [
" Attenuation of glucocorticoid functions in an Anx-A1-/- cell line. The Ca(2+)- and phospholipid-binding protein Anx-A1 (annexin 1; lipocortin 1) has been described both as an inhibitor of phospholipase A(2) (PLA(2)) activity and as a mediator of glucocorticoid-regulated cell growth and eicosanoid generation. Here we show that, when compared with Anx-A1(+/+) cells, lung fibroblast cell lines derived from the Anx-A1(-/-) mouse exhibit an altered morphology characterized by a spindle-shaped appearance and an accumulation of intracellular organelles. Unlike their wild-type counterparts, Anx-A1(-/-) cells also overexpress cyclo-oxygenase 2 (COX 2), cytosolic PLA(2) and secretory PLA(2) and in response to fetal calf serum, exhibit an exaggerated release of eicosanoids, which is insensitive to dexamethasone ( (-8)- (-6) M) inhibition. Proliferation and serum-induced progression of Anx-A1(+/+) cells from G(0)/G(1) into S phase, and the associated expression of extracellular signal-regulated kinase 2 (ERK2), cyclin-dependent kinase 4 (cdk4) and COX 2, is strongly inhibited by dexamethasone, whereas Anx-A1(-/-) cells are refractory to the drug. Loss of the response to dexamethasone in Anx-A1(-/-) cells occurs against a background of no apparent change in glucocorticoid receptor expression or sensitivity to non-steroidal anti-inflammatory drugs. Taken together, these observations suggest strongly that Anx-A1 functions as an inhibitor of signal-transduction pathways that lead to cell proliferation and may help to explain how glucocorticoidsregulate these processes."
],
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[
0,
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}
] | [
{
"id": "entity-24-0",
"type": "FAMILY",
"text": [
"glucocorticoid"
],
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[
25,
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{
"id": "entity-24-1",
"type": "FAMILY",
"text": [
"glucocorticoid"
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[
257,
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{
"id": "entity-24-2",
"type": "TRIVIAL",
"text": [
"eicosanoid"
],
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[
298,
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],
"normalized": []
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{
"id": "entity-24-3",
"type": "TRIVIAL",
"text": [
"eicosanoids"
],
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[
772,
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"id": "entity-24-4",
"type": "TRIVIAL",
"text": [
"dexamethasone"
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[
809,
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"normalized": []
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{
"id": "entity-24-5",
"type": "TRIVIAL",
"text": [
"dexamethasone"
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"id": "entity-24-6",
"type": "FAMILY",
"text": [
"glucocorticoids"
],
"offsets": [
[
1553,
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],
"normalized": []
}
] | [] | [] | [] |
example-25 | 14591846 | [
{
"id": "passage-25",
"type": "abstract",
"text": [
"14591846 Cognitive assessment of geriatric schizophrenic patients with severe impairment. There is evidence that some elderly patients with chronic schizophrenia experience marked impairments in cognitive functioning. Assessment of these patients may be difficult with traditional neuropsychological measures. The purpose of the present study was to determine if cognitive functioning could be validly assessed with the Alzheimer's Disease Assessment Scale-Late Version Cognitive factor score (ADAS-L Cog) in patients whose scores on the Mini-Mental State Examination (MMSE) reflect profound cognitive impairment. Patients with MMSE scores from 0 to were selected from a larger database. Neuropsychological instruments designed for the assessment of mild to moderate dementia were found to be inadequate in this profoundly impaired population, due to floor effects. In contrast, there was a significant relationship between ADAS-L scores and several criterion measures, including the MMSE (R=-.71, P<.001), the Social Adaptive Functions Evaluation (SAFE) social functions scale (R=.47, P<.001), and the negative symptom total score of the Positive and Negative Syndrome Scale (PANSS) (R=.412, P<.001). The MMSE was somewhat less strongly correlated with both social functions (R=-.401, P<.001) and the negative symptom total score of the PANSS (R=-.366, P<.001). These results suggest that cognition can be reliably and validly assessed with instruments such as the ADAS-L that are designed for the assessment of severely impaired patients."
],
"offsets": [
[
0,
1545
]
]
}
] | [] | [] | [] | [] |
example-26 | 721701 | [
{
"id": "passage-26",
"type": "abstract",
"text": [
" Evidence for messenger ribonucleic acid of an ammonium-inducible glutamate dehydrogenase and synthesis, covalent modification, and degradation of enzyme subunits in uninduced Chlorella sorokiniana cells. The cells of Chlorella sorokiniana cultured in nitrate medium contain no detectable catalytic activity of an ammonium-inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH). However, several lines of experimental evidence indicated that the NADP-GDH messenger ribonucleic acid was present at high levels and was being translated in uninduced cells. First, binding studies with 125I-labeled anti-NADP-GDH immunoglobulin G and total polysomes isolated from uninduced and induced cells showed that NADP-GDH subunits were being synthesized on polysomes from both types of cells. Second, when polyadenylic acid-containing ribonucleic acid was extracted from polysomes from uninduced and induced cells and placed into a messenger ribonucleic acid-dependent in vitro translation system, NADP-GDH subunits were synthesized from the ribonucleic acid from both sources. Third, when ammonia was added to uninduced cells, NADP-GDH antigen accumulated without an apparent induction lag. Fourth, by use of a specific immunoprecipitation procedure coupled to pulse-chase studies with [35S]sulfate, it was shown that the NADP-GDH subunits are rapidly synthesized, covalently modified, and then degraded in uninduced cells."
],
"offsets": [
[
0,
1463
]
]
}
] | [
{
"id": "entity-26-0",
"type": "TRIVIAL",
"text": [
"nitrate"
],
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[
261,
268
]
],
"normalized": []
},
{
"id": "entity-26-1",
"type": "IUPAC",
"text": [
"polyadenylic acid"
],
"offsets": [
[
845,
862
]
],
"normalized": []
},
{
"id": "entity-26-2",
"type": "FAMILY",
"text": [
"ammonia"
],
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[
1129,
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]
],
"normalized": []
},
{
"id": "entity-26-3",
"type": "IUPAC",
"text": [
"[35S]sulfate"
],
"offsets": [
[
1326,
1338
]
],
"normalized": []
}
] | [] | [] | [] |
example-27 | 1350435 | [
{
"id": "passage-27",
"type": "abstract",
"text": [
" Nucleotide regulation of heat-stable enterotoxin receptor binding and of guanylate cyclase activation. Certain nucleotides were found to regulate the binding of the Escherichia coli heat-stable enterotoxin (STa) to its receptor in pig intestinal brush border membranes. ATP and adenine nucleotide analogues inhibited 125I-STa binding, while guanine nucleotide analogues stimulated binding, with maximal effects at 0.5-1.0 mM. The strongest inhibitors were adenosine 5'-[beta gamma-imido]triphosphate (App[NH]p) (36%) and adenosine 5'-[beta-thio]diphosphate (ADP[S]) (41%). Inhibition did not require Mg2+, and was blocked by p-chloromercuribenzenesulphonate (PCMBS). Stimulation of binding required Mg2+, was not prevented by PCMBS and was maximal with GDP[S] (41%). While App[NH]p and MgGDP[S] appeared to be acting at different sites, they also interfered with each other. These nucleotides exerted only inhibitory effects on STa-stimulated guanylate cyclase activity, in contrast with the stimulatory effects of adenine nucleotides on atrial natriuretic peptide (ANP)-stimulated guanylate cyclase. Inhibition by low concentrations ofMgApp [NH]p and MgATP was weaker above 0.1 mM, while MgGDP[S] and magnesium guanosine 5'-[gamma-thio]triphosphate (MgGTP[S]) inhibited in a single phase. Inhibition by MgApp[NH]p, at all concentrations, was competitive with the substrate (MgGTP), as was that by MgGDP[S] and MgGTP[S]. Whereas membrane guanylate cyclases usually show positively co-operative kinetics with respect to the substrate, STa-stimulated activity exhibited Michaelis-Menten kinetics with respect to MgGTP. This changed to positive co-operativity when Lubrol PX was the activator, or when the substrate was MnGTP. These results suggest the presence of both a regulatory and a catalytic nucleotide-binding site, which do not interact co-operatively with STa activation."
],
"offsets": [
[
0,
1888
]
]
}
] | [
{
"id": "entity-27-0",
"type": "FAMILY",
"text": [
"Nucleotide"
],
"offsets": [
[
9,
19
]
],
"normalized": []
},
{
"id": "entity-27-1",
"type": "FAMILY",
"text": [
"nucleotides"
],
"offsets": [
[
121,
132
]
],
"normalized": []
},
{
"id": "entity-27-2",
"type": "ABBREVIATION",
"text": [
"ATP"
],
"offsets": [
[
280,
283
]
],
"normalized": []
},
{
"id": "entity-27-3",
"type": "TRIVIAL",
"text": [
"adenine"
],
"offsets": [
[
288,
295
]
],
"normalized": []
},
{
"id": "entity-27-4",
"type": "FAMILY",
"text": [
"nucleotide"
],
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[
296,
306
]
],
"normalized": []
},
{
"id": "entity-27-5",
"type": "MODIFIER",
"text": [
"analogues"
],
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[
307,
316
]
],
"normalized": []
},
{
"id": "entity-27-6",
"type": "TRIVIAL",
"text": [
"guanine"
],
"offsets": [
[
351,
358
]
],
"normalized": []
},
{
"id": "entity-27-7",
"type": "FAMILY",
"text": [
"nucleotide"
],
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[
359,
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]
],
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},
{
"id": "entity-27-8",
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"text": [
"analogues"
],
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[
370,
379
]
],
"normalized": []
},
{
"id": "entity-27-9",
"type": "IUPAC",
"text": [
"adenosine 5'-[beta gamma-imido]triphosphate"
],
"offsets": [
[
466,
509
]
],
"normalized": []
},
{
"id": "entity-27-10",
"type": "ABBREVIATION",
"text": [
"App[NH]p"
],
"offsets": [
[
511,
519
]
],
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},
{
"id": "entity-27-11",
"type": "IUPAC",
"text": [
"adenosine 5'-[beta-thio]diphosphate"
],
"offsets": [
[
531,
566
]
],
"normalized": []
},
{
"id": "entity-27-12",
"type": "ABBREVIATION",
"text": [
"ADP[S]"
],
"offsets": [
[
568,
574
]
],
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},
{
"id": "entity-27-13",
"type": "SUM",
"text": [
"Mg2+"
],
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[
610,
614
]
],
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},
{
"id": "entity-27-14",
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"p-chloromercuribenzenesulphonate"
],
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[
635,
667
]
],
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},
{
"id": "entity-27-15",
"type": "ABBREVIATION",
"text": [
"PCMBS"
],
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[
669,
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]
],
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},
{
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"text": [
"Mg2+"
],
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709,
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],
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},
{
"id": "entity-27-17",
"type": "ABBREVIATION",
"text": [
"PCMBS"
],
"offsets": [
[
736,
741
]
],
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},
{
"id": "entity-27-18",
"type": "ABBREVIATION",
"text": [
"GDP[S]"
],
"offsets": [
[
763,
769
]
],
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},
{
"id": "entity-27-19",
"type": "ABBREVIATION",
"text": [
"App[NH]p"
],
"offsets": [
[
783,
791
]
],
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},
{
"id": "entity-27-20",
"type": "ABBREVIATION",
"text": [
"MgGDP[S]"
],
"offsets": [
[
796,
804
]
],
"normalized": []
},
{
"id": "entity-27-21",
"type": "FAMILY",
"text": [
"nucleotides"
],
"offsets": [
[
891,
902
]
],
"normalized": []
},
{
"id": "entity-27-22",
"type": "TRIVIAL",
"text": [
"adenine"
],
"offsets": [
[
1025,
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]
],
"normalized": []
},
{
"id": "entity-27-23",
"type": "ABBREVIATION",
"text": [
" MgApp[NH]p"
],
"offsets": [
[
1146,
1157
]
],
"normalized": []
},
{
"id": "entity-27-24",
"type": "ABBREVIATION",
"text": [
"MgATP"
],
"offsets": [
[
1162,
1167
]
],
"normalized": []
},
{
"id": "entity-27-25",
"type": "ABBREVIATION",
"text": [
"MgGDP[S]"
],
"offsets": [
[
1199,
1207
]
],
"normalized": []
},
{
"id": "entity-27-26",
"type": "IUPAC",
"text": [
"magnesium guanosine 5'-[gamma-thio]triphosphate"
],
"offsets": [
[
1212,
1259
]
],
"normalized": []
},
{
"id": "entity-27-27",
"type": "ABBREVIATION",
"text": [
"MgGTP[S]"
],
"offsets": [
[
1261,
1269
]
],
"normalized": []
},
{
"id": "entity-27-28",
"type": "ABBREVIATION",
"text": [
"MgApp[NH]p"
],
"offsets": [
[
1314,
1324
]
],
"normalized": []
},
{
"id": "entity-27-29",
"type": "ABBREVIATION",
"text": [
"MgGTP"
],
"offsets": [
[
1385,
1390
]
],
"normalized": []
},
{
"id": "entity-27-30",
"type": "ABBREVIATION",
"text": [
"MgGDP[S]"
],
"offsets": [
[
1408,
1416
]
],
"normalized": []
},
{
"id": "entity-27-31",
"type": "ABBREVIATION",
"text": [
"MgGTP[S]"
],
"offsets": [
[
1421,
1429
]
],
"normalized": []
},
{
"id": "entity-27-32",
"type": "ABBREVIATION",
"text": [
"MgGTP"
],
"offsets": [
[
1620,
1625
]
],
"normalized": []
},
{
"id": "entity-27-33",
"type": "TRIVIAL",
"text": [
"Lubrol PX"
],
"offsets": [
[
1672,
1681
]
],
"normalized": []
},
{
"id": "entity-27-34",
"type": "ABBREVIATION",
"text": [
"MnGTP"
],
"offsets": [
[
1727,
1732
]
],
"normalized": []
}
] | [] | [] | [] |
example-28 | 6292417 | [
{
"id": "passage-28",
"type": "abstract",
"text": [
"The syntheses of (3RS,4RS)-4-hydroxypiperidine-3-carboxylic acid (4), (3RS,5SR)-5-hydroxypiperidine-3-carboxylic acid ( ), (3RS,4SR)-4-acetamidopiperidine-3-carboxylic acid ( ), and (3RS,5SR)-5-acetamidopiperidine-3-carboxylic acid (18), related to the specific gamma-aminobutyric acid (GABA) uptake inhibitors (RS)-piperidine-3-carboxylic acid (nipecotic acid) and (3RS,4SR)-4-hydroxypiperidine-3-carboxylic acid (21), are described. Furthermore, (3RS,4SR)-3-hydroxypiperidine-4-carboxylic acid (14), related to the specific GABA agonist piperidine-4-carboxylic acid (isonipecotic acid), has been synthesized. The structures of 4, , 14, 18, and have been established by -MHz 1H NMR spectroscopic analyses. The affinity of the compounds for the GABA receptors and for the neuronal (synaptosomal) GABA uptake system in vitro has been measured. Compound 14 interacts selectively with the GABA receptors but less effectively than isonipecotic acid and the cis-isomer 22. Compounds 4, 18, and are inhibitors of the GABA uptake system, although much weaker than nipecotic acid and (3RS,4SR)-4-hydroxypiperidine-3-carboxylic acid( 21). Compound is inactive in both test systems."
],
"offsets": [
[
0,
1188
]
]
}
] | [
{
"id": "entity-28-0",
"type": "IUPAC",
"text": [
"(3RS,4RS)-4-hydroxypiperidine-3-carboxylic acid"
],
"offsets": [
[
17,
64
]
],
"normalized": []
},
{
"id": "entity-28-1",
"type": "IUPAC",
"text": [
"(3RS,5SR)-5-hydroxypiperidine-3-carboxylic acid"
],
"offsets": [
[
70,
117
]
],
"normalized": []
},
{
"id": "entity-28-2",
"type": "IUPAC",
"text": [
"(3RS,4SR)-4-acetamidopiperidine-3-carboxylic acid"
],
"offsets": [
[
124,
173
]
],
"normalized": []
},
{
"id": "entity-28-3",
"type": "IUPAC",
"text": [
"(3RS,5SR)-5-acetamidopiperidine-3-carboxylic acid"
],
"offsets": [
[
184,
233
]
],
"normalized": []
},
{
"id": "entity-28-4",
"type": "IUPAC",
"text": [
"gamma-aminobutyric acid"
],
"offsets": [
[
264,
287
]
],
"normalized": []
},
{
"id": "entity-28-5",
"type": "ABBREVIATION",
"text": [
"GABA"
],
"offsets": [
[
289,
293
]
],
"normalized": []
},
{
"id": "entity-28-6",
"type": "IUPAC",
"text": [
"(RS)-piperidine-3-carboxylic acid"
],
"offsets": [
[
313,
346
]
],
"normalized": []
},
{
"id": "entity-28-7",
"type": "IUPAC",
"text": [
"nipecotic acid"
],
"offsets": [
[
348,
362
]
],
"normalized": []
},
{
"id": "entity-28-8",
"type": "IUPAC",
"text": [
"(3RS,4SR)-4-hydroxypiperidine-3-carboxylic acid"
],
"offsets": [
[
368,
415
]
],
"normalized": []
},
{
"id": "entity-28-9",
"type": "IUPAC",
"text": [
"(3RS,4SR)-3-hydroxypiperidine-4-carboxylic acid"
],
"offsets": [
[
450,
497
]
],
"normalized": []
},
{
"id": "entity-28-10",
"type": "ABBREVIATION",
"text": [
"GABA"
],
"offsets": [
[
528,
532
]
],
"normalized": []
},
{
"id": "entity-28-11",
"type": "IUPAC",
"text": [
"piperidine-4-carboxylic acid"
],
"offsets": [
[
541,
569
]
],
"normalized": []
},
{
"id": "entity-28-12",
"type": "IUPAC",
"text": [
"isonipecotic acid"
],
"offsets": [
[
571,
588
]
],
"normalized": []
},
{
"id": "entity-28-13",
"type": "ABBREVIATION",
"text": [
"GABA"
],
"offsets": [
[
806,
810
]
],
"normalized": []
},
{
"id": "entity-28-14",
"type": "IUPAC",
"text": [
"isonipecotic acid"
],
"offsets": [
[
937,
954
]
],
"normalized": []
},
{
"id": "entity-28-15",
"type": "ABBREVIATION",
"text": [
"GABA"
],
"offsets": [
[
1024,
1028
]
],
"normalized": []
},
{
"id": "entity-28-16",
"type": "IUPAC",
"text": [
"nipecotic acid"
],
"offsets": [
[
1070,
1084
]
],
"normalized": []
},
{
"id": "entity-28-17",
"type": "IUPAC",
"text": [
"(3RS,4SR)-4-hydroxypiperidine-3-carboxylic acid"
],
"offsets": [
[
1089,
1136
]
],
"normalized": []
}
] | [] | [] | [] |
example-29 | 16946562 | [
{
"id": "passage-29",
"type": "abstract",
"text": [
"16946562 Novel genetic variations and haplotypes of hepatocyte nuclear factor 4alpha (HNF4A) found in Japanese type II diabetic patients. Thirty-nine single nucleotide variations, including 16 novel ones, were found in the 5' promoter region, all of the exons and their surrounding introns of HNF4A in 74 Japanese type II diabetic patients. The following novel variations were identified (based on the amino acid numbering of splicing variant 2): - >C in the 5' promoter region; 1154C>T (A385V) and 1193T>C (M398T) in the coding exons; >A, 1852G>T, >T, >A, and 2362_2380delAAGAATGGTGTGGGAGAGG in the 3'-untranslated region, and IVS1+231G>A, IVS2-83C>T, IVS3+ >T, IVS3-54delC, IVS5+173_176delTTAG, IVS5-181_- , IVS8- >G, and IVS9-151A>C in the introns. The allele frequencies were 0.311 for 2362_2380delAAGAATGGTGTGGGAGAGG, 0.054 for >A, 0.047 for 1852G>T, 0.020 for IVS1+231G>A, 0.014 for IVS9-151A>C, and 0.007 for the other 11 variations. In addition, one known nonsynonymous single nucleotide polymorphism, 416C>T (T139I), was detected at a 0.007 frequency. Based on the linkage disequilibrium profiles, the region analyzed was divided into three blocks. Haplotype analysis determined/inferred , 16, and 12 haplotypes for block 1, 2, and 3, respectively. Our results on HNF4A variations and haplotypes would be useful for pharmacogenetic studies in Japanese."
],
"offsets": [
[
0,
1400
]
]
}
] | [] | [] | [] | [] |
example-30 | 15620433 | [
{
"id": "passage-30",
"type": "abstract",
"text": [
" Predictive clinical parameters for therapeutic efficacy of rosiglitazone in Korean type 2 diabetes mellitus. This study evaluated the efficacy of rosiglitazone in non-obese and obese Korean type 2 diabetic patients of long duration. A total of 125 patients (M:F=44:81, mean age: 58.4+/-9.1 years, BMI: 24.2+/-2.7 kg/m2, duration of diabetes: 11.0+/-6.4 years) were randomly allocated to 12 weeks of rosiglitazone treatment (4 mg per day) or a control group. Responders were defined as patients who experienced fasting plasma glucose (FPG) reduction of > or HbA1c reduction of >1 (%). Rosiglitazone significantly improved glycemic control by reducing FPG and HbA1c (-3.4 mmol/l and -1.1%, P<0.001, respectively). It also significantly increased HOMA(beta-cell function) (+9.7, P<0.01) and QUICKI (+0.029, P<0.001), and decreased HOMA(IR) (-1.73, P<0.001). Females and those with higher waist-hip ratio made up a greater portion of rosiglitazone-responders. Responders (45 patients, 75%) also showed significantly higher FPG, HbA1c, systolic blood pressures, fasting insulin levels and HOMA(IR), and lower QUICKI than nonresponders. Among these parameters of responders, waist-hip ratio of non-obese subgroup, initial glycemic control of obese subgroup, and systolic blood pressure of both subgroups lost their significance after subdivision analysis. However, the baseline HOMA(IR) and QUICKI were significantly correlated with the response rate to rosiglitazone. Moreover, in multiple logistic regression analysis, HOMA(IR) and QUICKI retained their significance as the independent predictors. Even in Korean type 2 diabetic patients of long duration but with relatively preserved beta-cell function, rosiglitazone improved glycemic control, insulin sensitivity, and beta-cell function. In this ethnic group, female gender, central obesity, and especially severe insulin resistance were identified as predictive clinical parameters of rosiglitazone-responders."
],
"offsets": [
[
0,
1974
]
]
}
] | [
{
"id": "entity-30-0",
"type": "TRIVIAL",
"text": [
"rosiglitazone"
],
"offsets": [
[
69,
82
]
],
"normalized": []
},
{
"id": "entity-30-1",
"type": "TRIVIAL",
"text": [
"rosiglitazone"
],
"offsets": [
[
157,
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]
],
"normalized": []
},
{
"id": "entity-30-2",
"type": "TRIVIAL",
"text": [
"rosiglitazone"
],
"offsets": [
[
410,
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]
],
"normalized": []
},
{
"id": "entity-30-3",
"type": "TRIVIAL",
"text": [
"glucose"
],
"offsets": [
[
536,
543
]
],
"normalized": []
},
{
"id": "entity-30-4",
"type": "TRIVIAL",
"text": [
"Rosiglitazone"
],
"offsets": [
[
598,
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]
],
"normalized": []
},
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"id": "entity-30-5",
"type": "TRIVIAL",
"text": [
"rosiglitazone"
],
"offsets": [
[
1462,
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]
],
"normalized": []
},
{
"id": "entity-30-6",
"type": "TRIVIAL",
"text": [
"rosiglitazone"
],
"offsets": [
[
1949,
1962
]
],
"normalized": []
}
] | [] | [] | [] |
example-31 | 2231607 | [
{
"id": "passage-31",
"type": "abstract",
"text": [
"The synthesis of 2'-fluoro- -propargyl-5,8-dideazafolic acid and its 2-desamino, 2-desamino-2-hydroxymethyl, and 2-desamino-2-methoxy analogues is described. In general the synthetic route involved the coupling of diethyl N-[2-fluoro-4-(prop-2-ynylamino)benzoyl]-L-glutamate with the appropriate 6-(bromomethyl)quinazoline followed by deprotection with mild alkali. These four compounds together with the 2-desamino-2-methyl analogue were tested for their activity against L1210 thymidylate synthase (TS). They were also examined for their inhibition of the growth of the L1210 cell line and of two mutant L1210 cell lines, the L1210:R7A that overproduces dihydrofolate reductase (DHFR) and the L1210:1565 that has impaired uptake of reduced folates. Compared with their non-fluorinated parent compounds, the 2'-fluoro analogueswere all approximately 2-fold more potent as TS inhibitors. Similarly, they also showed improved inhibition of L1210 cell growth (1.5-5-fold), and this activity was prevented by co-incubation with thymidine. All had retained or improved activity against both the L1210:R7A and L1210:1565 cell lines."
],
"offsets": [
[
0,
1129
]
]
}
] | [
{
"id": "entity-31-0",
"type": "IUPAC",
"text": [
"2'-fluoro-10-propargyl-5,8-dideazafolic acid"
],
"offsets": [
[
17,
61
]
],
"normalized": []
},
{
"id": "entity-31-1",
"type": "PARTIUPAC",
"text": [
"2-desamino"
],
"offsets": [
[
70,
80
]
],
"normalized": []
},
{
"id": "entity-31-2",
"type": "PARTIUPAC",
"text": [
"2-desamino-2-hydroxymethyl"
],
"offsets": [
[
82,
108
]
],
"normalized": []
},
{
"id": "entity-31-3",
"type": "PARTIUPAC",
"text": [
"2-desamino-2-methoxy"
],
"offsets": [
[
114,
134
]
],
"normalized": []
},
{
"id": "entity-31-4",
"type": "MODIFIER",
"text": [
"analogues"
],
"offsets": [
[
135,
144
]
],
"normalized": []
},
{
"id": "entity-31-5",
"type": "IUPAC",
"text": [
"diethyl N-[2-fluoro-4-(prop-2-ynylamino)benzoyl]-L-glutamate"
],
"offsets": [
[
215,
275
]
],
"normalized": []
},
{
"id": "entity-31-6",
"type": "IUPAC",
"text": [
"6-(bromomethyl)quinazoline"
],
"offsets": [
[
297,
323
]
],
"normalized": []
},
{
"id": "entity-31-7",
"type": "PARTIUPAC",
"text": [
"2-desamino-2-methyl"
],
"offsets": [
[
406,
425
]
],
"normalized": []
},
{
"id": "entity-31-8",
"type": "MODIFIER",
"text": [
"analogue"
],
"offsets": [
[
426,
434
]
],
"normalized": []
},
{
"id": "entity-31-9",
"type": "PARTIUPAC",
"text": [
"2'-fluoro"
],
"offsets": [
[
810,
819
]
],
"normalized": []
},
{
"id": "entity-31-10",
"type": "MODIFIER",
"text": [
"analogues"
],
"offsets": [
[
820,
829
]
],
"normalized": []
}
] | [] | [] | [] |
example-32 | 11985471 | [
{
"id": "passage-32",
"type": "abstract",
"text": [
"A novel class of 5-substituted acyclic pyrimidine nucleosides, 1-[(2-hydroxyethoxy)methyl]-5-(1-azidovinyl)uracil (9a), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]-5-(1-azidovinyl)uracil (9b), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azidovinyl)uracil (9c), were synthesized by regiospecific addition of bromine azide to the 5-vinyl substituent of the respective 5-vinyluracils (2a-c) followed by treatment of the obtained 5-(1-azido-2-bromoethyl) compounds (3a-c) with t-BuOK, to affect the base-catalyzed elimination of HBr. Thermal decomposition of 9b and 9c at degrees C in dioxane yielded corresponding 5-[2-(1-azirinyl)]uracil analogues ( ,c). The 5-(1-azidovinyl)uracil derivatives 9a-c were found to exhibit potent and selective in vitro anti-HBV activity against duck hepatitis B virus (DHBV) infected primary duck hepatocytes at low concentrations (EC( ) = 0.01-0.1 microg/mL range). The most active anti-DHBV agent (9c), possessing a [4-hydroxy-3-(hydroxymethyl)-1-butyl] substituent at N-1, exhibited an activity (EC( ) of 0.01-0.05 microg/mL) comparable to that of reference compound (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3-TC) (EC( ) = 0.01-0.05 microg/mL). In contrast, related 5-[2-(1-azirinyl)]uracil analogues ( ,c) were devoid of anti-DHBV activity, indicating that an acyclic side chain at C-5 position of the pyrimidine ring is essential for anti-HBV activity. The pyrimidine nucleosides( 9a-c, ,c) exhibited no cytotoxic activity against a panel of human cancer cell lines. All of the compounds investigated did not show any detectable toxicity to several stationary and proliferating host cell lines or to mitogen stimulated proliferating human T lymphocytes, up to the highest concentration tested."
],
"offsets": [
[
0,
1753
]
]
}
] | [
{
"id": "entity-32-0",
"type": "IUPAC",
"text": [
"5-substituted acyclic pyrimidine nucleosides"
],
"offsets": [
[
17,
61
]
],
"normalized": []
},
{
"id": "entity-32-1",
"type": "IUPAC",
"text": [
"1-[(2-hydroxyethoxy)methyl]-5-(1-azidovinyl)uracil"
],
"offsets": [
[
63,
113
]
],
"normalized": []
},
{
"id": "entity-32-2",
"type": "IUPAC",
"text": [
"1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]-5-(1-azidovinyl)uracil"
],
"offsets": [
[
120,
188
]
],
"normalized": []
},
{
"id": "entity-32-3",
"type": "IUPAC",
"text": [
"1-[4-hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azidovinyl)uracil"
],
"offsets": [
[
199,
261
]
],
"normalized": []
},
{
"id": "entity-32-4",
"type": "IUPAC",
"text": [
"bromine azide"
],
"offsets": [
[
314,
327
]
],
"normalized": []
},
{
"id": "entity-32-5",
"type": "PARTIUPAC",
"text": [
"5-vinyl"
],
"offsets": [
[
335,
342
]
],
"normalized": []
},
{
"id": "entity-32-6",
"type": "MODIFIER",
"text": [
"substituent"
],
"offsets": [
[
343,
354
]
],
"normalized": []
},
{
"id": "entity-32-7",
"type": "IUPAC",
"text": [
"5-vinyluracils"
],
"offsets": [
[
373,
387
]
],
"normalized": []
},
{
"id": "entity-32-8",
"type": "IUPAC",
"text": [
"5-(1-azido-2-bromoethyl)"
],
"offsets": [
[
433,
457
]
],
"normalized": []
},
{
"id": "entity-32-9",
"type": "MODIFIER",
"text": [
"compounds"
],
"offsets": [
[
458,
467
]
],
"normalized": []
},
{
"id": "entity-32-10",
"type": "TRIVIAL",
"text": [
"t-BuOK"
],
"offsets": [
[
480,
486
]
],
"normalized": []
},
{
"id": "entity-32-11",
"type": "SUM",
"text": [
"HBr"
],
"offsets": [
[
532,
535
]
],
"normalized": []
},
{
"id": "entity-32-12",
"type": "TRIVIAL",
"text": [
"dioxane"
],
"offsets": [
[
592,
599
]
],
"normalized": []
},
{
"id": "entity-32-13",
"type": "IUPAC",
"text": [
"5-[2-(1-azirinyl)]uracil"
],
"offsets": [
[
622,
646
]
],
"normalized": []
},
{
"id": "entity-32-14",
"type": "MODIFIER",
"text": [
"analogues"
],
"offsets": [
[
647,
656
]
],
"normalized": []
},
{
"id": "entity-32-15",
"type": "IUPAC",
"text": [
"5-(1-azidovinyl)uracil"
],
"offsets": [
[
670,
692
]
],
"normalized": []
},
{
"id": "entity-32-16",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
693,
704
]
],
"normalized": []
},
{
"id": "entity-32-17",
"type": "PARTIUPAC",
"text": [
"[4-hydroxy-3-(hydroxymethyl)-1-butyl]"
],
"offsets": [
[
962,
999
]
],
"normalized": []
},
{
"id": "entity-32-18",
"type": "MODIFIER",
"text": [
"substituent"
],
"offsets": [
[
1000,
1011
]
],
"normalized": []
},
{
"id": "entity-32-19",
"type": "IUPAC",
"text": [
"(-)-beta-L-2',3'-dideoxy-3'-thiacytidine"
],
"offsets": [
[
1115,
1155
]
],
"normalized": []
},
{
"id": "entity-32-20",
"type": "IUPAC",
"text": [
"5-[2-(1-azirinyl)]uracil"
],
"offsets": [
[
1216,
1240
]
],
"normalized": []
},
{
"id": "entity-32-21",
"type": "MODIFIER",
"text": [
"analogues"
],
"offsets": [
[
1241,
1250
]
],
"normalized": []
},
{
"id": "entity-32-22",
"type": "FAMILY",
"text": [
"pyrimidine"
],
"offsets": [
[
1355,
1365
]
],
"normalized": []
},
{
"id": "entity-32-23",
"type": "FAMILY",
"text": [
"pyrimidine"
],
"offsets": [
[
1411,
1421
]
],
"normalized": []
},
{
"id": "entity-32-24",
"type": "MODIFIER",
"text": [
"nucleosides"
],
"offsets": [
[
1422,
1433
]
],
"normalized": []
}
] | [] | [] | [] |
example-33 | 10813108 | [
{
"id": "passage-33",
"type": "abstract",
"text": [
" Antiestrogens reduce plasma levels of endothelin-1 without affecting nitrate levels in breast cancer patients. Tamoxifen protects against myocardial infarction through mechanisms that are poorly understood. We studied the effects of tamoxifen and another antiestrogen, toremifene, on the production of vasoconstrictive endothelin-1 and of vasodilatory nitric oxide in 44 postmenopausal patients with breast cancer. These started treatment, in randomized order, with either tamoxifen ( mg/day; n = 25) or toremifene ( mg/day; n = 19). Plasma samples collected before treatment and after 6 and 12 months of both regimens were assayed for endothelin-1 with a specific radioimmunoassay and for nitrite/nitrate with a method based on the Griess reaction. The antiestrogen group as a whole showed a fall in endothelin-1 at 6 months (5.9 +/- 3.3%; p = 0.06) (mean +/- SE) and at 12 months (7.1 +/- 5.5%; p = 0.03). This fall was solely due to toremifene, the use of which was associated with falls in endothelin-1 at 6 months (12.9 +/- 4.7%; p = 0.01) and 12 months (9.2 +/- 6.2%; p = 0.06). The antiestrogen regimen failed to affect plasma nitric oxide significantly but nevertheless the ratio between nitric oxide and endothelin-1 rose by 31.6 +/- 13.3% at 6 months and by 35.6 +/- 15.3% at 12 months in the antiestrogen users, an effect similar in the tamoxifen and toremifene groups. We conclude that antiestrogens may protect against myocardial infarction by preventing the release of endothelin-1 and by shifting the balance between nitric oxide and endothelin-1 to the dominance of the former. Our data predict that toremifene and tamoxifenat the doses studied here will provide similar cardiovascular protection."
],
"offsets": [
[
0,
1729
]
]
}
] | [
{
"id": "entity-33-0",
"type": "IUPAC",
"text": [
"nitrate"
],
"offsets": [
[
79,
86
]
],
"normalized": []
},
{
"id": "entity-33-1",
"type": "TRIVIAL",
"text": [
"Tamoxifen"
],
"offsets": [
[
122,
131
]
],
"normalized": []
},
{
"id": "entity-33-2",
"type": "TRIVIAL",
"text": [
"tamoxifen"
],
"offsets": [
[
244,
253
]
],
"normalized": []
},
{
"id": "entity-33-3",
"type": "TRIVIAL",
"text": [
"toremifene"
],
"offsets": [
[
280,
290
]
],
"normalized": []
},
{
"id": "entity-33-4",
"type": "IUPAC",
"text": [
"nitric oxide"
],
"offsets": [
[
363,
375
]
],
"normalized": []
},
{
"id": "entity-33-5",
"type": "TRIVIAL",
"text": [
"tamoxifen"
],
"offsets": [
[
484,
493
]
],
"normalized": []
},
{
"id": "entity-33-6",
"type": "TRIVIAL",
"text": [
"nitrite"
],
"offsets": [
[
705,
712
]
],
"normalized": []
},
{
"id": "entity-33-7",
"type": "TRIVIAL",
"text": [
"nitrate"
],
"offsets": [
[
713,
720
]
],
"normalized": []
},
{
"id": "entity-33-8",
"type": "TRIVIAL",
"text": [
"toremifene"
],
"offsets": [
[
951,
961
]
],
"normalized": []
},
{
"id": "entity-33-9",
"type": "IUPAC",
"text": [
"nitric oxide"
],
"offsets": [
[
1149,
1161
]
],
"normalized": []
},
{
"id": "entity-33-10",
"type": "IUPAC",
"text": [
"nitric oxide"
],
"offsets": [
[
1211,
1223
]
],
"normalized": []
},
{
"id": "entity-33-11",
"type": "TRIVIAL",
"text": [
"tamoxifen"
],
"offsets": [
[
1363,
1372
]
],
"normalized": []
},
{
"id": "entity-33-12",
"type": "TRIVIAL",
"text": [
"toremifene"
],
"offsets": [
[
1377,
1387
]
],
"normalized": []
},
{
"id": "entity-33-13",
"type": "IUPAC",
"text": [
"nitric oxide"
],
"offsets": [
[
1547,
1559
]
],
"normalized": []
},
{
"id": "entity-33-14",
"type": "TRIVIAL",
"text": [
"toremifene"
],
"offsets": [
[
1631,
1641
]
],
"normalized": []
},
{
"id": "entity-33-15",
"type": "TRIVIAL",
"text": [
"tamoxifen"
],
"offsets": [
[
1646,
1655
]
],
"normalized": []
}
] | [] | [] | [] |
example-34 | 2299637 | [
{
"id": "passage-34",
"type": "abstract",
"text": [
"A series of new 5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine and uridine compounds (11, 16) was synthesized by the regiospecific addition of HOI to the vinyl substituent of 5-vinyl-2'-deoxyuridine ( ), 5-vinyl-2'-fluoro-2'-deoxyuridine ( ), 5-vinyluridine ( ), and (E)-5-(2-iodovinyl)-2'-deoxyuridine (4b). Treatment of the iodohydrins 11a-c with methanolic sulfuric acid afforded the corresponding 5-(1-methoxy-2-iodoethyl) derivatives (12a-c). In contrast, reaction of 5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine (11a) with sodium carbonate in methanol afforded a mixture of 5-(1-hydroxy-2-methoxyethyl)-2'-deoxyuridine (13) and 2,3-dihydro-3-hydroxy-5-(2'-deoxy-beta-D-ribofuranosyl)- furano[2,3-d]pyrimidin-6(5H)-one (14). The most active compound, 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine (12a, ID50 = 0.1 micrograms/mL), which exhibited antiviral activity (HSV-1) -fold higher than that of the 5-(1-hydroxy-2-iodoethyl) analogue (11a), was less active than IVDU or acyclovir (ID50 = 0.01-0.1 micrograms/mL range). The C-5 substituent in the 2'-deoxyuridine series was a determinant of cytotoxic activity, as determined in the in vitro L1210 screen, where the relative activity order was CH(OH)CHI2 (16) greater than CH(OMe)CH2I (12a) greater than CH(OH)CH2I (11a) congruent to CH(OH)CH2OMe (13). The 2'-substituent was also a determinant of cytotoxic activity in the 5-(1-hydroxy-2-iodoethyl) (11a-c) and 5-(1-methoxy-2-iodoethyl) series of compounds, where the relative activity profile was 2'-deoxyuridine greater than 2'-fluoro-2'-deoxyuridine greater than uridine (11a greater than 11b greater than or equal to 11c; 12a greater than 12b greater than 12c). The most active cytotoxic agent (16), possessing a 5-(1-hydroxy-2,2-diiodoethyl) substituent (ED50 = 0.77 micrograms/mL), exhibited an activity approaching that of melphalan (ED50 = 0.15 micrograms/mL). All compounds tested, except for 13 and 14, exhibited high affinity (Ki = 0.035-0.22 mM range relative to deoxyuridine, Ki = 0.125) for the murine NBMPR-sensitive erythrocyte nucleoside transport system, suggesting that these iodohydrinsare good permeants of cell membranes."
],
"offsets": [
[
0,
2149
]
]
}
] | [
{
"id": "entity-34-0",
"type": "IUPAC",
"text": [
"5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine"
],
"offsets": [
[
16,
57
]
],
"normalized": []
},
{
"id": "entity-34-1",
"type": "TRIVIAL",
"text": [
"uridine"
],
"offsets": [
[
62,
69
]
],
"normalized": []
},
{
"id": "entity-34-2",
"type": "MODIFIER",
"text": [
"compounds"
],
"offsets": [
[
70,
79
]
],
"normalized": []
},
{
"id": "entity-34-3",
"type": "SUM",
"text": [
"HOI"
],
"offsets": [
[
138,
141
]
],
"normalized": []
},
{
"id": "entity-34-4",
"type": "TRIVIAL",
"text": [
"vinyl"
],
"offsets": [
[
149,
154
]
],
"normalized": []
},
{
"id": "entity-34-5",
"type": "MODIFIER",
"text": [
"substituent"
],
"offsets": [
[
155,
166
]
],
"normalized": []
},
{
"id": "entity-34-6",
"type": "IUPAC",
"text": [
"5-vinyl-2'-deoxyuridine"
],
"offsets": [
[
170,
193
]
],
"normalized": []
},
{
"id": "entity-34-7",
"type": "IUPAC",
"text": [
"5-vinyl-2'-fluoro-2'-deoxyuridine"
],
"offsets": [
[
201,
234
]
],
"normalized": []
},
{
"id": "entity-34-8",
"type": "IUPAC",
"text": [
"5-vinyluridine"
],
"offsets": [
[
242,
256
]
],
"normalized": []
},
{
"id": "entity-34-9",
"type": "IUPAC",
"text": [
"(E)-5-(2-iodovinyl)-2'-deoxyuridine"
],
"offsets": [
[
268,
303
]
],
"normalized": []
},
{
"id": "entity-34-10",
"type": "FAMILY",
"text": [
"iodohydrins"
],
"offsets": [
[
327,
338
]
],
"normalized": []
},
{
"id": "entity-34-11",
"type": "IUPAC",
"text": [
"methanolic sulfuric acid"
],
"offsets": [
[
350,
374
]
],
"normalized": []
},
{
"id": "entity-34-12",
"type": "IUPAC",
"text": [
"5-(1-methoxy-2-iodoethyl)"
],
"offsets": [
[
402,
427
]
],
"normalized": []
},
{
"id": "entity-34-13",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
428,
439
]
],
"normalized": []
},
{
"id": "entity-34-14",
"type": "IUPAC",
"text": [
"5-(1-hydroxy-2-iodoethyl)-2'-deoxyuridine"
],
"offsets": [
[
474,
515
]
],
"normalized": []
},
{
"id": "entity-34-15",
"type": "IUPAC",
"text": [
"sodium carbonate"
],
"offsets": [
[
527,
543
]
],
"normalized": []
},
{
"id": "entity-34-16",
"type": "TRIVIAL",
"text": [
"methanol"
],
"offsets": [
[
547,
555
]
],
"normalized": []
},
{
"id": "entity-34-17",
"type": "IUPAC",
"text": [
"5-(1-hydroxy-2-methoxyethyl)-2'-deoxyuridine"
],
"offsets": [
[
578,
622
]
],
"normalized": []
},
{
"id": "entity-34-18",
"type": "IUPAC",
"text": [
"2,3-dihydro-3-hydroxy-5-(2'-deoxy-beta-D-ribofuranosyl)- furano[2,3-d]pyrimidin-6(5H)-one"
],
"offsets": [
[
632,
721
]
],
"normalized": []
},
{
"id": "entity-34-19",
"type": "IUPAC",
"text": [
"5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine"
],
"offsets": [
[
754,
795
]
],
"normalized": []
},
{
"id": "entity-34-20",
"type": "IUPAC",
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"5-(1-hydroxy-2-iodoethyl)"
],
"offsets": [
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905,
930
]
],
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},
{
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"analogue"
],
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931,
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"type": "ABBREVIATION",
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"IVDU"
],
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968,
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"acyclovir"
],
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976,
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],
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"id": "entity-34-24",
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"text": [
"C-5"
],
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1029,
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],
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1033,
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{
"id": "entity-34-26",
"type": "IUPAC",
"text": [
"2'-deoxyuridine"
],
"offsets": [
[
1052,
1067
]
],
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},
{
"id": "entity-34-27",
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"series"
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1068,
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{
"id": "entity-34-28",
"type": "SUM",
"text": [
"CH(OH)CHI2"
],
"offsets": [
[
1198,
1208
]
],
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},
{
"id": "entity-34-29",
"type": "SUM",
"text": [
"CH(OMe)CH2I"
],
"offsets": [
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1227,
1238
]
],
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},
{
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],
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1258,
1268
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],
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{
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1288,
1300
]
],
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{
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"type": "PARTIUPAC",
"text": [
"2'-"
],
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1311,
1314
]
],
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},
{
"id": "entity-34-33",
"type": "IUPAC",
"text": [
"5-(1-hydroxy-2-iodoethyl)"
],
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1378,
1403
]
],
"normalized": []
},
{
"id": "entity-34-34",
"type": "IUPAC",
"text": [
"5-(1-methoxy-2-iodoethyl)"
],
"offsets": [
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1416,
1441
]
],
"normalized": []
},
{
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"type": "MODIFIER",
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"series"
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1442,
1448
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],
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"type": "IUPAC",
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"2'-deoxyuridine"
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1503,
1518
]
],
"normalized": []
},
{
"id": "entity-34-37",
"type": "IUPAC",
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"2'-fluoro-2'-deoxyuridine"
],
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1532,
1557
]
],
"normalized": []
},
{
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"type": "TRIVIAL",
"text": [
"uridine"
],
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[
1571,
1578
]
],
"normalized": []
},
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"id": "entity-34-39",
"type": "PARTIUPAC",
"text": [
"5-(1-hydroxy-2,2-diiodoethyl)"
],
"offsets": [
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1722,
1751
]
],
"normalized": []
},
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],
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1752,
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],
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},
{
"id": "entity-34-41",
"type": "TRIVIAL",
"text": [
"melphalan"
],
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1835,
1844
]
],
"normalized": []
},
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"id": "entity-34-42",
"type": "TRIVIAL",
"text": [
"deoxyuridine"
],
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1980,
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]
],
"normalized": []
},
{
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"type": "FAMILY",
"text": [
"iodohydrins"
],
"offsets": [
[
2100,
2111
]
],
"normalized": []
}
] | [] | [] | [] |
example-35 | 3735316 | [
{
"id": "passage-35",
"type": "abstract",
"text": [
"N-Methylacetazolamide was shown to be active topically in reducing intraocular pressure (IOP) to a small but statistically significant level in the normotensive rabbit eye. In vivo experiments with N-methylacetazolamide suggest that ocular metabolism to acetazolamide was responsible for the observed topical activity. Examination of initial rate kinetics of carbonic anhydrase catalyzed p-nitrophenyl acetate hydrolysis showed that N-methylacetazolamide was a competitive inhibitor, in contrast to noncompetitive inhibition seen with acetazolamide and other primary sulfonamide inhibitors. N-Substituted and unsubstituted 4-chlorobenzene- and 4-nitrobenzenesulfonamides were also synthesized, and their biochemical characteristics and in vivo ability to lower IOP when applied topically were determined. The primary sulfonamides were reversible noncompetitive inhibitors of carbonic anhydrase, with no effect on IOP after topical administration. 4-Nitrobenzene- and 4-chlorobenzenesulfonamides containing both N-hydroxy and N-methyl substituents were model irreversible inhibitors of carbonic anhydrase and exhibited a trend toward topical activity in reducing IOP in normotensive rabbit eyes. Therefore, this paper describes the synthesis and characterization of two types of carbonic anhydrase inhibitors; the N-methyl-substituted sulfonamides are reversible competitive inhibitors of carbonic anhydrase, while the N-hydroxy-N-methyl-substituted sulfonamidesare irreversible inhibitors."
],
"offsets": [
[
0,
1490
]
]
}
] | [
{
"id": "entity-35-0",
"type": "IUPAC",
"text": [
"N-methylacetazolamide"
],
"offsets": [
[
198,
219
]
],
"normalized": []
},
{
"id": "entity-35-1",
"type": "TRIVIAL",
"text": [
"acetazolamide"
],
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[
254,
267
]
],
"normalized": []
},
{
"id": "entity-35-2",
"type": "IUPAC",
"text": [
"p-nitrophenyl acetate"
],
"offsets": [
[
388,
409
]
],
"normalized": []
},
{
"id": "entity-35-3",
"type": "IUPAC",
"text": [
"N-methylacetazolamide"
],
"offsets": [
[
433,
454
]
],
"normalized": []
},
{
"id": "entity-35-4",
"type": "TRIVIAL",
"text": [
"acetazolamide"
],
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[
535,
548
]
],
"normalized": []
},
{
"id": "entity-35-5",
"type": "TRIVIAL",
"text": [
"sulfonamide"
],
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[
567,
578
]
],
"normalized": []
},
{
"id": "entity-35-6",
"type": "PARTIUPAC",
"text": [
"N-Substituted"
],
"offsets": [
[
591,
604
]
],
"normalized": []
},
{
"id": "entity-35-7",
"type": "PARTIUPAC",
"text": [
"unsubstituted 4-chlorobenzene-"
],
"offsets": [
[
609,
639
]
],
"normalized": []
},
{
"id": "entity-35-8",
"type": "IUPAC",
"text": [
"4-nitrobenzenesulfonamides"
],
"offsets": [
[
644,
670
]
],
"normalized": []
},
{
"id": "entity-35-9",
"type": "FAMILY",
"text": [
"sulfonamides"
],
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817,
829
]
],
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},
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"id": "entity-35-10",
"type": "PARTIUPAC",
"text": [
"4-Nitrobenzene-"
],
"offsets": [
[
947,
962
]
],
"normalized": []
},
{
"id": "entity-35-11",
"type": "IUPAC",
"text": [
"4-chlorobenzenesulfonamides"
],
"offsets": [
[
967,
994
]
],
"normalized": []
},
{
"id": "entity-35-12",
"type": "PARTIUPAC",
"text": [
"N-hydroxy"
],
"offsets": [
[
1011,
1020
]
],
"normalized": []
},
{
"id": "entity-35-13",
"type": "PARTIUPAC",
"text": [
"N-methyl"
],
"offsets": [
[
1025,
1033
]
],
"normalized": []
},
{
"id": "entity-35-14",
"type": "MODIFIER",
"text": [
"substituents"
],
"offsets": [
[
1034,
1046
]
],
"normalized": []
},
{
"id": "entity-35-15",
"type": "IUPAC",
"text": [
"N-methyl-substituted sulfonamides"
],
"offsets": [
[
1313,
1346
]
],
"normalized": []
},
{
"id": "entity-35-16",
"type": "IUPAC",
"text": [
"N-hydroxy-N-methyl-substituted sulfonamides"
],
"offsets": [
[
1418,
1461
]
],
"normalized": []
}
] | [] | [] | [] |
example-36 | 6827523 | [
{
"id": "passage-36",
"type": "abstract",
"text": [
"Condensation of 14-bromodaunorubicin with thiols in methanol, in the presence of potassium carbonate, resulted in the formation of 14-thia analogues of the antitumor antibiotic adriamycin. However, similar condensation of N-(trifluoroacetyl)-14-iododaunorubicin with thiols invariably led to a redox reaction, with the formation of N-(trifluoroacetyl)daunorubicin and disulfides. Accordingly, N-(trifluoroacetyl)-14-bromodaunorubicin was used for reaction with thiols to yield thia analogues of the clinically active but non-DNA-binding adriamycin analogue N-(trifluoroacetyl)adriamycin 14-valerate (AD 32). Reaction of 14-bromoadunorubicin with alpha, omega-alkanedithiols gave bis(thiaadriamycin) analogues as potential difunctional intercalating agents. The aforementioned products, plus two related phenylselena derivatives, were examined for in vitro growth inhibition, in vivo antitumor activity, and, where appropriate, DNA binding. A number of agents, most notably 14-(carbethoxymethyl)-14-thiaadriamycin and N-(trifluoroacetyl)-14-phenyl-14-selenaadriamycin, were active against murine L1210 leukemia in vivo. Several of the amino glycoside unsubstituted 14-thiaadriamycin analogues exhibited DNA-binding properties equivalent to those of adriamycin."
],
"offsets": [
[
0,
1259
]
]
}
] | [
{
"id": "entity-36-0",
"type": "IUPAC",
"text": [
"14-bromodaunorubicin"
],
"offsets": [
[
16,
36
]
],
"normalized": []
},
{
"id": "entity-36-1",
"type": "FAMILY",
"text": [
"thiols"
],
"offsets": [
[
42,
48
]
],
"normalized": []
},
{
"id": "entity-36-2",
"type": "TRIVIAL",
"text": [
"methanol"
],
"offsets": [
[
52,
60
]
],
"normalized": []
},
{
"id": "entity-36-3",
"type": "TRIVIAL",
"text": [
"potassium carbonate"
],
"offsets": [
[
81,
100
]
],
"normalized": []
},
{
"id": "entity-36-4",
"type": "PARTIUPAC",
"text": [
"14-thia"
],
"offsets": [
[
131,
138
]
],
"normalized": []
},
{
"id": "entity-36-5",
"type": "MODIFIER",
"text": [
"analogues"
],
"offsets": [
[
139,
148
]
],
"normalized": []
},
{
"id": "entity-36-6",
"type": "TRIVIAL",
"text": [
"adriamycin"
],
"offsets": [
[
177,
187
]
],
"normalized": []
},
{
"id": "entity-36-7",
"type": "IUPAC",
"text": [
"N-(trifluoroacetyl)-14-iododaunorubicin"
],
"offsets": [
[
222,
261
]
],
"normalized": []
},
{
"id": "entity-36-8",
"type": "IUPAC",
"text": [
"N-(trifluoroacetyl)daunorubicin"
],
"offsets": [
[
332,
363
]
],
"normalized": []
},
{
"id": "entity-36-9",
"type": "FAMILY",
"text": [
"disulfides"
],
"offsets": [
[
368,
378
]
],
"normalized": []
},
{
"id": "entity-36-10",
"type": "IUPAC",
"text": [
"N-(trifluoroacetyl)-14-bromodaunorubicin"
],
"offsets": [
[
393,
433
]
],
"normalized": []
},
{
"id": "entity-36-11",
"type": "FAMILY",
"text": [
"thiols"
],
"offsets": [
[
461,
467
]
],
"normalized": []
},
{
"id": "entity-36-12",
"type": "TRIVIAL",
"text": [
"adriamycin"
],
"offsets": [
[
537,
547
]
],
"normalized": []
},
{
"id": "entity-36-13",
"type": "MODIFIER",
"text": [
"analogue"
],
"offsets": [
[
548,
556
]
],
"normalized": []
},
{
"id": "entity-36-14",
"type": "IUPAC",
"text": [
"N-(trifluoroacetyl)adriamycin 14-valerate"
],
"offsets": [
[
557,
598
]
],
"normalized": []
},
{
"id": "entity-36-15",
"type": "IUPAC",
"text": [
"14-bromoadunorubicin"
],
"offsets": [
[
620,
640
]
],
"normalized": []
},
{
"id": "entity-36-16",
"type": "IUPAC",
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"alpha, omega-alkanedithiols"
],
"offsets": [
[
646,
673
]
],
"normalized": []
},
{
"id": "entity-36-17",
"type": "TRIVIAL",
"text": [
"bis(thiaadriamycin)"
],
"offsets": [
[
679,
698
]
],
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},
{
"id": "entity-36-18",
"type": "MODIFIER",
"text": [
"analogues"
],
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[
699,
708
]
],
"normalized": []
},
{
"id": "entity-36-19",
"type": "TRIVIAL",
"text": [
"phenylselena"
],
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[
803,
815
]
],
"normalized": []
},
{
"id": "entity-36-20",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
816,
827
]
],
"normalized": []
},
{
"id": "entity-36-21",
"type": "IUPAC",
"text": [
"14-(carbethoxymethyl)-14-thiaadriamycin"
],
"offsets": [
[
973,
1012
]
],
"normalized": []
},
{
"id": "entity-36-22",
"type": "IUPAC",
"text": [
"N-(trifluoroacetyl)-14-phenyl-14-selenaadriamycin"
],
"offsets": [
[
1017,
1066
]
],
"normalized": []
},
{
"id": "entity-36-23",
"type": "IUPAC",
"text": [
"amino glycoside unsubstituted 14-thiaadriamycin"
],
"offsets": [
[
1134,
1181
]
],
"normalized": []
},
{
"id": "entity-36-24",
"type": "MODIFIER",
"text": [
"analogues"
],
"offsets": [
[
1182,
1191
]
],
"normalized": []
},
{
"id": "entity-36-25",
"type": "TRIVIAL",
"text": [
"adriamycin"
],
"offsets": [
[
1248,
1258
]
],
"normalized": []
}
] | [] | [] | [] |
example-37 | 10783907 | [
{
"id": "passage-37",
"type": "abstract",
"text": [
" Enalapril in subantihypertensive dosage attenuates kidney proliferation and functional recovery in normotensive ablation nephropathy of the rat. Most studies on the antiproliferative action of angiotensin converting enzyme inhibitors (ACEI) were performed in a rat hypertensive remnant kidney model with 5/6 kidney ablation which raised objections about the antihypertensive effect of ACEI and the influence of other antihypertensive drugs administered to remnant kidney control rats. To prevent these objections, a normotensive 4/6 remnant kidney model was elaborated and a subantihypertensive dosage of enalapril was used to evaluate its antiproliferative action. Subtotally nephrectomized rats (Nx) markedly increased the remnant kidney weight during a 4-week period and this rise was prevented by the treatment with enalapril (NxE) (Nx +297+/-35 mg vs. sham-operated +145+/-32 mg, p<0.001; NxE +154+/-35 mg vs. Nx p<0.001). While collagen concentration in the kidney cortex was not increased in sham-operated rats (Sham) in comparison with the control group (Ctrl) at the beginning of the study, the subsequent increase was significant in the Nx group and enalapril did not attenuate this increase (Sham 148+/-5 mg/ g w.w. vs. Nx 164+/-2 mg/ g w.w., p<0.01; NxE 161+/-4 mg/ g w.w. vs. Sham p<0.05). The tubular protein/DNA ratio increase, which was significant in the Nx group, was inhibited by enalapril (Nx 26.2+/- vs. NxE 15.3+/-2.6, p<0.05). The protein/DNA ratio was much lower in glomeruli, with no significant changes in either the Nx or NxE groups. Serum urea concentrations were slightly higher in the Nx group than in the sham-operated group, but markedly elevated in the NxE group (Nx +/-0.76 mmol/l vs. Sham 6.10+/-0.33 mmol/l, p<0.001; NxE 28.9+/-2.6 mmol/l vs. Sham p<0.001). Creatinine concentrations in the Nx group were increased in comparison with the sham-operated group and markedly increased in the NxE group (Nx 63.7+/-3.56 micromol/l vs. Sham 37.2+/-2.84 micromol/l, p<0.001; NxE +/-5.2 micromol/l vs. Sham p<0.001). The clearance of creatinine was lower in the Nx group than in the sham-operated group and was markedly reduced in the NxE group (Nx 0.89+/-0.06 ml/min.g kidney wt. vs. Sham 1.05+/-0.16 ml/min x g kidney wt., p<0.01; NxE 0.58+/-0.029 ml/min x g kidney wt. vs. Sham, p<0.001). Enalapril improved proteinuria in comparison with the Nx group (NxE 5.6+/-0.6 mg/24 h vs. Nx 16.1+/-3.4 mg/24 h, p<0.05). Thus remnant kidney proliferation is substantial even in normotensive rats. It includes both proliferation and collagen accumulation with partial recovery of kidney weight and function, but is accompanied by enhanced proteinuria. Enalaprilattenuates the proliferation and decreases proteinuria but prolongs kidney function recovery."
],
"offsets": [
[
0,
2808
]
]
}
] | [
{
"id": "entity-37-0",
"type": "TRIVIAL",
"text": [
"Enalapril"
],
"offsets": [
[
10,
19
]
],
"normalized": []
},
{
"id": "entity-37-1",
"type": "TRIVIAL",
"text": [
"enalapril"
],
"offsets": [
[
616,
625
]
],
"normalized": []
},
{
"id": "entity-37-2",
"type": "TRIVIAL",
"text": [
"enalapril"
],
"offsets": [
[
831,
840
]
],
"normalized": []
},
{
"id": "entity-37-3",
"type": "TRIVIAL",
"text": [
"enalapril"
],
"offsets": [
[
1171,
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]
],
"normalized": []
},
{
"id": "entity-37-4",
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"text": [
"enalapril"
],
"offsets": [
[
1419,
1428
]
],
"normalized": []
},
{
"id": "entity-37-5",
"type": "TRIVIAL",
"text": [
"urea"
],
"offsets": [
[
1591,
1595
]
],
"normalized": []
},
{
"id": "entity-37-6",
"type": "TRIVIAL",
"text": [
"Creatinine"
],
"offsets": [
[
1823,
1833
]
],
"normalized": []
},
{
"id": "entity-37-7",
"type": "TRIVIAL",
"text": [
"creatinine"
],
"offsets": [
[
2095,
2105
]
],
"normalized": []
},
{
"id": "entity-37-8",
"type": "TRIVIAL",
"text": [
"Enalapril"
],
"offsets": [
[
2353,
2362
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],
"normalized": []
},
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"id": "entity-37-9",
"type": "TRIVIAL",
"text": [
"Enalapril"
],
"offsets": [
[
2705,
2714
]
],
"normalized": []
}
] | [] | [] | [] |
example-38 | 9082041 | [
{
"id": "passage-38",
"type": "abstract",
"text": [
" Replacing dietary palmitic acid with elaidic acid (t-C18:1 delta9) depresses HDL and increases CETP activity in cebus monkeys. The question whether dietary trans fatty acids affect lipoprotein metabolism similarly to specific saturated fatty acids was investigated in 11 normolipemic cebus monkeys by exchanging 5% dietary energy (%en) between elaidic (t-C18:1 delta9) and palmitic acid (16:0) in two test diets ( en fat + mg cholesterol/ kcal diet) conforming to the American Heart Association (AHA) Step 1 guidelines. These were compared with a normal control diet rich in saturated fat and cholesterol (38%en fat + mg cholesterol/ kcal diet). The control diet was fed initially for 14 wk, followed by each of the the two test diets in a crossover design. Plasma lipid concentrations were determined four times between the 6th and 14th wk. Turnover studies (using 125I-HDL and 131I-LDL) were conducted after 9 wk in each dietary period. Relative to the control diet, both test diets significantly reduced plasma total cholesterol (TC), HDL cholesterol (HDL-C) and VLDL plus LDL cholesterol (LDL-C) concentrations; triglyceride (TG) concentrations tended to be lower. However, the trans diet resulted in a significantly greater reduction in HDL-C than the palmitate diet (124 +/- 17, 117 +/- 18 and +/- 13 mg/dL for the control, palmitate and trans diets, respectively). The palmitate diet significantly decreased the TC/HDL-C ratio by 11% when compared with the control diet (1.68 +/- 0.17 vs. 1.89 +/- 0.30), whereas the trans diet had no effect (1.81 +/- 0.20 vs. 1.89 +/- 0.30). Kinetic studies revealed that, relative to the control diet, both test diets significantly lowered the LDL apolipoprotein B (apoB) pool size, principally reflecting an increase in the LDL apoB fractional catabolic rate (FCR) related to the reduced cholesterol intake. Between the two test diets, no significant differences in LDL kinetic parameters were observed. Both test diets significantly decreased HDL apoA1 concentrations in comparison with the control diet, which was partly explained by an increase in the fractional catabolic rate of HDL. Of the two test diets, the trans diet was associated with a 9.5% greater HDL FCR than the palmitate diet (P < 0.08) and a significant increase in plasma cholesteryl ester transfer protein (CETP) activity (% transfer 114 +/- 7 vs. 91 +/- 7; P < 0.03). Thus, palmitic acid- and elaidic acid-rich diets produced identical effects on LDL metabolism in normocholesterolemic cebus monkeys fed diets with low levels of cholesterol, whereas elaidic aciddepressed HDL-C, attributable to both increased CETP activity and HDL clearance."
],
"offsets": [
[
0,
2691
]
]
}
] | [
{
"id": "entity-38-0",
"type": "IUPAC",
"text": [
"palmitic acid"
],
"offsets": [
[
27,
40
]
],
"normalized": []
},
{
"id": "entity-38-1",
"type": "IUPAC",
"text": [
"elaidic acid"
],
"offsets": [
[
46,
58
]
],
"normalized": []
},
{
"id": "entity-38-2",
"type": "FAMILY",
"text": [
"saturated fatty acids"
],
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[
236,
257
]
],
"normalized": []
},
{
"id": "entity-38-3",
"type": "PARTIUPAC",
"text": [
"elaidic"
],
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[
354,
361
]
],
"normalized": []
},
{
"id": "entity-38-4",
"type": "IUPAC",
"text": [
"palmitic acid"
],
"offsets": [
[
383,
396
]
],
"normalized": []
},
{
"id": "entity-38-5",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
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[
442,
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]
],
"normalized": []
},
{
"id": "entity-38-6",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
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[
613,
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]
],
"normalized": []
},
{
"id": "entity-38-7",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
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[
645,
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]
],
"normalized": []
},
{
"id": "entity-38-8",
"type": "FAMILY",
"text": [
"lipid"
],
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[
793,
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]
],
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},
{
"id": "entity-38-9",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
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1048,
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]
],
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},
{
"id": "entity-38-10",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
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[
1070,
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]
],
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},
{
"id": "entity-38-11",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
"offsets": [
[
1108,
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]
],
"normalized": []
},
{
"id": "entity-38-12",
"type": "FAMILY",
"text": [
"triglyceride"
],
"offsets": [
[
1144,
1156
]
],
"normalized": []
},
{
"id": "entity-38-13",
"type": "ABBREVIATION",
"text": [
"TG"
],
"offsets": [
[
1158,
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]
],
"normalized": []
},
{
"id": "entity-38-14",
"type": "TRIVIAL",
"text": [
"palmitate"
],
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[
1408,
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]
],
"normalized": []
},
{
"id": "entity-38-15",
"type": "TRIVIAL",
"text": [
"palmitate"
],
"offsets": [
[
2255,
2264
]
],
"normalized": []
},
{
"id": "entity-38-16",
"type": "IUPAC",
"text": [
"palmitic acid"
],
"offsets": [
[
2422,
2435
]
],
"normalized": []
},
{
"id": "entity-38-17",
"type": "IUPAC",
"text": [
"elaidic acid"
],
"offsets": [
[
2441,
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]
],
"normalized": []
},
{
"id": "entity-38-18",
"type": "TRIVIAL",
"text": [
"cholesterol"
],
"offsets": [
[
2577,
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]
],
"normalized": []
},
{
"id": "entity-38-19",
"type": "IUPAC",
"text": [
"elaidic acid"
],
"offsets": [
[
2598,
2610
]
],
"normalized": []
}
] | [] | [] | [] |
example-39 | 10447954 | [
{
"id": "passage-39",
"type": "abstract",
"text": [
"Radiolabeled m-iodobenzylguanidine (MIBG) is a tumor-seeking radioactive drug used in the diagnosis and treatment of pheochromocytomas and neuroblastomas. It is transported into the tumor cells by the neuronal norepinephrine (NE) transporter (NET) which is expressed in almost all neuroblastoma cells. Here, we describe the synthesis and some pharmacological properties of a series of fluorescent compounds structurally related to the NET substrate, MIBG, or to the NET inhibitors, (-)-(2R,3S)-cocaine and nisoxetine. Three of synthesized fluorescent compounds, 1-(1-naphthylmethyl)guanidinium sulfate (1), 1-[2-(dibenz[b, f]azepin-5-yl)ethyl]guanidinium sulfate (2), and (2R, 3S)-2beta-ethoxycarbonyl-3beta-tropanyl 5-(dimethylamino)naphthalene-1-sulfonate (6), exhibited high affinity (IC( ) about nM) for the NET. Thenisoxetine derivatives 8 (rac-N-[(3-methylamino-1-phenyl)propyl]-5-(dimethylamino)-1-naphthale nesulfonamide) and 9 (rac-4-[(3-methylamino-1-phenyl)propyl]amino-7-nitro-2,1, 3-benzoxadiazole) and especially the guanidine derivative 4 (1-[4-(4-phenyl-1,3-butadienyl)benzyl]guanidinium sulfate) which are characterized by intermediate affinity for the NET (IC( ) nM) caused significant and nisoxetine-sensitive cell fluorescence. At least the guanidine derivative4 might represent a potentially useful agent for imaging of neuroblastoma cells."
],
"offsets": [
[
0,
1379
]
]
}
] | [
{
"id": "entity-39-0",
"type": "IUPAC",
"text": [
"m-iodobenzylguanidine"
],
"offsets": [
[
13,
34
]
],
"normalized": []
},
{
"id": "entity-39-1",
"type": "ABBREVIATION",
"text": [
"MIBG"
],
"offsets": [
[
36,
40
]
],
"normalized": []
},
{
"id": "entity-39-2",
"type": "TRIVIAL",
"text": [
"norepinephrine"
],
"offsets": [
[
210,
224
]
],
"normalized": []
},
{
"id": "entity-39-3",
"type": "ABBREVIATION",
"text": [
"NE"
],
"offsets": [
[
226,
228
]
],
"normalized": []
},
{
"id": "entity-39-4",
"type": "ABBREVIATION",
"text": [
"MIBG"
],
"offsets": [
[
450,
454
]
],
"normalized": []
},
{
"id": "entity-39-5",
"type": "IUPAC",
"text": [
"(-)-(2R,3S)-cocaine"
],
"offsets": [
[
482,
501
]
],
"normalized": []
},
{
"id": "entity-39-6",
"type": "TRIVIAL",
"text": [
"nisoxetine"
],
"offsets": [
[
506,
516
]
],
"normalized": []
},
{
"id": "entity-39-7",
"type": "IUPAC",
"text": [
"1-(1-naphthylmethyl)guanidinium sulfate"
],
"offsets": [
[
565,
604
]
],
"normalized": []
},
{
"id": "entity-39-8",
"type": "IUPAC",
"text": [
"1-[2-(dibenz[b, f]azepin-5-yl)ethyl]guanidinium sulfate"
],
"offsets": [
[
610,
665
]
],
"normalized": []
},
{
"id": "entity-39-9",
"type": "IUPAC",
"text": [
"(2R, 3S)-2beta-ethoxycarbonyl-3beta-tropanyl 5-(dimethylamino)naphthalene-1-sulfonate"
],
"offsets": [
[
675,
760
]
],
"normalized": []
},
{
"id": "entity-39-10",
"type": "TRIVIAL",
"text": [
" nisoxetine"
],
"offsets": [
[
827,
838
]
],
"normalized": []
},
{
"id": "entity-39-11",
"type": "MODIFIER",
"text": [
"derivatives"
],
"offsets": [
[
839,
850
]
],
"normalized": []
},
{
"id": "entity-39-12",
"type": "IUPAC",
"text": [
"rac-N-[(3-methylamino-1-phenyl)propyl]-5-(dimethylamino)-1-naphthale nesulfonamide"
],
"offsets": [
[
854,
936
]
],
"normalized": []
},
{
"id": "entity-39-13",
"type": "IUPAC",
"text": [
"rac-4-[(3-methylamino-1-phenyl)propyl]amino-7-nitro-2,1, 3-benzoxadiazole"
],
"offsets": [
[
945,
1018
]
],
"normalized": []
},
{
"id": "entity-39-14",
"type": "TRIVIAL",
"text": [
"guanidine"
],
"offsets": [
[
1039,
1048
]
],
"normalized": []
},
{
"id": "entity-39-15",
"type": "MODIFIER",
"text": [
"derivative"
],
"offsets": [
[
1049,
1059
]
],
"normalized": []
},
{
"id": "entity-39-16",
"type": "IUPAC",
"text": [
"1-[4-(4-phenyl-1,3-butadienyl)benzyl]guanidinium sulfate"
],
"offsets": [
[
1063,
1119
]
],
"normalized": []
},
{
"id": "entity-39-17",
"type": "TRIVIAL",
"text": [
"nisoxetine"
],
"offsets": [
[
1225,
1235
]
],
"normalized": []
},
{
"id": "entity-39-18",
"type": "TRIVIAL",
"text": [
"guanidine"
],
"offsets": [
[
1278,
1287
]
],
"normalized": []
},
{
"id": "entity-39-19",
"type": "MODIFIER",
"text": [
"derivative"
],
"offsets": [
[
1288,
1298
]
],
"normalized": []
}
] | [] | [] | [] |
example-40 | 11358723 | [
{
"id": "passage-40",
"type": "abstract",
"text": [
"11358723 Influence of estrogens on the androgen metabolism in different subunits of human hair follicles. The molecular pathways involved in estrogen-mediated induction of hair growth in androgenetic alopecia are unknown. Some authors found that estradiol (E) inhibited 5alpha-reductase (5alpha-R) activity and therefore we addressed the question whether 17alpha- or 17beta-E are able to modulate the activity of 5alpha-R, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in isolated compartments of human hair follicles. For this purpose, scalp biopsies from volunteers were taken and from each biopsy root sheaths, connective tissue sheaths and dermal papillae (DP) were dissected and incubated in the presence of 3H-testosterone (T) and, in addition, either 17alpha-E, 17beta-E, progesterone orfinasteride for up to 48 hrs. Thereafter high-performance liquid chromatography analysis of culture supernatants was performed to detect T-metabolites. At the tested concentrations, finasteride was found to be a major inhibitor of dihydrotestosterone (DHT) formation. Even 1 nM finasteride inhibited DHT synthesis in DP by 86% and 1 nM progesterone by 75%. Estrogens were less able to inhibit the synthesis of DHT in DP (e.g. nM 17alpha-E: ; nM 17beta-E: ). Whether E directly inhibits 5alpha-R in DP's or whether the effect of estrogens might be explained by an increased conversion of T to the weaker androgens such as androstendione (via 17beta-HSD), androstenediol (via 3beta-HSD) or 17beta-E (via aromatase), thereby diminishing the amount of T available for the conversion to DHT, remains to be shown."
],
"offsets": [
[
0,
1671
]
]
}
] | [
{
"id": "entity-40-0",
"type": "FAMILY",
"text": [
"estrogens"
],
"offsets": [
[
23,
32
]
],
"normalized": []
},
{
"id": "entity-40-1",
"type": "FAMILY",
"text": [
"androgen"
],
"offsets": [
[
40,
48
]
],
"normalized": []
},
{
"id": "entity-40-2",
"type": "FAMILY",
"text": [
"estrogen"
],
"offsets": [
[
143,
151
]
],
"normalized": []
},
{
"id": "entity-40-3",
"type": "TRIVIAL",
"text": [
"estradiol"
],
"offsets": [
[
248,
257
]
],
"normalized": []
},
{
"id": "entity-40-4",
"type": "ABBREVIATION",
"text": [
"E"
],
"offsets": [
[
259,
260
]
],
"normalized": []
},
{
"id": "entity-40-5",
"type": "PARTIUPAC",
"text": [
"17alpha-"
],
"offsets": [
[
357,
365
]
],
"normalized": []
},
{
"id": "entity-40-6",
"type": "IUPAC",
"text": [
"17beta-E"
],
"offsets": [
[
369,
377
]
],
"normalized": []
},
{
"id": "entity-40-7",
"type": "IUPAC",
"text": [
"3H-testosterone"
],
"offsets": [
[
768,
783
]
],
"normalized": []
},
{
"id": "entity-40-8",
"type": "ABBREVIATION",
"text": [
"T"
],
"offsets": [
[
785,
786
]
],
"normalized": []
},
{
"id": "entity-40-9",
"type": "IUPAC",
"text": [
"17alpha-E"
],
"offsets": [
[
813,
822
]
],
"normalized": []
},
{
"id": "entity-40-10",
"type": "IUPAC",
"text": [
"17beta-E"
],
"offsets": [
[
824,
832
]
],
"normalized": []
},
{
"id": "entity-40-11",
"type": "TRIVIAL",
"text": [
"progesterone"
],
"offsets": [
[
834,
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]
],
"normalized": []
},
{
"id": "entity-40-12",
"type": "TRIVIAL",
"text": [
" finasteride"
],
"offsets": [
[
849,
861
]
],
"normalized": []
},
{
"id": "entity-40-13",
"type": "TRIVIAL",
"text": [
"finasteride"
],
"offsets": [
[
1032,
1043
]
],
"normalized": []
},
{
"id": "entity-40-14",
"type": "TRIVIAL",
"text": [
"dihydrotestosterone"
],
"offsets": [
[
1081,
1100
]
],
"normalized": []
},
{
"id": "entity-40-15",
"type": "ABBREVIATION",
"text": [
"DHT"
],
"offsets": [
[
1102,
1105
]
],
"normalized": []
},
{
"id": "entity-40-16",
"type": "TRIVIAL",
"text": [
"finasteride"
],
"offsets": [
[
1128,
1139
]
],
"normalized": []
},
{
"id": "entity-40-17",
"type": "ABBREVIATION",
"text": [
"DHT"
],
"offsets": [
[
1150,
1153
]
],
"normalized": []
},
{
"id": "entity-40-18",
"type": "FAMILY",
"text": [
"Estrogens"
],
"offsets": [
[
1207,
1216
]
],
"normalized": []
},
{
"id": "entity-40-19",
"type": "ABBREVIATION",
"text": [
"DHT"
],
"offsets": [
[
1260,
1263
]
],
"normalized": []
},
{
"id": "entity-40-20",
"type": "IUPAC",
"text": [
"17alpha-E"
],
"offsets": [
[
1283,
1292
]
],
"normalized": []
},
{
"id": "entity-40-21",
"type": "IUPAC",
"text": [
"17beta-E"
],
"offsets": [
[
1306,
1314
]
],
"normalized": []
},
{
"id": "entity-40-22",
"type": "ABBREVIATION",
"text": [
"E"
],
"offsets": [
[
1330,
1331
]
],
"normalized": []
},
{
"id": "entity-40-23",
"type": "FAMILY",
"text": [
"estrogens"
],
"offsets": [
[
1392,
1401
]
],
"normalized": []
},
{
"id": "entity-40-24",
"type": "ABBREVIATION",
"text": [
"T"
],
"offsets": [
[
1451,
1452
]
],
"normalized": []
},
{
"id": "entity-40-25",
"type": "FAMILY",
"text": [
"androgens"
],
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[
1467,
1476
]
],
"normalized": []
},
{
"id": "entity-40-26",
"type": "TRIVIAL",
"text": [
"androstendione"
],
"offsets": [
[
1485,
1499
]
],
"normalized": []
},
{
"id": "entity-40-27",
"type": "TRIVIAL",
"text": [
"androstenediol"
],
"offsets": [
[
1518,
1532
]
],
"normalized": []
},
{
"id": "entity-40-28",
"type": "IUPAC",
"text": [
"17beta-E"
],
"offsets": [
[
1552,
1560
]
],
"normalized": []
},
{
"id": "entity-40-29",
"type": "ABBREVIATION",
"text": [
"T"
],
"offsets": [
[
1612,
1613
]
],
"normalized": []
},
{
"id": "entity-40-30",
"type": "ABBREVIATION",
"text": [
"DHT"
],
"offsets": [
[
1646,
1649
]
],
"normalized": []
}
] | [] | [] | [] |
example-41 | 12890682 | [
{
"id": "passage-41",
"type": "abstract",
"text": [
" Involvement of phospholipase D2 in lysophosphatidate-induced transactivation of platelet-derived growth factor receptor-beta in human bronchial epithelial cells. Lysophosphatidate (LPA) mediates multiple cellular responses via heterotrimeric G protein coupled LPA-1, LPA-2, and LPA-3 receptors. Many G protein-coupled receptors stimulate ERK following tyrosine phosphorylation of growth factor receptors; however, the mechanism(s) of transactivation of receptor tyrosine kinases are not well defined. Here, we provide evidence for the involvement of phospholipase D (PLD) in LPA-mediated transactivation of platelet-derived growth factor receptor-beta (PDGF-R beta). In primary cultures of human bronchial epithelial cells (HBEpCs), LPA stimulated tyrosine phosphorylation of PDGF-R beta and threonine/tyrosine phosphorylation of ERK1/2. The LPA-mediated activation of ERK and tyrosine phosphorylation of PDGF-R beta was attenuated by tyrphostin AG 1296, an inhibitor of PDGF-R kinase, suggesting transactivation of PDGF-R by LPA. Furthermore, LPA-, but not PDGF beta-chain homodimer-induced tyrosine phosphorylation of PDGF-R beta was partially blocked by pertussis toxin, indicating coupling of LPA-R(s) to Gi. Exposure of HBEpCs to LPA activated PLD. Butan-1-ol, which acts as an acceptor of phosphatidate generated by the PLD pathway, blocked LPA-mediated transactivation of PDGF-R beta. This effect was not seen with butan-3-ol, suggesting PLD involvement. The role of PLD1 and PLD2 in the PDGF-R beta transactivation by LPA was investigated by infection of cells with adenoviral constructs of wild type and catalytically inactive mutants of PLD. LPA activated both PLD1 and PLD2 in HBEpCs; however, infection of cells with cDNA for wild type PLD2, but not PLD1, increased the tyrosine phosphorylation of PDGF-R beta in response to LPA. Also, the LPA-mediated tyrosine phosphorylation of PDGF-R beta was attenuated by the catalytically inactive mutant mPLD2-K758R. Infection of HBEpCs with adenoviral constructs of wild type hPLD1, mPLD2, and the inactive mutants of hPLD1 and mPLD2 resulted in association of PLD2 wild type and inactive mutant proteins with the PDGF-R beta compared with PLD1. These results show for the first time that transactivation of PDGF-R beta by LPAin HBEpCs is regulated by PLD2."
],
"offsets": [
[
0,
2323
]
]
}
] | [
{
"id": "entity-41-0",
"type": "TRIVIAL",
"text": [
"lysophosphatidate"
],
"offsets": [
[
45,
62
]
],
"normalized": []
},
{
"id": "entity-41-1",
"type": "TRIVIAL",
"text": [
"Lysophosphatidate"
],
"offsets": [
[
173,
190
]
],
"normalized": []
},
{
"id": "entity-41-2",
"type": "ABBREVIATION",
"text": [
"LPA"
],
"offsets": [
[
192,
195
]
],
"normalized": []
},
{
"id": "entity-41-3",
"type": "TRIVIAL",
"text": [
"tyrosine"
],
"offsets": [
[
363,
371
]
],
"normalized": []
},
{
"id": "entity-41-4",
"type": "ABBREVIATION",
"text": [
"LPA"
],
"offsets": [
[
586,
589
]
],
"normalized": []
},
{
"id": "entity-41-5",
"type": "ABBREVIATION",
"text": [
"LPA"
],
"offsets": [
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] | [] | [] | [] |
example-42 | 2229079 | [
{
"id": "passage-42",
"type": "abstract",
"text": [
" Thyrotropin modulates low density lipoprotein binding activity in FRTL-5 thyroid cells. FRTL-5 cells possess high affinity low density lipoprotein (LDL) receptors which bind, internalize, and degrade LDL. When FRTL-5 cells are deprived of thyrotropin (TSH) the binding of LDL increases more than 2-fold. Upon addition of TSH, at a concentration of 1 x (- ) M or greater, LDL binding decreases rapidly and within 24 h reaches the level which is typical of FRTL-5 cells chronically stimulated by TSH. The data available suggest that TSH-dependent down-regulation of LDL receptor activity is exerted through a reduction of the number of active LDL receptors, with no change in affinity. It is unlikely that the synthesis of LDL receptors is impaired, since LDL receptor messenger RNA is not decreased by TSH. The effect of the hormone on LDL receptor activity can be mimicked by 8-Br-cAMP and is completely abolished by the protein synthesis inhibitor cycloheximide but not by actinomycin D. TSH regulation of LDL receptor activity is lost in v-ras Ki-transformed FRTL-5 cells (Ki Mol) which also have lost TSH dependence for adenylate cyclase activation and growth. However, 8-Br-cAMP decreases LDL binding in Ki Mol FRTL-5 cells. The reduced availability of LDL receptor in TSH-stimulated FRTL-5 cells may be related to the increased membrane fluidity (Beguinot, F., Beguinot, L., Tramontano, D., Duilio, C., Formisano, S., Bifulco, M., Ambesi-Impiombato, F. S., and Aloj, S. M. (1987) J. Biol. Chem. 262, 1575-1582) or may reflect increased degradation of LDL receptors. We propose that a lower cholesterol uptake is needed in an actively proliferating cell population, to increase the production of isoprenoids whether it be for cholesterolbiosynthesis or for the synthesis of other compounds requiring isoprenoid precursors."
],
"offsets": [
[
0,
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889,
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}
] | [] | [] | [] |
example-43 | 8230102 | [
{
"id": "passage-43",
"type": "abstract",
"text": [
"In order to develop tracers with higher specific activity to supplant the currently used [3H]-8-OH-DPAT [8-hydroxy-2-(N,N-di-n-propylamino)tetralin] for in vitro and in vivo evaluation of 5-HT1A receptors, a new radioiodinated ligand was prepared. (R,S)-trans-8- Hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin (trans-8-OH-PIPAT), 8, was synthesized by a -step reaction. Binding studies with rat hippocampal membrane homogenates showed that 8 exhibited a Ki value of 0.92 nM against (R,S)-[3H]-8-OH-DPAT. Radiolabeled [125I]-8 was prepared from the corresponding tri-n-butyltin precursor via an oxidative iododestannylation reaction with sodium [125I]iodide. Binding studies in the hippocampal homogenates revealed that [125I]-8 bound to a single high-affinity site (Kd = 0.38 +/- 0.03 nM,Bmax = +/- fmol/mg of protein). Competition binding experiments clearly indicated that the new ligand displayed the expected 5-HT1A receptor binding profile. The rank order of potency was (R,S)-trans-8-OH-PIPAT > (R,S)- 8-OH-DPAT > WB4101 > 5-HT > (R,S)-trans-7-OH-PIPAT > (R,S)-7-OH-DPAT > (R,S)-propranolol > spiperone >> ketanserin >> dopamine > atropine. This new ligand offers several unique advantages, including high specific activity, high binding affinity, and low nonspecific binding, all of which make it an excellent probe for the investigation and characterization of 5-HT1A receptors."
],
"offsets": [
[
0,
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]
}
] | [
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]
],
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],
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}
] | [] | [] | [] |
example-44 | 10479279 | [
{
"id": "passage-44",
"type": "abstract",
"text": [
"The synthesis and pharmacological profile of a series of neuroprotective adenosine agonists are described. Novel A(1) agonists with potent central nervous system effects and diminished influence on the cardiovascular system are reported and compared to selected reference adenosine agonists. The novel compounds featured are derived structurally from two key lead structures: 2-chloro-N-(1-phenoxy-2-propyl)adenosine (NNC 21-0041, 9) and 2-chloro-N-(1-piperidinyl)adenosine (NNC , 4). The agonists are characterized in terms of their in vitro profiles, both binding and functional, and in vivo activity in relevant animal models. Neuroprotective properties assessed after postischemic dosing in a Mongolian gerbil severe temporary forebrain ischemia paradigm, using hippocampal CA1 damage endpoints, and the efficacy of these agonists in an A(1) functional assay show similarities to some reference adenosine agonists. However, the new compounds we describe exhibit diminished cardiovascular effects in both anesthetized and awake rats when compared to reference A(1) agonists such as (R)-phenylisopropyladenosine (R-PIA, 5), N-cyclopentyladenosine (CPA, 2), 4, N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR 79236, 26), N-cyclohexyl-2'-O-methyladenosine (SDZ WAG 994, 27), and N-[(2-methylphenyl)methyl]adenosine (Metrifudil, 28). In mouse permanent middle cerebral artery occlusion focal ischemia, 2-chloro-N-[(R)-[(2-benzothiazolyl)thio]-2-propyl]adenosine (NNC 21-0136, 12) exhibited significant neuroprotection at the remarkably low total intraperitoneal dose of 0.1 mg/kg, a dose at which no cardiovascular effects are observed in conscious rats. The novel agonists described inhibit 6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate-induced seizures, and in mouse locomotor activity higher doses are required to reach ED( ) values than for reference A(1) agonists. We conclude that two of the novel adenosine derivatives revealed herein, 12 and 5'-deoxy-5'-chloro-N-[4-(phenylthio)-1-piperidinyl]adenosine (NNC 21-0147, 13), representatives of a new series of P(1) ligands, reinforce the fact that novel selective adenosine A(1) agonists have potential in the treatment of cerebral ischemia in humans."
],
"offsets": [
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0,
2220
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]
}
] | [
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376,
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]
],
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"id": "entity-44-4",
"type": "IUPAC",
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"(R)-phenylisopropyladenosine"
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1092,
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"id": "entity-44-5",
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"R-PIA"
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1122,
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1133,
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"id": "entity-44-7",
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1157,
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1169,
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],
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1230,
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1409,
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1964,
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],
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],
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}
] | [] | [] | [] |
example-45 | 1732554 | [
{
"id": "passage-45",
"type": "abstract",
"text": [
"A series of 8-(trifluoromethyl)-substituted quinolones has been prepared and evaluated for in vitro and in vivo antibacterial activity, and phototolerance in a mouse phototolerance assay. These analogues were compared to the corresponding series of 6,8-difluoro- and 6-fluoro-8H-quinolones (ciprofloxacin type). Although their in vitro antibacterial activities are less than the 6,8-difluoro analogues, the 8-(trifluoromethyl)quinolones are generally equivalent to their 8H analogues. In vivo, they are comparable to the 6,8-difluoro series and show up to -fold improvement in efficacy when compared to their ciprofloxacin counterparts vs Streptococcus pyogenes and Streptococcus pneumonia. In the phototolerance model, the 8-(trifluoromethyl)quinolones are comparable to the 8H-quinolones. Both of these series display much higher no effect doses (greater tolerance) than the corresponding 6,8-difluoroquinolones."
],
"offsets": [
[
0,
916
]
]
}
] | [
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],
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12,
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],
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249,
262
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],
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},
{
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267,
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]
],
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"id": "entity-45-14",
"type": "IUPAC",
"text": [
"6,8-difluoroquinolones"
],
"offsets": [
[
893,
915
]
],
"normalized": []
}
] | [] | [] | [] |
example-46 | 3761308 | [
{
"id": "passage-46",
"type": "abstract",
"text": [
"This study emphasizes the importance of the metabolic conversion of the enantiomers of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) into their catechol analogues, the enantiomers of 3-(3,4-dihydroxyphenyl)-N-n-propylpiperidine. These isomers are both shown to be excellent substrates for COMT, with a slight preference for the S-(-) enantiomer. Assessment of the dopaminergic activity of these catechols and the results from the determination of brain levels of the enantiomers of 3-PPP and their metabolites indicate that the metabolites probably do not alter the pharmacological profiles established for (R)-(+)- and (S)-(-)-3-PPP. The conversion of the monophenols into catecholic metabolites is only 1-5%, and the further conversion of these catecholic metabolites into methoxylated analogues is very rapid. However, the very interesting observation was made that, when inhibiting COMT by means of tropolone and subsequently treating the rats with high doses of (S)-(-)-3-PPP (ip), postsynaptic dopaminergic activity was elicited. This has never been seen for (S)-(-)-3-PPP without tropolone pretreatment and might indicate that, in this special case, the catecholic metabolite affects the in vivo pharmacological profile of (S)-(-)-3-PPP."
],
"offsets": [
[
0,
1247
]
]
}
] | [
{
"id": "entity-46-0",
"type": "IUPAC",
"text": [
"3-(3-hydroxyphenyl)-N-n-propylpiperidine"
],
"offsets": [
[
87,
127
]
],
"normalized": []
},
{
"id": "entity-46-1",
"type": "ABBREVIATION",
"text": [
"3-PPP"
],
"offsets": [
[
129,
134
]
],
"normalized": []
},
{
"id": "entity-46-2",
"type": "TRIVIAL",
"text": [
"catechol"
],
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147,
155
]
],
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},
{
"id": "entity-46-3",
"type": "MODIFIER",
"text": [
"analogues"
],
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[
156,
165
]
],
"normalized": []
},
{
"id": "entity-46-4",
"type": "IUPAC",
"text": [
"3-(3,4-dihydroxyphenyl)-N-n-propylpiperidine"
],
"offsets": [
[
186,
230
]
],
"normalized": []
},
{
"id": "entity-46-5",
"type": "ABBREVIATION",
"text": [
"3-PPP"
],
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[
485,
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]
],
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},
{
"id": "entity-46-6",
"type": "PARTIUPAC",
"text": [
"(R)-(+)-"
],
"offsets": [
[
610,
618
]
],
"normalized": []
},
{
"id": "entity-46-7",
"type": "IUPAC",
"text": [
"(S)-(-)-3-PPP"
],
"offsets": [
[
623,
636
]
],
"normalized": []
},
{
"id": "entity-46-8",
"type": "FAMILY",
"text": [
"monophenols"
],
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660,
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]
],
"normalized": []
},
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"id": "entity-46-9",
"type": "TRIVIAL",
"text": [
"tropolone"
],
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[
906,
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]
],
"normalized": []
},
{
"id": "entity-46-10",
"type": "IUPAC",
"text": [
"(S)-(-)-3-PPP"
],
"offsets": [
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970,
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]
],
"normalized": []
},
{
"id": "entity-46-11",
"type": "IUPAC",
"text": [
"(S)-(-)-3-PPP"
],
"offsets": [
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1068,
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]
],
"normalized": []
},
{
"id": "entity-46-12",
"type": "TRIVIAL",
"text": [
"tropolone"
],
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1090,
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]
],
"normalized": []
},
{
"id": "entity-46-13",
"type": "IUPAC",
"text": [
"(S)-(-)-3-PPP"
],
"offsets": [
[
1233,
1246
]
],
"normalized": []
}
] | [] | [] | [] |
example-47 | 1512594 | [
{
"id": "passage-47",
"type": "abstract",
"text": [
"1512594 Genetic absence epilepsy in rats from Strasbourg--a review. We have selected a strain of rats and designated it the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this strain, of the animals present recurrent generalized non-convulsive seizures characterized by bilateral and synchronous spike-and-wave discharges accompanied with behavioural arrest, staring and sometimes twitching of the vibrissae. Spontaneous SWD (7-11 cps, microV, 0.5-75 sec) start and end abruptly on a normal background EEG. They usually occur at a mean frequency of 1.5 per min when the animals are in a state of quiet wakefulness. Drugs effective against absence seizures in humans (ethosuccimide, trimethadione, valproate, benzodiazepines) suppress the SWD dose-dependently, whereas drugs specific for convulsive or focal seizures (carbamazepine, phenytoin) are ineffective. SWD are increased by epileptogenic drugs inducing petit mal-like seizures, such as pentylenetetrazol, gamma-hydroxybutyrate, THIP and penicillin. Depth EEG recordings and lesion experiments show that SWD in GAERs depend on cortical and thalamic structures with a possible rhythmic triggering by the lateral thalamus. Most neurotransmitters are involved in the control of SWD (dopamine, noradrenaline, NMDA, acetylcholine), but GABA and gamma-hydroxybutyrate (GHB) seem to play a critical role. SWD are genetically determined with an autosomal dominant inheritance. The variable expression of SWD in offsprings from GAERS x control reciprocal crosses may be due to the existence of multiple genes. Neurophysiological, behavioural, pharmacological and genetic studies demonstrate that spontaneous SWD in GAERS fulfill all the requirements for an experimental model of absence epilepsy. As the mechanisms underlying absence epilepsy in humans are still unknown, the analysis of the genetic thalamocortical dysfunction in GAERS may be fruitful in investigations of the pathogenesis of generalized non-convulsive seizures."
],
"offsets": [
[
0,
2004
]
]
}
] | [
{
"id": "entity-47-0",
"type": "TRIVIAL",
"text": [
"ethosuccimide"
],
"offsets": [
[
694,
707
]
],
"normalized": []
},
{
"id": "entity-47-1",
"type": "TRIVIAL",
"text": [
"trimethadione"
],
"offsets": [
[
709,
722
]
],
"normalized": []
},
{
"id": "entity-47-2",
"type": "TRIVIAL",
"text": [
"valproate"
],
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[
724,
733
]
],
"normalized": []
},
{
"id": "entity-47-3",
"type": "TRIVIAL",
"text": [
"benzodiazepines"
],
"offsets": [
[
735,
750
]
],
"normalized": []
},
{
"id": "entity-47-4",
"type": "TRIVIAL",
"text": [
"carbamazepine"
],
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[
844,
857
]
],
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},
{
"id": "entity-47-5",
"type": "TRIVIAL",
"text": [
"phenytoin"
],
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[
859,
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]
],
"normalized": []
},
{
"id": "entity-47-6",
"type": "TRIVIAL",
"text": [
"pentylenetetrazol"
],
"offsets": [
[
970,
987
]
],
"normalized": []
},
{
"id": "entity-47-7",
"type": "IUPAC",
"text": [
"gamma-hydroxybutyrate"
],
"offsets": [
[
989,
1010
]
],
"normalized": []
},
{
"id": "entity-47-8",
"type": "ABBREVIATION",
"text": [
"THIP"
],
"offsets": [
[
1012,
1016
]
],
"normalized": []
},
{
"id": "entity-47-9",
"type": "TRIVIAL",
"text": [
"penicillin"
],
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[
1021,
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]
],
"normalized": []
},
{
"id": "entity-47-10",
"type": "TRIVIAL",
"text": [
"dopamine"
],
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[
1263,
1271
]
],
"normalized": []
},
{
"id": "entity-47-11",
"type": "TRIVIAL",
"text": [
"noradrenaline"
],
"offsets": [
[
1273,
1286
]
],
"normalized": []
},
{
"id": "entity-47-12",
"type": "ABBREVIATION",
"text": [
"NMDA"
],
"offsets": [
[
1288,
1292
]
],
"normalized": []
},
{
"id": "entity-47-13",
"type": "TRIVIAL",
"text": [
"acetylcholine"
],
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[
1294,
1307
]
],
"normalized": []
},
{
"id": "entity-47-14",
"type": "ABBREVIATION",
"text": [
"GABA "
],
"offsets": [
[
1314,
1319
]
],
"normalized": []
},
{
"id": "entity-47-15",
"type": "IUPAC",
"text": [
"gamma-hydroxybutyrate"
],
"offsets": [
[
1323,
1344
]
],
"normalized": []
},
{
"id": "entity-47-16",
"type": "ABBREVIATION",
"text": [
"GHB"
],
"offsets": [
[
1346,
1349
]
],
"normalized": []
}
] | [] | [] | [] |
example-48 | 11879044 | [
{
"id": "passage-48",
"type": "abstract",
"text": [
" Diphenol activation of the monophenolase and diphenolase activities of field bean (Dolichos lablab) polyphenol oxidase. This paper reports a study on the hydroxylation of ferulic acid and tyrosine by field bean (Dolichos lablab) polyphenol oxidase, a reaction that does not take place without the addition of catechol. A lag period similar to the characteristic lag of tyrosinase activity was observed, the length of which decreased with increasing catechol concentration and increased with increasing ferulic acid concentration. The activation constant K(a) of catechol for ferulic acid hydroxylation reaction was 5 mM. The kinetic parameters of field bean polyphenol oxidase toward ferulic acid and tyrosine were evaluated in the presence of catechol. 4-Methyl catechol, L-dihydroxyphenylalanine, pyrogallol, and 2,3,4-trihydroxybenzoic acid, substrates with high binding affinity to field bean polyphenol oxidase, could stimulate this hydroxylation reaction. In contrast, diphenols such as protocatechuic acid, gallic acid, chlorogenic acid, and caffeic acid, which were not substrates for the oxidation reaction, were unable to bring about this activation. It is most likely that only o-diphenols that are substrates for the diphenolase serve as cosubstrates by donating electrons at the active site for the monophenolase activity. The reaction mechanism for this activation is consistent with that proposed for tyrosinase (Sanchez-Ferrer, A.; Rodriguez-Lopez, J. N.; Garcia-Canovas, F.; Garcia-Carmona, F. Biochim. Biophys. Acta 1995, 1247, 1-11). The presence of o-diphenols, viz. catechol, L-dihydroxyphenylalanine, and 4-methyl catechol, is also necessary for the oxidation of the diphenols, caffeic acid, and catechin to their quinones by the field bean polyphenol oxidase. This oxidation reaction occurs immediately with no lag period and does not occur without the addition of diphenol. The kinetic parameters for caffeic acid (K(m) = 0.08 mM, V(max) = u/mg) in the presence of catechol and the activation constant K(a) of catechol (4.6 mM) for this reaction were enumerated. The absence of a lag period for this reaction indicates that the diphenol mechanism of diphenolase activation differs from the way in which the same o-diphenolsactivate the monophenolase activity."
],
"offsets": [
[
0,
2301
]
]
}
] | [
{
"id": "entity-48-0",
"type": "FAMILY",
"text": [
"Diphenol"
],
"offsets": [
[
10,
18
]
],
"normalized": []
},
{
"id": "entity-48-1",
"type": "IUPAC",
"text": [
"ferulic acid"
],
"offsets": [
[
182,
194
]
],
"normalized": []
},
{
"id": "entity-48-2",
"type": "TRIVIAL",
"text": [
"tyrosine"
],
"offsets": [
[
199,
207
]
],
"normalized": []
},
{
"id": "entity-48-3",
"type": "TRIVIAL",
"text": [
"catechol"
],
"offsets": [
[
320,
328
]
],
"normalized": []
},
{
"id": "entity-48-4",
"type": "TRIVIAL",
"text": [
"catechol"
],
"offsets": [
[
460,
468
]
],
"normalized": []
},
{
"id": "entity-48-5",
"type": "IUPAC",
"text": [
"ferulic acid"
],
"offsets": [
[
513,
525
]
],
"normalized": []
},
{
"id": "entity-48-6",
"type": "TRIVIAL",
"text": [
"catechol"
],
"offsets": [
[
573,
581
]
],
"normalized": []
},
{
"id": "entity-48-7",
"type": "IUPAC",
"text": [
"ferulic acid"
],
"offsets": [
[
586,
598
]
],
"normalized": []
},
{
"id": "entity-48-8",
"type": "IUPAC",
"text": [
"ferulic acid"
],
"offsets": [
[
695,
707
]
],
"normalized": []
},
{
"id": "entity-48-9",
"type": "TRIVIAL",
"text": [
"tyrosine"
],
"offsets": [
[
712,
720
]
],
"normalized": []
},
{
"id": "entity-48-10",
"type": "TRIVIAL",
"text": [
"catechol"
],
"offsets": [
[
755,
763
]
],
"normalized": []
},
{
"id": "entity-48-11",
"type": "IUPAC",
"text": [
"4-Methyl catechol"
],
"offsets": [
[
765,
782
]
],
"normalized": []
},
{
"id": "entity-48-12",
"type": "IUPAC",
"text": [
"L-dihydroxyphenylalanine"
],
"offsets": [
[
784,
808
]
],
"normalized": []
},
{
"id": "entity-48-13",
"type": "TRIVIAL",
"text": [
"pyrogallol"
],
"offsets": [
[
810,
820
]
],
"normalized": []
},
{
"id": "entity-48-14",
"type": "IUPAC",
"text": [
"2,3,4-trihydroxybenzoic acid"
],
"offsets": [
[
826,
854
]
],
"normalized": []
},
{
"id": "entity-48-15",
"type": "FAMILY",
"text": [
"diphenols"
],
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[
986,
995
]
],
"normalized": []
},
{
"id": "entity-48-16",
"type": "IUPAC",
"text": [
"protocatechuic acid"
],
"offsets": [
[
1004,
1023
]
],
"normalized": []
},
{
"id": "entity-48-17",
"type": "IUPAC",
"text": [
"gallic acid"
],
"offsets": [
[
1025,
1036
]
],
"normalized": []
},
{
"id": "entity-48-18",
"type": "IUPAC",
"text": [
"chlorogenic acid"
],
"offsets": [
[
1038,
1054
]
],
"normalized": []
},
{
"id": "entity-48-19",
"type": "IUPAC",
"text": [
"caffeic acid"
],
"offsets": [
[
1060,
1072
]
],
"normalized": []
},
{
"id": "entity-48-20",
"type": "FAMILY",
"text": [
"o-diphenols"
],
"offsets": [
[
1200,
1211
]
],
"normalized": []
},
{
"id": "entity-48-21",
"type": "FAMILY",
"text": [
"o-diphenols"
],
"offsets": [
[
1580,
1591
]
],
"normalized": []
},
{
"id": "entity-48-22",
"type": "TRIVIAL",
"text": [
"catechol"
],
"offsets": [
[
1598,
1606
]
],
"normalized": []
},
{
"id": "entity-48-23",
"type": "IUPAC",
"text": [
"L-dihydroxyphenylalanine"
],
"offsets": [
[
1608,
1632
]
],
"normalized": []
},
{
"id": "entity-48-24",
"type": "IUPAC",
"text": [
"4-methyl catechol"
],
"offsets": [
[
1638,
1655
]
],
"normalized": []
},
{
"id": "entity-48-25",
"type": "FAMILY",
"text": [
"diphenols"
],
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[
1700,
1709
]
],
"normalized": []
},
{
"id": "entity-48-26",
"type": "TRIVIAL",
"text": [
"caffeic acid"
],
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[
1711,
1723
]
],
"normalized": []
},
{
"id": "entity-48-27",
"type": "TRIVIAL",
"text": [
"catechin"
],
"offsets": [
[
1729,
1737
]
],
"normalized": []
},
{
"id": "entity-48-28",
"type": "FAMILY",
"text": [
"quinones"
],
"offsets": [
[
1747,
1755
]
],
"normalized": []
},
{
"id": "entity-48-29",
"type": "FAMILY",
"text": [
"diphenol"
],
"offsets": [
[
1899,
1907
]
],
"normalized": []
},
{
"id": "entity-48-30",
"type": "TRIVIAL",
"text": [
"caffeic acid"
],
"offsets": [
[
1936,
1948
]
],
"normalized": []
},
{
"id": "entity-48-31",
"type": "TRIVIAL",
"text": [
"catechol"
],
"offsets": [
[
2006,
2014
]
],
"normalized": []
},
{
"id": "entity-48-32",
"type": "TRIVIAL",
"text": [
"catechol"
],
"offsets": [
[
2051,
2059
]
],
"normalized": []
},
{
"id": "entity-48-33",
"type": "FAMILY",
"text": [
"diphenol"
],
"offsets": [
[
2169,
2177
]
],
"normalized": []
},
{
"id": "entity-48-34",
"type": "FAMILY",
"text": [
"o-diphenols"
],
"offsets": [
[
2253,
2264
]
],
"normalized": []
}
] | [] | [] | [] |
example-49 | 8960550 | [
{
"id": "passage-49",
"type": "abstract",
"text": [
"In the present investigation, the last two possible modes of generating conformationally semirigid diacylglycerol (DAG) analogues embedded into five-membered ring lactones as templates III and IV are investigated. The first two templates studied in previous investigations corresponded to 2-deoxyribonolactone (template I) and 4,4-disubstituted gamma-butyrolactone (template II), with the latter producing potent protein kinase C (PK-C) ligands with low nanomolar binding affinities. The templates reported in this work correspond to 2,3-dideoxy-L-erythro- or -threo-hexono-1,4-lactone (template III) and 2-deoxyapiolactone (template IV). Compounds constructed with the dideoxy-L-erythro- or -threo-hexono-1,4-lactone template were synthesized stereospecifically from tri-O-acetyl-L-glucal and L-galactono-1,4-lactone, respectively. Compounds constructed with the 2-deoxyapiolactone template were synthesized stereoselectively from di-O-isopropylidene-alpha-D-apiose. Inhibition of the binding of [3H]phorbol-12,13-dibutyrate to PK-C alpha showed that only the threo-isomer, 5-O-tetradecanoyl-2,3-dideoxy-L-threo-hexono-1,4-lactone (2) was a good PK-C ligand (Ki = 1 microM). The rest of the ligands had poorer affinities with Ki values between and 28 microM. With these results, the order of importance of five-membered ring lactones as competent templates for the construction of semirigid DAGsurrogates with effective PK-C binding affinity can be established as II >> I approximately III > IV."
],
"offsets": [
[
0,
1509
]
]
}
] | [
{
"id": "entity-49-0",
"type": "TRIVIAL",
"text": [
"diacylglycerol"
],
"offsets": [
[
99,
113
]
],
"normalized": []
},
{
"id": "entity-49-1",
"type": "ABBREVIATION",
"text": [
"DAG"
],
"offsets": [
[
115,
118
]
],
"normalized": []
},
{
"id": "entity-49-2",
"type": "MODIFIER",
"text": [
"analogues"
],
"offsets": [
[
120,
129
]
],
"normalized": []
},
{
"id": "entity-49-3",
"type": "FAMILY",
"text": [
"lactones"
],
"offsets": [
[
163,
171
]
],
"normalized": []
},
{
"id": "entity-49-4",
"type": "IUPAC",
"text": [
"2-deoxyribonolactone"
],
"offsets": [
[
289,
309
]
],
"normalized": []
},
{
"id": "entity-49-5",
"type": "IUPAC",
"text": [
"4,4-disubstituted gamma-butyrolactone"
],
"offsets": [
[
327,
364
]
],
"normalized": []
},
{
"id": "entity-49-6",
"type": "PARTIUPAC",
"text": [
"2,3-dideoxy-L-erythro-"
],
"offsets": [
[
534,
556
]
],
"normalized": []
},
{
"id": "entity-49-7",
"type": "IUPAC",
"text": [
"-threo-hexono-1,4-lactone"
],
"offsets": [
[
560,
585
]
],
"normalized": []
},
{
"id": "entity-49-8",
"type": "IUPAC",
"text": [
"2-deoxyapiolactone"
],
"offsets": [
[
605,
623
]
],
"normalized": []
},
{
"id": "entity-49-9",
"type": "PARTIUPAC",
"text": [
"dideoxy-L-erythro-"
],
"offsets": [
[
670,
688
]
],
"normalized": []
},
{
"id": "entity-49-10",
"type": "IUPAC",
"text": [
"-threo-hexono-1,4-lactone"
],
"offsets": [
[
692,
717
]
],
"normalized": []
},
{
"id": "entity-49-11",
"type": "IUPAC",
"text": [
"tri-O-acetyl-L-glucal"
],
"offsets": [
[
768,
789
]
],
"normalized": []
},
{
"id": "entity-49-12",
"type": "IUPAC",
"text": [
"L-galactono-1,4-lactone"
],
"offsets": [
[
794,
817
]
],
"normalized": []
},
{
"id": "entity-49-13",
"type": "IUPAC",
"text": [
"2-deoxyapiolactone"
],
"offsets": [
[
864,
882
]
],
"normalized": []
},
{
"id": "entity-49-14",
"type": "IUPAC",
"text": [
"di-O-isopropylidene-alpha-D-apiose"
],
"offsets": [
[
932,
966
]
],
"normalized": []
},
{
"id": "entity-49-15",
"type": "IUPAC",
"text": [
"[3H]phorbol-12,13-dibutyrate"
],
"offsets": [
[
997,
1025
]
],
"normalized": []
},
{
"id": "entity-49-16",
"type": "FAMILY",
"text": [
"threo-isomer"
],
"offsets": [
[
1061,
1073
]
],
"normalized": []
},
{
"id": "entity-49-17",
"type": "IUPAC",
"text": [
"5-O-tetradecanoyl-2,3-dideoxy-L-threo-hexono-1,4-lactone"
],
"offsets": [
[
1075,
1131
]
],
"normalized": []
},
{
"id": "entity-49-18",
"type": "FAMILY",
"text": [
"lactones"
],
"offsets": [
[
1329,
1337
]
],
"normalized": []
},
{
"id": "entity-49-19",
"type": "ABBREVIATION",
"text": [
"DAG"
],
"offsets": [
[
1395,
1398
]
],
"normalized": []
}
] | [] | [] | [] |
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Dataset Card for SCAI Chemical
SCAI Chemical is a corpus of MEDLINE abstracts that has been annotated to give an overview of the different chemical name classes found in MEDLINE text.
Citation Information
@inproceedings{kolarik:lrec-ws08,
author = {Kol{'a}{ r}ik, Corinna and Klinger, Roman and Friedrich, Christoph M and Hofmann-Apitius, Martin and Fluck, Juliane},
title = {Chemical Names: {T}erminological Resources and Corpora Annotation},
booktitle = {LREC Workshop on Building and Evaluating Resources for Biomedical Text Mining},
year = {2008},
}
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