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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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