AR082633A1 - TETRACICLINE ANALOGS - Google Patents

TETRACICLINE ANALOGS

Info

Publication number
AR082633A1
AR082633A1 ARP110102925A ARP110102925A AR082633A1 AR 082633 A1 AR082633 A1 AR 082633A1 AR P110102925 A ARP110102925 A AR P110102925A AR P110102925 A ARP110102925 A AR P110102925A AR 082633 A1 AR082633 A1 AR 082633A1
Authority
AR
Argentina
Prior art keywords
alkyl
carbocyclyl
alkylene
heterocyclyl
fluoroalkyl
Prior art date
Application number
ARP110102925A
Other languages
Spanish (es)
Original Assignee
Tetraphase Pharmaceuticals Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Tetraphase Pharmaceuticals Inc filed Critical Tetraphase Pharmaceuticals Inc
Publication of AR082633A1 publication Critical patent/AR082633A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/601,4-Diazines; Hydrogenated 1,4-diazines
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • A61P31/06Antibacterial agents for tuberculosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D205/00Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/04Heterocyclic 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
    • C07D207/08Heterocyclic 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
    • C07D207/09Radicals substituted by nitrogen atoms, not forming part of a nitro radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/04Heterocyclic 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
    • C07D207/10Heterocyclic 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
    • C07D207/12Oxygen or sulfur atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/18Heterocyclic 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 one double bond between ring members or between a ring member and a non-ring member
    • C07D207/20Heterocyclic 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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/52Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/08Heterocyclic 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
    • C07D211/18Heterocyclic 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
    • C07D211/26Heterocyclic 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 nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/36Heterocyclic 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
    • C07D211/38Halogen atoms or nitro radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
    • C07D213/72Nitrogen atoms
    • C07D213/73Unsubstituted amino or imino radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D223/00Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/04Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10Heterocyclic 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
    • C07D231/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic 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
    • C07D233/64Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/04Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D261/00Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/20Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D265/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/281,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/301,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08Bridged systems

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Environmental Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Dentistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

También se describe una composición farmacéutica que comprende el compuesto de fórmula estructural (1) y su uso terapéutico, en infecciones bacterianas.Reivindicación 1: Un compuesto de fórmula (1), o una sal farmacéuticamente aceptable del mismo, donde X se selecciona entre hidrógeno, bromo, flúor, cloro, alquilo C1-6, -O-alquilo C1-6, carbociclilo C3-10, -O-carbociclilo C3-10, heterociclilo de 4 - 13 miembros, -O-heterociclilo de 4 - 13 miembros, S(O)m-R2, -CN, N(R2)(R3), -S(O)mN(R2)(R3), -C(O)-O-R2, -C(O)-N(R2)(R3) y -NH-C(O)-alquileno C1-6-N(R2)(R3), donde cada alquilo o alquileno en el grupo representado por X está opcionalmente sustituido con uno o más flúor; y cada carbociclilo o heterociclilo en el grupo representado por X está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente entre flúor, cloro, =O, -OH, fluoroalquilo C1-4, alquilo C1-4, -O-alquilo C1-4, -O-fluoroalquilo C1-4, -NH2, -NH(alquilo C1-4) o -N(alquilo C1-4)2, carbociclilo C3-10 o un heterociclilo de 4 - 13 miembros; el anillo E se selecciona entre carbociclilo C3-10 y un heterociclilo de (4 - 13 miembros); W se selecciona entre C(R6), C(R6)2, N y N(R7); Q se selecciona entre C(R6), C(R6)2, N, N(R7), O y S; Y se selecciona entre hidrógeno, flúor, bromo, -CN, -[C(R1a)(R1b)]n-N(R2)(R3), -N(R4)(R5), NO2, -NH-C(O)-alquileno C1-4-N(R4)(R5), alquilo C1-6, -NH-C(O)-alquilo C1-6, -NH-S(O)m-alquilo C1-6, -NH-S(O)m-carbociclilo C3-10, -NH-S(O)m-heterociclilo de 4 - 13 miembros; cada R1a y R1b se selecciona independientemente entre hidrógeno, alquilo C1-4 y carbociclilo C3-10; R2 se selecciona entre hidrógeno, alquilo C1-12, -alquileno C0-6-carbociclilo C3-10 y -alquileno C0-6-heterociclilo de 4 - 13 miembros; R3 se selecciona entre hidrógeno, alquilo C1-8, -alquileno C0-6-carbociclilo C3-10, -alquileno C0-6-heterociclilo de 4 - 13 miembros, -C(O)-alquilo C1-6, -alquileno C0-6-C(O)N(R4)(R5), -C(O)-alquileno C1-6-N(R4)(R5), -alquileno C2-6-N(R4)(R5), -S(O)m-alquilo C1-6, -S(O)m-carbociclilo C3-10 y -S(O)m-heterociclilo de 4 - 13 miembros, donde: cada alquilo, carbociclilo, alquileno o heterociclilo en el grupo representado por R2 o R3 está opcional e independientemente sustituido con uno o más sustituyentes seleccionados independientemente entre flúor, cloro, -OH, -O-alquilo C1-4, alquilo C1-4, alquilo C1-4 sustituido con flúor, -N(R4)(R5), carbociclilo C3-10 o un heterociclilo de 4 - 13 miembros; o R2 y R3 tomados junto con el átomo de nitrógeno al que están unidos forman un anillo heterocíclico monocíclico de 4 - 7 miembros, o un anillo heterocíclico, bicíclico, espirocíclico o puenteado, donde el anillo heterocíclico monocíclico de 4 - 7 miembros, o el anillo heterocíclico, bicíclico, espirocíclico o puenteado, de 6 - 13 miembros, comprende opcionalmente de 1 a 4 heteroátomos adicionales seleccionados independientemente entre N, S y O; el anillo heterocíclico monocíclico de 4 - 7 miembros, o el anillo heterocíclico, bicíclico, espirocíclico o puenteado, de 6 - 13 miembros, está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente entre carbociclilo C3-10, heterociclilo de 4 - 13 miembros, flúor, cloro, -OH, -fluoroalquilo C1-4, -alquilo C1-4, -O-carbociclilo C3-10, -O-heterociclilo de 4 - 13 miembros, -alquileno C0-4-O-alquilo C1-4, -alquileno C0-4-O-fluoroalquilo C1-4, =O, -C(O)-alquilo C1-4, -C(O)N(R4)(R5), -N(R4)-C(O)-alquilo C1-4 y -alquileno C0-4-N(R4)(R5), y cada sustituyente carbociclilo o heterociclilo está opcionalmente sustituido con flúor, cloro, -OH, =O, fluoroalquilo C1-4, alquilo C1-4, -O-alquilo C1-4, -O-fluoroalquilo C1-4, -NH2, -NH(alquilo C1-4) o -N(alquilo C1-4)2; cada uno de R4 y R5 se selecciona independientemente entre hidrógeno y alquilo C1-4; o R4 y R5 tomados junto con el átomo de nitrógeno al que están unidos forman un anillo heterocíclico de 4 - 7 miembros que comprende opcionalmente un heteroátomo adicional seleccionado entre N, S y O, donde el anillo heterocíclico de 4 - 7 miembros está opcionalmente sustituido con flúor, cloro, -OH, =O, alquilo C1-4 sustituido con flúor, -alquilo C1-4 o -alquileno C1-4-O-alquilo C1-4, y está opcionalmente condensado con fenilo; cada R6 se selecciona independientemente entre hidrógeno, carbociclilo C3-10, heterociclilo de 4 - 13 miembros, flúor, cloro, -OH, fluoroalquilo C1-4, alquilo C1-4, -O-carbociclilo C3-10, -O-heterociclilo de 4 - 13 miembros, -alquil C0-4-O-alquilo C1-4, -alquil C0-4-O-fluoroalquilo C1-4, -C(O)-alquilo C1-4, -C(O)N(R4)(R5), -N(R4)-C(O)-alquilo C1-4 y -alquileno C0-4-N(R4)(R5); o C(R6)2 es C=O; cada R7 se selecciona independientemente entre hidrógeno, -alquileno C0-4-carbociclilo C3-10, -alquileno C0-4-heterociclilo de 4 - 13 miembros, -fluoroalquilo C1-6, -alquilo C1-6, hidroxialquilo C1-6, -O-carbociclilo C3-10, -O-heterociclilo de 4 - 13 miembros, -alquileno C0-4-O-alquilo C1-4, -alquileno C0-4-O-fluoroalquilo C1-4, -C(O)-alquilo C1-4, -alquileno C1-4-C(O)-alquilo C1-4, -alquileno C1-4-C(O)-OH, -C(O)N(R4)(R5), -N(R4)-C(O)-alquilo C1-4, -C(O)-(alquileno C1-4)-NR4R5 y -alquileno C0-4-N(R4)(R5); y cada porción carbociclilo o heterociclilo de R6 y R7 está opcionalmente sustituida con flúor, cloro, -OH, =O, fluoroalquilo C1-4, alquilo C1-4, -O-alquilo C1-4, -O-fluoroalquilo C1-4, -NH2, -NH(alquilo C1-4) o -N(alquilo C1-4)2; cada R8 se selecciona independientemente entre hidrógeno, carbociclilo C3-10, heterociclilo de 4 - 13 miembros, flúor, cloro, -OH, fluoroalquilo C1-4, alquilo C1-4, -O-carbociclilo C3-10, -O-heterociclilo de 4 - 13 miembros, -alquil C0-4-O-alquilo C1-4, -alquil C0-4-O-fluoroalquilo C1-4, =O, -C(O)-alquilo C1-4, -C(O)N(R4)(R5), -N(R4)-C(O)-alquilo C1-4, -alquileno C0-4-N(R4)(R5) y - S(O)2alquilo C1-4; R9 está ausente o se selecciona independientemente entre hidrógeno, carbociclilo C3-10, heterociclilo de 4 - 13 miembros, flúor, cloro, -OH, fluoroalquilo C1-4, alquilo C1-4, -O-carbociclilo C3-10, -O-heterociclilo de 4 - 13 miembros, -alquil C0-4-O-alquilo C1-4, -alquil C0-4-O-fluoroalquilo C1-4, =O, -C(O)-alquilo C1-4, -C(O)N(R4)(R5), -N(R4)-C(O)-alquilo C1-4 y -alquileno C0-4-N(R4)(R5); cada m es independientemente 0, 1 ó 2; n es 1 ó 2; p es 0 o un número entero entre 1 y 4; y cada - - - - - representa un enlace sencillo o un doble enlace, donde al menos uno de - - - - - representa un enlace sencillo, con la condición de que cuando el Anillo E es un anillo aromático opcionalmente sustituido o heteroaromático opcionalmente sustituido, X no sea hidrógeno.A pharmaceutical composition comprising the compound of structural formula (1) and its therapeutic use in bacterial infections is also described. Claim 1: A compound of formula (1), or a pharmaceutically acceptable salt thereof, wherein X is selected from hydrogen , bromine, fluorine, chlorine, C1-6 alkyl, -O-C1-6 alkyl, C3-10 carbocyclyl, -O-C3-10 carbocyclyl, 4-13 membered heterocyclyl, 4-13-membered heterocyclyl, S (O) m-R2, -CN, N (R2) (R3), -S (O) mN (R2) (R3), -C (O) -O-R2, -C (O) -N ( R2) (R3) and -NH-C (O) -C 1-6 -N alkylene (R2) (R3), where each alkyl or alkylene in the group represented by X is optionally substituted with one or more fluorine; and each carbocyclyl or heterocyclyl in the group represented by X is optionally substituted with one or more substituents independently selected from fluorine, chlorine, = O, -OH, C1-4 fluoroalkyl, C1-4 alkyl, -O-C1-4 alkyl, -O-C1-4 fluoroalkyl, -NH2, -NH (C1-4 alkyl) or -N (C1-4 alkyl) 2, C3-10 carbocyclyl or a 4-13 membered heterocyclyl; the E ring is selected from C3-10 carbocyclyl and a (4-13 member) heterocyclyl; W is selected from C (R6), C (R6) 2, N and N (R7); Q is selected from C (R6), C (R6) 2, N, N (R7), O and S; Y is selected from hydrogen, fluorine, bromine, -CN, - [C (R1a) (R1b)] nN (R2) (R3), -N (R4) (R5), NO2, -NH-C (O) - C1-4-N (R4) alkylene (R5), C1-6 alkyl, -NH-C (O) -C 1-6 alkyl, -NH-S (O) m-C1-6 alkyl, -NH-S ( O) C3-10 m-carbocyclyl, -NH-S (O) 4-13 member m-heterocyclyl; each R1a and R1b is independently selected from hydrogen, C1-4 alkyl and C3-10 carbocyclyl; R2 is selected from hydrogen, C1-12 alkyl, C0-6 alkylene-C3-10 carbocyclyl and C0-6 alkylene-4-13 membered heterocyclyl; R3 is selected from hydrogen, C1-8 alkyl, -C0-6 alkylene-C3-10 carbocyclyl, C0-6 alkylene-4-13 membered heterocyclyl, -C (O) -C 1-6 alkyl, -C0 alkylene 6-C (O) N (R4) (R5), -C (O) -C1-6-N-alkylene (R4) (R5), -C2-6-N alkylene (R4) (R5), -S ( O) m- C 1-6 alkyl, -S (O) C 3-10 m-carbocyclyl and -S (O) 4-13 m-heterocyclyl, where: each alkyl, carbocyclyl, alkylene or heterocyclyl in the group represented by R2 or R3 is optionally and independently substituted with one or more substituents independently selected from fluorine, chlorine, -OH, -O-C1-4 alkyl, C1-4 alkyl, fluorine substituted C1-4 alkyl, -N (R4) ( R5), C3-10 carbocyclyl or a 4-13 membered heterocyclyl; or R2 and R3 taken together with the nitrogen atom to which they are attached form a 4-7 membered monocyclic heterocyclic ring, or a heterocyclic, bicyclic, spirocyclic or bridged ring, where the 4-7 membered monocyclic heterocyclic ring, or the 6-13 membered heterocyclic, bicyclic, spirocyclic or bridged ring, optionally comprises 1 to 4 additional heteroatoms independently selected from N, S and O; the 4-7 membered monocyclic heterocyclic ring, or the 6-13 membered heterocyclic, bicyclic, spirocyclic or bridged ring, is optionally substituted with one or more substituents independently selected from C3-10 carbocyclyl, 4-13 membered heterocyclyl, fluorine, chlorine, -OH, -C 1-4 fluoroalkyl, -C 1-4 alkyl, -C 3-10 carbocyclyl, 4-13 membered -O-heterocyclyl, -C 0-4 alkylene-C 1-4 alkyl, -C0-4-O-C 1-4 fluoroalkyl, = O, -C (O) -C 1-4 alkyl, -C (O) N (R4) (R5), -N (R4) -C (O) -C1-4 alkyl and -C0-4-N (R4) alkylene (R5), and each carbocyclyl or heterocyclyl substituent is optionally substituted with fluorine, chlorine, -OH, = O, C1-4 fluoroalkyl, C1-4 alkyl, -O-C1-4 alkyl, -O-C1-4 fluoroalkyl, -NH2, -NH (C1-4 alkyl) or -N (C1-4 alkyl) 2; each of R4 and R5 is independently selected from hydrogen and C1-4 alkyl; or R4 and R5 taken together with the nitrogen atom to which they are attached form a 4-7 membered heterocyclic ring optionally comprising an additional heteroatom selected from N, S and O, where the 4-7 membered heterocyclic ring is optionally substituted. with fluorine, chlorine, -OH, = O, C 1-4 alkyl substituted with fluorine, -C 1-4 alkyl or -C 1-4 alkylene-O-C 1-4 alkyl, and is optionally condensed with phenyl; each R6 is independently selected from hydrogen, C3-10 carbocyclyl, 4-13 membered heterocyclyl, fluorine, chlorine, -OH, C1-4 fluoroalkyl, C1-4 alkyl, -O-C3-10 carbocyclyl, -O-heterocyclyl 4-13 members, -C0-4-O-C1-4 alkyl, -C0-4-O-C1-4 fluoroalkyl, -C (O) -C1-4 alkyl, -C (O) N (R4 ) (R5), -N (R4) -C (O) -C1-4 alkyl and -C0-4-N alkylene (R4) (R5); or C (R6) 2 is C = O; each R7 is independently selected from hydrogen, -C0-4 -alkyl-C3-10 carbocyclyl, -C0-4 -alkyl-4-13-membered heterocyclyl, -C1-6 fluoroalkyl, -C1-6 alkyl, C1-6 hydroxyalkyl, C3-10 O-carbocyclyl, 4-13 membered -O-heterocyclyl, -C0-4-O-C 1-4 alkyl, -C0-4 alkylene-C 1-4 fluoroalkyl, -C (O) -alkyl C1-4, -C1-4-C (O) alkylene -C 1-4 alkyl, -C 1-4 -C (alkylene) -OH, -C (O) N (R4) (R5), -N (R4 ) -C (O) -C1-4 alkyl, -C (O) - (C1-4 alkylene) -NR4R5 and -C0-4-N alkylene (R4) (R5); and each carbocyclyl or heterocyclyl portion of R6 and R7 is optionally substituted with fluorine, chlorine, -OH, = O, C1-4 fluoroalkyl, C1-4 alkyl, -O-C1-4 alkyl, -O-C1-4 fluoroalkyl, -NH2, -NH (C1-4 alkyl) or -N (C1-4 alkyl) 2; each R8 is independently selected from hydrogen, C3-10 carbocyclyl, 4-13 membered heterocyclyl, fluorine, chlorine, -OH, C1-4 fluoroalkyl, C1-4 alkyl, -O-C3-10 carbocyclyl, -O-heterocyclyl 4-13 members, -C0-4-O-C1-4 alkyl, -C0-4-O-C1-4 fluoroalkyl, = O, -C (O) -C1-4 alkyl, -C (O) N (R4) (R5), -N (R4) -C (O) -C1-4alkyl, -C0-4 -alkylene (R4) (R5) and -S (O) 2C 1-4 alkyl; R9 is absent or independently selected from hydrogen, C3-10 carbocyclyl, 4-13 membered heterocyclyl, fluorine, chlorine, -OH, C1-4 fluoroalkyl, C1-4 alkyl, -O-C3-10 carbocyclyl, -O- 4-13 membered heterocyclyl, -C0-4-O-C1-4 alkyl, -C0-4-O-C1-4 fluoroalkyl, = O, -C (O) -C1-4 alkyl, -C ( O) N (R4) (R5), -N (R4) -C (O) -C1-4 alkyl and -C0-4-N alkylene (R4) (R5); each m is independently 0, 1 or 2; n is 1 or 2; p is 0 or an integer between 1 and 4; and each - - - - - represents a single bond or a double bond, where at least one of - - - - - represents a single bond, with the proviso that when Ring E is an optionally substituted aromatic ring or optionally substituted heteroaromatic , X is not hydrogen.

ARP110102925A 2010-08-12 2011-08-11 TETRACICLINE ANALOGS AR082633A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US37319010P 2010-08-12 2010-08-12
US201061424552P 2010-12-17 2010-12-17
US201161483025P 2011-05-05 2011-05-05

Publications (1)

Publication Number Publication Date
AR082633A1 true AR082633A1 (en) 2012-12-19

Family

ID=45567944

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP110102925A AR082633A1 (en) 2010-08-12 2011-08-11 TETRACICLINE ANALOGS

Country Status (3)

Country Link
AR (1) AR082633A1 (en)
TW (1) TW201245116A (en)
WO (1) WO2012021712A1 (en)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5496202B2 (en) 2008-08-08 2014-05-21 テトラフェース ファーマシューティカルズ,インコーポレイテッド C7-fluoro substituted tetracycline compounds
WO2010033757A1 (en) 2008-09-18 2010-03-25 Naurex, Inc. Nmda receptor modulators and uses thereof
PL2427425T3 (en) 2009-05-08 2017-08-31 Tetraphase Pharmaceuticals, Inc. Tetracycline compounds
ES2654987T3 (en) 2009-08-28 2018-02-15 Tetraphase Pharmaceuticals, Inc. Tetracycline compounds
DK2890673T3 (en) * 2012-08-31 2019-03-18 Tetraphase Pharmaceuticals Inc tetracycline
PE20151416A1 (en) 2013-01-29 2015-10-10 Naurex Inc SPIRO-LACTAMA NMDA RECEIVER MODULATORS AND THEIR USES
JP6793715B2 (en) 2015-03-23 2020-12-02 バイオファーミクス・インコーポレイテッドBioPharmX, Inc. Tetracycline skin pharmaceutical composition
WO2018026763A1 (en) 2016-08-01 2018-02-08 Aptinyx Inc. Spiro-lactam nmda receptor modulators and uses thereof
AU2017305240B2 (en) 2016-08-01 2021-12-09 Aptinyx Inc. Spiro-lactam NMDA receptor modulators and uses thereof
EP3490990B1 (en) 2016-08-01 2023-12-06 Tenacia Biotechnology (Hong Kong) Co., Limited Spiro-lactam nmda modulators and methods of using same
CN109937204B (en) 2016-08-01 2022-11-25 阿普廷伊克斯股份有限公司 Spiro-lactam NMDA receptor modulators and uses thereof
IL264496B (en) 2016-08-01 2022-09-01 Aptinyx Inc Spiro-lactam and bis-spiro-lactam nmda receptor modulators and uses thereof
CN110167560B (en) 2016-08-30 2023-08-18 四相制药公司 Tetracycline compounds and methods of treatment
KR102660864B1 (en) 2016-10-19 2024-04-25 테트라페이즈 파마슈티컬스, 인코포레이티드 Crystalline form of eravacycline
US11578072B2 (en) 2018-01-31 2023-02-14 Aptinyx Inc. Spiro-lactam NMDA receptor modulators and uses thereof
US12012413B2 (en) 2019-11-11 2024-06-18 Tenacia Biotechnology (Hong Kong) Co., Limited Methods of treating painful diabetic peripheral neuropathy
CN113444070A (en) * 2021-07-28 2021-09-28 深圳市真味生物科技有限公司 Preparation method for synthesizing chiral nicotine from chiral tert-butyl sulfinamide

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1303479B1 (en) * 2000-07-07 2011-04-06 Trustees Of Tufts College 7-, 8- and 9-substituted tetracycline compounds
US20060194773A1 (en) * 2001-07-13 2006-08-31 Paratek Pharmaceuticals, Inc. Tetracyline compounds having target therapeutic activities
EP2311451A1 (en) * 2002-03-08 2011-04-20 Paratek Pharmaceuticals, Inc. Amino-methyl substituted tetracycline compounds
US20070093455A1 (en) * 2005-07-21 2007-04-26 Paul Abato 10-substituted tetracyclines and methods of use thereof
JP5496202B2 (en) * 2008-08-08 2014-05-21 テトラフェース ファーマシューティカルズ,インコーポレイテッド C7-fluoro substituted tetracycline compounds

Also Published As

Publication number Publication date
WO2012021712A1 (en) 2012-02-16
TW201245116A (en) 2012-11-16

Similar Documents

Publication Publication Date Title
AR082633A1 (en) TETRACICLINE ANALOGS
PE20110835A1 (en) PYRIDYLOXY-INHIBITORS OF VEGF-R2 AND USE OF THE SAME FOR THE TREATMENT OF DISEASES
AR053195A1 (en) INHIBITING COMPOUNDS OF DIPEPTIDIL PEPTIDASA-IV METHODS TO PREPARE THE SAME AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AS AN ACTIVE AGENT
AR077505A1 (en) PIRIDINE COMPOUNDS AND ITS USES
AR087184A1 (en) USEFUL AZAINDOL DERIVATIVES TO TREAT HIV INFECTIONS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
AR054035A1 (en) BENZODIOXAN AND BENZODIOXOLAN DERIVATIVES AND USE OF THE SAME
PE20140011A1 (en) NOVELTY COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
ECSP11011561A (en) AMINOBUTYRIC DERIVATIVES REPLACED AS NEPRILISINE INHIBITORS
PE20142456A1 (en) OXAZOLIDIN-2-ONA COMPOUNDS AND USES OF THE SAME AS INHIBITORS OF PI3Ks
PE20151951A1 (en) HETEROARYLDIHYDROPYRIMIDINES LINKED BY 6 BRIDGES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
AR067757A1 (en) IMIDAZO DERIVATIVES [4,5-C] PIRIDIN-2-ONA, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, PROCEDURE FOR THE PREPARATION AND USE OF THE SAME AS ANTIVIRAL AGENTS.
AR082391A1 (en) BICYCLE INHIBITORS OF ACETIL-COA AND USES OF THE SAME
UY32462A (en) NEW BIFENYLL DERIVATIVES FOR HEPATITIS C 644 VIRUS INFECTION TREATMENT
EA201490634A1 (en) POLIMIXIN DERIVATIVES
AR063240A1 (en) DERIVATIVES OF N-ARIL PIRAZOL, PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND USES FOR THE TREATMENT OF TYPE2 DIABETES, AND RELATED ILLNESSES.
AR083760A1 (en) ANTIBACTERIAL AGENTS AND PHARMACEUTICAL COMPOSITIONS
GB201201744D0 (en) Novel compounds
AR055401A1 (en) BENZOTIAZOLONA DERIVATIVES
AR064657A1 (en) 8- ALQUINILXANTINAS AND DERIVATIVES
MY184433A (en) 2,6-substituted purine derivatives and their use in the treatment of proliferative disorders
AR063804A1 (en) AZONIABICICLO COMPOUNDS [2.2.2] OCTANO
AR086100A1 (en) CHROMENONE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
RU2015125591A (en) BENZYL SULPHONAMIDE DERIVATIVES AS RORc MODULATORS
AR055617A1 (en) DERIVATIVES OF BENZOTIAZOLONA, PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM, PREPARATION PROCESS AND USES AS BETA2 ADRENORECEPTORS AGONISTS
EA201590022A1 (en) NEW DERIVATIVES 1,3-DIHYDRO-2H-BENZIMIDAZOL-2-SHE, FILLED WITH HETEROCYCLES, AS ANTI-VIRUS AGENTS AGAINST THE RESPIRATORY SYNCTIAL VIRUS

Legal Events

Date Code Title Description
FB Suspension of granting procedure