ES2655911T3 - Compuestos de tetraciclina sustituidos con C7-fluoro - Google Patents
Compuestos de tetraciclina sustituidos con C7-fluoro Download PDFInfo
- Publication number
- ES2655911T3 ES2655911T3 ES15180611.4T ES15180611T ES2655911T3 ES 2655911 T3 ES2655911 T3 ES 2655911T3 ES 15180611 T ES15180611 T ES 15180611T ES 2655911 T3 ES2655911 T3 ES 2655911T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- alkoxy
- independently selected
- halo
- heteroaryl
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- 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
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
-
- 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
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
-
- 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
- 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
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- 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
- C07D207/06—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 radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- 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
- C07D207/08—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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
- C07D207/08—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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
-
- 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
- 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 two 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
-
- 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
-
- 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
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- C07D295/08—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 singly bound oxygen or sulfur atoms
- C07D295/084—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 singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- 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
- C07D295/12—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 singly or doubly bound 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
- C07D295/145—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- 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
- C07D295/22—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 hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/38—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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyridine Compounds (AREA)
- Indole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Un compuesto representado por la Formula Estructural (II):**Fórmula** o una sal farmaceuticamente aceptable del mismo, en la que: X esta seleccionado entre hidrogeno, -alquilo (C1-C7), carbociclilo, arilo y heteroarilo; cada uno de R1 y R2 estan seleccionados independientemente entre hidrogeno, alquilo (C1-C7), cicloalquil (C3- C6)- alquilo (C1-C4), alcoxi (C1-C7)-alquilo (C1-C4), cicloalcoxi (C3-C6)-alquilo (C1-C4), cicloalquilo (C3-C6), arilo, arilalquilo (C1-C4), ariloxialquilo (C1-C4), ariltioalquilo (C1-C4), arilsufinil-alquilo (C1-C4), arilsulfonilalquilo (C1-C4) y - O-alquilo (C1-C7), o R1 y R2, tomados junto con el atomo de nitrogeno al que estan enlazados, forman un heteroarilo monociclico o biciclico, o un heterociclo monociclico, condensado biciclico, puenteado biciclico o espiro biciclico, en donde el heteroarilo o el heterociclo contienen opcionalmente uno o dos heteroatomos adicionales seleccionados independientemente entre N, O y S; y RF esta seleccionado entre hidrogeno, alquilo (C1-C7), carbociclilo, arilo y heteroarilo; en donde cada resto alquilo, cicloalquilo, alcoxi y cicloalcoxi en los grupos representados por R1 y R2 y cada heterociclo representado por NR1R2 tomados juntos esta opcionalmente sustituido con uno o mas sustituyentes seleccionados independientemente entre el grupo que consiste en alquilo (C1-C4), halo, -OH, alcoxi (C1-C4), alquiltio (C1-C4), alquilsulfinilo (C1-C4), alquilsulfonilo (C1-C4), alcoxi (C1-C4)-alquilo (C1-C4) y -N(R3)(R4); y cada resto arilo, ariloxi, ariltio, arilsufinilo y arilsulfonilo en los grupos representados por R1 y R2 y cada heteroarilo representado por NR1R2 tomados juntos estan opcionalmente sustituidos con uno o mas sustituyentes seleccionados independientemente entre el grupo que consiste en alquilo (C1-C4), halo, -OH, alcoxi (C1-C4), -Salquilo (C1-C4), -S(O)alquilo (C1-C4), -S(O)2alquilo (C1-C4), alcoxi (C1-C4)-alquilo (C1-C4), -N(R3)(R4); -CN, haloalquilo (C1-C4) y haloalcoxi (C1-C4), y cada uno de R3 y R4 esta seleccionado independientemente entre el grupo que consiste en -H y alquilo (C1-C4), en donde el alquilo (C1-C4) representado por R3 y R4 esta opcionalmente sustituido con uno o mas sustituyentes seleccionados independientemente entre el grupo que consiste en alquilo (C1-C4), halo, -OH, alcoxi (C1-C4) y alcoxi (C1-C4)-alquilo (C1-C4), y cada carbociclilo, arilo o heteroarilo en los grupos representados por X y RF esta opcionalmente e independientemente sustituido con uno o mas sustituyentes seleccionados independientemente entre halo, -alquilo (C1-C4), -OH, >=O, -O-alquilo (C1-C4), -alquil (C1-C4)-O-alquilo (C1-C4), -alquilo (C1-C4) halo sustituido, -O-alquilo (C1-C4) halo sustituido, -C(O)-alquilo (C1-C4), -C(O)-(alquilo (C1-C4) fluoro sustituido), - S(O)m-alquilo (C1-C4), -N(RG)(RG) y CN; en donde m es 1 o 2; cada RG es hidrogeno o alquilo (C1-C4), en donde cada alquilo en el grupo representado por RG esta opcionalmente e independientemente sustituido con uno o mas sustituyentes seleccionados independientemente entre -alquilo (C1-C4), cicloalquilo (C3-C6), halo, -OH, -O-alquilo (C1-C4) y alquil (C1-C4)-O-alquilo (C1-C4).
Description
- 12
- 13
- 14
- 15
- 16
- 17
- 18
- 19
10
- 20
- 21
- 22
- 23
- 24
- 25
- 26
- 27
11
- 28
- 29
- 30
- 31
- 32
- 33 (referencia)
- 34
- 35
12
- 36
- 37
- 38
- 39
- 40
- 41
- 42
- 43
13
- 44
- 45
- 46
"Alquilo" se refiere un radical hidrocarburo alifático, monovalente de cadena lineal o ramificada que tiene el número especificado de átomos de carbono. Por lo tanto, "alquilo (C1-C7) " significa un radical que tiene de 1-7 átomos de carbono en una disposición lineal o ramificada. "alquilo (C1-C7)" incluye metilo, etilo, propilo, butilo, pentilo, hexilo y
5 heptilo. Las sustituciones adecuadas para un "alquilo sustituido" incluyen, pero sin limitación, -halógeno, -OH, alquilo (C1-C4), alcoxi (C1-C4), alquiltio (C1-C4), alquilsulfinilo (C1-C4), alquilsulfonilo (C1-C4), alcoxi (C1-C4)-alquilo (C1-C4) y N(R3)(R4), donde R3 y R4 son como se han descrito anteriormente.
"Cicloalquilo" se refiere a un radical hidrocarburo cíclico, alifático, saturado que tiene el número especificado de
10 átomos de carbono. El Cicloalquilo (C3-C6) incluye ciclopropilo, ciclobutilo, ciclopentilo y ciclohexilo. Los sustituyentes adecuados para a "cicloalquilo sustituido" incluyen halógeno, -OH, alquilo (C1-C4), alcoxi (C1-C4), alquiltio (C1-C4), alquilsulfinilo (C1-C4), alquil (C1-C4)-sulfonilo, alcoxi (C1-C4)-alquilo (C1-C4) y -N(R3)(R4), donde R3 y R4 son como se han descrito anteriormente.
15 "Heterociclo" se refiere a un anillo heterocíclico saturado o parcialmente insaturado de 4-12 miembros que contiene 1, 2 o 3 heteroátomos seleccionados independientemente entre N, O o S. Cuando un heteroátomo es S, éste puede estar opcionalmente mono o dioxigenado (es decir -S(O)-o -S(O)2-). El heterociclo puede ser monocíclico, bicíclico condensado, bicíclico puenteado o espiro bicíclico.
20 Los ejemplos de heterociclo monocíclico incluyen, pero sin limitación, azetidina, pirrolidina, piperidina, piperazina, hexahidropirimidina, tetrahidrofurano, tetrahidropirano, morfolina, tiomorfolina, 1,1-dioxido tiomorfolina, tetrahidro-2H1,2-tiazina, 1,1-dióxido de tetrahidro-2H-1,2-tiazina, isotiazolidina, 1,1-dioxido de isotiazolidina.
Un heterociclo bicíclico condensado tiene dos anillos que tienen dos átomos adyacentes en el anillo en común. El
25 primer anillo es un heterociclo monocíclico y el segundo anillo es un cicloalquilo, carbociclo parcialmente insaturado, fenilo, heteroarilo o un heterocilo monocíclico. Por ejemplo, el segundo anillo es un cicloalquilo (C3-C6), tal como ciclopropilo, ciclobutilo, ciclopentilo y ciclohexilo. Como alternativa, el segundo anillo es fenilo. Los ejemplos de heterociclos bicíclicos condensados incluyen, pero sin limitación, indolina, isoindolina, 2,3-dihidro-1Hbenzo[d]imidazol, 2,3-dihidrobenzo[d]oxazol, 2,3-dihidrobenzo[d]tiazol, octahidrobenzo[d]oxazol, octahidro-1H
30 benzo[d]imidazol, octahidrobenzo[d]tiazol, octahidrociclopenta[c]pirrol, 3-azabiciclo[3,1,0]hexano y 3azabiciclo[3,2,0]heptano.
Un heterociclo espiro bicíclico tiene dos anillos que tienen únicamente un átomo de anillo en común. El primer anillo es un heterociclo monocíclico y el segundo anillo es un cicloalquilo, carbociclo parcialmente insaturado o un
35 heterociclo bicíclico. Por ejemplo, el segundo anillo es un cicloalquilo (C3-C6). Los ejemplos de heterociclo espiro bicíclico incluyen, pero sin limitación, azaespiro[4,4]nonano, 7-azaespiro[4,4]nonano, azaesprio[4,5]decano, 8azaespiro[4,5]decano, azaespiro[5,5]undecano, 3-azaespiro[5,5]undecano y 3,9-diazaespiro[5,5]undecano.
Un heterociclo bicíclico puenteado tiene dos anillos que tienen tres o más átomos adyacentes en el anillo en común.
40 El primer anillo es un heterociclo monocíclico y el otro anillo es un cicloalquilo (tal como cicloalquilo (C3-C6)), carbociclo parcialmente insaturado o un heterociclo bicíclico. Los ejemplos de heterocíclicos bicíclicos puenteados incluyen, pero sin limitación, azabiciclo[3,3,1]nonano, 3-azabiciclo[3,3,1]nonano, azabiciclo[3,2,1]octano, 3azabiciclo[3,2,1]octano, 6-azabiciclo[3,2,1]octano y azabiciclo[2,2,2]octano, 2-azabiciclo[2,2,2]octano.
14
terapéutico puede ser cualquier agente que sea capaz de tratar, prevenir o reducir los síntomas de una enfermedad
o trastorno sensible a tetraciclina. Como alternativa, el otro agente terapéutico puede ser cualquier agente beneficioso para un paciente cuando se administra en combinación con el compuesto de tetraciclina en la presente invención.
5 Aunque la presente invención se ha mostrado y descrito particularmente con referencias a realizaciones de ejemplo de la misma, se entenderá por los expertos en la materia que pueden hacerse diversos cambios en la forma de los mismos sin alejarse del ámbito de la invención abarcada por las reivindicaciones adjuntas.
10 Ejemplos
Las siguientes abreviaturas y términos tienen los significados indicados:
- Abreviatura/Término
- Significado
- Ac
- acetilo
- AIBN
- 2,2'-azobis(2-metilpropionitrilo)
- ac.
- acuoso
- Bn
- bencilo
- salmuera
- cloruro sódico acuoso saturado
- Boc
- terc-butoxi carbonilo o t-butoxi carbonilo
- (Boc)2O
- dicarbonato de di-terc-butilo
- BBr3
- tribromuro de boro
- Bu
- butilo
- Cbz
- benciloxicarbonilo
- CH2Cl2
- cloruro de metileno
- CH3CN o ReCN
- acetonitrilo
- Cy
- triciclohexilfosfina
- dba
- dibencilidenoacetona
- DIBAL-H
- hidruro de diisobutilaluminio
- DIEA
- N,N-diisopropiletilamina
- DMAP
- 4-(dimetilamino)piridina
- DME
- 1,2-dimetoxietano
- DMF
- N,N-dimetilformamida
- DMPU
- 1,3-dimetil-3,4-5,6-tetrahidro-2(1 H)-pirimidona
- DMSO
- dimetilsulfóxido
- EDC
- N-(3-dimetilaminopropil)-N'-etilcarbodiimida
- IEN
- ionización por electronebulización
- equiv.
- equivalente
- Et
- etilo
- Et2O
- éter etílico
- EtOAc
- acetato de etilo
- h
- hora
- HCl
- ácido clorhídrico
- KHPO4
- hidrogenofosfato potásico
- HPLC
- cromatografía líquida de alto rendimiento
- HOBt
- 1-hidroxibenzotriazol
- i
- iso
- IBX
- ácido 2-yodoxibenzoico
- LDA
- diisopropilamida de litio
- LHMDS
- bis(trimetilsilil)amida de litio
- LTMP
- 2,2,6,6-tetrametilpiperiduro de litio
- Me
- metilo
- MeOH
- metanol
- MeI
- yoduro de metilo
- min
- minuto
- Ms
- metanosulfonilo
- EM
- espectro de masas
- MTBE
- metil terc-butil éter
- PM
- peso molecular
- NaHCO3
- bicarbonato sódico
- NaOH
- hidróxido sódico
- Na2SO4
- sulfato sódico
- NBS
- N-bromosuccinimida
24
a la mezcla de reacción. La reacción se agitó de -78 ºC a 25 ºC durante 1 h, se detuvo con NH4Cl saturado y se extrajo con EtOAc. Los extractos de EtOAc combinados se secaron (Na2SO4) y se concentraron para producir el producto en bruto. La purificación por HPLC preparativa de fase inversa en un sistema Waters Autopurification usando una columna OBD Prep C18 de Sunfire [5 μm, 19 x 50 mm; caudal, 20 ml/min; Disolvente A: H2O con 5 HCO2H al 0,1 %; Disolvente B: CH3CN con HCO2H al 0,1 %; volumen de inyección: 4,0 ml (CH3CN); gradiente: B al 80→100 % durante 15 min; recogida de fracción dirigida a masas]. Las fracciones con el PM deseado, eluyendo a 6,3-8,0 min, se recogieron y se concentraron en un evaporador rotatorio a ta para retirar la mayoría del acetonitrilo. La solución, en su mayoría acuosa, resultante se extrajo con EtOAc. Los extractos de EtOAc combinados se secaron (Na2SO4) y se concentraron para dar 185 mg de 5 puro (35 %): RMN 1H (400 MHz, CDCl3) δ 15,67 (s, 1 H), 7,51
10 7,46 (m, 2 H), 7,39-7,29 (m, 3 H), 7,21 (dd, J= 8,9, 8,9 Hz, 1 H), 7,03 (dd, J =8,9, 4,0 Hz, 1 H), 5,34 (s, 2 H), 3,93 (d, J= 10,4 Hz, 1 H), 3,30-3,21 (m, 1 H), 3,10-3,00 (m, 1 H), 2,57-2,41 (m, 3 H), 2,48 (s, 6 H), 2,17-2,12 (m, 1 H), 1,53 (s, 9 H), 0,82 (s, 9 H), 0,26 (s, 3 H), 0,12 (s, 3 H); EM (IEN) m/z 735,45 (M+H).
Compuesto de Preparación 6 15
Se añadieron HF acuoso (3 ml, 48 %) y TFA (4 μl) a una solución en CH3CN (7 ml) de 5 (210 mg, 0,29 mmol) en un tubo de polipropileno a 25 ºC. La reacción se agitó a 25 ºC durante 18 h. La mezcla resultante se vertió en una 20 solución acuosa de K2HPO4 (21 g, se disolvió en 150 ml de agua). La mezcla se extrajo con EtOAc. Los extractos de EtOAc combinados se secaron (Na2SO4) y se concentraron para producir 180 mg de 6 en bruto: RMN 1H (400 MHz, CDCl3) δ 14,64 (s, 1 H), 11,47 (s, 1 H), 7,49-7,45 (m, 2 H), 7,39-7,32 (m, 3 H), 7,14 (dd, J= 9,2, 8,8 Hz, 1 H), 6,77 (dd, J= 9,2, 4,3 Hz, 1 H), 5,36 (s, 2 H), 3,68 (d, J= 3,7 Hz, 1 H), 3,09 (dd, J= 15,6, 4,6 Hz, 1 H), 3,02-2,92 (m, 1 H), 2,84-2,79 (m, 1 H), 2,49 (s, 6 H), 2,34-2,22 (m, 1 H), 2,09-2,02 (m, 1 H), 1,55-1,44 (m, 1 H); EM (IEN) m/z 521,30
Compuesto de Preparación 7
30 Se añadió paladio sobre carbono (35 mg, 10 % en peso) a una solución en MeOH/dioxano (4 ml/4 ml) de 6 en bruto (180 mg). La reacción se purgó con hidrógeno y se agitó en una atmósfera de H2 (globo) a 25 ºC durante 1 h. La mezcla de reacción se filtró a través de un lecho corto de Celite. El filtrado se concentró para producir el producto en bruto. La purificación por HPLC preparativa de fase inversa en un sistema Waters Autopurification usando una
35 columna 10 μ RP-1 100A de Phenomenex Polymerx [10 μm, 150 x 21,20 mm; caudal, 20 ml/min; Disolvente A: HCl 0,05 N/agua; Disolvente B: CH3CN; volumen de inyección: 4,0 ml (HCl 0,05 N/agua); gradiente: B al 0→100 % durante 15 min; recogida de fracción dirigida a masas]. Las fracciones con el PM deseado, eluyendo a 6,4-8,2 min, se recogieron y se deshidrataron por congelación para producir 51 mg del compuesto 7 (41 % en 2 etapas): RMN 1H (400 MHz, CD3OD) δ 7,26 (dd, J= 9,2, 9,2 Hz, 1 H), 6,80 (dd, J= 9,2, 4,3 Hz, 1 H), 4,09 (s a, 1 H), 3,14 (dd, J=
40 15,0, 4,6 Hz, 1 H), 3,04 (s, 3 H), 2,96 (s, 3 H), 3,09-2,91 (m, 2 H), 2,31-2,18 (m, 2 H), 1,68-1,56 (m, 1 H); EM (IEN) m/z 433,28 (M+H).
Compuesto de Preparación 8
28
varias veces con más cantidad de éter dietílico. Después, el lecho de Celite se eluyó con MeOH hasta que el eluyente se volvió incoloro. El eluyente de MeOH de color amarillo se recogió y se concentró a presión reducida para proporcionar 32 en bruto. Se realizó purificación por HPLC preparativa de fase inversa en un sistema Waters Autopurification, usando una columna 10 μ RP-1 100A de Phenomenex Polymem [10 μm, 150 x 21,20 mm, caudal, 5 20 ml/min; Disolvente A: HCl 0,05 N; Disolvente B: CH3CN; volumen de inyección: 2,0 ml (HCl 0,05 N/agua); gradiente: B 10→20 % durante 30 min, recogida de fracción dirigida a masas]. Las fracciones con el PM deseado, eluyendo a 10,8-12,5 min, se recogieron y se deshidrataron por congelación para producir 2,0 mg de 32 puro: RMN 1H (400 MHz, CD3OD) δ 8,18 (d, J= 11,0 Hz, 1 H), 4,41 -4,31 (m, 2 H), 4,32 (s, 2 H), 4,24-4,13 (m, 2), 4,08 (s a, 1 H), 3,18-2,86 (m, 3 H), 3,03 (s, 3 H), 2,95 (s, 3 H), 2,71-2,57 (m, 1 H), 2,54-2,42 (m, 1 H), 2,33-2,16 (m ,2 H), 1,69
10 1,57 (m, 1 H), EM (IEN) m/z 545,20 (M+H).
Los Compuestos 12-31 y los Compuestos 33-46 se prepararon de manera similar a los Compuestos 11 o 32, sustituyendo cloruro de 2-t-butilaminoacetilo en la síntesis del Compuesto 11 por el haluro de acilo adecuado, o azetidina por amina cíclica en la síntesis del Compuesto 32.
15 Compuesto 12
20 RMN 1H (400 MHz, CD3OD) δ 8,23 (d, J= 11,2 Hz, 1 H), 4,08 (s, 3 H), 3,17-2,97 (m, 11 H), 2,31 (dd, J= 14,8, 14,8 Hz, 1 H), 2,24 (dd, J= 14,0, 5,2, 2,8 Hz, 1H), 1,79-1,72 (m, 2 H), 1,66 (ddd, J= 13,6, 13,6, 13,6 Hz, 1 H), 1,05 (t, J= 7,2 Hz, 3 H); EM (IEN) m/z 547,2 (M+H).
Compuesto de Referencia 13 25
RMN 1H (400 MHz, CD3OD) δ 8,23 (d, J= 11,2 Hz, 1 H), 4,08 (s, 3 H), 3,16-2,97 (m, 11 H), 2,30 (dd, J= 14,8, 14,8 Hz, 1 H), 2,24 (ddd, J= 14,4, 5,2, 2,8 Hz, 1 H), 1,75-1,69 (m, 2 H), 1,66 (ddd, J= 13,6, 13,6, 13,6 Hz, 1 H), 1,49-1,41 30 (m, 2 H), 1,01 (t, J= 7,2 Hz, 3 H); EM (IEN) m/z 561,2 (M+H).
Compuesto 14
- 35
- RMN 1H (400 MHz, CD3OD) δ 8,21 (d, J = 11,2 Hz, 1 H), 4,08 (s, 1 H), 4,06 (s, 2 H), 3,16-2,96 (m, 11 H), 2,28 (dd, J = 14,8, 14,8 Hz, 1 H), 2,22 (ddd, J = 14,4, 5,2, 2,8 Hz, 1H), 1,77-1,71 (m, 2 H), 1,66 (ddd, J = 14,0, 14,0, 14,0 Hz, 1 H), 1,43-1,35 (m, 6 H),0,93 (t, J = 7,2 Hz, 3 H); EM (IEN) m/z 589,2 (M+H).
- 40
30
Compuesto 34
RMN 1H (400 MHz, CD3OD) δ 8,22 (d, J= 11,0 Hz, 1H), 4,33 (s, 2H), 4,10 (s, 1H), 3,83-3,72 (m, 2H), 3,25-2,89 (m, 12H), 2,32-2,00 (m, 6H), 1,69-1,56 (m, 1H); EM (IEN) m/z 559,39 (M+H).
Compuesto 35
10
RMN 1H (400 MHz, CD3OD) δ 8,25 (d, J= 11,0 Hz, 1H), 5,54-5,31 (m, 1H), 4,39-4,20 (m, 2H), 4,09-4,01 (m, 1H), 3,40-3,30 (m, 2H), 3,09-2,89 (m, 12H), 2,50-2,34 (m, 2H), 2,34-2,25 (m, 1H), 2,24-2,16 (m, 1H), 1,71-1,58 (m, 1H); EM (IEN) m/z 577,32 (M+H).
15 Compuesto 36
20 RMN 1H (400 MHz, CD3OD) δ 8,23 (d, J= 10,4 Hz, 1H), 5,57-5,37 (m, 1H), 4,47-4,33 (m, 2H), 4,15-3,87 (m, 2H), 3,72-3,40 (m, 1H), 3,17-2,83 (m, 12H), 2,55-2,34 (m, 2H), 2,33-2,18 (m, 2H), 1,69-1,57 (m, 1H); EM (IEN) m/z 577,37 (M+H).
Compuesto 37 25
RMN 1H (400 MHz, CD3OD) δ 8,28 (d, J= 10,7 Hz, 1H), 4,08 (s, 1H), 4,00-3,91 (m, 2H), 3,09-2,57 (m, 18H), 3,263,18 (m, 3H), 2,49-2,34 (m, 2H), 2,35-2,06 (m, 2H), 1,72-1,59 (m, 1H); EM (IEN) m/z 602,37 (M+H).
Compuesto 38
35
Compuesto 58
5 RMN 1H (400 MHz, CD3OD) δ 8,24 (d, J= 10,8 Hz, 1 H), 4,48 (s, 2 H), 4,12 (s, 1 H), 4,10-4,07 (m, 2 H), 3,93-3,86 (m, 2 H), 3,19-2,90 (m, 9 H), 2,79-2,67 (m, 2 H), 2,37-2,21 (m, 2 H), 1,59-1,51 (m, 1 H); EM (IEN) m/z 595,0 (M+H).
10
Los siguientes compuestos se prepararon de acuerdo con el Esquema 2. 15 Compuesto de Preparación 2-1
En un matraz de fondo redondo de 250 ml se añadió el compuesto 3 (14,47 g, 56,30 mmol, 1,0 equiv, en bruto), 20 bromuro de tetrabutilamonio (0,90 g, 2,80 mmol, 0,05 equiv.), 1,2-dicloroetano (60 ml) y agua (60 ml). La bi-fase transparente se enfrió en un baño de agua a 20 ºC. Se añadió ácido cítrico (7,2 ml, 70 % en peso, 112,60 mmol, 2,0
40
- Punto del Pocillo
- 1 2 3 4 5 6
- Factor de Dilución
- 102 103 104 105 106 107
Cepas bacterianas
Se examinaron quince cepas bacterianas, enumeradas a continuación, en ensayos de concentración inhibidora mínima (MIC).
- ID
- Organismo Fuente Resistencia Comentarios Rx Gram
- SA100
- S. aureus ATCC 13709 MSSA Cepa Smith (modelo animal) positivo
- SA101
- S. aureus ATCC 29213 MSSA control positivo
- SA158
- S. aureus MR, SK75 resistente a tet: tetK (salida) positivo
- SA161
- S. aureus Micromyx, LLC resistente a tet: tet(M) protección ribosómica positivo
- EF103
- E. faecalis ATCC 29212 intermedio de tet/resistente – mecanismo no especificado control positivo
- EF159
- E. faecalis MR, DS160 resistente a tet:tetM (protección de rib) cip-R, ery-1 positivo
- SP106
- S. pneumoniae ATCC 49619 wt control positivo
- SP160
- S. pneumoniae MR, 54 resistente a tet:tet M (protección de rib) pen-R, ery-R positivo
- EC107
- E. coli ATCC 25922 wt control negativo
- EC155
- E. coli MR, 10 resistente a tet:tetA (salida) negativo
- KP109
- K. pneumoniae ATCC 13883 wt negativo
- KP153
- K. pneumoniae MR, 1 resistente a tet: tetA (salida) cip-R, gen-R negativo
- EC108
- E. cloacae ATCC 13047 wt negativo
- AB110
- A. baumanii ATCC 19606 wt negativo
- PA111
- P. aeruginosa ATCC 27853 wt control negativo
- MSSA = S. aureus susceptible a meticilina wt = natural ATCC = Colección Americana de Cultivos Tipo MR = Marilyn Roberts, Universidad de Washington tet = tetraciclina cip = ciprofloxacina R = resistente gen = gentamicina ery = eritromicina pen = penicilina
Resultados Se proporcionan los valores de concentración inhibidora mínima (MIC) para los compuestos en las Tablas 1a, 1b, 2a, 10 2by3. Tabla 1a
- ID del compuesto
- MIC (µg/ml)
- SA101
- SA100 SA161 SA158 EF103 EF159 SP106 S0160
- 11
- 0,125 0,25 0,25 0,0625 0,0625 0,125 ≤0,0156 ≤0,0156
- 12
- ≤0,0156 ≤0,0156 0,125 0,5 ≤0,0156 0,0625 ≤0,0156 ≤0,0156
- 13
- ≤0,0156 ≤0,0156 0,0625 0,25 ≤0,0156 0,0625 ≤0,0156 ≤0,0156
- 14
- 0,5 0,25 0,5 0,25 0,125 0,25 0,03 0,125
- 15
- 0,5 0,5 0,5 0,25 0,5 0,5 0,016 0,016
- 16
- 0,125 0,25 0,25 0,5 0,0625 0,0625 ≤0,0156 ≤0,0156
- 17
- 0,25 0,5 1 2 0,25 1 0,0625 0,0625
- 18
- 0,0625 ≤0,0156 0,0625 0,125 ≤0,0156 0,0313 ≤0,0156 ≤0,0156
- 19
- 0,125 0,25 0,25 0,25 ≤0,0156 0,125 ≤0,0158 ≤0,0156
- 20
- ≤0,0156 0,25 0,25 0,5 ≤0,0156 0,0625 ≤0,0156 ≤0,0156
- 21
- 0,25 0,25 0,5 4 0,125 1 ≤0,0156 0,0625
- 22
- 1 1 2 4 2 4 0,5 1
- 23
- ≤0,0156 0,5 0,125 0,25 ≤0,0156 0,0313 ≤0,0156 ≤0,0156
- 24
- 0,25 0,25 0,125 0,125 ≤0,0156 ≤0,0156 ≤0,0156 ≤0,0156
- 25
- 0,125 0,125 0,125 0,0313 ≤0,0156 0,0625 ≤0,0156 ≤0,0156
82
87
Claims (1)
-
imagen1 imagen2 imagen3 imagen4
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US18830708P | 2008-08-08 | 2008-08-08 | |
US188307P | 2008-08-08 |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2655911T3 true ES2655911T3 (es) | 2018-02-22 |
Family
ID=41110902
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES13172357.9T Active ES2558512T3 (es) | 2008-08-08 | 2009-08-07 | Compuestos de tetraciclina sustituida con C7-fluoro |
ES09791290T Active ES2430254T3 (es) | 2008-08-08 | 2009-08-07 | Compuestos de tetraciclina sustituidos con c7-fluoro |
ES15180611.4T Active ES2655911T3 (es) | 2008-08-08 | 2009-08-07 | Compuestos de tetraciclina sustituidos con C7-fluoro |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES13172357.9T Active ES2558512T3 (es) | 2008-08-08 | 2009-08-07 | Compuestos de tetraciclina sustituida con C7-fluoro |
ES09791290T Active ES2430254T3 (es) | 2008-08-08 | 2009-08-07 | Compuestos de tetraciclina sustituidos con c7-fluoro |
Country Status (32)
Country | Link |
---|---|
US (9) | US8906887B2 (es) |
EP (3) | EP2682387B1 (es) |
JP (3) | JP5496202B2 (es) |
KR (3) | KR101746795B1 (es) |
CN (3) | CN102177134B (es) |
AR (3) | AR072990A1 (es) |
AU (1) | AU2009279473B2 (es) |
BR (1) | BRPI0916985B1 (es) |
CA (1) | CA2732883C (es) |
CO (1) | CO6351777A2 (es) |
CY (3) | CY1114689T1 (es) |
DK (2) | DK2682387T3 (es) |
ES (3) | ES2558512T3 (es) |
FR (1) | FR19C1012I2 (es) |
HK (3) | HK1155150A1 (es) |
HR (2) | HRP20130928T1 (es) |
HU (2) | HUE026562T2 (es) |
IL (3) | IL211120A (es) |
LT (1) | LTC2323972I2 (es) |
LU (1) | LUC00107I2 (es) |
MX (2) | MX2011001367A (es) |
NL (1) | NL300971I2 (es) |
NO (1) | NO2019010I1 (es) |
NZ (3) | NZ624272A (es) |
PL (3) | PL3000805T3 (es) |
PT (2) | PT2682387E (es) |
RS (2) | RS54485B1 (es) |
SG (1) | SG10201806714PA (es) |
SI (2) | SI2323972T1 (es) |
SM (1) | SMT201600045B (es) |
TW (3) | TWI453183B (es) |
WO (1) | WO2010017470A1 (es) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG10201806714PA (en) | 2008-08-08 | 2018-09-27 | Tetraphase Pharmaceuticals Inc | C7-fluoro substituted tetracycline compounds |
CA2761241C (en) | 2009-05-08 | 2018-02-27 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
CA2772386C (en) | 2009-08-28 | 2017-09-19 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
WO2012021829A1 (en) * | 2010-08-12 | 2012-02-16 | Tetraphase Pharmaceuticals, Inc. | Methods of treating bacterial infections |
AR082633A1 (es) * | 2010-08-12 | 2012-12-19 | Tetraphase Pharmaceuticals Inc | Analogos de tetraciclina |
WO2012065028A2 (en) | 2010-11-11 | 2012-05-18 | Concert Pharmaceuticals Inc. | Substituted tetracyclines |
BR112015004523B1 (pt) | 2012-08-31 | 2020-08-04 | Tetraphase Pharmaceuticals, Inc | Compostos de tetraciclina, composições farmacêuticas e seus usos |
CN104230960B (zh) * | 2013-06-06 | 2017-02-15 | 山东轩竹医药科技有限公司 | 四并环类间变性淋巴瘤激酶抑制剂 |
MA40836A (fr) * | 2014-10-23 | 2017-08-29 | Tetraphase Pharmaceuticals Inc | Procédures de semi-synthèse |
WO2017097891A1 (en) | 2015-12-10 | 2017-06-15 | Sandoz Ag | Crystalline eravacycline |
PT3390358T (pt) | 2016-01-22 | 2020-11-09 | Sandoz Ag | Bis-cloridrato de eravaciclina cristalino |
RU2018140463A (ru) * | 2016-05-02 | 2020-06-03 | Паратек Фармасьютикалс, Инк. | 9-аминометилминоциклиновые соединения и способы их применения для лечения инфекций мочевых путей (имп) |
CN107759503A (zh) * | 2016-08-16 | 2018-03-06 | 四川科伦博泰生物医药股份有限公司 | 一种四环素衍生物及其用途 |
CA3034891A1 (en) * | 2016-08-30 | 2018-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds and methods of treatment |
SG11201903327PA (en) | 2016-10-19 | 2019-05-30 | Tetraphase Pharmaceuticals Inc | Crystalline forms of eravacycline |
RU2019113715A (ru) | 2016-11-01 | 2020-12-03 | Паратек Фармасьютикалс, Инк. | 9-аминометилминоциклиновые соединения и их применение для лечениия внебольничной бактериальной пневмонии(вбп) |
US20210395198A1 (en) | 2018-11-09 | 2021-12-23 | Tetraphase Pharmaceuticals, Inc. | Polymorphic forms of a compound and uses thereof |
WO2023233397A1 (en) * | 2022-05-29 | 2023-12-07 | B. G. Negev Technologies And Applications Ltd., At Ben-Gurion University | Eravacycline for treating cancer |
Family Cites Families (82)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB935384A (en) * | 1959-03-30 | 1963-08-28 | Pfizer & Co C | Tetracycline derivatives and preparation thereof |
US3338963A (en) * | 1960-10-28 | 1967-08-29 | American Cyanamid Co | Tetracycline compounds |
GB1034933A (en) | 1962-10-29 | 1966-07-06 | American Cyanamid Co | 4-demethylamino-4-substituted amino 6-demethyl tetracyclines |
US3304227A (en) | 1965-07-15 | 1967-02-14 | Loyal E Loveless | Antibiotic-containing animal feed |
US3433709A (en) * | 1965-12-07 | 1969-03-18 | American Cyanamid Co | Biological transformation of alpha-6-deoxytetracyclines to tetracyclines |
US4666897A (en) | 1983-12-29 | 1987-05-19 | Research Foundation Of State University | Inhibition of mammalian collagenolytic enzymes by tetracyclines |
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 |
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 |
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 |
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 |
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 |
US5494903A (en) * | 1991-10-04 | 1996-02-27 | American Cyanamid Company | 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
SG52361A1 (en) * | 1991-10-04 | 1998-09-28 | American Cyanamid Co | Novel 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
USRE40183E1 (en) | 1991-10-04 | 2008-03-25 | Wyeth Holdings Corporation | 7-Substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
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 |
US5420272A (en) * | 1992-08-13 | 1995-05-30 | American Cyanamid Company | 7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
SG47520A1 (en) | 1992-08-13 | 1998-04-17 | American Cyanamid Co | New method for the production of 9-amino-6-demethyl-6-deoxytetracycline |
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 |
US5328902A (en) * | 1992-08-13 | 1994-07-12 | American Cyanamid Co. | 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
DK0599397T3 (da) | 1992-11-17 | 1996-09-16 | Univ New York State Res Found | Tetracycliner, herunder non-mikrobielle, kemisk-modificerede tetracycliner, inhiberer overdreven collagentværbinding ved 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 |
CA2183565A1 (en) | 1994-02-17 | 1995-08-24 | Wei-Guo Su | 9-(substituted amino)-alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics |
US5574026A (en) | 1994-12-13 | 1996-11-12 | American Cyanamid Company | Methods for inhibiting angiogenesis proliferation of endothelial or tumor cells and tumor growth |
US5843925A (en) | 1994-12-13 | 1998-12-01 | American Cyanamid Company | Methods for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
US5495301A (en) * | 1994-12-27 | 1996-02-27 | Zenith Electronics Corporation | Three wire pillow speaker with full television remote control functions |
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 |
US5929055A (en) | 1997-06-23 | 1999-07-27 | The Research Foundation Of State University Of New York | Therapeutic method for management of diabetes mellitus |
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 |
US6914057B1 (en) * | 1998-09-28 | 2005-07-05 | The Research Foundation Of State University Of New York | Inhibitor of cataract formation |
US5998390A (en) | 1998-09-28 | 1999-12-07 | The Research Foundation Of State University Of New York | Combination of bisphosphonate and tetracycline |
KR20010073190A (ko) | 1998-09-28 | 2001-07-31 | 제임스 알. 데니히 | 백내장 형성 억제제 |
US6231894B1 (en) | 1999-10-21 | 2001-05-15 | Duke University | Treatments based on discovery that nitric oxide synthase is a paraquat diaphorase |
AU2000257445A1 (en) | 2000-06-16 | 2002-01-02 | Trustees Of Tufts College | 7-n-substituted phenyl tetracycline compounds |
US6624168B2 (en) | 2000-07-07 | 2003-09-23 | Trustees Of Tufts College | 7,8 and 9-substituted tetracycline compounds |
ATE544745T1 (de) * | 2000-07-07 | 2012-02-15 | Tufts College | 9-substituierte minocyclinverbindungen |
US7045507B2 (en) * | 2001-03-14 | 2006-05-16 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds as synergistic antifungal agents |
US6841546B2 (en) * | 2001-03-14 | 2005-01-11 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds as antifungal agents |
CA2444899C (en) | 2001-04-24 | 2011-06-21 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
US8088820B2 (en) * | 2001-04-24 | 2012-01-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
EP2332548A1 (en) | 2001-07-13 | 2011-06-15 | Paratek Pharmaceuticals, Inc. | Tetracyclines for the treatment of stroke |
US20060194773A1 (en) * | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
EP1482926A4 (en) * | 2002-03-08 | 2006-04-12 | Paratek Pharm Innc | AMINO METHYL SUBSTITUTED TETRACYCLINE COMPOUNDS |
KR101025400B1 (ko) | 2002-03-21 | 2011-03-28 | 파라테크 파마슈티컬스, 인크. | 치환된 테트라시클린 화합물 |
AU2003261161B2 (en) | 2002-07-12 | 2009-09-10 | Paratek Pharmaceuticals, Inc | 3, 10, and 12a substituted tetracycline compounds |
EP2277504A1 (en) | 2002-10-24 | 2011-01-26 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
WO2004038000A2 (en) * | 2002-10-24 | 2004-05-06 | Paratek Pharmaceuticals, Inc. | Methods of using substituted tetracycline compounds to modulate rna |
EP2319829A1 (en) * | 2003-07-09 | 2011-05-11 | Paratek Pharmaceuticals, Inc. | 9-substituted tetracycline compounds |
SI1753713T1 (sl) | 2004-05-21 | 2017-01-31 | President And Fellows Of Harvard College | Sinteza tetraciklinov in njihovih analogov |
CA2585418A1 (en) | 2004-10-25 | 2006-05-04 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
EP1848685A1 (en) | 2005-02-04 | 2007-10-31 | Paratek Pharmaceuticals, Inc. | 11a, 12-derivatives of tetracycline compounds |
BRPI0607353A2 (pt) * | 2005-02-15 | 2009-09-01 | Wyeth Corp | composto de fórmula (i); composição farmacêutica; uso do composto para o tratamento ou controle de infecções bacterianas em animais de sangue quente; processo para a preparação de tetraciclinas 9-(n-substituìdas-n-substituìdas-glicil) de fórmulas 5; 7; 10; e tetraciclina 9-(n-substituìda-n-substituìda glicil) de fómulas 5; 7; 10 |
AU2006272698B2 (en) * | 2005-07-21 | 2012-11-01 | Paratek Pharmaceuticals, Inc. | 10-substituted tetracyclines and methods of use thereof |
AU2007208214B2 (en) | 2006-01-24 | 2013-02-14 | Paratek Pharmaceuticals, Inc. | Methods of increasing oral bioavailability of tetracyclines |
WO2007117639A2 (en) | 2006-04-07 | 2007-10-18 | The President And Fellows Of Harvard College | Synthesis of tetracyclines and analogues thereof |
EP2537934A3 (en) | 2006-05-15 | 2013-04-10 | Paratek Pharmaceuticals, Inc. | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
EP2479169B1 (en) | 2006-10-11 | 2014-12-03 | President and Fellows of Harvard College | Synthesis of Enone Intermediate |
US8440646B1 (en) | 2006-10-11 | 2013-05-14 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for treatment of Bacillus anthracis infections |
WO2008127722A1 (en) | 2007-04-12 | 2008-10-23 | Paratek Pharmaceuticals, Inc. | Methods for treating spinal muscular atrophy using tetracycline compounds |
WO2009032326A1 (en) * | 2007-09-07 | 2009-03-12 | Dr. Reddy's Laboratories Ltd. | New tetracycline derivatives as antiinfective agents |
AU2009236631A1 (en) | 2008-04-14 | 2009-10-22 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
SG10201806714PA (en) * | 2008-08-08 | 2018-09-27 | Tetraphase Pharmaceuticals Inc | C7-fluoro substituted tetracycline compounds |
US9073829B2 (en) | 2009-04-30 | 2015-07-07 | President And Fellows Of Harvard College | Synthesis of tetracyclines and intermediates thereto |
CA2761241C (en) | 2009-05-08 | 2018-02-27 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
ES2440000T3 (es) | 2009-05-08 | 2014-01-27 | Tetraphase Pharmaceuticals, Inc. | Compuestos de 8-aza-tetraciclina |
CA2772386C (en) * | 2009-08-28 | 2017-09-19 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
AR082633A1 (es) | 2010-08-12 | 2012-12-19 | Tetraphase Pharmaceuticals Inc | Analogos de tetraciclina |
WO2012047907A1 (en) | 2010-10-04 | 2012-04-12 | President And Fellows Of Harvard College | Synthesis of c5-substituted tetracyclines, uses thereof, and intermediates thereto |
BR112015004523B1 (pt) | 2012-08-31 | 2020-08-04 | Tetraphase Pharmaceuticals, Inc | Compostos de tetraciclina, composições farmacêuticas e seus usos |
-
2009
- 2009-08-07 SG SG10201806714PA patent/SG10201806714PA/en unknown
- 2009-08-07 PL PL15180611T patent/PL3000805T3/pl unknown
- 2009-08-07 ES ES13172357.9T patent/ES2558512T3/es active Active
- 2009-08-07 WO PCT/US2009/053142 patent/WO2010017470A1/en active Application Filing
- 2009-08-07 PT PT131723579T patent/PT2682387E/pt unknown
- 2009-08-07 RS RS20150879A patent/RS54485B1/en unknown
- 2009-08-07 SI SI200930734T patent/SI2323972T1/sl unknown
- 2009-08-07 PL PL13172357T patent/PL2682387T3/pl unknown
- 2009-08-07 EP EP13172357.9A patent/EP2682387B1/en active Active
- 2009-08-07 US US12/462,795 patent/US8906887B2/en active Active
- 2009-08-07 SI SI200931338T patent/SI2682387T1/sl unknown
- 2009-08-07 DK DK13172357.9T patent/DK2682387T3/en active
- 2009-08-07 CN CN200980140171.1A patent/CN102177134B/zh active Active
- 2009-08-07 MX MX2011001367A patent/MX2011001367A/es active IP Right Grant
- 2009-08-07 AR ARP090103046A patent/AR072990A1/es active IP Right Grant
- 2009-08-07 ES ES09791290T patent/ES2430254T3/es active Active
- 2009-08-07 CN CN201410123209.7A patent/CN103936645B/zh not_active Expired - Fee Related
- 2009-08-07 BR BRPI0916985-7A patent/BRPI0916985B1/pt active IP Right Grant
- 2009-08-07 NZ NZ624272A patent/NZ624272A/en not_active IP Right Cessation
- 2009-08-07 CA CA2732883A patent/CA2732883C/en active Active
- 2009-08-07 NZ NZ603568A patent/NZ603568A/en not_active IP Right Cessation
- 2009-08-07 EP EP09791290.1A patent/EP2323972B1/en active Active
- 2009-08-07 EP EP15180611.4A patent/EP3000805B1/en not_active Revoked
- 2009-08-07 JP JP2011522274A patent/JP5496202B2/ja active Active
- 2009-08-07 NZ NZ591051A patent/NZ591051A/xx unknown
- 2009-08-07 DK DK09791290.1T patent/DK2323972T3/da active
- 2009-08-07 CN CN201510656850.1A patent/CN105367440A/zh active Pending
- 2009-08-07 MX MX2013009145A patent/MX358961B/es unknown
- 2009-08-07 ES ES15180611.4T patent/ES2655911T3/es active Active
- 2009-08-07 AU AU2009279473A patent/AU2009279473B2/en active Active
- 2009-08-07 KR KR1020167011703A patent/KR101746795B1/ko active IP Right Grant
- 2009-08-07 PT PT97912901T patent/PT2323972E/pt unknown
- 2009-08-07 HU HUE13172357A patent/HUE026562T2/hu unknown
- 2009-08-07 KR KR1020117005491A patent/KR101679023B1/ko active IP Right Grant
- 2009-08-07 PL PL09791290T patent/PL2323972T3/pl unknown
- 2009-08-07 RS RS20130431A patent/RS53003B/en unknown
- 2009-08-07 KR KR1020177003709A patent/KR101856178B1/ko active IP Right Grant
- 2009-08-10 TW TW098126664A patent/TWI453183B/zh active
- 2009-08-10 TW TW103114360A patent/TWI508934B/zh not_active IP Right Cessation
- 2009-08-10 TW TW104121823A patent/TWI585077B/zh not_active IP Right Cessation
-
2011
- 2011-02-08 IL IL211120A patent/IL211120A/en active IP Right Grant
- 2011-03-07 CO CO11027711A patent/CO6351777A2/es active IP Right Grant
- 2011-09-07 HK HK11109457.4A patent/HK1155150A1/xx unknown
-
2012
- 2012-08-09 US US13/570,837 patent/US8501716B2/en active Active
- 2012-12-18 US US13/718,909 patent/US8796245B2/en active Active
-
2013
- 2013-10-03 CY CY20131100856T patent/CY1114689T1/el unknown
- 2013-10-03 HR HRP20130928AT patent/HRP20130928T1/hr unknown
-
2014
- 2014-03-04 JP JP2014041460A patent/JP5690957B2/ja not_active Expired - Fee Related
- 2014-04-06 IL IL231955A patent/IL231955B/en active IP Right Grant
- 2014-04-06 IL IL231954A patent/IL231954A/en active IP Right Grant
- 2014-07-07 HK HK14106850.0A patent/HK1193412A1/zh not_active IP Right Cessation
- 2014-11-04 US US14/532,882 patent/US20150274643A1/en not_active Abandoned
-
2015
- 2015-02-02 JP JP2015018405A patent/JP6041911B2/ja not_active Expired - Fee Related
- 2015-12-11 HR HRP20151368TT patent/HRP20151368T1/hr unknown
- 2015-12-23 CY CY20151101188T patent/CY1117085T1/el unknown
-
2016
- 2016-02-12 SM SM201600045T patent/SMT201600045B/it unknown
- 2016-09-21 HK HK16111074.8A patent/HK1222840A1/zh not_active IP Right Cessation
- 2016-11-09 US US15/347,352 patent/US20170275244A1/en not_active Abandoned
-
2018
- 2018-01-29 US US15/882,475 patent/US20190002398A1/en not_active Abandoned
- 2018-08-29 AR ARP180102451 patent/AR112533A2/es unknown
- 2018-08-29 AR ARP180102450 patent/AR112532A2/es unknown
-
2019
- 2019-03-01 NO NO2019010C patent/NO2019010I1/no unknown
- 2019-03-04 FR FR19C1012C patent/FR19C1012I2/fr active Active
- 2019-03-06 NL NL300971C patent/NL300971I2/nl unknown
- 2019-03-11 LU LU00107C patent/LUC00107I2/fr unknown
- 2019-03-15 LT LTPA2019009 patent/LTC2323972I2/lt unknown
- 2019-03-18 CY CY2019011C patent/CY2019011I1/el unknown
- 2019-03-19 HU HUS1900016C patent/HUS1900016I1/hu unknown
- 2019-04-01 US US16/372,119 patent/US20200055813A1/en not_active Abandoned
-
2020
- 2020-06-10 US US16/898,039 patent/US20210122709A1/en not_active Abandoned
-
2022
- 2022-04-12 US US17/718,915 patent/US20230122651A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2655911T3 (es) | Compuestos de tetraciclina sustituidos con C7-fluoro | |
US11547704B2 (en) | Chemical compounds | |
JP7502337B2 (ja) | Kras g12cインヒビター及びその使用 | |
AU2013288265B2 (en) | Tetrahydroquinazolinone derivatives as PARP inhibitors | |
WO2017212423A1 (en) | Chemcical compounds | |
PE20212023A1 (es) | Compuestos, composiciones y metodos | |
AR076765A1 (es) | Compuestos antivirales | |
WO2019008506A1 (en) | N- (3- (2- (4-CHLOROPHENOXY) ACETAMIDO) BICYCLO [1.1.1] PENTAN-1-YL) -2-CYCLOBUTANE-1-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ATF4 INHIBITORS FOR THE TREATMENT OF CANCER AND OTHER DISEASES | |
EP3039025A1 (en) | Antimicrobial compounds and methods of making and using the same | |
AU2017292522A1 (en) | Combination comprising EP4 antagonist and immune checkpoint inhibitor | |
ES2678770T3 (es) | Derivados de amida de compuestos de 1-oxa-4,9-diazaespiro undecano que tienen actividad multimodal contra el dolor | |
US20200140383A1 (en) | 2-(4-chlorophenoxy)-n-((1 -(2-(4-chlorophenoxy)ethynazetidin-3-yl)methyl)acetamide derivatives and related compounds as atf4 inhibitors for treating cancer and other diseases | |
ES2413704T3 (es) | Procedimiento de fabricación de derivados de ácido neuramínico | |
SG10201907667RA (en) | Morphinan derivative | |
EP3617204A1 (en) | Indoleamine 2,3-dioxygenase inhibitor and application | |
ES2566755T3 (es) | Inhibidores de FXa con amidoxima cíclica o amidrazona cíclica como subunidad P4, procedimientos para sus preparaciones, y composiciones farmacéuticas y derivados de los mismos | |
CO2022004391A2 (es) | Derivados de 5-oxa-2–azaespiro[3.4]octano como agonistas de m4 | |
ES2354550A1 (es) | Biblioteca de n-(1-fenil-2-oxo-3-piperidil)sulfonamidas para el descubrimiento de fármacos. | |
CA3015098A1 (en) | New toxin and method for preparing intermediate thereof | |
ES2794801T3 (es) | Compuestos oxaazaespíricos con actividad contra el dolor | |
AR119092A1 (es) | Compuestos tricíclicos y su uso | |
NZ789384A (en) | Combination comprising EP4 antagonist and immune checkpoint inhibitor | |
NZ733899A (en) | [9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido-[2,1-a]isoquinolin-2-yl]methanol and compounds, compositions and methods relating thereto | |
AR056683A1 (es) | INHIBIDORES DE PROTEASA DEL VIH, COMPOSICIoN FARMACÉUTICA Y USO DEL COMPUESTO PARA PREPARAR UN MEDICAMENTO |