ES2551708T3 - Compuestos de 4-desdimetilamino tetraciclina - Google Patents
Compuestos de 4-desdimetilamino tetraciclina Download PDFInfo
- Publication number
- ES2551708T3 ES2551708T3 ES10183340.8T ES10183340T ES2551708T3 ES 2551708 T3 ES2551708 T3 ES 2551708T3 ES 10183340 T ES10183340 T ES 10183340T ES 2551708 T3 ES2551708 T3 ES 2551708T3
- Authority
- ES
- Spain
- Prior art keywords
- dedimethylamino
- mmol
- added
- reaction
- filtered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- XCCHQGIGHCRZOS-KBKZQPOHSA-N (4as,5as,6s,12ar)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical class C1=CC=C2[C@@](C)(O)[C@@H](C[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)C3)(O)C3=O)C3=C(O)C2=C1O XCCHQGIGHCRZOS-KBKZQPOHSA-N 0.000 title description 2
- -1 tetracycline compound Chemical class 0.000 abstract description 4
- 239000004098 Tetracycline Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 229960002180 tetracycline Drugs 0.000 abstract 1
- 229930101283 tetracycline Natural products 0.000 abstract 1
- 235000019364 tetracycline Nutrition 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 229950000614 sancycline Drugs 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- XDVCLKFLRAWGIT-ADOAZJKMSA-N sancycline Chemical compound C([C@H]1C2)C3=CC=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O XDVCLKFLRAWGIT-ADOAZJKMSA-N 0.000 description 13
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003480 eluent Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 229960004023 minocycline Drugs 0.000 description 6
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
- 238000004262 preparative liquid chromatography Methods 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- CMHPUBKZZPSUIQ-UHFFFAOYSA-N 1,3-benzodioxol-5-ylboronic acid Chemical compound OB(O)C1=CC=C2OCOC2=C1 CMHPUBKZZPSUIQ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DKFHWNGVMWFBJE-UHFFFAOYSA-N 1-ethynylcyclohexene Chemical group C#CC1=CCCCC1 DKFHWNGVMWFBJE-UHFFFAOYSA-N 0.000 description 1
- WTJXVDPDEQKTCV-UHFFFAOYSA-N 4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydron;chloride Chemical class Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2C1CC1C(N(C)C)C(=O)C(C(N)=O)=C(O)C1(O)C2=O WTJXVDPDEQKTCV-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- HFSFJMVZIWRGNH-UHFFFAOYSA-N [5-[(dimethylamino)methyl]-2-methoxyphenyl]boronic acid Chemical compound COC1=CC=C(CN(C)C)C=C1B(O)O HFSFJMVZIWRGNH-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical class Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 210000003254 palate Anatomy 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/65—Tetracyclines
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P1/12—Antidiarrhoeals
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/42—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/54—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/58—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/46—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
- C07C275/48—Y being a hydrogen or a carbon atom
- C07C275/54—Y being a carbon atom of a six-membered aromatic ring, e.g. benzoylureas
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/08—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C335/22—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
- C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
- C07F9/2454—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic
- C07F9/2475—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic of aralkylamines
-
- 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
- C07F9/28—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
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/44—Naphthacenes; Hydrogenated naphthacenes
- C07C2603/46—1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Otolaryngology (AREA)
- Cardiology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Reproductive Health (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
Abstract
Un compuesto de tetraciclina sustituido seleccionado del grupo que consiste de**Fórmula** y sales farmacéuticamente aceptables de los mismos.
Description
E10183340
28-10-2015
30.0 mL de ácido sulfúrico concentrado se agrega a 1.00 g de 4-desdimetilamino sanciclina con agitación y la solución luego se enfría a 0° C. Se agrega 1.09g de N-yodosuccinimida en forma de porciones a la solución durante una hora y la mezcla de reacción se monitorea por HPLC y TLC. La mezcla de reacción se vierte en 250 mL de agua helada, y se extrae tres veces con n-butanol, y el solvente se elimina bajo presión reducida. El residuo crudo se purifica mediante HPLC preparativo proporcionando 7-yodosanciclina y 7,9-diiodosanciclina.
7,9-Bis(3,4-Metilenodioxifenil)-Sanciclina
Esquema 20
0.74 mmol de 7,9-diyodo 4-desdimetilamino sanciclina (20C) y 8.3 mg (0.37 mmol) acetato de paladio se disuelven
10 en 25 ml de metanol, bajo una atmósfera de nitrógeno. La solución se calienta a 60° C. Después de agitación durante diez minutos se agrega 234 mg (2.22 mmol), carbonato de sodio seguido por 246 mg (1.48 mmol) de ácido 3,4-metilenodioxifenil borónico (20B). Después de que se completa la reacción, la mezcla de reacción se filtra a través de un lecho de celita y se concentra bajo presión reducida. Este producto crudo se purifica mediante cromatografía líquida preparativa utilizando una fase estacionaria C18 con un eluyente A: 0.1 % de TFA en agua y
15 eluyente B: 0.1 % de TFA en acetonitrilo.
7 Yodo 4-Desdimetilamino Sanciclina
Un gramo de 4-desdimetilamino sanciclina se disuelve en 25 mL de TFA (ácido trifluoroacético) que se enfría a 0 C (en hielo). Se agrega 1.2 equivalentes de N-yodosuccinimida (NIS) a la mezcla de reacción y se hace reaccionar durante cuarenta minutos. La reacción se elimina del baño helado y luego se deja reaccionar a temperatura 20 ambiente durante unas cinco horas adicionales. La mezcla luego se analiza mediante HPLC y TLC, se lleva a terminación mediante la adición en forma de etapas de NIS. Después de la terminación de la reacción, el TFA se elimina en vacío y 3 mL de MeOH se agrega para disolver el residuo. La solución metanólica luego se agrega lentamente a una solución rápidamente agitada de éter de dietilo para formar un precipitado. El isómero 7-yodo de sanciclina se purifica al tratar el producto de 7-yodo con carbón activado, se filtra a través de Celita, y se elimina
25 posteriormente el solvente en vacío para producir el compuesto isómero 7 como un sólido puro.
7-Tetrametilsililetinil-4-Desdimetilamino Sanciclina
Esquema 21
A una solución de 10 mmol de trifluoroacetato de 7-yodo-4-desdimetilamino-sanciclina 500 mg de tetrakis30 trifenilfosfino-paladato, 500 mg yoduro de cobre (I), 100 mg de acetato de paladio y 30 mL de trietilamina se agrega 3 ml de trimetilsililacetileno. La mezcla de reacción se agita a temperatura ambiente durante dos horas luego se filtra
20
E10183340
28-10-2015
7-Etil-4-desdimetilamino sanciclina (23B, 6.7 mmol, 3.2 g) se disuelve en 75 ml de ácido metanosulfónico a temperatura ambiente. Se agrega N-yodo succinimida (24B, 13.5 mmol, 3.05 g) durante dos horas en 6 porciones. Después de dos horas se agrega éter de dietilo, y el precipitado se filtra y se seca. El producto crudo se purifica mediante cromatografía líquida preparativa utilizando una fase estacionaria C18 con eluyente A: 0.1% de TFA en agua y eluyente B: 0.1% de TFA en acetonitrilo.
7-Etil-9-Ciclohexeniletinil-4-Desdimetilamino Sanciclina
Esquema 25
A una solución de 7-etil-4-desdimetilamino sanciclina (1.13 mmol), 50 mg de tetrakis-trifenilfosfino-paladato, 50 mg
10 de yoduro de cobre (I), 10 mg de acetato de paladio y 3 ml de trietilamina se agrega 0.1 ml de ciclohexenil-acetileno. La mezcla de reacción se agita a 60° C durante una hora, se filtra a través de un lecho de celita y se concentra. El material seco se disuelve en metanol y se filtra. La solución luego se concentra y se purifica utilizando cromatografía líquida preparativa. La cromatografía líquida preparativa utiliza una fase estacionaria C18 con eluyente A: 0.1% de TFA en agua y eluyente B: 0.1% de TFA en acetonitrilo.
15 7-Yodo-9-t-Butil-4-Desdimetilamino Sanciclina
Esquema 26
9-t-butil-4-desdimetilamino sanciclina (26A, 1.13 g, 2 mmol) se disuelve en 5 ml de ácido metanosulfónico (0.448, 2 mmol). Se agrega N-yodosuccinimida (26B) a temperatura ambiente durante una hora en cuatro porciones. El 20 producto (26C) se precipita con éter de dietilo, se filtra y se utiliza en otra reacción sin purificación adicional.
7-(2-Metoxi-5-Dimetilaminometilfenil)-9-t-Butil-4-Desdimetilamino Sanciclina
Esquema 27
7-Yodo-9-t-butil-4-desdimetilamino sanciclina (26B, 710 mg, 1.0 mmol) y acetato de paladio (22.4 mg, 0.1 mmol) se
25 disuelven en 25 ml de metanol bajo una atmósfera de nitrógeno. Se agregan carbonato de cesio (3.25 g, 10 mmol) y ácido 2-metoxi-5-dimetilaminometilfenil-borónico (27B, 0.435 g, 0.15 mmol). La mezcla de reacción se agita a 60 °C durante dos horas y luego se filtra a través de un lecho de celita y se concentra bajo presión reducida. El producto
22
5
10
15
20
25
30
35
E10183340
28-10-2015
crudo se purifica mediante cromatografía líquida preparativa utilizando una fase estacionaria C18 en eluyente A: 0.1% de TFA en agua y eluyente B: 0.1% de TFA en acetonitrilo.
Ejemplo de referencia 3: Preparación de compuestos de 4-desdimetilamino tetraciclina 9-sustituida
Preparación de 9-yodo 4-desdimetilamino minociclina
A 200 ml de 97% de ácido metanosulfónico se agrega lentamente, a temperatura ambiente, en forma de porciones
[56.56 mM] de sal de clorhidato de 4-desdimetilamino minociclina. La solución oscura luego se agita a temperatura ambiente mientras que se agrega [38 g; 169.7 mM] de N-yodosuccinimida, en seis porciones iguales durante un tiempo de 3.0 horas. La reacción se monitorea a través de LC analítico, observando la desaparición del material de partida.
La reacción se detiene lentamente en 2L de agua enfriada con hielo que contiene [17.88 g; 1134.1 mM] de tiosulfato de sodio con agitación rápida. Este enfriamiento se agita durante aproximadamente 30 minutos a temperatura ambiente. La capa acuosa luego se extrae con 6x200ml de acetato de etilo antes la capa acuosa se vertió sobre
[259.8 g; 3.08 M] de hidrógeno carbonato de sodio que contiene 300 ml de n-butanol. Las fases se separan y la fase acuosa se extrae con 4x250ml de n-butanol. Las fracciones orgánicas se combinan y se lavan con 3x250ml de agua y una vez con 250 ml de solución salina saturada. La fase orgánica resultante se reduce hasta sequedad bajo presión reducida. El residuo se suspende en metanol (~ 600 ml) y el gas HCl anhidro se burbujea en esta mezcla hasta que ocurre la solución. Esta solución se reduce hasta sequedad bajo presión reducida. Los filtrados se reducen a sequedad bajo presión reducida. El material resultante se tritura con 300 ml de éter de metilo y t-Butilo se aísla mediante filtración. Este material se vuelve a disolver en 300 ml de metanol y se trata con 0.5 g de carbón de madera, se filtra y los filtrados se reducen hasta sequedad bajo presión reducida. El material es de nuevo en forma de polvo bajo metil t-butil éter, aislado mediante filtración por succión y se lava adicionalmente con éter, y finalmente con hexanos. El material se seca al vacío para dar el producto.
Procedimiento general para la preparación de Compuestos de 9-alquinil 4-desdimetilamino minociclina
1 mmol de 9-yodo 4-desdimetilamino minociclina, 50 mg de tetrakis trifenilfosfinato paladato, 12 mg de acetato de paladio, 32 mg de yoduro de cobre (I) se disuelven/suspenden en 10 ml de acetonitrilo. Se agregan 2 a 5 mL de trietilamina y 3 a 5 mmol de derivado de alquinil 4-desdimetilamino minociclina. La mezcla de reacción se agita vigorosamente entre temperatura ambiente a 70° C. El tiempo de reacción es 2-24 horas. Cuando la reacción se completa la suspensión oscura se filtra a través de un lecho de celita y se concentra. El producto crudo se purifica mediante HPLC prep. Las fracciones combinadas se concentran y toman en ~1 ml de metanol. Se agrega ~3 ml de HCl metanol saturado, y el producto se precipita con éter.
Procedimiento General para la Preparación de Compuestos de 9-Aril 4-Desdimetilamino Minociclina
0.15 mmol de 9-yodo 4-desdimetilamino minociclina, PdOAc (3.2mg), 229 µl de Na2CO3 2M y 2 equivalentes de ácido fenil borónico se disuelven/suspenden en 10 ml de metanol. El matraz de reacción se purga con argón y la reacción se corren durante un mínimo de cuatro horas o hasta que el monitoreo de HPLC muestra el consumo del material de partida y/o la aparición de productos. La suspensión se filtra a través de celita, y se somete a purificación mediante HPLC prep sobre una columna de divinilbenceno.
9-(4-Trifluorometoxifenilureido)-Metil Minociclina
Esquema 28
23
Claims (1)
-
imagen1
Applications Claiming Priority (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US34706502P | 2002-01-08 | 2002-01-08 | |
US34692902P | 2002-01-08 | 2002-01-08 | |
US34693002P | 2002-01-08 | 2002-01-08 | |
US34695602P | 2002-01-08 | 2002-01-08 | |
US346956P | 2002-01-08 | ||
US346929P | 2002-01-08 | ||
US347065P | 2002-01-08 | ||
US346930P | 2002-01-08 | ||
US36704902P | 2002-03-21 | 2002-03-21 | |
US367049P | 2002-03-21 |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2551708T3 true ES2551708T3 (es) | 2015-11-23 |
Family
ID=27541208
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES10183340.8T Expired - Lifetime ES2551708T3 (es) | 2002-01-08 | 2003-01-06 | Compuestos de 4-desdimetilamino tetraciclina |
Country Status (6)
Country | Link |
---|---|
US (4) | US7056902B2 (es) |
EP (7) | EP2311796A1 (es) |
JP (4) | JP2005514410A (es) |
AU (1) | AU2003235759A1 (es) |
ES (1) | ES2551708T3 (es) |
WO (1) | WO2003057169A2 (es) |
Families Citing this family (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6756365B2 (en) * | 1991-11-06 | 2004-06-29 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
US8106225B2 (en) * | 1999-09-14 | 2012-01-31 | Trustees Of Tufts College | Methods of preparing substituted tetracyclines with transition metal-based chemistries |
DE60027465T2 (de) * | 1999-09-14 | 2007-02-01 | The Trustees Of Tufts College, Medford | Verfahren zur herstellung von substituierten tetracyclinen mit hilfe von auf übergangsmetalle basierten chemien |
WO2001052858A1 (en) * | 2000-01-24 | 2001-07-26 | Trustees Of Tufts College | Tetracycline compounds for treatment of cryptosporidium parvum related disorders |
CA2404628A1 (en) * | 2000-03-31 | 2001-10-11 | Stuart B. Levy | 7-and 9-carbamate, urea, thiourea, thiocarbamate, and heteroaryl-amino substituted tetracycline compounds |
EP2308863A1 (en) * | 2000-05-15 | 2011-04-13 | Paratek Pharmaceuticals, Inc. | 7-substituted fused ring tetracycline compounds |
US20040224927A1 (en) * | 2000-06-16 | 2004-11-11 | Trustees Of Tufts College | 7-N-substituted phenyl tetracycline compounds |
US20020132798A1 (en) * | 2000-06-16 | 2002-09-19 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
AU2001268475A1 (en) * | 2000-06-16 | 2002-01-02 | Trustees Of Tufts College | 7-phenyl-substituted tetracycline compounds |
KR101083571B1 (ko) * | 2000-07-07 | 2011-11-14 | 파라테크 파마슈티컬스, 인크. | 7-치환 테트라사이클린 화합물 |
US7094806B2 (en) * | 2000-07-07 | 2006-08-22 | Trustees Of Tufts College | 7, 8 and 9-substituted tetracycline compounds |
CN1690047B (zh) | 2000-07-07 | 2010-10-06 | 塔夫茨大学信托人 | 9-取代的二甲胺四环素化合物 |
AU2002250331A1 (en) * | 2001-03-13 | 2002-09-24 | Paratek Pharmaceuticals, Inc. | 7-pyrollyl tetracycline compounds and methods of use thereof |
US7553828B2 (en) | 2001-03-13 | 2009-06-30 | Paratek Pharmaceuticals, Inc. | 9-aminomethyl substituted minocycline compounds |
BR0116935A (pt) | 2001-03-13 | 2005-04-12 | Paratek Pharm Innc | Composto de tetraciclina, método para tratar um estado responsivo à tetraciclina em um indivìduo, e, composição farmacêutica |
JP2005504722A (ja) | 2001-03-14 | 2005-02-17 | パラテック ファーマシューティカルズ インコーポレイテッド | 相乗的抗真菌薬剤としての置換テトラサイクリン化合物 |
US8088820B2 (en) * | 2001-04-24 | 2012-01-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
US20060194773A1 (en) * | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
EP2332550A1 (en) * | 2001-07-13 | 2011-06-15 | Paratek Pharmaceuticals, Inc. | Tetracyclines for the treatment of neurodegenerative diseases |
WO2003055441A2 (en) * | 2001-08-02 | 2003-07-10 | Paratek Pharmaceuticals, Inc. | Medicaments |
JP2005514410A (ja) * | 2002-01-08 | 2005-05-19 | パラテック ファーマシューティカルズ インコーポレイテッド | 4−デジメチルアミノテトラサイクリン化合物 |
AU2003220123B2 (en) * | 2002-03-08 | 2009-05-07 | Paratek Pharmaceuticals, Inc. | Amino-methyl substituted tetracycline compounds |
CN101712632A (zh) * | 2002-03-21 | 2010-05-26 | 帕拉特克药品公司 | 取代的四环素化合物 |
CN1700922A (zh) * | 2002-07-12 | 2005-11-23 | 帕拉特克药品公司 | 3、10或12a位取代的四环素化合物 |
EP1562608A4 (en) | 2002-10-24 | 2010-09-01 | Paratek Pharm Innc | METHOD OF USE OF SUBSTITUTED TETRACYCLINE COMPOUNDS FOR MODULATING THE RNA |
CA2531728A1 (en) | 2003-07-09 | 2005-02-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
US20060287283A1 (en) * | 2003-07-09 | 2006-12-21 | Paratek Pharmaceuticals, Inc. | Prodrugs of 9-aminomethyl tetracycline compounds |
US7786099B2 (en) | 2004-01-15 | 2010-08-31 | Paratek Pharmaceuticals, Inc. | Aromatic a-ring derivatives of tetracycline compounds |
CN101027279B (zh) | 2004-05-21 | 2013-03-27 | 哈佛大学校长及研究员协会 | 四环素及其类似物的合成 |
AU2012202559B2 (en) * | 2004-05-21 | 2014-07-17 | President And Fellows Of Harvard College | Synthesis of tetracyclines and analogues thereof |
AU2014250722B2 (en) * | 2004-05-21 | 2016-05-26 | President And Fellows Of Harvard College | Synthesis of tetracyclines and analogues thereof |
TWI261038B (en) * | 2004-08-11 | 2006-09-01 | Bo-Cheng Chen | Bicycle gear-shifting handgrip |
EP2295419A3 (en) | 2004-10-25 | 2011-09-21 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
EP1805134B1 (en) | 2004-10-25 | 2012-06-20 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
CA2597212A1 (en) * | 2005-02-04 | 2006-08-10 | Paratek Pharmaceuticals, Inc. | 11a, 12-derivatives of tetracycline compounds |
AR057033A1 (es) * | 2005-05-27 | 2007-11-14 | Wyeth Corp | Tigeciclina y metodos para preparar 9-nitrominociclina |
AR057032A1 (es) * | 2005-05-27 | 2007-11-14 | Wyeth Corp | Tigeciclina y metodos de preparacion |
WO2007014154A2 (en) * | 2005-07-21 | 2007-02-01 | Paratek Pharmaceuticals, Inc. | 10-substituted tetracyclines and methods of use thereof |
AU2006331688A1 (en) * | 2005-12-22 | 2007-07-05 | Wyeth | Oral formulations comprising tigecycline |
KR20080085184A (ko) * | 2005-12-22 | 2008-09-23 | 와이어쓰 | 티게사이클린을 사용한 위장관 감염의 치료방법 |
EP1991236A2 (en) * | 2006-01-24 | 2008-11-19 | Paratek Pharmaceuticals, Inc. | Methods of increasing oral bioavailability of tetracyclines |
CA2648668C (en) | 2006-04-07 | 2015-06-23 | The President And Fellows Of Harvard College | Synthesis of tetracyclines and analogues thereof |
US20080118979A1 (en) | 2006-05-15 | 2008-05-22 | Paratek Pharmaceuticals, Inc. | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
WO2008127361A2 (en) | 2006-10-11 | 2008-10-23 | President And Fellows Of Harvard College | Synthesis of enone intermediate |
WO2008045507A2 (en) | 2006-10-11 | 2008-04-17 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for treatment of bacillus anthracis infections |
EP2120963B1 (en) | 2006-12-21 | 2018-09-12 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for treatment of inflammatory skin disorders |
PL2109602T3 (pl) * | 2006-12-21 | 2014-09-30 | Paratek Pharm Innc | Pochodne tetracyliny do leczenia zakażeń bakteryjnych, wirusowych i pasożytniczych |
JP2010523684A (ja) | 2007-04-12 | 2010-07-15 | パラテック ファーマシューティカルズ インコーポレイテッド | テトラサイクリン化合物を用いる、脊髄筋委縮症を治療するための方法 |
US8518912B2 (en) | 2007-11-29 | 2013-08-27 | Actelion Pharmaceuticals Ltd. | Phosphonic acid derivates and their use as P2Y12 receptor antagonists |
MX2010009693A (es) * | 2008-03-05 | 2010-12-20 | Paratek Pharm Innc | Compuestos de monociclina y metodos de uso de la misma. |
WO2009128913A1 (en) * | 2008-04-14 | 2009-10-22 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
CA2730377C (en) | 2008-07-11 | 2017-09-19 | Neumedics | Tetracycline derivatives with reduced antibiotic activity and neuroprotective benefits |
KR20110081197A (ko) * | 2008-09-19 | 2011-07-13 | 파라테크 파마슈티컬스, 인크. | 류마티스 관절염의 치료를 위한 테트라시클린 화합물 및 관련된 치료 방법 |
WO2010126607A2 (en) | 2009-04-30 | 2010-11-04 | President And Fellows Of Harvard College | Synthesis of tetracyclines and intermediates thereto |
EP2427425B1 (en) | 2009-05-08 | 2017-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
EP3461809A1 (en) | 2012-08-31 | 2019-04-03 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
KR20240058958A (ko) | 2016-10-19 | 2024-05-07 | 테트라페이즈 파마슈티컬스, 인코포레이티드 | 에라바사이클린의 결정질 형태 |
CN110087655A (zh) | 2016-11-01 | 2019-08-02 | 帕拉特克药品公司 | 9-氨基甲基米诺环素化合物及其在治疗社区获得性细菌性肺炎(cabp)中的用途 |
AU2021233829A1 (en) * | 2020-03-10 | 2022-10-20 | Texas Tech University System | Novel modified tetracyclines for treatment of alcohol use disorder, pain and other disorders involving potential inflammatory processes |
WO2022167954A1 (en) | 2021-02-03 | 2022-08-11 | Skybio Llc | Chemically coupled transporter for low-hydrophobicity bioactive drugs into the central nervous system |
Family Cites Families (116)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US21366A (en) | 1858-08-31 | Valve-cock | ||
USRE26271E (en) * | 1967-09-26 | Reductive alkylation process | ||
US2990331A (en) | 1956-11-23 | 1961-06-27 | Pfizer & Co C | Stable solutions of salts of tetracyclines for parenteral administration |
US2980584A (en) | 1957-10-29 | 1961-04-18 | Pfizer & Co C | Parenteral magnesium oxytetracycline acetic or lactic acid carboxamide vehicle preparation |
US3062717A (en) | 1958-12-11 | 1962-11-06 | Pfizer & Co C | Intramuscular calcium tetracycline acetic or lactic acid carboxamide vehicle preparation |
US3043875A (en) * | 1959-10-22 | 1962-07-10 | Pfizer & Co C | Halogenated tetracycline derivatives and processes for their preparation |
FR1430859A (es) * | 1960-05-23 | 1966-05-25 | ||
US3338963A (en) * | 1960-10-28 | 1967-08-29 | American Cyanamid Co | Tetracycline compounds |
US3862225A (en) * | 1961-08-18 | 1975-01-21 | Pfizer | D-ring substituted tetracyclines |
US3165531A (en) | 1962-03-08 | 1965-01-12 | Pfizer & Co C | 13-substituted-6-deoxytetracyclines and process utilizing the same |
US3148212A (en) * | 1961-12-22 | 1964-09-08 | American Cyanamid Co | Reductive alkylation process |
USRE26253E (en) * | 1963-05-17 | 1967-08-15 | And z-alkylamino-g-deoxytetracycline | |
US3609188A (en) * | 1964-10-29 | 1971-09-28 | American Cyanamid Co | 4-dedimethylamino-4-substituted-amino-6-demethyltetracyclines |
US3454697A (en) | 1965-06-08 | 1969-07-08 | American Cyanamid Co | Tetracycline antibiotic compositions for oral use |
US3304227A (en) | 1965-07-15 | 1967-02-14 | Loyal E Loveless | Antibiotic-containing animal feed |
US3397230A (en) * | 1966-03-14 | 1968-08-13 | American Cyanamid Co | Nitration of tetracyclines |
US3433834A (en) * | 1966-03-14 | 1969-03-18 | American Cyanamid Co | Nitration of 11a-chloro tetracyclines |
US3341585A (en) * | 1966-05-06 | 1967-09-12 | American Cyanamid Co | Substituted 7-and/or 9-amino-6-deoxytetracyclines |
NL6607516A (es) * | 1966-05-31 | 1967-12-01 | ||
US3403179A (en) * | 1967-01-10 | 1968-09-24 | American Cyanamid Co | Novel 7-(1, 2-bis-substituted-hydrazino)-tetracyclines and methods of preparing same |
US3373196A (en) * | 1967-03-21 | 1968-03-12 | American Cyanamid Co | 7-and/or 9-(lower alkyl) amino-5a, 6-anhydrotetracyclines |
US3518306A (en) * | 1968-02-19 | 1970-06-30 | American Cyanamid Co | 7- and/or 9-(n-nitrosoalkylamino)-6-demethyl-6-deoxytetracyclines |
US3579579A (en) * | 1968-04-18 | 1971-05-18 | American Cyanamid Co | Substituted 7- and/or 9-amino-6-demethyl-6-deoxytetracyclines |
DE1767891C3 (de) | 1968-06-28 | 1980-10-30 | Pfizer | Verfahren zur Herstellung von wäßrigen arzneilichen Lösungen für die parenterale, perorale und lokale Anwendung mit einem Gehalt an einem Tetracyclinderivat |
US3795707A (en) * | 1970-12-28 | 1974-03-05 | Rachelle Labor Italia Spa | Manufacture of alpha-6-deoxytetracyclines |
CA999855A (en) * | 1972-09-18 | 1976-11-16 | Societa' Farmaceutici Italia S.P.A. | Process for the preparation of tetracyclines derivatives in the 7 position |
US3957980A (en) | 1972-10-26 | 1976-05-18 | Pfizer Inc. | Doxycycline parenteral compositions |
JPS5119757A (ja) | 1974-06-25 | 1976-02-17 | Farmaceutici Italia | Arukirutetorasaikurinjudotainoseizoho |
DE2442829A1 (de) | 1974-09-06 | 1976-03-18 | Merck Patent Gmbh | Tetracyclische verbindungen und verfahren zu ihrer herstellung |
US4018889A (en) | 1976-01-02 | 1977-04-19 | Pfizer Inc. | Oxytetracycline compositions |
US4126680A (en) | 1977-04-27 | 1978-11-21 | Pfizer Inc. | Tetracycline antibiotic compositions |
US4925833A (en) | 1983-12-29 | 1990-05-15 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of osteoporosis |
US4935412A (en) | 1983-12-29 | 1990-06-19 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
US4704383A (en) | 1983-12-29 | 1987-11-03 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
US4666897A (en) | 1983-12-29 | 1987-05-19 | Research Foundation Of State University | Inhibition of mammalian collagenolytic enzymes by tetracyclines |
USRE34656E (en) | 1983-12-29 | 1994-07-05 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of bone deficiency |
US4946453A (en) * | 1988-04-14 | 1990-08-07 | Monson Demetrius A | Weight reducing athletic garment |
US5388391A (en) | 1988-12-19 | 1995-02-14 | Parker; Richard D. | Apparatus and process for packaging biohazardous wastes |
US5308839A (en) | 1989-12-04 | 1994-05-03 | The Research Foundation Of State University Of New York | Composition comprising non-steroidal anti-inflammatory agent tenidap and effectively non-antibacterial tetracycline |
JP3016587B2 (ja) | 1989-12-04 | 2000-03-06 | ザ・リサーチ・ファンデーション・オブ・ステート・ユニバーシティ・オブ・ニューヨーク | 非ステロイド抗炎症剤及びテトラサイクリンの配合 |
US5770588A (en) | 1991-02-11 | 1998-06-23 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions of the prevention and treatment of root caries |
US5231017A (en) | 1991-05-17 | 1993-07-27 | Solvay Enzymes, Inc. | Process for producing ethanol |
US5281628A (en) * | 1991-10-04 | 1994-01-25 | American Cyanamid Company | 9-amino-7-(substituted)-6-demethyl-6-deoxytetracyclines |
US5494903A (en) * | 1991-10-04 | 1996-02-27 | American Cyanamid Company | 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
DE69232302T4 (de) | 1991-10-04 | 2003-02-13 | American Cyanamid Co., Wayne | 7-Substituierte-9-substituierte Amino-6-Demethyl-6-Deoxy-Tetracycline |
US6756365B2 (en) * | 1991-11-06 | 2004-06-29 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
US5258371A (en) | 1992-05-29 | 1993-11-02 | Kuraray Co., Ltd. | Method to reduce connective tissue destruction |
US6043225A (en) | 1992-06-12 | 2000-03-28 | Board Of Regents Of The University Of Washington | Diagnosis and treatment of arterial chlamydial granuloma |
US5328902A (en) * | 1992-08-13 | 1994-07-12 | American Cyanamid Co. | 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
US5284963A (en) * | 1992-08-13 | 1994-02-08 | American Cyanamid Company | Method of producing 7-(substituted)-9-[(substituted glycyl)-amidol]-6-demethyl-6-deoxytetra-cyclines |
SG47520A1 (en) * | 1992-08-13 | 1998-04-17 | American Cyanamid Co | New method for the production of 9-amino-6-demethyl-6-deoxytetracycline |
US5420272A (en) * | 1992-08-13 | 1995-05-30 | American Cyanamid Company | 7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
US5442059A (en) * | 1992-08-13 | 1995-08-15 | American Cyanamid Company | 9-[(substituted glycyl)amido)]-6-demethyl-6-deoxytetracyclines |
CA2103189C (en) * | 1992-11-17 | 2005-05-03 | Lorne M. Golub | Tetracyclines including non-antimicrobial chemically-modified tetracyclines inhibit excessive collagen crosslinking during diabetes |
US5523297A (en) | 1993-03-02 | 1996-06-04 | The Research Foundation Of State University Of New York | Inhibition of excessive phospholipase A2 activity and/or production by non-antimicrobial tetracyclines |
US6043231A (en) | 1993-03-02 | 2000-03-28 | The Research Foundation Of State Univ. Of New York | Inhibition of excessive phospholipase A2 activity and/or production by non-antimicrobial tetracyclines |
US5371076A (en) * | 1993-04-02 | 1994-12-06 | American Cyanamid Company | 9-[(substituted glycyl)amido]-6-(substituted)-5-hydroxy-6-deoxytetracyclines |
US5668122A (en) | 1993-07-28 | 1997-09-16 | Fife; Rose S. | Method to treat cancer with tetracyclines |
WO1995022529A1 (en) | 1994-02-17 | 1995-08-24 | Pfizer Inc. | 9-(substituted amino)-alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics |
US5843925A (en) * | 1994-12-13 | 1998-12-01 | American Cyanamid Company | Methods for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
US5834449A (en) | 1996-06-13 | 1998-11-10 | The Research Foundation Of State University Of New York | Treatment of aortic and vascular aneurysms with tetracycline compounds |
US5827840A (en) | 1996-08-01 | 1998-10-27 | The Research Foundation Of State University Of New York | Promotion of wound healing by chemically-modified tetracyclines |
US5789395A (en) | 1996-08-30 | 1998-08-04 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds for inhibition of endogenous nitric oxide production |
US5919774A (en) | 1996-12-10 | 1999-07-06 | Eli Lilly And Company | Pyrroles as sPLA2 inhibitors |
US5837696A (en) | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
US5773430A (en) | 1997-03-13 | 1998-06-30 | Research Foundation Of State University Of New York | Serine proteinase inhibitory activity by hydrophobic tetracycline |
US6063775A (en) * | 1997-04-29 | 2000-05-16 | Berman; Charles L. | Retardation of metalloproteinase incidental to HIV and/or AIDS |
US5929055A (en) | 1997-06-23 | 1999-07-27 | The Research Foundation Of State University Of New York | Therapeutic method for management of diabetes mellitus |
WO1999037307A1 (en) * | 1998-01-23 | 1999-07-29 | Trustees Of Tufts College | Pharmaceutically active compounds and methods of use thereof |
US6277061B1 (en) | 1998-03-31 | 2001-08-21 | The Research Foundation Of State University Of New York | Method of inhibiting membrane-type matrix metalloproteinase |
US6015804A (en) | 1998-09-11 | 2000-01-18 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds to enhance interleukin-10 production |
US5977091A (en) | 1998-09-21 | 1999-11-02 | The Research Foundation Of State University Of New York | Method of preventing acute lung injury |
KR20010073190A (ko) * | 1998-09-28 | 2001-07-31 | 제임스 알. 데니히 | 백내장 형성 억제제 |
US5998390A (en) | 1998-09-28 | 1999-12-07 | The Research Foundation Of State University Of New York | Combination of bisphosphonate and tetracycline |
US6506740B1 (en) * | 1998-11-18 | 2003-01-14 | Robert A. Ashley | 4-dedimethylaminotetracycline derivatives |
EP1743632A1 (en) * | 1998-11-18 | 2007-01-17 | Collagenex Pharmaceuticals, Inc. | Novel 4-dedimethy laminotetracycline derivatives |
DE60027465T2 (de) | 1999-09-14 | 2007-02-01 | The Trustees Of Tufts College, Medford | Verfahren zur herstellung von substituierten tetracyclinen mit hilfe von auf übergangsmetalle basierten chemien |
US8106225B2 (en) * | 1999-09-14 | 2012-01-31 | Trustees Of Tufts College | Methods of preparing substituted tetracyclines with transition metal-based chemistries |
US6500812B2 (en) * | 1999-09-14 | 2002-12-31 | Paratek Pharmaceuticals, Inc. | 13-substituted methacycline compounds |
US6849615B2 (en) * | 1999-09-14 | 2005-02-01 | Paratek Pharmaceuticals, Inc. | 13-substituted methacycline compounds |
US6231894B1 (en) | 1999-10-21 | 2001-05-15 | Duke University | Treatments based on discovery that nitric oxide synthase is a paraquat diaphorase |
WO2001052858A1 (en) * | 2000-01-24 | 2001-07-26 | Trustees Of Tufts College | Tetracycline compounds for treatment of cryptosporidium parvum related disorders |
AU2001281489A1 (en) * | 2000-03-10 | 2001-10-03 | Trustees Of Tufts College | NIMR compositions and their methods of use |
CA2404628A1 (en) * | 2000-03-31 | 2001-10-11 | Stuart B. Levy | 7-and 9-carbamate, urea, thiourea, thiocarbamate, and heteroaryl-amino substituted tetracycline compounds |
EP2308863A1 (en) | 2000-05-15 | 2011-04-13 | Paratek Pharmaceuticals, Inc. | 7-substituted fused ring tetracycline compounds |
US20020128237A1 (en) * | 2000-06-16 | 2002-09-12 | Nelson Mark L. | 7-N-substituted phenyl tetracycline compounds |
AU2001268475A1 (en) * | 2000-06-16 | 2002-01-02 | Trustees Of Tufts College | 7-phenyl-substituted tetracycline compounds |
AU2000254942A1 (en) | 2000-06-16 | 2002-01-02 | Trustees Of Tufts College | 7-phenyl-substituted tetracycline compounds |
US20020132798A1 (en) * | 2000-06-16 | 2002-09-19 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
CN1690047B (zh) * | 2000-07-07 | 2010-10-06 | 塔夫茨大学信托人 | 9-取代的二甲胺四环素化合物 |
US7094806B2 (en) * | 2000-07-07 | 2006-08-22 | Trustees Of Tufts College | 7, 8 and 9-substituted tetracycline compounds |
US20050143353A1 (en) * | 2000-07-07 | 2005-06-30 | Paratek Pharmaceuticals, Inc. | 13-Substituted methacycline compounds |
EP2166000A1 (en) * | 2000-07-07 | 2010-03-24 | Trustees Of Tufts College | 7-, 8- and 9-substituted tetracycline compounds |
KR101083571B1 (ko) * | 2000-07-07 | 2011-11-14 | 파라테크 파마슈티컬스, 인크. | 7-치환 테트라사이클린 화합물 |
EP1241160A1 (en) * | 2001-03-13 | 2002-09-18 | Glaxo Group Limited | Tetracycline derivatives and their use as antibiotic agents |
AU2002250331A1 (en) * | 2001-03-13 | 2002-09-24 | Paratek Pharmaceuticals, Inc. | 7-pyrollyl tetracycline compounds and methods of use thereof |
US7553828B2 (en) * | 2001-03-13 | 2009-06-30 | Paratek Pharmaceuticals, Inc. | 9-aminomethyl substituted minocycline compounds |
BR0116935A (pt) * | 2001-03-13 | 2005-04-12 | Paratek Pharm Innc | Composto de tetraciclina, método para tratar um estado responsivo à tetraciclina em um indivìduo, e, composição farmacêutica |
JP2005504722A (ja) * | 2001-03-14 | 2005-02-17 | パラテック ファーマシューティカルズ インコーポレイテッド | 相乗的抗真菌薬剤としての置換テトラサイクリン化合物 |
US6841546B2 (en) * | 2001-03-14 | 2005-01-11 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds as antifungal agents |
EP1716856A3 (en) * | 2001-04-05 | 2009-02-18 | Collagenex Pharmaceuticals, Inc. | The treatment of acne |
AU2002254714C1 (en) * | 2001-04-24 | 2010-01-07 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
WO2003056294A2 (en) * | 2001-07-13 | 2003-07-10 | Paratek Pharmaceuticals, Inc. | Methods for identifying and using marr family polypeptide binding compounds |
EP2332550A1 (en) * | 2001-07-13 | 2011-06-15 | Paratek Pharmaceuticals, Inc. | Tetracyclines for the treatment of neurodegenerative diseases |
US20060194773A1 (en) * | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
CN1564690A (zh) * | 2001-10-05 | 2005-01-12 | 泰特拉吉尼克斯医药公司 | 四环素衍生物及其使用方法 |
JP2005514410A (ja) * | 2002-01-08 | 2005-05-19 | パラテック ファーマシューティカルズ インコーポレイテッド | 4−デジメチルアミノテトラサイクリン化合物 |
AU2003220123B2 (en) * | 2002-03-08 | 2009-05-07 | Paratek Pharmaceuticals, Inc. | Amino-methyl substituted tetracycline compounds |
CN101712632A (zh) * | 2002-03-21 | 2010-05-26 | 帕拉特克药品公司 | 取代的四环素化合物 |
US7553827B2 (en) * | 2003-08-13 | 2009-06-30 | Depuy Spine, Inc. | Transdiscal administration of cycline compounds |
CA2531732C (en) * | 2003-07-09 | 2012-04-10 | Paratek Pharmaceuticals, Inc. | Prodrugs of 9-aminomethyl tetracycline compounds |
CA2531728A1 (en) * | 2003-07-09 | 2005-02-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
US7786099B2 (en) * | 2004-01-15 | 2010-08-31 | Paratek Pharmaceuticals, Inc. | Aromatic a-ring derivatives of tetracycline compounds |
EP2295419A3 (en) * | 2004-10-25 | 2011-09-21 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
EP1805134B1 (en) * | 2004-10-25 | 2012-06-20 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
WO2007014154A2 (en) * | 2005-07-21 | 2007-02-01 | Paratek Pharmaceuticals, Inc. | 10-substituted tetracyclines and methods of use thereof |
-
2003
- 2003-01-06 JP JP2003557528A patent/JP2005514410A/ja not_active Withdrawn
- 2003-01-06 EP EP20100183302 patent/EP2311796A1/en not_active Withdrawn
- 2003-01-06 EP EP20100183323 patent/EP2311798A1/en not_active Withdrawn
- 2003-01-06 EP EP10183340.8A patent/EP2322501B1/en not_active Expired - Lifetime
- 2003-01-06 WO PCT/US2003/000336 patent/WO2003057169A2/en active Application Filing
- 2003-01-06 EP EP15176495.8A patent/EP2995610A1/en not_active Withdrawn
- 2003-01-06 EP EP20100183307 patent/EP2311797A1/en not_active Withdrawn
- 2003-01-06 EP EP20100183331 patent/EP2311799A1/en not_active Withdrawn
- 2003-01-06 AU AU2003235759A patent/AU2003235759A1/en not_active Abandoned
- 2003-01-06 US US10/337,914 patent/US7056902B2/en not_active Expired - Lifetime
- 2003-01-06 EP EP03729351A patent/EP1474380A4/en not_active Withdrawn
- 2003-01-06 ES ES10183340.8T patent/ES2551708T3/es not_active Expired - Lifetime
-
2005
- 2005-11-18 US US11/283,571 patent/US20060089336A1/en not_active Abandoned
-
2009
- 2009-12-28 JP JP2009297366A patent/JP2010111690A/ja active Pending
-
2014
- 2014-02-10 US US14/176,923 patent/US9278911B2/en not_active Expired - Fee Related
- 2014-12-24 JP JP2014260626A patent/JP2015063557A/ja active Pending
-
2015
- 2015-12-08 US US14/962,347 patent/US20160324880A1/en not_active Abandoned
-
2017
- 2017-05-29 JP JP2017105346A patent/JP2017178962A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
US20040157806A1 (en) | 2004-08-12 |
EP2322501B1 (en) | 2015-08-05 |
EP2322501A1 (en) | 2011-05-18 |
EP2311796A1 (en) | 2011-04-20 |
EP2311797A1 (en) | 2011-04-20 |
EP2995610A1 (en) | 2016-03-16 |
JP2015063557A (ja) | 2015-04-09 |
EP1474380A4 (en) | 2007-04-18 |
JP2017178962A (ja) | 2017-10-05 |
WO2003057169A2 (en) | 2003-07-17 |
US20150105355A1 (en) | 2015-04-16 |
US20160324880A1 (en) | 2016-11-10 |
US7056902B2 (en) | 2006-06-06 |
EP2311799A1 (en) | 2011-04-20 |
EP2311798A1 (en) | 2011-04-20 |
US20060089336A1 (en) | 2006-04-27 |
JP2005514410A (ja) | 2005-05-19 |
AU2003235759A8 (en) | 2003-07-24 |
WO2003057169A3 (en) | 2003-12-04 |
US9278911B2 (en) | 2016-03-08 |
AU2003235759A1 (en) | 2003-07-24 |
EP1474380A2 (en) | 2004-11-10 |
JP2010111690A (ja) | 2010-05-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2551708T3 (es) | Compuestos de 4-desdimetilamino tetraciclina | |
Sun et al. | Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregation | |
ES2635088T3 (es) | Macrociclos novedosos como inhibidores del factor XIa | |
EP3632910A1 (en) | Lactam compound as fxr receptor agonist | |
ES2563445T3 (es) | Ligadores P1 cíclicos como inhibidores del factor XIa | |
CN113784963B (zh) | 用作ret激酶抑制剂的化合物及其应用 | |
CN114072411B (zh) | 作为Wee1抑制剂的嘧啶衍生物 | |
Teng et al. | Synthesis and biological evaluation of novel sinomenine derivatives as anti-inflammatory agents | |
CA2882119A1 (en) | Solid forms of an antiviral compound | |
AU2021248368B2 (en) | Compounds for inhibition of fibroblast activation protein | |
PT90339B (pt) | Processo para a preparacao de benzodiazepinas, uteis em terapia, e de intermediarios para esse fim | |
RU2715233C2 (ru) | Способ получения производных азотистого иприта | |
BRPI0720465B1 (pt) | processo para produção de composto de precursor para composto orgânico marcado com halogênio radioativo | |
CA3230331A1 (en) | Solid forms of spirotricyclic apol1 inhibitors and methods of using same | |
WO2008092335A1 (fr) | Nouveaux dérivées de la vinblastine, leur préparation, et compositions pharmaceutiques les comprenant. | |
Guerrero et al. | Oxidative radical cyclization on enamide systems using n-Bu3SnH and dilauroyl peroxide | |
WO1994020106A1 (en) | Sensitivity enhancer for antineoplastic agent | |
ES2911447T3 (es) | Resolución de derivados de diazaspiro[4.5]decano ópticamente activos | |
ES2222351T3 (es) | Isolucion de isomeros de n-(n-(3,3-dimetilbutil)-l-alfa-aspartil)-l-fenilalanina-1-metilester por medio de iones metalicos. | |
Costero et al. | Synthesis of a new allosteric carrier containing three conformationally related subunits | |
ES2373172A1 (es) | Proceso de obtención de derivados solubles en agua de 20 (s) camptotecina como agentes antitumorales. | |
NAKAGAWA et al. | Synthesis of the imidazo [1, 2-a] indole-spirolactone ring system by oxidative double cyclization. A synthetic approach to tryptoquivalines | |
Takahashi et al. | Photochemistry of diazonium salts. Syntheses of 2, 4-difluoroimidazole-5-carboxylic acid and related compounds | |
ES2299184T3 (es) | Derivados de diamidas de acido antranilico, su preparacion y uso farmaceutico como agentes anti-gastrina. | |
ITBO980063A1 (it) | Processo per la produzione di alcossicarbonildipeptidi intermedi nella sintesi del lisinopril. |