OA12166A - Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetestherewith. - Google Patents
Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetestherewith. Download PDFInfo
- Publication number
- OA12166A OA12166A OA1200200226A OA1200200226A OA12166A OA 12166 A OA12166 A OA 12166A OA 1200200226 A OA1200200226 A OA 1200200226A OA 1200200226 A OA1200200226 A OA 1200200226A OA 12166 A OA12166 A OA 12166A
- Authority
- OA
- OAPI
- Prior art keywords
- sait
- compound
- carboxy
- methyl
- hexyloxy
- Prior art date
Links
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims description 70
- 238000000034 method Methods 0.000 title claims description 40
- 239000011575 calcium Substances 0.000 title claims description 36
- 229910052791 calcium Inorganic materials 0.000 title claims description 33
- 208000019553 vascular disease Diseases 0.000 title description 13
- 150000002170 ethers Chemical class 0.000 title description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 205
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 91
- 229910001868 water Inorganic materials 0.000 claims abstract description 85
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 60
- 239000000047 product Substances 0.000 claims description 55
- 235000019441 ethanol Nutrition 0.000 claims description 54
- 239000007787 solid Substances 0.000 claims description 34
- 239000002904 solvent Substances 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- UVSDAPVYVXZPDP-UHFFFAOYSA-N calcium;6-(5-carboxy-5-methylhexoxy)-2,2-dimethylhexanoic acid Chemical group [Ca].OC(=O)C(C)(C)CCCCOCCCCC(C)(C)C(O)=O UVSDAPVYVXZPDP-UHFFFAOYSA-N 0.000 claims description 21
- 239000000292 calcium oxide Substances 0.000 claims description 20
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 20
- 239000000843 powder Substances 0.000 claims description 19
- 239000012265 solid product Substances 0.000 claims description 17
- -1 1-butvl Chemical class 0.000 claims description 15
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 14
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 14
- 238000010992 reflux Methods 0.000 claims description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 7
- 238000010626 work up procedure Methods 0.000 claims description 7
- 239000000969 carrier Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 238000000634 powder X-ray diffraction Methods 0.000 claims 3
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
- TWEMLCACKJJFAC-UHFFFAOYSA-N calcium;2,2-dimethylhexanoic acid Chemical compound [Ca].CCCCC(C)(C)C(O)=O TWEMLCACKJJFAC-UHFFFAOYSA-N 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- ZJKZKKPIKDNHDM-UHFFFAOYSA-L calcium;6-(5-carboxylato-5-methylhexoxy)-2,2-dimethylhexanoate Chemical compound [Ca+2].[O-]C(=O)C(C)(C)CCCCOCCCCC(C)(C)C([O-])=O ZJKZKKPIKDNHDM-UHFFFAOYSA-L 0.000 abstract description 41
- 208000032928 Dyslipidaemia Diseases 0.000 abstract description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 abstract description 3
- 239000012453 solvate Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 25
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 20
- 235000012255 calcium oxide Nutrition 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 17
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 17
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 238000013019 agitation Methods 0.000 description 14
- 229940087373 calcium oxide Drugs 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000004448 titration Methods 0.000 description 12
- 108010010234 HDL Lipoproteins Proteins 0.000 description 11
- 102000015779 HDL Lipoproteins Human genes 0.000 description 11
- 238000002441 X-ray diffraction Methods 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 238000011005 laboratory method Methods 0.000 description 10
- 210000002381 plasma Anatomy 0.000 description 10
- SDMBRCRVFFHJKR-UHFFFAOYSA-N 6-(5-carboxy-5-methylhexoxy)-2,2-dimethylhexanoic acid Chemical compound OC(=O)C(C)(C)CCCCOCCCCC(C)(C)C(O)=O SDMBRCRVFFHJKR-UHFFFAOYSA-N 0.000 description 9
- 108010007622 LDL Lipoproteins Proteins 0.000 description 8
- 102000007330 LDL Lipoproteins Human genes 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000010926 purge Methods 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 230000007423 decrease Effects 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 241000282693 Cercopithecidae Species 0.000 description 4
- 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 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 159000000007 calcium salts Chemical class 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 229960001375 lactose Drugs 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000013341 scale-up Methods 0.000 description 4
- 206010016717 Fistula Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000000920 calcium hydroxide Substances 0.000 description 3
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000007958 cherry flavor Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000003028 elevating effect Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 108010023302 HDL Cholesterol Proteins 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 108010033266 Lipoprotein(a) Proteins 0.000 description 2
- 102000057248 Lipoprotein(a) Human genes 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- NMDHBICHFIUGDA-UHFFFAOYSA-N calcium;hexanoic acid Chemical compound [Ca].CCCCCC(O)=O NMDHBICHFIUGDA-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 238000010961 commercial manufacture process Methods 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003890 fistula Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000001044 red dye Substances 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YTTWDTVYXAEAJA-UHFFFAOYSA-N 2,2-dimethyl-hexanoic acid Chemical compound CCCCC(C)(C)C(O)=O YTTWDTVYXAEAJA-UHFFFAOYSA-N 0.000 description 1
- UZWFWTGDUXLNKR-UHFFFAOYSA-N 8-(4-methylpentan-2-yl)-3,7-dihydropurine-2,6-dione Chemical compound N1C(=O)NC(=O)C2=C1N=C(C(C)CC(C)C)N2 UZWFWTGDUXLNKR-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical class CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108010069201 VLDL Cholesterol Proteins 0.000 description 1
- FVOVJUPBNYMIDL-UHFFFAOYSA-K [Na+].[Na+].[Na+].OCC(O)CO.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O Chemical compound [Na+].[Na+].[Na+].OCC(O)CO.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FVOVJUPBNYMIDL-UHFFFAOYSA-K 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000010981 drying operation Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical class CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/125—Saturated compounds having only one carboxyl group and containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/305—Saturated compounds containing more than one carboxyl group containing ether groups, groups, groups, or groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17782300P | 2000-01-25 | 2000-01-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA12166A true OA12166A (en) | 2003-11-07 |
Family
ID=22650106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200200226A OA12166A (en) | 2000-01-25 | 2001-01-11 | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetestherewith. |
Country Status (39)
| Country | Link |
|---|---|
| EP (1) | EP1259474B1 (pl) |
| JP (1) | JP4750995B2 (pl) |
| KR (1) | KR20020073182A (pl) |
| CN (1) | CN1395555A (pl) |
| AP (1) | AP2002002587A0 (pl) |
| AR (1) | AR029436A1 (pl) |
| AT (1) | ATE431326T1 (pl) |
| AU (1) | AU2214001A (pl) |
| BG (1) | BG106851A (pl) |
| BR (1) | BR0107763A (pl) |
| CA (1) | CA2397960C (pl) |
| CO (1) | CO5261537A1 (pl) |
| CZ (1) | CZ20022474A3 (pl) |
| DE (1) | DE60138686D1 (pl) |
| DK (1) | DK1259474T3 (pl) |
| DZ (1) | DZ3239A1 (pl) |
| EA (1) | EA004862B1 (pl) |
| EE (1) | EE200200404A (pl) |
| ES (1) | ES2324281T3 (pl) |
| GE (1) | GEP20053428B (pl) |
| GT (1) | GT200100015A (pl) |
| HN (1) | HN2001000011A (pl) |
| HU (1) | HUP0204422A3 (pl) |
| IL (1) | IL150541A0 (pl) |
| IS (1) | IS6442A (pl) |
| MA (1) | MA26867A1 (pl) |
| MX (1) | MXPA02007223A (pl) |
| NO (1) | NO20023526L (pl) |
| NZ (1) | NZ519550A (pl) |
| OA (1) | OA12166A (pl) |
| PA (1) | PA8510601A1 (pl) |
| PE (1) | PE20011064A1 (pl) |
| PL (1) | PL357076A1 (pl) |
| SK (1) | SK10622002A3 (pl) |
| SV (1) | SV2002000290A (pl) |
| TN (1) | TNSN01013A1 (pl) |
| UY (1) | UY26550A1 (pl) |
| WO (1) | WO2001055078A1 (pl) |
| ZA (1) | ZA200205880B (pl) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1045691T1 (en) * | 1997-12-12 | 2005-04-30 | Warner-Lambert Company Llc | Statin-carboxyalkylether combinations |
| AU2003255937A1 (en) * | 2002-08-22 | 2004-03-11 | Warner-Lambert Company Llc | Method of treating osteoarthritis |
| US7816405B2 (en) | 2005-04-19 | 2010-10-19 | Eisai R&D Management Co., Ltd. | Calcium bis [(2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl ]-2-isopropoxypropionate] and intermediate thereof |
| EP1873141A4 (en) * | 2005-04-19 | 2010-09-22 | Eisai R&D Man Co Ltd | CALCIUM-BIS [2S] -3- [3- (2S) -3- (4-CHLORO-2-CYANOPHENOXY) -2-FLUORO-PROPOXYPHENYL] -2-ISOPROPOXYPROPIONATE] AND INTERMEDIATE PRODUCTS THEREOF |
| CN107108442A (zh) * | 2014-11-14 | 2017-08-29 | 燿石治疗公司 | 用于制备α,ω‑二羧酸封端的二烷醚的方法和中间体 |
| IL269884B2 (en) * | 2017-04-18 | 2023-09-01 | Gemphire Therapeutics Inc | Gamkaban its accepted pharmaceutical salts, their compositions and methods of their use |
| EP3867222A4 (en) * | 2018-10-18 | 2022-07-06 | Gemphire Therapeutics Inc. | GEMCABENE, PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, COMPOSITIONS THEREOF, AND METHODS OF USE THEREOF |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648387A (en) | 1995-03-24 | 1997-07-15 | Warner-Lambert Company | Carboxyalkylethers, formulations, and treatment of vascular diseases |
| NZ503982A (en) | 1997-12-12 | 2002-03-28 | Warner Lambert Co | Statin-carboxyalkylether combinations useful for treating vascular disorders and diabetes mellitus |
-
2001
- 2001-01-11 SK SK1062-2002A patent/SK10622002A3/sk not_active Application Discontinuation
- 2001-01-11 HU HU0204422A patent/HUP0204422A3/hu unknown
- 2001-01-11 JP JP2001555021A patent/JP4750995B2/ja not_active Expired - Fee Related
- 2001-01-11 PL PL01357076A patent/PL357076A1/pl not_active Application Discontinuation
- 2001-01-11 IL IL15054101A patent/IL150541A0/xx unknown
- 2001-01-11 AP APAP/P/2002/002587A patent/AP2002002587A0/en unknown
- 2001-01-11 CN CN01804045A patent/CN1395555A/zh active Pending
- 2001-01-11 GE GE4872A patent/GEP20053428B/en unknown
- 2001-01-11 AU AU22140/01A patent/AU2214001A/en not_active Abandoned
- 2001-01-11 CA CA002397960A patent/CA2397960C/en not_active Expired - Lifetime
- 2001-01-11 AT AT01900037T patent/ATE431326T1/de not_active IP Right Cessation
- 2001-01-11 EE EEP200200404A patent/EE200200404A/xx unknown
- 2001-01-11 NZ NZ519550A patent/NZ519550A/en unknown
- 2001-01-11 BR BR0107763-5A patent/BR0107763A/pt not_active IP Right Cessation
- 2001-01-11 KR KR1020027009519A patent/KR20020073182A/ko not_active Ceased
- 2001-01-11 DZ DZ013239A patent/DZ3239A1/fr active
- 2001-01-11 EP EP01900037A patent/EP1259474B1/en not_active Expired - Lifetime
- 2001-01-11 DK DK01900037T patent/DK1259474T3/da active
- 2001-01-11 MX MXPA02007223A patent/MXPA02007223A/es active IP Right Grant
- 2001-01-11 OA OA1200200226A patent/OA12166A/en unknown
- 2001-01-11 EA EA200200641A patent/EA004862B1/ru not_active IP Right Cessation
- 2001-01-11 CZ CZ20022474A patent/CZ20022474A3/cs unknown
- 2001-01-11 DE DE60138686T patent/DE60138686D1/de not_active Expired - Lifetime
- 2001-01-11 WO PCT/IB2001/000026 patent/WO2001055078A1/en not_active Ceased
- 2001-01-11 ES ES01900037T patent/ES2324281T3/es not_active Expired - Lifetime
- 2001-01-22 UY UY26550A patent/UY26550A1/es not_active Application Discontinuation
- 2001-01-22 SV SV2001000290A patent/SV2002000290A/es not_active Application Discontinuation
- 2001-01-23 AR ARP010100284A patent/AR029436A1/es unknown
- 2001-01-23 GT GT200100015A patent/GT200100015A/es unknown
- 2001-01-23 PA PA20018510601A patent/PA8510601A1/es unknown
- 2001-01-24 TN TNTNSN01013A patent/TNSN01013A1/fr unknown
- 2001-01-24 CO CO01005267A patent/CO5261537A1/es not_active Application Discontinuation
- 2001-01-24 PE PE2001000076A patent/PE20011064A1/es not_active Application Discontinuation
- 2001-01-24 HN HN2001000011A patent/HN2001000011A/es unknown
-
2002
- 2002-06-20 BG BG106851A patent/BG106851A/xx unknown
- 2002-06-25 IS IS6442A patent/IS6442A/is unknown
- 2002-07-22 MA MA26735A patent/MA26867A1/fr unknown
- 2002-07-23 ZA ZA200205880A patent/ZA200205880B/xx unknown
- 2002-07-24 NO NO20023526A patent/NO20023526L/no not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20250243163A1 (en) | Salt of omecamtiv mecarbil and process for preparing salt | |
| US5480875A (en) | Crystal of monohydrate of heterocyclic bis(phosphonic acid) derivative | |
| JPWO1994000462A1 (ja) | ヘテロ環ビス（フォスフォン酸）誘導体１水和物の新規結晶 | |
| US6861555B2 (en) | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith | |
| TWI863930B (zh) | 用於製備α-酮戊二酸鈣之方法 | |
| JP7283832B2 (ja) | ピリジンスルホンアミドリン酸エステル系化合物又はその医薬上許容される塩、その製造方法、その用途及び薬物組成物 | |
| OA12166A (en) | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetestherewith. | |
| CA2468234C (en) | Acetyl l-carnitine fumarate and process for preparing the same | |
| EP1723157B1 (en) | Amorphous forms of risedronate monosodium | |
| CN1980666B (zh) | 制备阿扎那韦硫酸氢盐的方法和新的形式 | |
| US3907869A (en) | Method of producing calcium pangamate | |
| KR20020091077A (ko) | α-(2-4-디술포페닐)-Ｎ-ｔｅｒｔ-부틸니트론 및 제약상허용되는 그의 염의 신규 제조 방법 | |
| US4145558A (en) | Ester derivatives of ether polycarboxylic acids | |
| JP3637019B2 (ja) | 新規な結晶性パミドロン酸二ナトリウム水和物及びその製造方法 | |
| EP4667465A1 (en) | Salt of benzo-nitrogen heteroaromatic ring derivative, crystalline form, and pharmaceutical use thereof | |
| US2895927A (en) | Synthesis of thyronine compounds | |
| EP0016460B1 (en) | Salicylamide esters having therapeutical activity, process for their preparation and related pharmaceutical composition | |
| JPH07316173A (ja) | リン酸ジエステルのモノカリウム塩結晶の製造方法 |