IL210294A - Salts and Polymorphs of Desazadesprithiocine Analogues Polyurethane as Metal Adsorbents - Google Patents

Info

Publication number

IL210294A

IL210294A IL210294A IL21029410A IL210294A IL 210294 A IL210294 A IL 210294A IL 210294 A IL210294 A IL 210294A IL 21029410 A IL21029410 A IL 21029410A IL 210294 A IL210294 A IL 210294A

Authority

IL

Israel

Prior art keywords

recited

polymorph

solid composition

salt

magnesium

Prior art date

2008-07-14

Links

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• 150000003839 salts Chemical class 0.000 title claims description 174
• 229920000570 polyether Polymers 0.000 title claims description 30
• 239000004721 Polyphenylene oxide Substances 0.000 title claims description 27
• 229910052751 metal Inorganic materials 0.000 title claims description 23
• 239000002184 metal Substances 0.000 title claims description 23
• 239000002738 chelating agent Substances 0.000 title description 17
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 77
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 55
• 238000000034 method Methods 0.000 claims description 47
• -1 p-TSA monohydrate Chemical class 0.000 claims description 44
• 229910052742 iron Inorganic materials 0.000 claims description 38
• 239000008247 solid mixture Substances 0.000 claims description 32
• 239000011777 magnesium Substances 0.000 claims description 31
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 30
• 229910052749 magnesium Inorganic materials 0.000 claims description 30
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 30
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 29
• 159000000003 magnesium salts Chemical class 0.000 claims description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• 230000001575 pathological effect Effects 0.000 claims description 24
• 229960000281 trometamol Drugs 0.000 claims description 23
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 21
• 239000011575 calcium Substances 0.000 claims description 20
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 19
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 19
• 229910052791 calcium Inorganic materials 0.000 claims description 19
• 238000000113 differential scanning calorimetry Methods 0.000 claims description 19
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 238000001228 spectrum Methods 0.000 claims description 19
• 238000002336 sorption--desorption measurement Methods 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 15
• 229910052757 nitrogen Inorganic materials 0.000 claims description 15
• 239000011701 zinc Substances 0.000 claims description 15
• 239000004472 Lysine Substances 0.000 claims description 14
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 14
• 235000018977 lysine Nutrition 0.000 claims description 14
• 229910052725 zinc Inorganic materials 0.000 claims description 14
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 13
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 12
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
• 239000011591 potassium Substances 0.000 claims description 12
• 229910052700 potassium Inorganic materials 0.000 claims description 12
• 239000011734 sodium Substances 0.000 claims description 12
• 229910052708 sodium Inorganic materials 0.000 claims description 12
• 238000010521 absorption reaction Methods 0.000 claims description 11
• 201000010099 disease Diseases 0.000 claims description 11
• 206010065973 Iron Overload Diseases 0.000 claims description 10
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 230000002496 gastric effect Effects 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• 235000005911 diet Nutrition 0.000 claims description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
• 229910052768 actinide Inorganic materials 0.000 claims description 8
• 150000001255 actinides Chemical class 0.000 claims description 8
• 230000009920 chelation Effects 0.000 claims description 8
• 230000000378 dietary effect Effects 0.000 claims description 8
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 8
• 235000012254 magnesium hydroxide Nutrition 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• 229910052747 lanthanoid Inorganic materials 0.000 claims description 7
• 150000002602 lanthanoids Chemical class 0.000 claims description 7
• 239000000347 magnesium hydroxide Substances 0.000 claims description 7
• 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 7
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 238000009826 distribution Methods 0.000 claims description 6
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 159000000000 sodium salts Chemical class 0.000 claims description 6
• 238000001757 thermogravimetry curve Methods 0.000 claims description 6
• 210000001185 bone marrow Anatomy 0.000 claims description 5
• 235000011116 calcium hydroxide Nutrition 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 150000002367 halogens Chemical class 0.000 claims description 5
• 229910021511 zinc hydroxide Inorganic materials 0.000 claims description 5
• 208000033981 Hereditary haemochromatosis Diseases 0.000 claims description 4
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 4
• 208000022806 beta-thalassemia major Diseases 0.000 claims description 4
• AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 4
• 239000000920 calcium hydroxide Substances 0.000 claims description 4
• 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 4
• 230000029142 excretion Effects 0.000 claims description 4
• 208000019423 liver disease Diseases 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 235000011121 sodium hydroxide Nutrition 0.000 claims description 4
• HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 claims description 3
• 102100033051 40S ribosomal protein S19 Human genes 0.000 claims description 3
• 206010003591 Ataxia Diseases 0.000 claims description 3
• 208000033932 Blackfan-Diamond anemia Diseases 0.000 claims description 3
• 206010053138 Congenital aplastic anaemia Diseases 0.000 claims description 3
• 108700037009 Congenital atransferrinemia Proteins 0.000 claims description 3
• 201000004449 Diamond-Blackfan anemia Diseases 0.000 claims description 3
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 3
• ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 3
• 208000037919 acquired disease Diseases 0.000 claims description 3
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
• 201000007867 atransferrinemia Diseases 0.000 claims description 3
• 229960003237 betaine Drugs 0.000 claims description 3
• 229940075419 choline hydroxide Drugs 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 3
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
• 208000024132 familial porphyria cutanea tarda Diseases 0.000 claims description 3
• 210000002216 heart Anatomy 0.000 claims description 3
• 208000007475 hemolytic anemia Diseases 0.000 claims description 3
• 208000006454 hepatitis Diseases 0.000 claims description 3
• 231100000283 hepatitis Toxicity 0.000 claims description 3
• 210000003734 kidney Anatomy 0.000 claims description 3
• 208000032839 leukemia Diseases 0.000 claims description 3
• 210000004185 liver Anatomy 0.000 claims description 3
• UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 3
• 239000011654 magnesium acetate Substances 0.000 claims description 3
• 235000011285 magnesium acetate Nutrition 0.000 claims description 3
• 229940069446 magnesium acetate Drugs 0.000 claims description 3
• 208000007056 sickle cell anemia Diseases 0.000 claims description 3
• 208000031162 sideroblastic anemia Diseases 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 231100000331 toxic Toxicity 0.000 claims description 3
• 230000002588 toxic effect Effects 0.000 claims description 3
• 239000004246 zinc acetate Substances 0.000 claims description 3
• KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 claims description 2
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 2
• 229930064664 L-arginine Natural products 0.000 claims description 2
• 235000014852 L-arginine Nutrition 0.000 claims description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 2
• 210000004100 adrenal gland Anatomy 0.000 claims description 2
• 208000022809 beta-thalassemia intermedia Diseases 0.000 claims description 2
• 229940043237 diethanolamine Drugs 0.000 claims description 2
• 150000004683 dihydrates Chemical class 0.000 claims description 2
• 230000008030 elimination Effects 0.000 claims description 2
• 238000003379 elimination reaction Methods 0.000 claims description 2
• XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 claims description 2
• 229960002885 histidine Drugs 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 claims description 2
• 230000009919 sequestration Effects 0.000 claims description 2
• 210000000952 spleen Anatomy 0.000 claims description 2
• WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims description 2
• 210000001541 thymus gland Anatomy 0.000 claims description 2
• KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 claims 2
• 150000002431 hydrogen Chemical class 0.000 claims 2
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims 1
• VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 claims 1
• 150000001875 compounds Chemical class 0.000 description 114
• 239000004698 Polyethylene Substances 0.000 description 83
• 239000000203 mixture Substances 0.000 description 42
• 239000000243 solution Substances 0.000 description 41
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• 239000000463 material Substances 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
• 239000002904 solvent Substances 0.000 description 31
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• 238000002474 experimental method Methods 0.000 description 20
• 239000002585 base Substances 0.000 description 18
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 17
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