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ME02089B - Inhibitori beta-laktamaze - Google Patents

Inhibitori beta-laktamaze

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Publication number
ME02089B
ME02089B MEP-2013-511A MEP51113A ME02089B ME 02089 B ME02089 B ME 02089B ME P51113 A MEP51113 A ME P51113A ME 02089 B ME02089 B ME 02089B
Authority
ME
Montenegro
Prior art keywords
alkyl
compound
sulfoxy
diazabicyclo
octane
Prior art date
Application number
MEP-2013-511A
Other languages
English (en)
French (fr)
Inventor
Christopher J Mortko
Ian Mangion
Nelo Rivera
Rebecca T Ruck
Michael Shevlin
Timothy A Blizzard
Helen Chen
Candido Gude
Jeffrey D Hermes
Jason E Imbriglio
Seongkon Kim
Jane Y Wu
Sookhee Ha
Original Assignee
Merck Sharp & Dohme
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 Merck Sharp & Dohme filed Critical Merck Sharp & Dohme
Publication of ME02089B publication Critical patent/ME02089B/me

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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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    • C07D471/02—Heterocyclic 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
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
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    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pyrrole Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)

Claims (32)

1. Jedinjenje formule I: ili njegova farmaceutski prihvatljiva so, gde: X je: (1) CH2, (2)    CH2CH2, ili (3)    CH2CH2CH2; R1 je C(O)N(R3)R4; R2 je SO3M, OSO3M, SO2NH2, PO3M, OPO3M, CH2CO2M, CF2CO2M ili CF3; M je H ili farmaceutski prihvatljiv katjon; R3 je HetA; R4 je H ili C1-8 alkil izborno supstituisan sa N(RA)RB; ili alternativno, R3 i R4 zajedno sa N atomom za koji su oba vezani formiraju 4- do 9-člani, zasićeni monociklični prsten koji izborno sadrži 1 heteroatom pored azota koji je vezan za R3 i R4 izabran od N, O i S, gde je S izborno oksidovan do S(O) ili S(O)2; gde je monocikličan prsten izborno fuzionisan sa, premošćen sa ili spiro za 4- do 7-člani, zasićeni heterociklični prsten koji sadrži od 1 do 3 heteroatoma nezavisno izabrana od N, O i S, gde je S izborno oksidovan do S(O) ili S(O)2, da bi se formirao bicikličan sistem prstena, gde je monocikličan prsten ili bicikličan sistem prstena koji je tako formiran izborno supstituisan sa 1 ili 2 supstituenta od kojih je svaki nezavisno: (1) C1-6 alkil, (2) C1-6fluoroalkil, (3) (CH2)|1-2G, gde je G jednako OH, OC1-6 alkil, 0-C1-6, fluoroalkil, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, ili SO2RA, (4) O-C1-6 alkil, (5) 0-C1-6 fluoroalkil (6) OH, (7) okso, (8) halogen, (9) N(RA)RB, (10) C(O)N(Ra)Rb, (11) C(O)Ra, (12) C(O)-C1-6 fluoroalkil (13) C(O)0RA ili (14) S(O)2RA; HetA je 4- do 9-člani zasićeni ili mono-nezasićeni heterociklični prsten koji sadrži od 1 do 3 heteroatoma nezavisno izabrana od N, O i S, gde je svaki S u prstenu izborno oksidovan do S(O) ili S(O)2 i 1 ili 2 ugljenika iz prstena su izborno oksidovani do C(O); pri čemu je prsten izborno fuzionisan sa C3-7 cikloalkil; i pri čemu je izborno fuzionisani, zasićeni i li mono-nezasićeni heterociklični prsten izborno supstituisan sa ukupno od 1 do 4 supstituenata izabranih od nula do 2 (CH2)n,N(RA)RB i nula do 2 (CH2)r,RC; svaki n je nezavisno ceo broj koji je 0, 1, 2 ili 3; svaki RA je nezavisno H ili C1-8 alkil; svaki Rb je nezavisno H ili C1-8 alkil; svaki Rc je nezavisno C1-6 alkil, OH, 0-C1-8 alkil, 0C(O)-C1-8 alkil, C(=NH)NH2, NH-C(=NH)NH2, halogen, CN, C(O)RA, C(O)ORA, C(O)N(RA)RB, SOzRA, SO2N(RA)RB, piridil, pirolidinil, piperidinil, piperazinil, morfolinil ili tiomorfolinil.
2.    Jedinjenje prema patentnom zahtevu 1, ili njegova fannaceutski prihvatljiva so, naznačeno time stoje X jednako -CH2- ili -CH2CH2-.
3.    Jedinjenje prema patentnom zahtevu 1 ili patentnom zahtevu 2, ili njegova farmaceutski prihvatljiva so, naznačeno time stoje R2 jednako OSO3M.
4.    Jedinjenje prema patentnom zahtevu 3, ili njegova farmaceutski prihvatljiva so, naznačeno time što je R2 jednako OSO3H.
5.    Jedinjenje prema bilo kom prethodnom patentnom zahtevu naznačeno time što je HetA jednako zasićeni heterociklus izabran iz grupe koju čine pirolidinil, piperidinil, azepanil i azokanil; izborno supstituisan sa N(RA)RB i izborno supstituisan sa 1 ili 2 (CH2)nRC; gde je svaki Rc nezavisno C1-6 alkil, C(=NH)NH2, NH-C(=NH2)NH2, halogen, CN, piridil, pirolidinil ili piperidinil.
6.    Jedinjenje prema bilo kom prethodnom patentnom zahtevu naznačeno time što je HetA jednak: gde zvezdica označava tačku vezivanja HetA za ostatak jedinjenja; T je H ili Rc; Rc je C1-6alkil, OH, 0-C1-8 alkil, C(=NH)NH2, NH-C(=NH)NH2, halogen, CN, piridil, pirolidinil ili piperidinil.
7. Jedinjenje prema patentnom zahtevu prema bilo kom prethodnom patentnom zahtevu, ili njegova farmaceutski prihvatljiva so, naznačeno time što je HetA izborno fuzionisan, zasićen heterocikličan prsten izabran iz grupe koju čine azetidinil, pirolidinil, oksopirolidinil, piperidinil, piperazinil, tetrahidropiranil, tetrahidrotiopiranil, morfolinil, 1,1-dioksidotetrahidrotiopiranil, azepanil, oksazepanil, azokanil i azabiciklo[3.1 .Ojcikloheksil, gde je heterociklik izborno supstituisan sa 1 ili 2 (CH2)nN(RA)RB i izborno supstituisan sa 1 ili 2 (CH2)nRc
8.    Jedinjenje prema bilo kom prethodnom patentnom zahtevu naznačeno time što je HetA -heterocikličan prsten izabran iz grupe koju čine azetidinil, pirolidinil, pirazolidinil, piperidinil, piperazinil, azepanil, oksazepanil, oksazolidinil, izoksazolidinil, morfolinil i tetrahidropiranil, gde je heterociklični prsten izborno supstituisan sa 1 ili 2 supstituenta od koji je svaki nezavisno CH3, CH2NH2, CH2N(H)CH3, CH2N(CH3)2, OCH3, Cl, Br, F, NH2, N(H)CH3, N(CH3)2, C(O)NH2, C(O)N(H)CH3, C(O)N(CH3)2, C(O)CH3, C(O)0CH3, 0C(O)CH3, S(O)2CH3, S(O)2NH2, S(O)2N(H)CH3 ili S(O)2N(CH3)2.
9.    Jedinjenje prema patentnom zahtevu 8, ili njegova farmaceutski prihvatljiva so, naznačeno time što je jednako: gde je R2 kao što je defmisan u patentnom zahtevu 1; T je H, C1-3 alkil, pirolidin-3-il, piperidin-4-il, (CH2)2.3-0-C1-3 alkil, (CH2)2-30H, (CH2)2-3F, (CH2)2-3-piperidinil, (CH2)2-3-pirolidinil; i T je H, Cl, Br, F, C1-3 alkil, 0-C1-3 alkil, OH, NH2, N(H)-C1-3alkil ili N(-C1-3 alkil)2.
10.    Jedinjenje prema patentnom zahtevu 9, ili njegova farmaceutski prihvatljiva so, naznačeno time što je T jednako H, CH3, pirolidin-3-il, piperidin-4-il, (CH2)2-30CH3, (CH2)2-30H, (CH2)2-3F, (CH2)2-3-piperidinil, (CH2)2-3-pirolidinil; i T je H, P, O-C1-3 alkil, OH, NH2, N(H)CH3, N(CH3)2.
11.    Jedinjenje prema bilo kom od patentnih zahteva do 4, ili njegova farmaceutski prihvatljiva so, naznačeno time što R3 i R4 zajedno sa N atomom za koji su oba vezani formiraju heterociklil izabran iz grupe koju čine: gde je prsten izborno supstituisan sa 1 ili 2 supstituenta od kojih je svaki nezavisno C1-3 alkil, CF3, CH2OH, CH2OH, CH20-C1-3 alkil, CH2OCF3, CH2NH2, CH2N(H)-C1-3 alkil, CH2N(-C1-3alkil)2, 0-C1-3 alkil, OCF3, okso, Cl, Br, F, NH2, N(H)-C1-3 alkil, N(-C1-3 alkil)2, C(0)NH2, C(0)N(H)-C1-3 alkil, C(O)N(C1-3 alkil)2, C(0)-C1-3alkil, C(0)0-C1-3 alkil ili S(0)2-C1-3 alkil.
12. Jedinjenje prema patentnom zahtevu 1, naznačeno time što je to jedinjenje izabrano iz grupe koju čine: (2S,5R)-7-okso-N-piperidin-4-il-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2-karboksamid; (2S,5R)-N-[(4S)-azepan-4-il]-7-okso-6-(sulfooksi)-l,6.diazabiciklo[3.2.1]oktan-2- karboksamid; (2S,5R)-N-[(4R)-azepan-4-il]-7-okso-6-(sulfooksi)-1,6-diazabiciklo[3.2.1 ]-oktan-2-karboksamid; (2S,5R)-7-okso-N-[(3R)-pirolidin-3-il-6-(sulfooksi)-l ,6-diazabiciklo[3.2.1 ]-oktan-2-karboksamid; (2S,5R)-7-okso-N-[(3S)-pirolidin-3-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]-oktan-2- karboksamid; (2S,5R)-N-azokan-5-il-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2-karboksamid; (2S,5R)-7-okso-2-[(piperidin-4-ilamino)karbonil]-l,6-diazabiciklo[3.2.1]oktan-6-sulfonska kiselina; (4R,6S)-2-okso-N-piperidin-4-il-3-(sulfooksi)-l,3-diazabiciklo[2.2.1]-heptan-6-karboksamid; (4R,6S)-2-okso-N-[(4S)-azepan-4-il]-3-(sulfooksi)-l,3-diazabiciklo[2.2.1]-heptan-6- karboksamid; njihove farmaceutski prihvatljive soli.
13. Jedinjenje prema patentnom zhatevu 1, naznačeno time što je to jedinjenje izabrano iz grupe koju čine: (2S,5R)-7-okso-N-[(3R)-pirolidin-3-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2- karboksamid; (2S,5R)-N-[(3R,4S)-3-fluoropiperidin-4-il]-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1] oktan-2-karboksamid; diastereomer 1 (25,5R)-7-okso-N-[(3)-piperidin-3-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1] oktan-2-karboksamida; diastereomer 2 (2S,5R)-7-okso-N-[(3)-piperidin-3-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1] oktan-2-karboksamida; (2S,5R)-7-okso-N-azetidin-3-il-6-(sulfooksi)-1,6-diaza-biciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-7-okso-N-[(3R)-pirolidin-3-il]-6-(sulfooksi)-l ,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-7-okso-N-[(4R)-azepan-4-il]-6-(sulfooksi)-l,6-diaza-biciklo[3.2.1]oktan-2- karboksamid; (2S,5R)-7-okso-N-[ 1 -metilpiperidin-4-il]-6-(sulfooksi)-1,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-7-okso-N-[(3S,4S)-3-fluoropiperidin-4-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2-karboksamid ili njegov 3R,4R diastereomer ili njihova smeša; (2S,5R)-7-okso-N-[(3S,4R)-3-fluoropiperidin-4-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-7-okso-N-[(3S,4R)-3-metoksipiperidin-4-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-N-(l,l-dioksidotetrahidro-2H-tiopiran-4-il)-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (25,5R)-N-[(3R,4R)-4-aminopirolidin-3-il]-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-N-[(3R,4R)-4-hidroksipirolidin-3-il]-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-N-[(3R,4S)-4-hidroksipirolidin-3-il]-7-okso-6-(sulfooksi)-l,6- diazabiciklo[3.2.1]oktan-2-karboksamid; (2S,5R)-N-[(3R,4S)-4-fluoropirolidin-3-il]-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan 2-karboksamid; (2S,5R)-N-[(3S,4R)-4-fluoropirolidin-3-il]-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan 2-karboksamid; (2S,5R)-7-okso-N-[(3S)-l-piperidin-4-il-2-oksopirolidin-3-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-7-okso-N-[(3R)-l-piperidin-4-il-2-oksopirolidin-3-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-N-[(3S,4R)-3-fluoroazepan-4-il]-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan- 2-karboksamid; (2S,5R)-N-[(3R,4S)-3-fluoroazepan-4-il]-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan- 2-karboksamid; (2S,5R)-N-3-azabiciklo[3.1.0.]heks-6-il-7-okso-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2- karboksamid; (2S,5R)-N-metil-7-okso-N-piperidin-4-il-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2- karboksamid; (2S,5R)-2-{[2-(aminometil)piperidin-l-il]karbonil)-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-7-on; (2S,5R)-2-[(4-aminopiperidin-1 -il)karbonil]-6-(sulfooksi)-1,6-diazabiciklo[3.2.1 ]oktan-7-on; (2S,5R)-2-(piperazin-l-ilkarbonil)-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-7-on; (2S,5R)-2-(2,7-diazaspiro[3.5]non-2-ilkarbonil)-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-7-on; (2S,5R)-2-(heksahidropirolo[3,4-c]pirol-2(lH)-ilkarbonil)-6-(sulfooksi)-l,6-diazabiciklo[3.2.1 ]oktan-7-on; (2S,5R)-2-{[(3R)-3-aminopirolidin-l-il]karbonil}-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan- 7-on; (2S,5R)-2- {[(3S)-3-aminopirolidin-l-il]karbonil}-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan 7-on; (2S,5R)-2- {[3 -(dimetilamino)pirolidin-1 -il]-karbonil} -6-(sulfooksi)-1,6-diazabiciklo[3.2.1 ]oktan-7-on; njihove farmaceutski prihvatljive soli.
14.    Jedinjenje prema patentnom zahtevu 1, naznačeno time što je to jedinjenje izabrano iz grupe koju čine: (2S,5R)-7-okso-N-piperidin-4-il-6-(sulfooksi)-l ,6-diazabiciklo[3.2.1 ]oktan-2-karboksamid; (2S,5R)-7-okso-N-[(3R)-pirolidin-3-il]-6-(sulfooksi)-l,6-diaksabiciklo[3.2.1]oktan-2-karboksamid; i njihove farmaceutski prihvatljive soli.
15.    Jedinjenje prema patentnom zahtevu 14, koje je (2S,5R)-7-okso-N-piperiđin-4-il-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2-karboksamid ili njegova farmaceutski prihvatljiva so.
16.    Jedinjenje prema patentnom zahtevu 1, naznačeno time stoje to (2S,5R)-7-okso-N-[(3S)-pirolidin-3-il]-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2-karboksamid ili njegova farmaceutski prihvatljiva so.
17.    Jedinjenje prema patentnom zahtevu 1, naznačeno time što je to (2S,5R)-7-okso-N-piperiđin-4-il-6-(sulfooksi)-l,6-diazabiciklo[3.2.1]oktan-2-karboksamid u obliku kristalnog monohidrata.
18.    Farmaceutska kompozicija naznačena time što sadrži jedinjenje prema bilo kom od patentnih zahteva 1 do 17, ili njegovu farmaceutski prihvatljivu so, i farmaceutski prihvatljiv nosač.
19.    Kombinacija jedinjenja prema bilo kom od patentnih zahteva 1 do 17 ili njegove farmaceutski prihvatljive soli i beta-laktamskog antibiotika.
20.    Jedinjenje prema bilo kom od patentnih zahteva 1 do 17 ili njegova farmaceutski prihvatljiva so za upotrebu u postupku za lečenje ljudskog ili životinjskog tela pomoću terapije.
21. Jedinjenje za upotrebu prema patentnom zahtevu 20 naznačeno time stoje terapija lečenje bakterijske infekcije.
22. Upotreba jedinjenja prema bilo kom od patentnih zahteva 1 do 17, ili njegove farmaceutski prihvatljive soli, izborno u kombinaciji sa beta laktamskim antibiotikom, u proizvodnji leka za lečenje bakterijske infekcije.
23. Postupak za pripremu jedinjenja formule P-II koji sadrži: (A) dovođenje u kontakt ketosulfoksonijum ilida formule P-I: sa iridijumskim, rodijumskim ili rutenijumskim katalizatorom da bi se dobilo jedinjenje P-II; gde: PG je zaštitna grupa amina izabrana iz grupe koju čine karbamati i benzilamini; Ru je CH3 ili fenil; Rv je CH3 ili fenil; R4 je H ili C1-4 alkil; T je H, Cl, Br, F, C,.3 alkil, O-C1-3 alkil, OH, NH2, N(H)-C1-3 alkil ili N(-C1-3 alkil)2; p je nula, 1 ili 2; q je nula, 1 ili 2; i p + q = nula, 1, 2 ili 3.
24. Postupak prema patentnom zahtevu 23, naznačen time što je PG jednako Cbz i jedinjenje P-II je jedinjenje P-IIa: i gde postupak dalje sadrži: (B) tretman jedinjenja P-IIa sa redukcionim sredstvom da bi se dobilo jedinjenje formule P-III: (C) dovođenje u kontakt jedinjenja P-III sa sulfonil halogenidom formule R˄-SO2W u prisustvu baze tercijarnog amina da bi se dobilo jedinjenje formule P-IV: gde: W je halogen; i R˄ je: (1)    fenil izborno supstituisan sa od 1 do 3 supstituenta od kojih je svaki nezavisno Cm alkil, C1-4 haloalkil, O-C1-4 alkil, O-C1-4 haloalkil, Cl, Br, F ili NO2; (2)    C1-4 alkil; ili (3)    C1-4 haloalkil.
25. Postupak prema patentnom zahtevu 24, naznačen time što dalje sadrži: (D) dovođenje u kontakt jedinjenja P-IV sa N-Boc-O-benzilhidroksilaminom u prisustvu baze da bi se dobilo jedinjenje formule P-V: i (E) tretman jedinjenja P-V sa kiselinom da bi se dobilo jedinjenje formule P-VI:
26. Postupak prema patentnom zahtevu 25, naznačen time što dalje sadrži: (F) dovođenje u kontakt jedinjenja P-VI sa fozgenom, difozgenom ili trifozgenom u prisustvu tercijarnog amina, i zatim dodavanje vodenog rastvora kiseline da bi se dobilo jedinjenje formule P-VII: (G) dovođenje u kontakt jedinjenja P-VII sa izvorom vodonika u prisustvu katalizatora hidrogenolize i u prisustvu sredstva koje proizvodi Boe da bi se dobilo jedinjenje formule P-VIII:
27. Postupak prema patentnom zahtevu 23, naznačen time što, jedinjenje formule P-II je jedinjenje p-2: koji sadrži: (A) dovođenje u kontakt ketosulfoksonijum ilida p-1: sa katalizatorom koji je izabran iz grupe koju čine iridijum ciklooktadien hloridni dimer, RuCl2(PPh3), Ru(DMSO)4Cl2 i Rh2(TFA)4, da bi se dobilo jedinjenje p-2.
28. Postupak prema patentnom zahtevu 27, naznačen time što dalje sadrži: (B) tretman jedinjenja p-2 sa redukcionim sredstvom koje je izabrano iz grupe koju čine Li borohidrid, Na borohidrid i K borohidrid, da bi se dobilo jedinjenje p-3: (G) dovođenje u kontakt jedinjenja p-3 sa sulfonil halogenidom formule R˄-SO2W u prisustvu baze tri-C1-4 alkilamina da bi se dobilo jedinjenje formule p-4: gde je W jednak hlor; i R˄ je metil, hlorometil, fenil, 4-bromofenil, 4-trifluorometilfenil ili 4-metilfenil.
29. Postupak prema patentnom zahtevu 28, naznačen time što dalje sadrži: (D) dovođenje u kontakt jedinjenja p-4 sa N-Boc-O-benzilhidroksilaminom u prisustvu baze izabrane iz grupe koju čine Li t-butoksid, Na t-butoksid, K t-butoksid i K amiloksid da bi se dobilo jedinjenje p-5: i (E) tretman jedinjenja p-5 sa kiselinom koja je izabrana iz grupe koju čine metansulfonska kiselina, hlormetansulfonska kiselina, p-toluensulfonska kiselina i benzensulfonska kiselina da bi se dobilo jedinjenje formule p-6:
30. Postupak prema patentnom zahtevu 29, naznačen time što dalje sadrži: (F) dovođenje u kontakt jedinjenja p-6 sa trifozgenom u prisustvu baze tri-C1-4 alkilamina, i zatim dodavanje vodenog rastvora fosforne kiseline da bi se dobilo jedinjenje p-7: 1 (G) dovođenje u kontakt jedinjenja p-7 sa vodonikom u prisustvu Pd katalizatora i sredstva koje proizvodi Boe koje je izabrano iz grupe koju čine di-t-butilkarbonat i Boc-ON da bi se dobilo jedinjenje p-8:
31. Jedinjenje izabrano iz grupe koju čine: gde: PG je zaštitna grupa amina izabrana iz grupe koju čine karbamati i benzilamini; Ru je CH3 ili fenil; Rv je CH3 ili fenil; R4 je H ili C1-4 alkil; T je H; Cl, Br, F, C,.3 alkil, 0-C,.3 alkil, OH, NH2, NH2-C1-3 alkil ili N(-C1-3 alkil)2; p je nula, 1 ili 2; q je nula, 1 ili 2; p + q = nula, 1, 2 ili 3; i R˄ je: (1) fenil izborno supstituisan sa od 1 do 3 supstituenta od kojih je svaki nezavisno C1-4 alkil, C1-4 haloalkil, O-C1-4 alkil, O-C1-4 haloalkil, Cl, Br, F ili N02; (2)    C1-4 alkil; ili (3)    C1-4 haloalkil.
32. Jedinjenje prema patentnom zahetvu 31, naznačeno time što je izabrano iz grupe koju čine: gde je R˄ jednak metil, hlorometil, fenil, 4-bromofenil, 4-trifluorometilfenil ili 4-metilfenil ili njegova farmaceutski prihvatljiva so.
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Families Citing this family (105)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2231667T3 (da) * 2008-01-18 2013-12-16 Merck Sharp & Dohme Beta-lactamase-hæmmere
RU2599791C2 (ru) 2010-08-10 2016-10-20 Ремпекс Фармасьютикэлз, Инч. Циклические бороновые кислотно-эфирные производные и их использование в терапии
TWI599355B (zh) * 2010-12-22 2017-09-21 明治製菓藥業股份有限公司 光學活性二氮雜二環辛烷衍生物及其製造法
US8772490B2 (en) 2010-12-22 2014-07-08 Meiji Seika Pharma Co., Ltd. Optically active diazabicyclooctane derivatives and process for preparing the same
BR112013032415B1 (pt) * 2011-06-17 2021-07-27 Pfizer Anti-Infectives Ab Processos para preparar compostos e compostos
PT2748165T (pt) * 2011-08-27 2016-12-28 Wockhardt Ltd Derivados de 1,6-diazabiciclo[3,2,1]octano-7-ona e sua utilização no tratamento de infeções bacterianas
KR101618424B1 (ko) 2011-08-30 2016-05-04 욱크하르트 리미티드 1,6-디아자비시클로[3,2,1]옥탄-7-온 유도체 및 세균 감염 치료에서의 그 유도체의 용도
WO2013033461A1 (en) 2011-08-31 2013-03-07 Rempex Pharmaceuticals, Inc. Heterocyclic boronic acid ester derivatives and therapeutic uses thereof
US8796257B2 (en) 2011-12-02 2014-08-05 Naeja Pharmaceutical Inc. Bicyclic compounds and their use as antibacterial agents and β-lactamase inhibitors
US9505761B2 (en) 2011-12-02 2016-11-29 Fedora Pharmaceuticals Inc. Bicyclic compounds and their use as antibacterial agents and beta-lactamase inhibitors
MX2014008278A (es) * 2012-01-06 2014-11-10 Univ South Florida Composiciones, metodos de uso y metodos de tratamiento.
US8916709B2 (en) 2012-03-30 2014-12-23 Cubist Pharmaceuticals, Inc. 1,2,4-oxadiazole and 1,2,4-thiadiazole β-lactamase inhibitors
MX2014011825A (es) 2012-03-30 2015-02-20 Cubist Pharm Inc INHIBIDORES DE ISOXAZOL ß-LACTAMASA.
US8969570B2 (en) 2012-03-30 2015-03-03 Cubist Pharmaceuticals, Inc. Beta-lactamase inhibitors
AU2013237939A1 (en) * 2012-03-30 2014-10-30 Cubist Pharmaceuticals, Inc. 1,3,4-oxadiazole and 1,3,4-thiadiazole beta-lactamase inhibitors
AR090539A1 (es) 2012-04-02 2014-11-19 Astrazeneca Ab COMPUESTOS INHIBIDORES DE b LACTAMASA
HUE042605T2 (hu) 2012-05-08 2019-07-29 Codexis Inc Biokatalizátorok és kémiai vegyületek hidroxilálására szolgáló eljárások
US9156858B2 (en) 2012-05-23 2015-10-13 Rempex Pharmaceuticals, Inc. Boronic acid derivatives and therapeutic uses thereof
PT2857401T (pt) 2012-05-30 2019-11-19 Meiji Seika Pharma Co Ltd Novo inibidor de β-lactamase e método para a produção do mesmo
US10561675B2 (en) 2012-06-06 2020-02-18 Rempex Pharmaceuticals, Inc. Cyclic boronic acid ester derivatives and therapeutic uses thereof
AU2013308127B2 (en) 2012-08-25 2015-08-13 Wockhardt Limited 1,6- Diazabicyclo [3,2,1] octan- 7- one derivatives and their use in the treatment of bacterial infections
EP2915805A4 (en) * 2012-11-01 2016-03-23 Kaneka Corp METHOD FOR PRODUCING AN OPTICALLY ACTIVE BICYCLIC UREA COMPOUND
WO2014089365A1 (en) 2012-12-07 2014-06-12 Venatorx Pharmaceuticals, Inc Beta-lactamase inhibitors
UA111925C2 (uk) * 2012-12-11 2016-06-24 Федора Фармасьютікалз Інк. БІЦИКЛІЧНІ СПОЛУКИ ТА ЇХ ВИКОРИСТАННЯ ЯК АНТИБАКТЕРІАЛЬНИХ АГЕНТІВ ТА ІНГІБІТОРІВ β-ЛАКТАМАЗИ
US9101638B2 (en) 2013-01-04 2015-08-11 Rempex Pharmaceuticals, Inc. Boronic acid derivatives and therapeutic uses thereof
MX2015008627A (es) 2013-01-04 2015-09-23 Rempex Pharmaceuticals Inc Derivados de acido boronico y usos terapeuticos de los mismos.
WO2014107535A1 (en) 2013-01-04 2014-07-10 Rempex Pharmaceuticals, Inc. Boronic acid derivatives and therapeutic uses thereof
US9241947B2 (en) 2013-01-04 2016-01-26 Rempex Pharmaceuticals, Inc. Boronic acid derivatives and therapeutic uses thereof
CN105101970B (zh) 2013-01-10 2018-11-20 维纳拓尔斯制药公司 β-内酰胺酶抑制剂
RU2625304C2 (ru) * 2013-03-08 2017-07-13 Вокхардт Лимитед Способ получения (2s,5r)-7-оксо-6-сульфоокси-2-[((3r)-пирролидин-3-карбонил)гидразинокарбонил]-1,6-диазабицикло[3.2.1]октана
KR101774132B1 (ko) 2013-03-08 2017-09-01 욱크하르트 리미티드 (2s, 5r)-7-옥소-6-술포옥시-2-[((3r)-피페리딘-3-카보닐)-히드라지노 카보닐]-1,6-디아자-비사이클로[3.2.1]-옥탄의 제조 방법
CN105143226A (zh) * 2013-03-08 2015-12-09 沃克哈特有限公司 制备(2s,5r)-2-甲酰胺基-7-氧代-6-磺酰氧基-1,6-二氮杂-双环[3.2.1]辛烷的钠盐的方法
WO2014135931A1 (en) * 2013-03-08 2014-09-12 Wockhardt Limited A process for preparation of (2s, 5r)-7-oxo-6-sulphooxy-2-[((3r)-piperidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza-bicyclo [3.2.1]- octane
MX2015011720A (es) 2013-03-08 2015-12-01 Wockhardt Ltd Proceso para la preparcion de monoacido de (2s,5r)-{[(4-aminopiper idin-4-il)carbonil]-7-oxo-1,6-diaza-biciclo[3.2.1 oct-6-il} ester sulfurico.
AU2013380574B2 (en) * 2013-03-08 2016-07-07 Wockhardt Limited A process for preparation of (2S, 5R)-7-oxo-6-sulphooxy-2-[((3R)-piperidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza-bicyclo [3.2.1]- octane
US9944658B2 (en) 2013-03-14 2018-04-17 VenatoRx Pharmaceuticals, Inc. Beta-lactamase inhibitors
WO2014152996A1 (en) * 2013-03-14 2014-09-25 Cubist Pharmaceuticals, Inc. Crystalline form of a beta-lactamase inhibitor
CA2911544A1 (en) * 2013-06-10 2014-12-18 Merck Sharp & Dohme Corp. Preparation of tert-butyl 4-((1r,2s,5r)-6-(benzyloxy)-7-0x0-1,6-diazabicycl0[3.2.1]octane-2-carboxamido)piperidine-1-carboxylate
MY176278A (en) 2013-09-24 2020-07-27 Meiji Seika Pharma Co Ltd Process for producing diazabicyclooctane derivative and intermediate thereof
WO2015051101A1 (en) * 2013-10-02 2015-04-09 Cubist Pharmaceuticals, Inc. B-lactamase inhibitor picoline salt
HUE051925T2 (hu) * 2013-10-08 2021-04-28 Meiji Seika Pharma Co Ltd Dizabiciklooktán származék kristályai és diazabiciklooktán származék kristályainak elõállítási eljárása
US9604986B2 (en) 2013-11-26 2017-03-28 Wockhardt Limited Polymorphs and process for preparation of (2S, 5R)-7-oxo-N-[(2S)-pyrrolidin-2-yl-methyloxy]-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide
WO2015148379A1 (en) 2014-03-24 2015-10-01 Novartis Ag Monobactam organic compounds for the treatment of bacterial infections
WO2015150891A1 (en) * 2014-03-29 2015-10-08 Wockhardt Limited A process for preparation of trans-sulfuric acid mono-[2-(5-azetidin-3-ylmethyl-[1,3,4]oxadiazol-2-yl)-7-oxo-1,6-diazabicyclo [3.2.1]oct-6-yl]ester
WO2015150890A1 (en) * 2014-03-29 2015-10-08 Wockhardt Limited A process for preparation of trans-sulfuric acid mono-{2-(5-(3-amino-propyl)-[1,3,4]oxadiazol-2-yl]-7-oxo-1,6-diazabicyclo [3.2.1] oct-6-yl}ester
EP3140310B1 (en) 2014-05-05 2019-08-07 Rempex Pharmaceuticals, Inc. Synthesis of boronate salts and uses thereof
US9687497B1 (en) 2014-05-05 2017-06-27 Rempex Pharmaceuticals, Inc. Salts and polymorphs of cyclic boronic acid ester derivatives and therapeutic uses thereof
MX2016015093A (es) 2014-05-19 2017-03-27 Rempex Pharmaceuticals Inc Derivados de acido boronico y sus usos terapeuticos.
US9511142B2 (en) 2014-06-11 2016-12-06 VenatoRx Pharmaceuticals, Inc. Beta-lactamase inhibitors
KR20220065084A (ko) 2014-06-11 2022-05-19 베나토알엑스 파마슈티컬스, 인크. 베타-락타마제 억제제
KR20170024087A (ko) 2014-07-01 2017-03-06 렘펙스 파머수티클스 인코퍼레이티드 보론산 유도체 및 그의 치료적 용도
SMT201900187T1 (it) * 2014-11-17 2019-05-10 Entasis Therapeutics Ltd Terapia di combinazione per il trattamento di infezioni batteriche resistenti
US10662205B2 (en) 2014-11-18 2020-05-26 Qpex Biopharma, Inc. Cyclic boronic acid ester derivatives and therapeutic uses thereof
ES2812848T3 (es) 2014-12-02 2021-03-18 Merck Sharp & Dohme Proceso para la preparación de 4-((2S,5R)-6-(benciloxi)-7-oxo-1,6-diazabiciclo[3.2.1]octano-2-carboxamido)piperidin-1-carboxilato de terc-butilo y análogos del mismo
MY190283A (en) 2014-12-05 2022-04-12 Meiji Seika Pharma Co Ltd Method for producing crystals of diazabicyclooctane derivative and stable lyophilized preparation
WO2016149393A1 (en) 2015-03-17 2016-09-22 Rempex Pharmaceuticals, Inc. Boronic acid derivatives and therapeutic uses thereof
RU2715058C2 (ru) * 2015-03-31 2020-02-25 Мутабилис Гетероциклические соединения и их применение для предупреждения или лечения бактериальных инфекций
US10183943B2 (en) * 2015-05-07 2019-01-22 Mutabilis Heterocyclic compounds and their use in preventing or treating bacterial infections
EP3347008B1 (en) 2015-09-11 2022-03-09 Venatorx Pharmaceuticals, Inc. Beta-lactamase inhibitors
WO2017045510A1 (zh) * 2015-09-16 2017-03-23 山东轩竹医药科技有限公司 β-内酰胺酶抑制剂及其用途
CA3000087A1 (en) 2015-10-02 2017-04-06 Legochem Biosciences, Inc. Compositions and methods for inhibiting beta-lactamase
WO2017100537A1 (en) 2015-12-10 2017-06-15 VenatoRx Pharmaceuticals, Inc. Beta-lactamase inhibitors
WO2017098425A1 (en) * 2015-12-11 2017-06-15 Wockhardt Limited 7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide containing compounds and their use in treating bacterial infections
WO2017136254A1 (en) 2016-02-04 2017-08-10 Merck Sharp & Dohme Corp. Methods of preparing hydroxylamine derivatives useful in the preparation of anti-infective agents
CN108778270B (zh) * 2016-03-31 2021-07-30 吉林四环制药有限公司 一种抗菌组合物及其用途
US10184117B2 (en) 2016-06-09 2019-01-22 Codexis, Inc. Biocatalysts and methods for hydroxylation of chemical compounds
EP3478693B1 (en) 2016-06-30 2021-07-21 Qpex Biopharma, Inc. Boronic acid derivatives and therapeutic uses thereof
WO2018027062A1 (en) 2016-08-04 2018-02-08 VenatoRx Pharmaceuticals, Inc. Boron-containing compounds
PT3512851T (pt) * 2016-09-16 2022-10-11 Entasis Therapeutics Ltd Compostos inibidores de beta-lactamase
EP3515915B1 (en) * 2016-09-19 2021-08-04 Merck Sharp & Dohme Corp. Process for preparing beta-lactamase inhibitor hydroxylurea intermediates
JOP20190061A1 (ar) * 2016-09-28 2019-03-26 Novartis Ag مثبطات بيتا-لاكتاماز
CN108078982B (zh) * 2016-11-21 2020-02-07 天津大学 脯氨酸衍生物在制备β-内酰胺酶抑制剂中的用途
SG11201908181XA (en) 2017-03-06 2019-10-30 Venatorx Pharmaceuticals Inc Solid forms and combination compositions comprising a beta-lactamase inhibitor and uses thereof
CN108619141B (zh) * 2017-03-16 2021-09-10 山东轩竹医药科技有限公司 一种抗菌组合物及其用途
DK3630111T3 (en) 2017-05-08 2022-03-14 Entasis Therapeutics Inc Compounds and methods for treating bacterial infections
US10085999B1 (en) * 2017-05-10 2018-10-02 Arixa Pharmaceuticals, Inc. Beta-lactamase inhibitors and uses thereof
EP3630782A4 (en) 2017-05-26 2021-03-03 Venatorx Pharmaceuticals, Inc. Penicillin-binding protein inhibitors
EP3630783A4 (en) 2017-05-26 2021-03-03 Venatorx Pharmaceuticals, Inc. PENICILLIN-BINDING PROTEIN INHIBITORS
BR112020001327A2 (pt) 2017-07-21 2020-08-11 Antabio Sas compostos químicos
CN109568323B (zh) * 2017-09-29 2022-09-30 吉林四环制药有限公司 抗菌组合物及其用途
CN111212843B (zh) 2017-10-11 2025-05-16 Qpex生物制药有限公司 硼酸衍生物及其合成
US11180501B2 (en) 2017-12-01 2021-11-23 Qilu Pharmaceutical Co., Ltd. Crystal form of β-lactamase inhibitor and preparation method therefor
CN109956941B (zh) * 2017-12-25 2020-08-04 新发药业有限公司 一种阿维巴坦的简便制备方法
EP3744722A4 (en) * 2018-01-25 2021-11-03 Suzhou Sinovent Pharmaceuticals Co., Ltd. Ss-LACTAMASE INHIBITOR AND ITS USE
JP7329260B2 (ja) 2018-04-20 2023-08-18 キューペックス バイオファーマ， インコーポレイテッド ボロン酸誘導体およびその治療的使用
EP3572411A1 (en) 2018-05-21 2019-11-27 Antabio SAS Thiazole derivatives as metallo-beta-lactamase inhibitors
US12173018B2 (en) 2018-05-25 2024-12-24 VenatoRx Pharmaceuticals, Inc. Penicillin-binding protein inhibitors
US11905286B2 (en) 2018-08-09 2024-02-20 Antabio Sas Diazabicyclooctanones as inhibitors of serine beta-lactamases
IL280770B2 (en) 2018-08-09 2024-05-01 Antabio Sas Diazabicyclooctanones as inhibitors of serine beta-lactamases
EP3670512A1 (en) * 2018-12-18 2020-06-24 Antabio SAS Diazabicyclooctanones as inhibitors of serine beta-lactamases
WO2020059891A1 (ja) * 2018-09-21 2020-03-26 株式会社エーピーアイ コーポレーション アミノ酸誘導体の製造方法
WO2020072442A1 (en) * 2018-10-01 2020-04-09 Arixa Pharmaceuticals, Inc. Derivatives of relebactam and uses thereof
CN111072660B (zh) * 2018-10-22 2021-05-18 新发药业有限公司 一种瑞来巴坦的简便制备方法
MX2021011026A (es) 2019-03-12 2021-10-13 Arixa Pharmaceuticals Inc Forma cristalina de un derivado de avibactam.
WO2020219405A1 (en) * 2019-04-26 2020-10-29 Merck Sharp & Dohme Corp. Process for the preparation of intermediates useful for making (2s,5r)-7-oxo-n-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide
JP7647110B2 (ja) * 2020-01-22 2025-03-18 日油株式会社 ポリエーテルエステル化合物
CN115151544B (zh) 2020-09-01 2024-08-16 宁夏农林科学院 β-内酰胺酶抑制剂及其制备
WO2022047790A1 (en) * 2020-09-07 2022-03-10 Ningxia Academy Of Agriculture And Forestry Sciences Amidine substituted bicyclic compounds, their preparation, their use as antibacterial agents and beta-lactamase inhibitors
CN111943950B (zh) * 2020-09-10 2022-03-29 山东安信制药有限公司 一种瑞来巴坦的制备方法
EP4146651A4 (en) 2021-05-07 2024-06-05 Ningxia Academy of Agriculture and Forestry Sciences SULFONYLAMIDINE SUBSTITUTED COMPOUNDS AND THEIR USE AS BETA-LACTAMASE INHIBITORS
US11814385B2 (en) 2021-06-25 2023-11-14 University Of South Florida Small molecule inhibitors targeting Clostridioides difficile sporulation
WO2023220324A1 (en) * 2022-05-11 2023-11-16 The Regents Of The University Of Colorado A Body Corporate Antibiotic composition and methods of use thereof
CN117384169B (zh) * 2022-07-05 2025-10-17 福安药业集团重庆三禾兴医药科技有限公司 一类噻唑胺-二氮杂双环辛酮缀合衍生物及其用途
GB202306833D0 (en) 2023-05-09 2023-06-21 Adjutec Pharma As Therapy
GB202306826D0 (en) 2023-05-09 2023-06-21 Adjutec Pharma As Therapy

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4880793A (en) 1978-07-24 1989-11-14 Merck & Co., Inc. Combination of thienamycin-type antibiotics with dipeptidase inhibitors
US4616038A (en) 1978-07-24 1986-10-07 Merck & Co., Inc. Combination of thienamycin-type antibiotics with dipeptidase inhibitors
US5071843A (en) 1978-07-24 1991-12-10 Merck & Co., Inc. Combination of 2-substituted carbapenems with dipeptidase inhibitors
US4539208A (en) 1980-09-17 1985-09-03 Merck & Co., Inc. Combination of thienamycin-type antibiotics with dipeptidase inhibitors
DK0508234T3 (da) 1991-04-11 1996-10-28 Hoffmann La Roche Beta-lactamer
NZ274915A (en) 1993-12-29 1997-11-24 Pfizer N-(hetero)aryl methyl diazabicycloalkane derivatives
JP3199300B2 (ja) * 1994-05-09 2001-08-13 三共株式会社 １−メチルカルバペネム誘導体
HUP9901376A3 (en) 1995-12-21 2000-03-28 Sankyo Company Ltd Chuo Ku 1-methylcarbapenem derivatives, their use, production thereof and medicaments containing the same
JP2965922B2 (ja) * 1995-12-21 1999-10-18 三共株式会社 １−メチルカルバペネム誘導体
JP2955276B2 (ja) * 1997-06-19 1999-10-04 三共株式会社 １−メチルカルバペネム誘導体を含有する抗菌剤
JP4490517B2 (ja) * 1998-03-19 2010-06-30 富山化学工業株式会社 ５−デオキシ−５−アルカノイルアミノ−β−Ｄ−アロフラノシルウロン酸誘導体またはその塩、それらを含有する抗真菌剤及びキチン合成酵素阻害剤
CA2377762C (en) 1999-07-06 2008-09-30 Methylgene Inc. Sulfonamidomethyl phosphonate inhibitors of .beta.-lactamase
BR0013112A (pt) 1999-08-10 2002-06-11 British Biotech Pharm Agentes antibacterianos
FR2812635B1 (fr) 2000-08-01 2002-10-11 Aventis Pharma Sa Nouveaux composes heterocycliques, preparation et utilisation comme medicaments notamment comme anti- bacteriens
CA2429346A1 (en) 2000-11-16 2002-05-23 Sankyo Company, Limited 1-methylcarbapenem derivatives
JP2002212182A (ja) * 2000-11-16 2002-07-31 Sankyo Co Ltd １−メチルカルバペネム誘導体
FR2825705B1 (fr) 2001-06-08 2005-05-20 Aventis Pharma Sa Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens
FR2835186B1 (fr) * 2002-01-28 2006-10-20 Aventis Pharma Sa Nouveaux composes heterocycliques, actifs comme inhibiteurs de beta-lactamases
JP2004043438A (ja) * 2002-05-15 2004-02-12 Sankyo Co Ltd １−メチルカルバペネム誘導体を含有する医薬
US7439253B2 (en) 2002-12-06 2008-10-21 Novexel Heterocyclic compounds, their preparation and their use as medicaments, in particular as antibacterials and beta-lactamase inhibitors
CN1845897A (zh) 2003-07-09 2006-10-11 帕拉特克药品公司 取代的四环素化合物
US6984652B2 (en) * 2003-09-05 2006-01-10 Warner-Lambert Company Llc Gyrase inhibitors
CA2540646A1 (en) * 2003-10-01 2005-04-14 Bayer Healthcare Ag Antibacterial amide macrocycles
WO2005082012A2 (en) 2004-02-24 2005-09-09 Ssci, Inc. Analysis and screening of solid forms using the atomic pair distribution function
ES2373461T3 (es) * 2005-12-07 2012-02-03 Basilea Pharmaceutica Ag Antibióticos útiles de monobactama.
EP2069347A2 (en) 2006-09-27 2009-06-17 Merck & Co., Inc. Novel inhibitors of beta-lactamase
DK2231667T3 (da) * 2008-01-18 2013-12-16 Merck Sharp & Dohme Beta-lactamase-hæmmere

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