CN106661060A - 菲罗啉膦酸类衍生物及其制备方法和应用 - Google Patents
菲罗啉膦酸类衍生物及其制备方法和应用 Download PDFInfo
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- CN106661060A CN106661060A CN201580018088.2A CN201580018088A CN106661060A CN 106661060 A CN106661060 A CN 106661060A CN 201580018088 A CN201580018088 A CN 201580018088A CN 106661060 A CN106661060 A CN 106661060A
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- 230000007017 scission Effects 0.000 description 1
- 125000003748 selenium group Chemical group *[Se]* 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- KEAYESYHFKHZAL-BJUDXGSMSA-N sodium-22 Chemical compound [22Na] KEAYESYHFKHZAL-BJUDXGSMSA-N 0.000 description 1
- LJRGBERXYNQPJI-UHFFFAOYSA-M sodium;3-nitrobenzenesulfonate Chemical compound [Na+].[O-][N+](=O)C1=CC=CC(S([O-])(=O)=O)=C1 LJRGBERXYNQPJI-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000002569 water oil cream Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229910000859 α-Fe Inorganic materials 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/6574—Esters of oxyacids of phosphorus
- C07F9/65742—Esters of oxyacids of phosphorus non-condensed with carbocyclic rings or heterocyclic rings or ring systems
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/60—Quinoline or hydrogenated quinoline ring systems
-
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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- C—CHEMISTRY; METALLURGY
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
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- C07F9/657181—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
0.25h | 0.75h | 8h | 24h | |
化合物16c | 521.50 | 662.5 | 584.50 | 50.88 |
化合物9c | 16.13 | 64.25 | 44.68 | 3.55 |
组别 | 血清AST | 肝脏AST |
SHAM | 67.7±4.67 | 67.40±5.28 |
MODEL | 207.2±30.96 | 198.75±27.70 |
27(30mg/kg) | 87.2±12.51** | 91.42±8.79** |
Claims (24)
- 一种由通式(I)或通式(II)表示的化合物或其药用盐:其中:X是氯或OR3,其中R3选自氢、-C(O)-(1-6个碳原子的烷基)、-PO(OH)2或-CH2OPO(OH)2,R1,R2各自独立的选自氢、1-6个碳原子的烷基、-CH2OCO-(1-6个碳原子的烷基)或-CH2OCOO-(1-6个碳原子的烷基);或R1和R2是如下式连接在一起的一个基团:其中Y是芳基或杂芳基;其中:Z选自氢或-CH2OPO(OH)2;R1,R2各自独立的选自氢、1-6个碳原子的烷基、-CH2OCO-(1-6个碳原子的烷基)或-CH2OCOO-(1-6个碳原子的烷基);或R1和R2是如下式连接在一起的一个基团:其中Y是芳基或杂芳基。
- 权利要求1所述的化合物或其药用盐,其中在通式I中X是羟基。
- 权利要求1所述的化合物或其药用盐,其中在通式I中X是-OPO(OH)2。
- 权利要求1所述的化合物或其药用盐,其中在通式I中X是 -OCH2OPO(OH)2。
- 权利要求1所述的化合物或其药用盐,其中在通式I中R1和R2均为氢。
- 权利要求1所述的化合物或其药用盐,其中在通式I中R1和R2是如下式连接在一起的基团:其中Y是芳基。
- 权利要求1所述的化合物或其药用盐,其中在通式I中R1和R2是如下式连接在一起的基团:其中Y是杂芳基。
- 如权利要求1所述的化合物或其药用盐,其中所述化合物选自以下结构:
- 如权利要求8所述的化合物或其药用盐,其中所述化合物具有以下结构:
- 如权利要求9所述的化合物或其药用盐,其中所述化合物选自以下结构:
- 如权利要求8所述的化合物或其药用盐,其中所述化合物选自以下结构:
- 如权利要求11所述的化合物或其药用盐,其中所述化合物选自以下结构:
- 如权利要求11所述的化合物或其药用盐,其中所述化合物选自以下结构:
- 权利要求1所述的化合物,其中在通式II中Z是-OCH2OPO(OH)2。
- 权利要求1所述的化合物,其中在通式II中R1和R2均为氢。
- 权利要求1所述的化合物,其中在通式II中R1和R2是如下式连接在一起的基团:其中Y是芳基。
- 权利要求1所述的化合物,其中在通式II中R1和R2是如下式连接在一起的基团:其中Y是杂芳基。
- 权利要求1所述的化合物或其药用盐,其中所述化合物有以下结构:
- 权利要求18所述的化合物或其药用盐,其中所述化合物选自以下结构:
- 权利要求1-19任一项所述的化合物或其药用盐作为胶原脯氨酰-4-羟化酶抑制剂的应用。
- 权利要求1-19任一项所述的化合物或其药用盐在制备预防或治疗与胶原脯氨酰-4-羟化酶相关的疾病的药物中的应用。
- 权利要求1-19任一项所述的化合物或其药用盐在制备预防或治疗纤维化疾病的药物中的应用。
- 权利要求1-19任一项所述的化合物或其药用盐在制备预防或治疗肝纤维化疾病的药物中的应用。
- 权利要求1-19任一项所述的化合物或其药用盐在制备保护肝脏功能的药物中的应用。
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CN2014101426088 | 2014-04-10 | ||
PCT/CN2015/076273 WO2015154716A1 (zh) | 2014-04-10 | 2015-04-10 | 菲罗啉膦酸类衍生物及其制备方法和应用 |
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AU754607B2 (en) * | 1997-10-24 | 2002-11-21 | Fibrogen, Inc. | Phenanthroline derivatives |
ES2262996T3 (es) * | 2002-01-07 | 2006-12-01 | Eisai Co., Ltd. | Deazapurinas y sus usos. |
US20100197687A1 (en) * | 2005-01-19 | 2010-08-05 | Benjamin Pelcman | Indoles Useful in the Treatment of Inflammation |
WO2014043380A1 (en) | 2012-09-14 | 2014-03-20 | Ligand Pharmaceuticals Incorporated | Novel nucleotide prodrug compounds and use |
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WO2015154716A1 (zh) | 2015-10-15 |
KR20160146791A (ko) | 2016-12-21 |
CN106661060B (zh) | 2019-04-19 |
US10072035B2 (en) | 2018-09-11 |
CN104974187A (zh) | 2015-10-14 |
CA2944805C (en) | 2022-11-29 |
EP3130593A4 (en) | 2017-11-01 |
EA201692045A1 (ru) | 2017-05-31 |
JP6545254B2 (ja) | 2019-07-17 |
EP3130593B1 (en) | 2020-09-23 |
CA2944805A1 (en) | 2015-10-15 |
JP2017513934A (ja) | 2017-06-01 |
SG11201608422VA (en) | 2016-11-29 |
EA030709B1 (ru) | 2018-09-28 |
KR102369908B1 (ko) | 2022-03-02 |
EP3130593A1 (en) | 2017-02-15 |
US20170029452A1 (en) | 2017-02-02 |
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