US20050215637A1 - Tuberculosis treatment - Google Patents
Tuberculosis treatment Download PDFInfo
- Publication number
- US20050215637A1 US20050215637A1 US10/509,502 US50950204A US2005215637A1 US 20050215637 A1 US20050215637 A1 US 20050215637A1 US 50950204 A US50950204 A US 50950204A US 2005215637 A1 US2005215637 A1 US 2005215637A1
- Authority
- US
- United States
- Prior art keywords
- compound
- formula
- mutilin
- acetyl
- meaning
- 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.)
- Abandoned
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- PNBRZBPREWEFBK-UHFFFAOYSA-N CC1CCCC(N(C)C(=O)C(N)C(C)C)C1 Chemical compound CC1CCCC(N(C)C(=O)C(N)C(C)C)C1 PNBRZBPREWEFBK-UHFFFAOYSA-N 0.000 description 1
- MXZGZYHJIZONTC-UHFFFAOYSA-N CC1CCCC(NC(=N)N)C1 Chemical compound CC1CCCC(NC(=N)N)C1 MXZGZYHJIZONTC-UHFFFAOYSA-N 0.000 description 1
- VNPATEARTJLAOT-UHFFFAOYSA-N CC1CCCCC(=NO)C1 Chemical compound CC1CCCCC(=NO)C1 VNPATEARTJLAOT-UHFFFAOYSA-N 0.000 description 1
- YZPKKBOYYJOKRW-UHFFFAOYSA-N CC1CCCCC(=NOCCN2CCCC2)C1 Chemical compound CC1CCCCC(=NOCCN2CCCC2)C1 YZPKKBOYYJOKRW-UHFFFAOYSA-N 0.000 description 1
- OORDVQYWJPYGFD-UHFFFAOYSA-N CC1CCCCC(=NOCCN2CCCCC2)C1 Chemical compound CC1CCCCC(=NOCCN2CCCCC2)C1 OORDVQYWJPYGFD-UHFFFAOYSA-N 0.000 description 1
- TUZPAUHPOFGFFQ-UHFFFAOYSA-N CC1CCCCC(N)C1 Chemical compound CC1CCCCC(N)C1 TUZPAUHPOFGFFQ-UHFFFAOYSA-N 0.000 description 1
- FEUISMYEFPANSS-UHFFFAOYSA-N CC1CCCCC1N Chemical compound CC1CCCCC1N FEUISMYEFPANSS-UHFFFAOYSA-N 0.000 description 1
- MRTRHBCIIKRSQZ-UHFFFAOYSA-N CC1CCCCC1NC(=O)C(N)CC1=CNC=N1 Chemical compound CC1CCCCC1NC(=O)C(N)CC1=CNC=N1 MRTRHBCIIKRSQZ-UHFFFAOYSA-N 0.000 description 1
- JPPNABMHXCGLRU-UHFFFAOYSA-N CC1CCCN(C(=O)C(N)C(C)(C)C)C1 Chemical compound CC1CCCN(C(=O)C(N)C(C)(C)C)C1 JPPNABMHXCGLRU-UHFFFAOYSA-N 0.000 description 1
- VENZXOILLBBTSH-UHFFFAOYSA-N CC1CCCN(C(=O)C(N)C(C)C)CC1 Chemical compound CC1CCCN(C(=O)C(N)C(C)C)CC1 VENZXOILLBBTSH-UHFFFAOYSA-N 0.000 description 1
- ZWSHVGNMCGKRKP-UHFFFAOYSA-N CC1CCCN(C(=O)C(N)C2=CC=C(O)C=C2)C1 Chemical compound CC1CCCN(C(=O)C(N)C2=CC=C(O)C=C2)C1 ZWSHVGNMCGKRKP-UHFFFAOYSA-N 0.000 description 1
- HJESSPUMQQKZAP-UHFFFAOYSA-N CC1CCCN(C(=O)C2CSCN2)C1 Chemical compound CC1CCCN(C(=O)C2CSCN2)C1 HJESSPUMQQKZAP-UHFFFAOYSA-N 0.000 description 1
- BQCJANBLNCQVNT-UHFFFAOYSA-N CC1CCCN(C(=O)CC(N)C(C)C)C1 Chemical compound CC1CCCN(C(=O)CC(N)C(C)C)C1 BQCJANBLNCQVNT-UHFFFAOYSA-N 0.000 description 1
- SUXWXEJDQZBDNL-UHFFFAOYSA-N CC1CCCNC(=O)C1 Chemical compound CC1CCCNC(=O)C1 SUXWXEJDQZBDNL-UHFFFAOYSA-N 0.000 description 1
- WKZHYWWKUYGHKO-UHFFFAOYSA-N CC1CCCNCC1 Chemical compound CC1CCCNCC1 WKZHYWWKUYGHKO-UHFFFAOYSA-N 0.000 description 1
- UKTZCJRGKOORIH-UHFFFAOYSA-N CC1CCN(C(=O)C(N)C(C)C)C1 Chemical compound CC1CCN(C(=O)C(N)C(C)C)C1 UKTZCJRGKOORIH-UHFFFAOYSA-N 0.000 description 1
- ZDXLYSKUSYNTAK-UHFFFAOYSA-N CC1CCN(C(=O)C2CCCCN2)CC1 Chemical compound CC1CCN(C(=O)C2CCCCN2)CC1 ZDXLYSKUSYNTAK-UHFFFAOYSA-N 0.000 description 1
- UZOFELREXGAFOI-UHFFFAOYSA-N CC1CCNCC1 Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 1
- HJZMLEOVXMKSOU-UHFFFAOYSA-N CC1CCNCC1O Chemical compound CC1CCNCC1O HJZMLEOVXMKSOU-UHFFFAOYSA-N 0.000 description 1
- PTYCBNUHKXMSSA-UHFFFAOYSA-N CC1CNCC1O Chemical compound CC1CNCC1O PTYCBNUHKXMSSA-UHFFFAOYSA-N 0.000 description 1
- AMQQABPTNCUDGF-PFONDFGASA-N CCN(CC)CCC/N=C1/CCCC(C)C1 Chemical compound CCN(CC)CCC/N=C1/CCCC(C)C1 AMQQABPTNCUDGF-PFONDFGASA-N 0.000 description 1
- CKSAVOXDMLOATE-SEYXRHQNSA-N CCN(CC)CCO/N=C1/CCC(C)C1 Chemical compound CCN(CC)CCO/N=C1/CCC(C)C1 CKSAVOXDMLOATE-SEYXRHQNSA-N 0.000 description 1
- GQYIPGUOTJEDOB-UHFFFAOYSA-N CCN(CC)CCON=C1CCCCC(C)C1 Chemical compound CCN(CC)CCON=C1CCCCC(C)C1 GQYIPGUOTJEDOB-UHFFFAOYSA-N 0.000 description 1
- GBDMNEXCNDJWKQ-UHFFFAOYSA-N CCNC(=O)C(N)C(C)(C)C Chemical compound CCNC(=O)C(N)C(C)(C)C GBDMNEXCNDJWKQ-UHFFFAOYSA-N 0.000 description 1
- MHNLUGJLKWJFTH-UHFFFAOYSA-N CNC(C(=O)N1CCCC(C)C1)C(C)C Chemical compound CNC(C(=O)N1CCCC(C)C1)C(C)C MHNLUGJLKWJFTH-UHFFFAOYSA-N 0.000 description 1
- HMDSHIZGTPRJHT-UHFFFAOYSA-N CNC1CCCCC1C Chemical compound CNC1CCCCC1C HMDSHIZGTPRJHT-UHFFFAOYSA-N 0.000 description 1
- LRWGUFXSQQJYAP-GEPGNKONSA-N [H][C@]12OCC(N(C)C)[C@@]1([H])OCC2C Chemical compound [H][C@]12OCC(N(C)C)[C@@]1([H])OCC2C LRWGUFXSQQJYAP-GEPGNKONSA-N 0.000 description 1
- DGQRQDJHLHBVKV-TVVDDFTJSA-N [H][C@]12OCC(N)[C@@]1([H])OCC2C Chemical compound [H][C@]12OCC(N)[C@@]1([H])OCC2C DGQRQDJHLHBVKV-TVVDDFTJSA-N 0.000 description 1
- KPRVQDSTPFFJHA-JXRSTODHSA-N [H][C@]12OCC(N)[C@@]1([H])OCC2C.[H][C@]12OCC(N)[C@@]1([H])OCC2C Chemical compound [H][C@]12OCC(N)[C@@]1([H])OCC2C.[H][C@]12OCC(N)[C@@]1([H])OCC2C KPRVQDSTPFFJHA-JXRSTODHSA-N 0.000 description 1
- UATXWZHQQKCDOC-NWUXKBAASA-N [H][C@]12OCC(NC(=O)[C@@H](N)C(C)C)[C@@]1([H])OCC2C Chemical compound [H][C@]12OCC(NC(=O)[C@@H](N)C(C)C)[C@@]1([H])OCC2C UATXWZHQQKCDOC-NWUXKBAASA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A—HUMAN NECESSITIES
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- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- 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
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- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/24—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by sulfur atoms to which a second hetero atom is attached
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/54—Sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
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- 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
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- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Definitions
- the present invention relates to tuberculosis treatment, such as treatment of diseases mediated by Mycobacterium , e.g. Mycobacterium tuberculosis , with pleuromutilins.
- Tuberculosis is a chronic infectious disease mediated by infection with Mycobacterium tuberculosis .
- Tuberculosis is a major disease in developing countries, as well as an increasing problem in developed areas of the world. Although the infection may be asymptomatic for a considerable period of time, the disease is most commonly manifested as an acute inflammation of the lungs, resulting in fever and a nonproductive cough. If untreated, serious complications and death typically result.
- Tuberculosis may be generally controlled by antibiotic therapy, such as by treatment with Isoniazid, see e.g. The Merck Index, 12th edition, item 5203; Rifampin (Rifampicin®), see e.g. The Merck Index, 12th edition, item 8382, Streptomycin, see e.g. The Merck Index, 12th edition, item 8983; but a major problem is the development of strain drug resistance against such antibiotics.
- the present invention provides the use of a pleuromutilin in the preparation of a medicament for the treatment of diseaeses mediated by Mycobacterium.
- the present invention provides a method of treating diseases mediated by Mycobacterium , comprising administering to a subject in need of such treatment an effective, e.g. an anti-mycobacterium effective; amount of a pleuromutilin.
- Mycobacterium includes M. tuberculosis . Diseaeses mediated by Mycobacterium include mycobacterium infections.
- a pleuromutilin for treatment includes one or more pleuromutilins, e.g. a combination of different pleuromutilins. Treatment includes treatment and prophylaxis.
- a pleuromutilin for use according to the present invention or for treating diseases according to the present invention is designated hereinafter as “a pleuromutilin(s) of (according to) the present invention”.
- a pleuromutilin of the present invention includes a pleuromutilin in the form of a free base, and, where existing, in the form of a salt, in the form of a solvate and in the form of a salt and a solvate, e.g. and in the form of a complex, such as a cyclodextrin complex.
- a pleuromutilin of the present invention may exist in the form of isomers and mixtures thereof, e.g. including diastereoisomers and mixtures thereof. Isomeric mixtures may be separated as appropriate, e.g. according to a method as conventional, to obtain pure isomers.
- the present invention includes a pleuromutilin according to the present invention in any isomeric form and in any isomeric mixture, such as described in patent literature cited below, which patent literature is introduced herein by reference with respect to isomeric forms of pleuromutlins.
- a pleuromutilin according to the present invention in any isomeric form and in any isomeric mixture, such as described in patent literature cited below, which patent literature is introduced herein by reference with respect to isomeric forms of pleuromutlins.
- the cofiguration in the mutilin ring is the same as in a naturally produced mutilin.
- Pleuromutilin a compound of formula is a naturally occurring antibiotic, e.g. produced by the basidomycetes Pleurotus mutilus and P. pasckerianus , see e.g. The Merck Index, 12th edition, item 7694.
- a pleuromutilin of the present invention includes a pleuromutilin having the basic structural elements as set out in formula wherein R is vinyl or ethyl and the dotted line is a bond or is no bond.
- the dotted line between positions 19 an 20 is a bond or is no bond.
- a hydrogen atom in positions 4, 7 and/or 8 of the ring system may be replaced by deuterium, and if the dotted line between positions 1 and 2 is no bond (single bond between positions 1 and 2) the ring system may be further substituted in positions 1 and/or 2, e.g. by halogen, deuterium or hydroxy.
- the group —O— in position 14 is further substituted, preferably by a substituted carbonyl group.
- pleuromutilins examples include e.g.
- the present invention provides a pleuromutilin, which is selected from the group consisting of compounds of formulae
- R EX is as set out in TABLE 1.
- the compounds are of formula I EX , with the exception of Example 12 in which the compound is of formula I′ EX .
- Example 2 14-O-[(2-(R*)-((R)-Histidinyl)-amino-cyclohexan-1-(S*)-yl)-sul- fanyl acetyl)]-mutilin in the form of a hydrochloride (d 6 -DMSO): Diastereoisomers: 8.4, 9.0(2xm, 2H, NH), 7.5,
- the present invention provides a compound of formula wherein
- the present invention provides 14-O-(oximino-(C 3-8 )cycloalkyl-sulfanylmethylcarbonyl)-pleuromutilins and 14-O-(hydrazono-(C 3-8 )cycloalkyl-sulfanylmethylcarbonyl)-pleuromutlins, such as a compound of formula wherein R 1B has the meaning of R 1A as defined above,
- Example 33 14-O- ⁇ [(3-(2-Diethylamino-ethoxyimino)-cycl
- Example 35 14-O- ⁇ [(3-(2-Piperidine-1-yl-ethoxyimino)-cyclohept-(R/S)-yl)-sul- fanyl]-acetyl ⁇ -mutilin in the form of a hydrochloride(E/Z mixture)
- the present invention provides 14-O-(hydroxy- or oxo)-(heterocyclyl-sulfanylmethylcarbonyl)-pleuromutlins, wherein heterocyclyl is an aliphatic ring of 4 to 8 ring members, preferably 5 to 7, comprising one nitrogen as the heteroarom, e.g. a compound of formula wherein
- R EX is as set out in TABLE 5.
- the compounds of TABLE 5 are compounds of formula I EX , with the exception of the compound of Example 41 which is a compound of formula I′′ EX .
- Novel compounds provided by the present invention including compounds, the formulae of which are as set out in TABLE 1 to TABLE 5, and compounds of formulae I A , I B , I C , I D , I EX , I′ EX and I′′ EX are herein designated as “novel compound(s) of (according to) the present invention”.
- the residue of an amino acid whenever defined in any one of the novel compounds of the present invention includes that part of an amino acid, e.g. including natural and synthetic amino acids, e.g. valine and other amino acids as defined herein, most preferably valine; which remains if the hydroxy group from the carboxylic acid group is splitt off, e.g. In case of valine [HO—CO—CH(NH 2 )—CH(CH 3 ) 2 ] the residue —CO—CH(NH 2 )—CH(CH 3 ) 2 .
- each single defined substitutent may be a preferred substituent, e.g. independently of each other substitutent defined.
- a novel compound of the present invention includes a compound in any form, e.g. In free form, in the form of a salt, in the form of a solvate and in the form of a salt and a solvate.
- the present invention provides a novel compound of the present invention in the form of a salt.
- a salt of a novel compound of the present invention includes a pharmaceutically acceptable salt, e.g. including a metal salt or an acid addition salt.
- Metal salts include for example alkali or earth alkali salts;
- acid addition salts include salts of a compound of formula I with an acid, e.g. hydrogen fumaric acid, fumaric acid, naphthalin-1,5-sulphonic acid, phosphoric acid, tartaric acid, citric acid, hydrochloric acid, deuterochloric acid; preferably hydrochloric acid.
- a novel compound of the present invention in free form may be converted into a corresponding compound in the form of a salt; and vice versa.
- a novel compound of the present invention in free form or in the form of a salt and in the form of a solvate may be converted into a corresponding compound in free form or in the form of a salt in unsolvated form; and vice versa.
- a novel compound of the present invention may exist in the form of isomers and mixtures thereof; e.g. optical isomers, diastereoisomers, cis-, trans-conformers.
- a compound of the present invention may e.g. contain asymmetric carbon atoms and may thus exist in the form of diastereoisomeres and mixtures thereof, e.g. racemates.
- a novel compound of the present invention may comprise the residue of an amino acid. In such amino acid residue the carbon atom to which the amino group is attached may be an asymmetric carbon atom and the amino group attached may thus be in the R- or S-configuration.
- a novel compound of the present invention may comprise a cycloalkyl, e.g.
- the carbon atom of a cycloalkyl group to which the sulfanylgroup is attached may be asymmetric, e.g. if said cycloalkyl Is further substituted, and substitutents attached to said cycloalkyl group may be in the R- or in the S-configuration.
- a novel compound of the present invention also may comprise an oxime group.
- the hydroxgroup attached to the imino group may be in syn- or in anti-configuration. Isomeric mixtures may be separated as appropriate, e.g.
- the present invention includes a novel compound of the present invention in any isomeric form and in any isomeric mixture.
- the present invention also includes tautomers of a novel compound of the present invention where such tautomers can exist.
- Any compound described herein, e.g. a novel compound of the present invention, may be prepared as appropriate, e.g. according to a method as conventional, e.g. analogously, e.g. or as specified herein.
- the present invention provides a process for the production of a compound of formula wherein
- a process provided by the present invention may e.g. be carried out analogously to processes as set out In any of the patent references cited herein, e.g. analogously to a process for the production of compounds as described in patent literature cited herein, such as in WO0109095, WO0204414 and WO0222580, or as described herein.
- a pleuromutilin of the present invention includes the novel compounds of the present invention of formula I P .
- a pleuromutilin of the present invention includes one or more, preferably one, pleuromutilins of the present invention, e.g. one pleuromutilin or a combination of different pleuromutlins of the present invention.
- novel compounds of the present invention exhibit pharmacological activity similar to pleuromutilins in similar indications as described in WO0109095, WO0204414 and WO0222580, e.g. in test systems similar as described in WO0109095, WO0204414 and WO0222580, and additionally in test systems described herein.
- Compounds of formula I P are therefore useful as pharmaceuticals.
- the present invention provides a compound of formula I P for use as a pharmaceutical, preferably as an antimicrobial, such as an antibiotic, e.g. and as an anti-anaerobic, including the use as a pharmaceutical in the treatment of diseases mediated by Mycobacterium , such as Mycobacterium tuberculosis.
- an antimicrobial such as an antibiotic
- Mycobacterium such as Mycobacterium tuberculosis
- the present invention provides a compound of formula I P for use in the preparation of a medicament for the treatment of microbial diseases, for example of diseases mediated by bacteria, e.g. selected from Staphylococci, Streptococci, Enterococci, Mycobacterium , e.g. Mycobacterium tuberculosis ; e.g. and of diseases mediated by Mycoplasms, Chlamydia and obligatory anaerobes.
- bacteria e.g. selected from Staphylococci, Streptococci, Enterococci, Mycobacterium , e.g. Mycobacterium tuberculosis ; e.g. and of diseases mediated by Mycoplasms, Chlamydia and obligatory anaerobes.
- the present Invention provides a method of treatment of microbial diseases, for example of diseases mediated by bacteria, e.g. selected from Staphylococci, Streptococci, Enterococci, Mycobacterium , e.g. Mycobacterium tuberculosis ; e.g. and of diseases mediated by Mycoplasms, Chlamydia and obligatory anaerobes, which method comprises administering to a subject in need of such treatment an effective amount of a noveel compound of the present invwention, e.g. including a compound of formula I P ; e.g. in the form of a pharmaceutical composition.
- a noveel compound of the present invwention e.g. including a compound of formula I P ; e.g. in the form of a pharmaceutical composition.
- Treatment includes treatment and prophylaxis.
- an indicated daily dosage is in the range from about 0.05 g to about 5.0 g, of a novel compound of of the present invention; conveniently administered, for example, in divided doses up to four times a day.
- a novel compound of the present invention may be administered by any conventional route, for example enterally, e.g. including nasal, buccal, rectal, oral administration; parenterally, e.g. including intravenous, intramuscular, subcutanous administration; or topically; e.g. including epicutaneous, intranasal, intratracheal administration; e.g. in form of coated or uncoated tablets, capsules, injectable solutions or suspensions, e.g. in the form of ampoules, vials, in the form of creams, gels, pastes, inhaler powder, foams, tinctures, lip sticks, drops, sprays, or in the form of suppositories.
- enterally e.g. including nasal, buccal, rectal, oral administration
- parenterally e.g. including intravenous, intramuscular, subcutanous administration
- topically e.g. including epicutaneous, intranasal, intratracheal administration
- injectable solutions or suspensions e.g.
- novel compounds of the present invention may be administered in the form of a pharmaceutically acceptable salt, e.g. an acid addition salt or metal salt; or in free form; optionally in the form of a solvate.
- a pharmaceutically acceptable salt e.g. an acid addition salt or metal salt
- the novel compounds of the present invention in the form of a salt exhibit the same order of activity as the novel compounds of the present invention in free form; optionally in the form of a solvate.
- a novel compound of the present invention may be used for pharmaceutical treatment according to the present invention alone, or in combination with one or more other pharmaceutically active agents.
- Such other pharmaceutically active agents e.g. include other antimicrobials, e.g. including antibiotics, e.g. cephalosporins, penicillins, erythromycins, tetracyclines.
- a pleuromutilin of to the present invention in diseases mediated by Mycobacterium , but appropriate other pharmaceutically active agents includes agents known to be active in the treatment of diseases mediated by Mycobacterium , such as Rifampicin (Rifampicin®), Streptomycin (Streptomycin®), Ethambutol (Ethambutol®), Pyrizinamid (Pyrizinamid®).
- Combinations include fixed combinations, in which two or more pharmaceutically active agents are in the same formulation; kits, in which two or more pharmaceutically active agents in separate formulations are sold in the same package, e.g. with instruction for co-administration; and free combinations in which the pharmaceutically active agents are packaged separately, but instruction for simultaneous or sequential administration are given.
- the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising a novel compound of the present invention, e.g. a compound of formula I P , in association with at least one pharmaceutical excipient, e.g. appropriate carrier and/or diluent, e.g. including fillers, binders, disintegrators, flow conditioners, lubricants, sugars and sweeteners, fragrances, preservatives, stabilizers, wetting agents and/or emulsifiers, solubilizers, salts for regulating osmotic pressure and/or buffers; e.g. further comprising another pharmaceutically active agent.
- a pharmaceutical excipient e.g. appropriate carrier and/or diluent, e.g. including fillers, binders, disintegrators, flow conditioners, lubricants, sugars and sweeteners, fragrances, preservatives, stabilizers, wetting agents and/or emulsifiers, solubilizers, salts for regulating
- composition comprising pleuromutilins of the present invention for administration in diseases mediated by Mycobtarium may comprise similar excipient as described above.
- the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising a pleuromutilin of the present invention in association with at least one pharmaceutical excipient, and further comprising another pharmaceutically active agent useful in the treatment of Mycobacterium , e.g. M. tuberculosis , infections, such as Rifampicin (Rifampicin®), Streptomycin (Streptomycin®), Ethambutol (Ethambutol®), Pyrizinamid (Pyrizinamid®).
- Rifampicin Roseptomycin
- Ethambutol Ethambutol
- Pyrizinamid Pyrizinamid
- compositions may be manufactured according, e.g. analogously to a method as conventional, e.g. by mixing, granulating, coating, dissolving or lyophilzing processes.
- Unit dosage forms may contain, for example, from about 0.5 mg to about 1500 mg, such as 1 mg to about 500 mg.
- Pleuromutilins of the present invention for administration in diseases mediated by Mycobtarium tuberculosis may be administered in a similar mode and in similar dosages as Rifampicin or Streptomycin.
- a pleuromutilin of the present invention is preferably selected from the group consisting of a compound of formula I—U.S. Pat. No. 4,278,674, a compound of formula I—EP0153277, a compound of formula I—WO0109095, a compound of formula I—WO0204414, a compound of formula I—WO0222580, a compound of TABLE 1, a compound of formula I B , or a of formula I D ; e.g. including
- Activity against strains of Mycobacterium e.g. M. tuberculosis may be determined according to the following General Test Procedure:
- Agar is used as a substrate. Shortly before solidifaction of the Agar TEST COMPOUNDS In different concentrations are added and mixed into the still liquid agar mass (according to the Agar dilution test). Controls without TEST COMPOUNDS are also prepared for determination of strain growth ability. The thus prepared agars are inoculated after solidification with Mycobacterium tuberculosis strains. Incubation is carried out in normal incubators at 37° C. As a nutrition medium Middlebrook 7H10+OADC (Oleic, Albumin, Dextrose, Catalase) Enrichment (pH 6.71-6.73) is used.
- the minimum inhibition concentration (MIC) which is the compound concentration in the agar which inhibits 99% of strain growth, is determined after 3 weeks, 4 weeks and 5 weeks after inoculation.
- Pleuromutilins of the present invention show activity against strains of Mycobacterium , e.g. M. tuberculosis and are thus useful in the treatment of infectios caused by Mycobacterium .
- Pleuromutilins of the present invention surprisingly are even active against resistant and multiresistant M. tuberculosis strains, e.g. strains which are resistant against treatment with known pharmaceuticals useful in the treatment of tuberculosis, e.g. Isoniacid, Rifampicin, Streptomycin.
- IBB 14-O-[(N-(3-Methyl-2(R)-amino-butyryl)-piperidine-3(S)-yl)-sulfanylacetyl]-2(S)-fluoro-mutilin in the form of a hydrochloride
- Example I-G is obtained analagosouly to the method of Example I-G, but using a 1:1 mixture of 14-O-[3-(R*)-((N-BOC-(R)-valyl-amino-cyclohexan-1-(S*)-yl)sulfanyl)-acetyl]mutilin and 14-O-[3-(S*)-((N-BOC-(R)-valyl-amino-cyclohexan-1-(R*)-yl sulfanyl)-acetyl]mutilin as a starting material.
- 1 H-NMR(d 6 -DMSO) Rotamers.
- a solution of 1.06 g of pleuromutilin-22-O-tosylate dissolved in 10 ml THF is slowly added to a solution of 420 mg of N-BOC-(4-(R/S)-azepane-thiol and 220 mg of potassium-tert.butylate in 25 ml of THF and the mixture obtained is stirred for 2 hours.
- the mixture obtained is distributed between brine and EtAc, the mixture obtained is extracted with 0.1N HCl, the organic phase obtained is dried, solvent is evaporated and the evaporation residue obtained is subjected to chromatography.
- Example 43 is obtained analagously to the method of Example IAB), starting from 4-(R/S)-mercapto-azepan-2-one. Characterisation data see TABLE 5, Example 43.
- 14-O-[((2-(R*)-(N-BOC-(R)-Valyl)-amino-cyclohexan-1-(R*)-yl)-sulfanyl acetyl)]-mutilin is obtained.
- the BOC-protecting group is cleaved by treatment with 5 ml of etheric HCl and 14-O-[(2-(R*)-((R)-valyl)-amino-cyclohexan-1-(R*)-yl)-sulfanyl acetyl)]-mutilin in the form of a hydrochloride is obtained.
- a solution of 4.7 g of Na 2 S 2 O 5 in 25 ml of H 2 O is added to a solution of 12.2 g of 14-O-[(carbamimidoylsulfanyl)acetyl]mutilin-tosylate in a mixture of 20 ml of EtOH and 35 ml of H 2 O (warmed to ca. 90°).
- 100 ml of CCl 4 are added to the reaction mixture obtained and the mixture obtained is heated under reflux for ca. 2 hours.
- the two-phase system obtained is separated, the organic phase is dried and solvent is evaporated. 14-mercapto-acetyl-mutilin is obtained.
- N-BOC-3-(R)-hydroxy-piperidine A solution of 2.2 g of N-BOC-3-(R)-hydroxy-piperidine in 10 ml of THF is added under argon and 1 ml of thiolacetic acid to a solution of 3.4 g of triphenylphosphine and 2.65 ml of azadicarbonic acid-isopropylate in 10 ml of THF.
- the mixture obtained is kept for 18 hours at 70°, solvent is evaporated and the evaporation residue obtained is subjected to chromatography.
- N-BOC-3-(S)-thioacetoxy-piperidine is obtained.
- Toluene-4-sulfonic acid (3S, 3aS, 6R, 6aR)-6-hydroxy-hexahydro-furo[3,2-b]furan-3-yl ester (a) and toluene-4-sulfonic acid (3R, 3aS, 6S, 6aR)-6-hydroxy-hexahydro-furo[3,2-b]furan-3-yl ester (b) are obtained.
- tuberculosis Isoniacid Rifampicin Streptomycin Strain 1 S S S Strain 2 S S S Strain 3 R R S Strain 4 R R R Strain 5 R R S Strain 6 S S Strain 7 R S R Strain 8 S R S Strain 9 R S R Strain 10 S S S Strain 11 S S S Strain 12 S S Strain 13 S S S Strain 14 S S S Strain 15 S S S Strain 15 is the labor strain 137 kV. Resistant and sensible strains are isolated from patients with known sensibilities/resistance. A strain is designated as resistant if its MIC in testing according to the General Test Procedure after 3 to 5 weeks is higher than 20 ⁇ g/ml.
- TEST COMPOUNDS Activity of TEST COMPOUNDS (TCs) against M. tuberculosis strains 1 to 5 and 7 as set out in TABLE A Is determined in the Agar Dilution Test under conditions as in Example A in different agar concentrations of the TEST COMPOUNDS. The MIC is determined after 3, 4 and 5 weeks.
- a compound of formula I-Tiamulin TC-1
- a compound of formula I-Valnemulin TC-2
- a compound of formula I-PREF1 TC-3
- a compound of formula I-PREF2 TC-4
- a compound of formula I-PREF3 TC-5
- a compound of formula I-PREF4 TC-6
- a compound of formula I-PREF5 TC-7
- a compound of formula I-PREF6 TC-8
- Example B Is carried out according to the method of Example B. Test results obtained are as set out in TABLE C and in TABLE D and in TABLE E: TABLE C MIC ( ⁇ g/ml) against Mycobacterium tuberculosis of strain number TC/week 1 2 3 4 5 6 7 8 TC-2/3 0.5 4 2 8 2 4 4 4 TC-2/4*) 0.5 4 2 8 4 4 8 8 TC-4/3 1 4 1 4 2 4 2 2 TC-4/4 2 4 1 4 2 4 4 2 TC-4/5 2 4 1 4 2 4 4 4 *)Tested after 31 days and thus no further testing after 5 weeks.
- TC-number indicates the TEST COMPOUND as defined above, e.g. TO-1 indicates a compound of formula I—Tiamulin; and “/week” indicates the MIC-determination point (in weeks from inoculation) in the testing of such TEST COMPOUND.
- TC-1/3 indicates that the MIC of a compound of formula I—Tiamulin was determined after 3 weeks from inoculation.
- MIC is the minimum inhibition concentration as defined above.
- the strain numbers 1 to 4 and 6 to 7 indicated In TABLE B, the strain numbers 1 to 9 indicated in TABLE C and the strain numbers 10 to 15 indicated in TABLE D, and the strain numbers 1, 12 and 15 indicated in TABEL E refer to the corresponding Mycobacterium tuberculosis strains of TABLE 6 R EX R EX R EX Compound I EX Compound I EX Compound I EX Compound I EX Compound I′ EX
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US11/818,094 US8088823B2 (en) | 2002-03-28 | 2007-06-13 | Tuberculosis treatment using pleuromutilin derivatives |
US13/317,666 US20120046276A1 (en) | 2002-03-28 | 2011-10-25 | Tuberculosis treatment using pleuromutilin derivatives |
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GBGB0207495.3A GB0207495D0 (en) | 2002-03-28 | 2002-03-28 | Organic compounds |
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GB0217149A GB0217149D0 (en) | 2002-07-24 | 2002-07-24 | Organic compounds |
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GB0217305A GB0217305D0 (en) | 2002-07-25 | 2002-07-25 | Organic compounds |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
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US20060276503A1 (en) * | 2003-09-03 | 2006-12-07 | Glaxo Group Limited | Novel process salts compositions and use |
EP1808431A1 (fr) * | 2006-01-16 | 2007-07-18 | Nabriva Therapeutics Forschungs GmbH | Dérivés de mutiline et leur utilisation en tant que composé pharmaceutique |
US20080161342A1 (en) * | 2005-03-02 | 2008-07-03 | Alan Collier | Novel Polymorph of Mutilin |
US20080171766A1 (en) * | 2005-03-10 | 2008-07-17 | Smithkline Beecham Corporation | Novel Method |
US20100197909A1 (en) * | 2007-05-24 | 2010-08-05 | Yasumichi Fukuda | Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in subtituent at 14-position |
US20100197734A1 (en) * | 2007-07-13 | 2010-08-05 | Nabriva Therapeutics Ag | Pleuromutilin derivatives and their use as antimicrobials |
CN102675172A (zh) * | 2012-04-27 | 2012-09-19 | 宁夏泰瑞制药股份有限公司 | 一种泰妙菌素碱的制备方法 |
US9278920B2 (en) | 2010-09-09 | 2016-03-08 | Nabriva Therapeutics Ag | Pleuromutilin derivatives for use in the treatment of diseases mediated by microbes |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PE20020676A1 (es) * | 2000-09-13 | 2002-08-27 | Biochemie Gmbh | Compuestos de mutilina como antibacterianos |
GB0308114D0 (en) * | 2003-04-08 | 2003-05-14 | Glaxo Group Ltd | Novel compounds |
EP1686115A1 (fr) * | 2005-01-26 | 2006-08-02 | Novartis AG | Sels d'acides organiques de Valnemulin |
GB0513058D0 (en) * | 2005-06-27 | 2005-08-03 | Sandoz Ag | Organic compounds |
EP2298733B1 (fr) * | 2005-06-27 | 2016-05-25 | Nabriva Therapeutics AG | Dérivés de la pleuromutiline contenant un groupe hydroxyamino- ou acyloxyaminocycloalkyle |
GB0515995D0 (en) * | 2005-08-03 | 2005-09-07 | Sandoz Ag | Organic compounds |
WO2007037518A1 (fr) * | 2005-09-29 | 2007-04-05 | Dainippon Sumitomo Pharma Co., Ltd. | Derive de mutiline et composition pharmaceutique la contenant |
EP1972618A1 (fr) | 2007-03-20 | 2008-09-24 | Nabriva Therapeutics AG | Dérivés de pleuromutilin pour le traitement des maladies médiées par des microbes |
EP2159220A1 (fr) * | 2008-09-02 | 2010-03-03 | Nabriva Therapeutics AG | Composés organiques |
CN101690717B (zh) * | 2009-09-30 | 2013-03-06 | 北京大北农动物保健科技有限责任公司 | 一种兽用沃尼妙林及其盐的预混剂及制备方法 |
CN103319496B (zh) * | 2012-03-23 | 2015-06-17 | 中国科学院微生物研究所 | 来源于海洋疣孢菌的多环聚酮类化合物及其制备方法与应用 |
CN105837530B (zh) * | 2016-04-18 | 2018-07-27 | 华南农业大学 | 一种具有哌嗪侧链的截短侧耳素衍生物及其制备方法和用途 |
CN106699690B (zh) * | 2016-12-07 | 2019-09-10 | 华南农业大学 | 一种具有酰基哌嗪基侧链的截短侧耳素衍生物及其制备方法和用途 |
TWI762573B (zh) | 2017-02-10 | 2022-05-01 | 奧地利商納畢瓦治療有限責任公司 | 截短側耳素之純化 |
WO2018152408A1 (fr) * | 2017-02-17 | 2018-08-23 | University Of Tennessee Research Foundation | Dérivés de pleuromutiline et leurs utilisations |
CN117500809A (zh) | 2021-04-16 | 2024-02-02 | 纳布里瓦治疗有限责任公司 | 新的12-差向异构-莫林化合物及其用途 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4278674A (en) * | 1971-10-05 | 1981-07-14 | Sandoz Ltd. | Substituted 14-desoxy-mutilin compositions |
US20050159377A1 (en) * | 2000-05-04 | 2005-07-21 | Smithkline Beecham Corporation | Methods of modulating activity of prokaryotic ribosomes |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH627940A5 (de) * | 1976-12-23 | 1982-02-15 | Sandoz Ag | Kokzidiostatisches kombinationspraeparat. |
JPS5594359A (en) * | 1979-01-12 | 1980-07-17 | Sandoz Ag | Novel pleuromutilin derivatives*their manufacture and use |
CY1353A (en) * | 1979-01-12 | 1987-04-24 | Sandoz Ag | New pleuromutilin derivatives, their production and use |
JPS5696163A (en) * | 1980-12-08 | 1981-08-04 | Toyota Motor Corp | Method of surface treatment for preventing radio noise from distributor |
CA1183789A (fr) * | 1981-08-04 | 1985-03-12 | Kiyoshi Isono | Antibiotique 76-11, procede de production, agent contre les coccidioses et agent favorisant la croissance des animaux domestiques contenant ledit antibiotique comme ingredient actif |
AT400674B (de) * | 1991-07-24 | 1996-02-26 | Biochemie Gmbh | Pharmazeutische pleuromutilin-zubereitung |
UY25225A1 (es) * | 1997-10-29 | 2000-12-29 | Smithkline Beecham Plc | Derivados de pleuromutilina utiles como agentes antimicrobianos |
JP2003523729A (ja) * | 1999-05-20 | 2003-08-12 | スミスクライン・ビーチャム・コーポレイション | 原核生物リボソームの活性を変調する方法 |
GB9918037D0 (en) | 1999-07-30 | 1999-09-29 | Biochemie Gmbh | Organic compounds |
GB0017031D0 (en) | 2000-07-11 | 2000-08-30 | Biochemie Gmbh | Antimicrobials |
GB0018951D0 (en) | 2000-08-03 | 2000-09-20 | Smithkline Beecham Plc | Novel compounds |
PE20020676A1 (es) | 2000-09-13 | 2002-08-27 | Biochemie Gmbh | Compuestos de mutilina como antibacterianos |
AU2002217784A1 (en) | 2000-11-28 | 2002-06-11 | Promega Corporation | Purification of dna sequencing reactions using silica magnetic particles |
-
2002
- 2002-03-28 GB GBGB0207495.3A patent/GB0207495D0/en not_active Ceased
-
2003
- 2003-03-27 DE DE60333605T patent/DE60333605D1/de not_active Expired - Lifetime
- 2003-03-27 PL PL371268A patent/PL214755B1/pl unknown
- 2003-03-27 AU AU2003219107A patent/AU2003219107A1/en not_active Abandoned
- 2003-03-27 WO PCT/EP2003/003215 patent/WO2003082260A2/fr not_active Application Discontinuation
- 2003-03-27 EP EP03714893A patent/EP1492518A2/fr not_active Withdrawn
- 2003-03-27 US US10/509,502 patent/US20050215637A1/en not_active Abandoned
- 2003-03-27 AT AT07012020T patent/ATE475414T1/de not_active IP Right Cessation
- 2003-03-27 JP JP2003579798A patent/JP4708708B2/ja not_active Expired - Fee Related
- 2003-03-27 SI SI200331884T patent/SI1875903T1/sl unknown
- 2003-03-27 TW TW092106937A patent/TWI331916B/zh not_active IP Right Cessation
- 2003-03-27 EP EP07012020A patent/EP1875903B1/fr not_active Expired - Lifetime
- 2003-03-27 BR BR0308813-8A patent/BR0308813A/pt not_active Application Discontinuation
- 2003-03-27 CN CNA038073617A patent/CN1642535A/zh active Pending
- 2003-03-27 MX MXPA04009454A patent/MXPA04009454A/es unknown
- 2003-03-27 ES ES07012020T patent/ES2352225T3/es not_active Expired - Lifetime
-
2004
- 2004-09-09 ZA ZA200407216A patent/ZA200407216B/xx unknown
-
2007
- 2007-06-13 US US11/818,094 patent/US8088823B2/en not_active Expired - Fee Related
-
2010
- 2010-01-14 JP JP2010005571A patent/JP2010143934A/ja not_active Withdrawn
-
2011
- 2011-10-25 US US13/317,666 patent/US20120046276A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4278674A (en) * | 1971-10-05 | 1981-07-14 | Sandoz Ltd. | Substituted 14-desoxy-mutilin compositions |
US20050159377A1 (en) * | 2000-05-04 | 2005-07-21 | Smithkline Beecham Corporation | Methods of modulating activity of prokaryotic ribosomes |
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7875630B2 (en) | 2003-09-03 | 2011-01-25 | Glaxo Group Limited | Process salts compositions and use |
US20060276503A1 (en) * | 2003-09-03 | 2006-12-07 | Glaxo Group Limited | Novel process salts compositions and use |
US8207191B2 (en) | 2003-09-03 | 2012-06-26 | Glaxo Group Limited | Process, salts, composition and use |
US20110144151A1 (en) * | 2003-09-03 | 2011-06-16 | Glaxo Group Limited | Novel process, salts, composition and use |
US8334303B2 (en) | 2005-03-02 | 2012-12-18 | Glazo Group Limited | Polymorph of mutilin |
US20080161342A1 (en) * | 2005-03-02 | 2008-07-03 | Alan Collier | Novel Polymorph of Mutilin |
US20080171766A1 (en) * | 2005-03-10 | 2008-07-17 | Smithkline Beecham Corporation | Novel Method |
US20080287442A1 (en) * | 2006-01-16 | 2008-11-20 | Nabriva Therapeutics Forschungs Gmbh | Organic Compounds |
US7816389B2 (en) | 2006-01-16 | 2010-10-19 | Nabriva Therapeutics Forschungs Gmbh | Organic compounds |
EP1808431A1 (fr) * | 2006-01-16 | 2007-07-18 | Nabriva Therapeutics Forschungs GmbH | Dérivés de mutiline et leur utilisation en tant que composé pharmaceutique |
US20100197909A1 (en) * | 2007-05-24 | 2010-08-05 | Yasumichi Fukuda | Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in subtituent at 14-position |
US8222407B2 (en) | 2007-05-24 | 2012-07-17 | Kyorin Pharmaceutical Co., Ltd. | Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in substituent at 14-position |
US20100197734A1 (en) * | 2007-07-13 | 2010-08-05 | Nabriva Therapeutics Ag | Pleuromutilin derivatives and their use as antimicrobials |
US8173685B2 (en) * | 2007-07-13 | 2012-05-08 | Nabriva Therapeutics Ag | Pleuromutilin derivatives and their use as antimicrobials |
US9278920B2 (en) | 2010-09-09 | 2016-03-08 | Nabriva Therapeutics Ag | Pleuromutilin derivatives for use in the treatment of diseases mediated by microbes |
CN102675172A (zh) * | 2012-04-27 | 2012-09-19 | 宁夏泰瑞制药股份有限公司 | 一种泰妙菌素碱的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
SI1875903T1 (sl) | 2010-12-31 |
AU2003219107A1 (en) | 2003-10-13 |
US20120046276A1 (en) | 2012-02-23 |
PL214755B1 (pl) | 2013-09-30 |
WO2003082260A2 (fr) | 2003-10-09 |
TWI331916B (en) | 2010-10-21 |
JP2005529088A (ja) | 2005-09-29 |
JP2010143934A (ja) | 2010-07-01 |
CN1642535A (zh) | 2005-07-20 |
GB0207495D0 (en) | 2002-05-08 |
EP1875903B1 (fr) | 2010-07-28 |
DE60333605D1 (de) | 2010-09-09 |
US8088823B2 (en) | 2012-01-03 |
PL371268A1 (en) | 2005-06-13 |
ES2352225T3 (es) | 2011-02-16 |
EP1492518A2 (fr) | 2005-01-05 |
US20070270404A1 (en) | 2007-11-22 |
AU2003219107A8 (en) | 2003-10-13 |
BR0308813A (pt) | 2005-01-04 |
TW200403051A (en) | 2004-03-01 |
ZA200407216B (en) | 2005-05-31 |
ATE475414T1 (de) | 2010-08-15 |
WO2003082260A3 (fr) | 2004-03-25 |
EP1875903A1 (fr) | 2008-01-09 |
JP4708708B2 (ja) | 2011-06-22 |
MXPA04009454A (es) | 2005-10-18 |
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