HRP20140655T1 - Sinteza supstituiranih derivata pirazolon karboksamidina - Google Patents
Sinteza supstituiranih derivata pirazolon karboksamidina Download PDFInfo
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- HRP20140655T1 HRP20140655T1 HRP20140655AT HRP20140655T HRP20140655T1 HR P20140655 T1 HRP20140655 T1 HR P20140655T1 HR P20140655A T HRP20140655A T HR P20140655AT HR P20140655 T HRP20140655 T HR P20140655T HR P20140655 T1 HRP20140655 T1 HR P20140655T1
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- 230000015572 biosynthetic process Effects 0.000 title claims 2
- 238000003786 synthesis reaction Methods 0.000 title claims 2
- GNKXGJFNGSLHFN-UHFFFAOYSA-N 1,3-dihydropyrazole-2-carboximidamide Chemical class N1(NC=CC1)C(=N)N GNKXGJFNGSLHFN-UHFFFAOYSA-N 0.000 title 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 16
- 125000000217 alkyl group Chemical group 0.000 claims 15
- 150000001875 compounds Chemical class 0.000 claims 14
- 229910052739 hydrogen Inorganic materials 0.000 claims 13
- 239000001257 hydrogen Substances 0.000 claims 13
- -1 benzyloxymethyl group Chemical group 0.000 claims 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 12
- 125000004432 carbon atom Chemical group C* 0.000 claims 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 8
- 238000006243 chemical reaction Methods 0.000 claims 7
- 238000000034 method Methods 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 5
- 238000002360 preparation method Methods 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- 125000003277 amino group Chemical group 0.000 claims 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 4
- 125000002950 monocyclic group Chemical group 0.000 claims 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 3
- MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical group C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 claims 3
- 125000003386 piperidinyl group Chemical group 0.000 claims 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 2
- HBNYJWAFDZLWRS-UHFFFAOYSA-N ethyl isothiocyanate Chemical compound CCN=C=S HBNYJWAFDZLWRS-UHFFFAOYSA-N 0.000 claims 2
- 125000000468 ketone group Chemical group 0.000 claims 2
- FIGQVKAQXFFDHK-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyl-n'-ethyl-2,3-diazaspiro[4.4]non-3-ene-2-carboximidamide Chemical compound C1C2(CCCC2)C=NN1C(NCC)=NS(=O)(=O)C1=CC=C(N)C=C1 FIGQVKAQXFFDHK-UHFFFAOYSA-N 0.000 claims 2
- HALPHMGONWQMOJ-UHFFFAOYSA-N n-[4-[[c-(2,3-diazaspiro[4.4]non-3-en-2-yl)-n-ethylcarbonimidoyl]sulfamoyl]phenyl]acetamide Chemical compound C1C2(CCCC2)C=NN1C(NCC)=NS(=O)(=O)C1=CC=C(NC(C)=O)C=C1 HALPHMGONWQMOJ-UHFFFAOYSA-N 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- DRPQDRUFNKLHNA-UHFFFAOYSA-N 2,3-diazaspiro[4.4]non-2-ene Chemical compound C1CCCC21CN=NC2 DRPQDRUFNKLHNA-UHFFFAOYSA-N 0.000 claims 1
- XXRBLXQKAWICQN-UHFFFAOYSA-N 2,3-diazaspiro[4.4]non-3-ene Chemical compound C1CCCC21C=NNC2 XXRBLXQKAWICQN-UHFFFAOYSA-N 0.000 claims 1
- HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims 1
- IQTDHDJDRIQESU-UHFFFAOYSA-N 3,4-dihydropyrazole-2-carbothioic s-acid Chemical compound SC(=O)N1CCC=N1 IQTDHDJDRIQESU-UHFFFAOYSA-N 0.000 claims 1
- MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical class C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 claims 1
- 229910006074 SO2NH2 Inorganic materials 0.000 claims 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 150000002540 isothiocyanates Chemical class 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 1
- PKOFBDHYTMYVGJ-UHFFFAOYSA-N n-(4-sulfamoylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(S(N)(=O)=O)C=C1 PKOFBDHYTMYVGJ-UHFFFAOYSA-N 0.000 claims 1
- ACZDFKYHBMWHFI-UHFFFAOYSA-N n-ethyl-2,3-diazaspiro[4.4]non-3-ene-2-carbothioamide Chemical compound C1=NN(C(=S)NCC)CC11CCCC1 ACZDFKYHBMWHFI-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical class C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/10—Spiro-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (8)
1. Postupak za pripremu spoja čija je formula (I):
[image]
ili tautomera, stereoizomera ili neke farmakološki prihvatljive soli bilo kojeg od prije navedenih gdje je
- R1 odabran iz grupe koju čini vodik ili skupina alkil (C1-4), opcionalno supstituiranih jednim do tri atoma fluora ili nekom hidroksi skupinom
- R2 predstavlja vodik ili skupinu alkil(C1-4), opcionalno supstituirane jednim do tri atoma fluora, hidroksi skupinom, benziloksimetil skupinom, amino skupinom, monometil amino skupinom, dimetilamino skupinom ili Boc-, Fmoc. ili Cbz-zaštićenom amino skupinom, koja alkil(C1-4) skupina može sadržavati jednu keto skupinu, sulfonil skupinu ili jedan N, O ili S atom,
- R3 predstavlja vodik ili skupinu alkil(C1-4), opcionalno supstituirane jednim do tri atoma fluora, hidroksi skupinom, benziloksimetil skupinom, amino skupinom, monometil amino skupinom, dimetilamino skupinom ili Boc-, Fmoc. ili Cbz-zaštićenom amino skupinom, koja alkil(C1-4) skupina može sadržavati jednu keto skupinu, sulfonil skupinu ili jedan N, O ili S atom, ili
R1 i R2, zajedno s atomima ugljika označenim s ’a’ i ’b’ tvore jedan C5-8-cikloalkil prsten, opcionalno supstituiran jednim do tri atoma fluora, hidroksi skupinom ili skupinom alkil(C1-4), ili
R2 i R3, zajedno s atomima ugljika označenim s ’b’ tvore jedan C3-8-cikloalkil prsten, opcionalno supstituiran jednim do četiri atoma fluora ili jednom ili dvije metil skupine ili hidroksi skupinom ili
R2 i R3, s atomima ugljika označenim s ’b’ tvore jedan C5-8-heterocikloalkil prsten opcionalno supstituiran jednim do četiri atoma fluora, jednom ili dvije metil skupine, jednom benzil skupinom ili jednom hidroksi skupinom,
- R4 predstavlja vodik ili skupinu alkil(C1-4) skupinu, opcionalno zamijenjenu jednim do tri atoma fluora ili jednom hidroksi skupinom, ili
R4 predstavlja jednu monociklički aril ili heteroaril skupinu opcionalno supstituiranu jednim do pet supstituenata Q koji mogu biti isti ili različiti, odabranih između halogena, trifluorometila, trifluorometoksi, cijano, C1-3-alkil, C1-3-alkoksi, hidroksi, amino, acetil, acetamido, trifluoroacetamido, -CONH2, -SO2NH2 ili -CO2H, ili
R3 i R4, zajedno s atomima ugljika označenim s ’b’ i ’c’ tvore jedan C3-8-cikloalkil prsten, opcionalno supstituiran jednim do četiri atoma fluora, jednom ili dvije metil skupine ili jednom hikroksi skupinom, ili
R3 i R4, zajedno s atomima ugljika označenim s ’b’ i ’c’ tvore jedan C5-8-heterocikloalkil prsten opcionalno supstituiran jednim do četiri atoma fluora, jednom ili dvije metil skupine ili jednom hikroksi skupinom, benzil skupinom ili hidroksi skupinom
- R5 predstavlja vodik ili metil,
- R6 je odabran iz atoma vodika ili jedne skupine alkil(C1-4), opcionalno supstituirane jednim do tri atoma fluora ili jednom hidroksi skupinom,
- R7 predstavlja jednu monocikličku ili stopljenu bicikličku aromatsku ili heteroraomatsku skupinu, koje skupine nisu supstituirane ili su supstituirane jednim do pet supstituenata Q, kako je gore definirano, ili
R7 predstavlja jednu 2-aril-etenil skupinu ili jednu 2-aril-etinil skupinu, ili
R7 predstavlja jednu piperidinil skupinu koja nije supstituirana ili je supstituirana jednim do četiri atoma fluora ili jednom skupinom CF3, ili
R7 predstavlja jednu 2,3-dihidroindolil skupinu ili jednu benzimidazol-2-jedan skupinu
a uključuje sljedeće korake:
(i) reakciju supstituiranog 4,5-dihidro-(1H)-pirazola čija je formula (IIa) ili izomer-supstituiranog 4,5-dihidro-3Hpirazola čija je formula (IIb):
[image]
gdje R1, R2, R3, R4 i R5 imaju značenja koja su im gore navedena, s izotiocijanatom čija je formula R6-N=C=S, gdje R6 ima značenje koje mu je gore navedeno, da bi se dobio supstituirani amid 4,5-dihidro-(1H)-pirazol-1-tiokarbonske kiseline čija je formula (IIIa) ili tautomer-supstituirana 4,5-dihidro-(1H)-pirazol-1-ditiokarbamatna kiselina čija je formula (IIIb):
[image]
(ii) reakcija dobivenog spoja čija je formula (IIIa) ili (IIIb), s nekim alkilirajućim reagensom opće formule Rx-L, gdje Rx predstavlja linearnu (C1-8)-alkil skupinu a L predstavlja ’odlazeću skupinu’,da bi se dobio spoj čija je formula (IV):
[image]
(iii) reakcija dobivenog spoja čija je formula (IV) s nekim derivatom sulfonamida čija je formula R7SO2NH2, gdje R7 ima značenje koje je gore navedeno, da bi se dobio spoj čija je formula (I):
[image]
(iv) izolacija spoja čija je formula (I) iz reakcijske mješavine.
2. Postupak prema zahtjevu 1, za pripremu spoja čija je formula (I), naznačen time:
- da je R1 odabran iz skupine koju čine vodik ili jedna skupina alkil(C1-2),
- da R2 predstavlja skupinu koju čine vodik ili skupina alkil(C1-3), opcionalno supstituirana jednim do tri atoma fluora ili jednom hidroksi skupinom,
- da R3 predstavlja vodik ili jedna skupina alkil(C1-3), opcionalno supstituirana jednim do tri atoma fluora ili jednom hidroksi skupinom, ili
R1 i R2, zajedno s atomima ugljika označenim s ’a’ i ’b’ tvore jedan C5-8-cikloalkil prsten, ili
R2 i R3, zajedno s atomima ugljika označenim s ’b’ tvore jedan C3-8-cikloalkil prsten, opcionalno supstituiran jednim do četiri atoma fluora ili jednom hidroksi skupinom, ili
R2 i R3, zajedno s atomima ugljika označenim s ’b’ tvore jedan C5-8-heterocikloalkil prsten opcionalno supstituiran jednom metil ili benzil skupinom ili jednom hidroksi skupinom,
- R4 predstavlja vodik ili skupinu alkil(C1-2), ili R4 predstavlja a monociklički aril ili skupinu heterocikličkog arila, opcionalno supstituiranu jednim do tri supstituenata Q kako je gore definirano, ili
R3 i R4, zajedno s atomima ugljika označenim s ’b’ i ’c’ tvore jedan C5-8-cikloalkil prsten, ili
R3 i R4, zajedno s atomima ugljika označenim s ’b’ i ’c’ tvore jedan C5-8-heterocikloalkil prsten opcionalno supstituiran jednom metil ili benzil skupinom,
- R5 predstavlja vodik,
- R6 je odabran između vodika ili jedne skupine alkil(C1-3), opcionalno supstituirane jednim do tri atoma fluora,
- R7 predstavlja jednu monocikličku ili stopljenu bicikličku aromatsku ili hetero-aromatsku skupinu, koje skupine nisu supstituirane ili su supstituirane jednim do pet supstituenata Q, kako je gore definirano, ili
- R7 predstavlja skupinu 2-aril-etenila ili skupinu 2-aril-etinila, ili
R7 predstavlja skupinu piperidinila, ili
R7 predstavlja skupinu 2,3-dihidroindolila ili skupinu benzimidazol-2-jedan.
3. Postupak prema zahtjevu 1, za pripremu spoja čija je formula (I), u kojoj je dio:
[image]
odabran između:
[image]
[image]
[image]
[image]
[image]
- R6 je odabran između vodika ili jedne skupine alkil(C1-3) opcionalno supstituirane jednim do tri atoma fluora,
- R7 predstavlja jednu monocikličku ili stopljenu bicikličku aromatsku ili heteroaromatsku skupinu, koje skupine nisu supstituirane ili su supstituirane jednim do pet supstituenata Q kako je gore definirano, ili
R7 predstavlja jednu skupinu 2-aril-etenil ili skupinu 2-aril-etinil, ili
R7 predstavlja jednu piperidinil skupinu, ili
R7 predstavlja skupinu 2,3-dihidroindolil ili benzimidazol-2-jedan
4. Postupak prema zahtjevu 1, za pripremu spoja čija je formula (I), pri čemu je dio:
[image]
odabran između:
[image]
- R6 je odabran između vodika ili jedne skupine alkil(C1-2) opcionalno supstituirane jednim do tri atoma fluora,
- R7 predstavlja jednu monocikličku ili stopljenu bicikličku aromatsku ili hetero-aromatsku skupinu, koje skupine nisu supstituirane ili su supstituirane jednim ili dva supstituenata odabranih između metil, metoksi, fluoro, kloro, bromo, cijano, acetamido, trifluoroacetamido, trifluorometil, amino ili hidroksi
5. Postupak prema zahtjevu 1, za pripremu spoja čija je formula
[image]
i njegovih tautomera i soli,
a koji uključuje sljedeće korake:
(i) reakciju 2,3-diaza-spiro[4.4]non-2-ena ili 2,3-diaza-spiro[4.4]non-1-ena ili njihovih soli, sintetiziranih na način kako je to otkriveno u patentu WO 2008/034863, s etil izotiocijanatom da bi se dobio, 2,3-diazaspiro[4.4]non-3-en-2-tiokarbonska kiselina etilamid ili njegov tautomer
(ii) reakciju ovog potonjeg s jodometanom ili metil p-toluenesulfonatom čime se dobije N-etil-2,3-diaza-spiro[4.4]non- 3-ene-2-tio-karboksimido-kiselina metil ester,
[image]
(iii) reakciju ovog potonjeg, kao slobodne baze ili njegove soli, sa 4-acetamidobenzensulfonamidom čime se dobije N-(4-{[(2,3-diaza-spiro[4.4]non-3-en-2-il)-etilamino-metilen]-sulfamoil}-fenil)-acetamid
(iv) uklanjanje zaštite ovog potonjeg pod kiselim uvjetima, čime se dobije 4-amino-N-[(2,3-diaza spiro[4.4]non-3-en-2-il)-etilamino-metilen]-benzensulfonamid
[image]
6. Postupak prema zahtjevu 5, naznačen time da se korak (iii) sastoji od reakcije N-etil-2,3-diaza-spiro[4.4]non-3-ene-2-ditiokarbamatna kiselina metil ester sa sulfanilamidom čime se dobije 4-amino-N-[(2,3-diaza-spiro[4.4]non-3-en-2-il)-etilamino-metilen]-benzenesulfonamid:
[image]
7. Spoj čija je formula (IIIa), (IIIb) ili (IV):
[image]
naznačen time da R1, R2, R3, R4 i R5 imaju značenja koja su za njih navedena u zahtjevu 1, kao i tautomeri, stereoizomeri i soli bilo kojeg od njih, pri čemu su ti spojevi korisni za sintezu spojeva čija je formula (I).
8. Spoj prema zahtjevu 7, odabran između onih čije su formule:
[image]
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| US29936310P | 2010-01-29 | 2010-01-29 | |
| EP10152097 | 2010-01-29 | ||
| PCT/EP2011/051100 WO2011092226A1 (en) | 2010-01-29 | 2011-01-27 | Synthesis of substituted pyrazoline carboxamidine derivatives |
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| HRP20140655T1 true HRP20140655T1 (hr) | 2014-10-10 |
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| HRP20140655AT HRP20140655T1 (hr) | 2010-01-29 | 2014-07-10 | Sinteza supstituiranih derivata pirazolon karboksamidina |
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| RU (1) | RU2550694C2 (hr) |
| SG (1) | SG182635A1 (hr) |
| SI (1) | SI2528900T1 (hr) |
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| US4156007A (en) | 1974-07-12 | 1979-05-22 | U.S. Philips Corporation | Pyrazoline compounds |
| US4200641A (en) * | 1976-12-21 | 1980-04-29 | Janssen Pharmaceutica, N.V. | 1-[(Heterocyclyl)-alkyl]-4-diarylmethoxy piperidine derivatives |
| JPS608211A (ja) | 1983-06-28 | 1985-01-17 | Showa Denko Kk | 農園芸用殺菌剤 |
| JPH062742B2 (ja) * | 1987-06-17 | 1994-01-12 | 三井東圧化学株式会社 | 新規２‐ピラゾリン類及びそれを有効成分とする脳血管障害治療剤 |
| SI1373216T1 (en) | 2001-03-22 | 2005-06-30 | Solvay Pharmaceuticals B.V. | 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity |
| KR100950430B1 (ko) * | 2001-09-21 | 2010-04-02 | 솔베이 파마슈티칼스 비. 브이 | 효력있는 ｃｂ1-길항 작용을 가지는4,5-디하이드로-1ｈ-피라졸 유도체 |
| TW200307539A (en) * | 2002-02-01 | 2003-12-16 | Bristol Myers Squibb Co | Cycloalkyl inhibitors of potassium channel function |
| AU2006328483A1 (en) | 2005-12-20 | 2007-06-28 | Solvay Pharmaceuticals B.V. | 4,5-dihydro- (1H)-pyrazole derivatives as cannabinoid CB1 receptor modulators |
| TW200730500A (en) | 2005-12-20 | 2007-08-16 | Solvay Pharm Bv | 4, 5-dihydro-(1H)-pyrazole derivatives as cannabinoid CB1 receptor modulators |
| TWI428334B (zh) | 2006-09-22 | 2014-03-01 | Abbvie Bahamas Ltd | 作為５-ｈｔ6拮抗劑之磺醯基吡唑及磺醯基吡唑啉的甲脒衍生物 |
| WO2009086303A2 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| AR070898A1 (es) * | 2008-03-18 | 2010-05-12 | Solvay Pharm Bv | Derivados de arilsulfonil pirazolin carboxamidina como antagonistas de 5-ht6 |
| RU2374233C1 (ru) | 2008-05-19 | 2009-11-27 | Государственное образовательное учреждение высшего профессионального образования "Российский химико-технологический университет им. Д.И. Менделеева" (РХТУ им. Д.И. Менделеева) | ЗАМЕЩЕННЫЕ 2-ТИОКАРБАМОИЛ-3-ФЕНИЛ-3,3а,4,5,6,7-ГЕКСАГИДРО-2Н-ИНДАЗОЛЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ (ВАРИАНТЫ) И ФУНГИЦИДНАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ |
| TW201010981A (en) | 2008-08-01 | 2010-03-16 | Solvay Pharm Bv | Synthesis of 3,4-diaryl-4,5-dihydro-(1H)-pyrazole-1-carboxamidine derivatives |
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| Publication number | Publication date |
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| RU2550694C2 (ru) | 2015-05-10 |
| CN102725272B (zh) | 2015-07-15 |
| WO2011092226A1 (en) | 2011-08-04 |
| SG182635A1 (en) | 2012-08-30 |
| JP2013518080A (ja) | 2013-05-20 |
| JP5792195B2 (ja) | 2015-10-07 |
| MX2012008798A (es) | 2012-08-17 |
| ES2485891T3 (es) | 2014-08-14 |
| DK2528900T3 (da) | 2014-08-25 |
| SMT201400119B (it) | 2014-11-10 |
| RU2012136831A (ru) | 2014-03-10 |
| PL2528900T3 (pl) | 2014-10-31 |
| AU2011209372B2 (en) | 2015-06-04 |
| AU2011209372A1 (en) | 2012-08-30 |
| US9422244B2 (en) | 2016-08-23 |
| SI2528900T1 (sl) | 2014-09-30 |
| CA2787289A1 (en) | 2011-08-04 |
| US20130060041A1 (en) | 2013-03-07 |
| CN102725272A (zh) | 2012-10-10 |
| WO2011092226A8 (en) | 2012-09-07 |
| PT2528900E (pt) | 2014-08-29 |
| TW201125852A (en) | 2011-08-01 |
| RS53498B1 (en) | 2015-02-27 |
| TWI547485B (zh) | 2016-09-01 |
| EP2528900A1 (en) | 2012-12-05 |
| KR20120129929A (ko) | 2012-11-28 |
| AR079935A1 (es) | 2012-02-29 |
| EP2528900B1 (en) | 2014-06-11 |
| HK1174638A1 (en) | 2013-06-14 |
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