LV10265B - Derivatives of pyridine and pyrimidine, their preparation, pharmaceutical composition and treating method - Google Patents
Derivatives of pyridine and pyrimidine, their preparation, pharmaceutical composition and treating method Download PDFInfo
- Publication number
- LV10265B LV10265B LVP-93-577A LV930577A LV10265B LV 10265 B LV10265 B LV 10265B LV 930577 A LV930577 A LV 930577A LV 10265 B LV10265 B LV 10265B
- Authority
- LV
- Latvia
- Prior art keywords
- hydrogen
- lower alkyl
- halogen
- hjih
- cyano
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 4
- 239000008194 pharmaceutical composition Substances 0.000 title claims 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title 1
- 150000003222 pyridines Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 6
- -1 2-pyrimidyl Chemical group 0.000 claims abstract 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims 24
- 150000002431 hydrogen Chemical class 0.000 claims 15
- 229910052736 halogen Inorganic materials 0.000 claims 11
- 150000002367 halogens Chemical class 0.000 claims 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 6
- 150000001408 amides Chemical group 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 239000001301 oxygen Substances 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- WGNUNYPERJMVRM-UHFFFAOYSA-N 3-pyridylacetic acid Chemical compound OC(=O)CC1=CC=CN=C1 WGNUNYPERJMVRM-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000975 dye Substances 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 208000020016 psychiatric disease Diseases 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 229910052717 sulfur Chemical group 0.000 claims 1
- 239000011593 sulfur Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- BGEBZHIAGXMEMV-UHFFFAOYSA-N 5-methoxypsoralen Chemical compound O1C(=O)C=CC2=C1C=C1OC=CC1=C2OC BGEBZHIAGXMEMV-UHFFFAOYSA-N 0.000 description 1
- 235000017399 Caesalpinia tinctoria Nutrition 0.000 description 1
- 101100366940 Mus musculus Stom gene Proteins 0.000 description 1
- 241000388430 Tara Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 101150067113 prxl2a gene Proteins 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Description
LV10265
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CoeflHHeHM3 c očBenHHeHHbiMH 5-HXg/flA cpoacTBOM, HanpHMep, KJiosannH, OKasuBaioT aHTηπομχοτη^θο κκΗ 3φφθκτ c hh3kož cTeneHbio 3KCTpannpaivO’iBajii>HHX ποΟοηηβιχ βΦΦθκτοβ. KpoMe τογο, 6biJio Hafe-HO, HTO COeflHHeHHH CO CpOflCTBOM K 5-¾ CBH3yi0mHM T^iaCTKaMM B03ļteiicTByK)T Ha aenpeccHBHbie čojiesHM, a Tatoe Ha coctohhhjī SecnoKoftCTBa.
Hjih TepaneBTHqecKnx uejiež βΦΦθκτμβημθ KOJinnecTBa jnoOoro H3 OnMCbIBaeMbK Bbnne <i>apMaKOJIOrHHeCKH aKTHBHHX COeflHHeHHii φορ-Myjiu /1/ MoryT HasHanaTBCH ajih npneMa corjiacHo ο6ηηηημ cnoco-6aM Ha3Ha<jeHHH μ b oābinHbix (J)opMax, Tarax κβκ opajīBHhie cnocočbi Ha3HaqeHHH b BMfle pacTBopoB, 3MyjiBCHiī, eycneH3Hft, nmunanb, TafiJieTOK m Kancyji, b cpapManeBTHnecKH npneMJieMbix HOCHTejiHX, h napsHTepaJiLHO, b φορΜβ CTepHJiBHbix pacTBopoB. Rjm napsHTepajiB-ηογο cnocoāa HasHa^eHMH aKTHBHoro BemecTBa HocHTejieM θκοηηπη-eHTa μο}κθτ 6ητβ cTepHJīBHaa napsHTepajīBHo npneMJieMan κηηκοοτβ, HanpHMep, Bosa, hjim napsHTepaJīBHo npneMJieMoe Macjro, HanpHMep, apaxHHOBOe Macjio.
ΧΟΤΗ θφφβΚΤΗΒΗΗΜΗ HBJIHiOTCH OHeHB HeČOJIBIIIHe KOJIHHeCTBa aK-τηβηβιχ MaTepnaJiOB HacTOHmero H3o6peTeHHH, Koraa peHB HfleT o He3HaynTejiBHOM hjih βτοροοτθπθηηομ jieneHHH hjih b cjiyHaHX Ha3Ha-ηθηηη cy6,BeKTaM c οτηοοητθλβηο hh3khm BecoM Tejia, jtosHpoBaHHbie eflHHHUbl OCblHHO COCTaBJIHiOT OT 2 MMJIJmrpaMM H Bbffiie, npeflnOMTM-TejiBHO 10, 25 hjih 50 MHJiJiHrpaMM hjih fia»e Bbnne, b 3aBHCHM0CTH OT coctohhhh, noflBepraeMoro jieHeHHio, h B03pacTa m Beca nanneH-tob, a TaKJKe οτ οτΒβτΗοή peaKUHH Ha npHHHMaeMoe JieKapcTBo. - 7 - LV10265 CTaHflapTHaa ao3a MoaceT coctcibjihti> ot 0,1 so 100 mmr-paMM, npeino^THTejibHO ot 10 ro 50 MHJUnurpaMM. HHeBHaa mjih cy-TO^Haa fl03a npefliio^TMTeJibHO KOJiečJieTcsi ot 10 MHjmurpaMM ro 200 MHJUIHrpaMM. TOUHbie HHflHBMflyaJIi>HUe B03MP0BKH, a Tara© CyTOMHhie fl03bl, ΚΟΗΘ^ΗΟ, OnpefleJIfliOTCH B ΟΟΟΤΒΘΤΟΤΒΗΜ CO CTaHaapTHHMH Me-flHiiHHCKHMH npHHiiffliaMH no yKa3aHHio Bpa<ia HJiH BeTepHHapa.
Cnocočbi noJiyqeHKH.
CoeflMHeHHH, MMejomne o6myio $opMyjiy /1/, MoryT 6htī> nojiy^e-Hbl C ΠΟΜΟΠφΙΟ o6biqHbix cnocoāoB.
CnocoG 1
R
η/'\—A
R & A / (C%)*
II III
CoeflHHeHHe ($opMyjihi /11/, b κοτοροζ R,, R^h X ημθιοτ 3Haqe-hhh, yKa3aHHHe paHee, μ Y npeflCTaBJiHeT coGoft noflXOflHinyio yaajiH-eMyio rpynny, TaKyio KaK raJioreH h ajiraui - mm apHJicyjib$oHaT, noflBepraeTca B3aHMOflefteTBHio c οοθληηθημομ $opMyjibi /111/, b ko- - 8 - τοροΑ , . R^, A un ημθιοτ 3HavieHHH, onpesejieHHbie Bume. PeaK-IIHH MoryT ocjnnecTBJiflTLCH c McnoJii>30BaHHeM cTaHflapTHbK πρηθμοβ N- anKMJmpoBaHHH.
Cnocoā 2
CoeflHHeHHe Φορμυλη /IV/, b κοτοροΗ R/, R^, Rj, R^, X h n ημθιοτ 3Ha^eHMH, onpeaejieHHbie paHee, noflBepraeTca B3anM0flež-CTBHIO C ΟΟΘΑΗΗΘΗΗΘΜ 4>OpMyjIH /V/, /VI/ HJIH /VII/, ΓΑΘ Rj-, R^ H R^ ημθιοτ 3HaHeHHH, onpeaejieHHhie Bhinie, η Z npeacTaBJifleT cočoiī - 9 - LV10265 yflattHeMyio rpynny, HanpHMep, γ&πογθη. ΠΡΜΜΘΡΗ
Cjieiyiomne mm npHMepu npeflHa3HaqeHH ajih mjijiioctpaunu, ho ΗΘ flJIH OrpaHH^eHMH ΟΌΊ£Μ& Μ30δρΘΤΘΗΙΪΗ, ΧΟΤΗ Ha3BaHHbie COe^HHe-hhs npeflCTaBJiHioT ocočeHHHM HHTepec j[jih npeflHa3Ha^eHHUX HaMH iļejteū. 3th οοθ^μηθημη očo3HaqeHhi κοαοβημη HOMepaMH, a: b, rae a 03HaqaeT ηομθρ npMMepa, b κοτοροΜ onncuBaeTca nojiyqeHne coeflH-ΗβΗΜΗ, 0 KOTOpOM ΜβθΤ peqb, H B OTHOCHTCH K nOpaflKOBOMy HOMepy coeflMHeHHH, ο κοτοροΜ μαθτ peqt, nojiyqaeMoro corjiacHo aaHHOMy npnMepy. TaK, eoeanHeHne 1:2 03HaqaeT BTopoe coesMHeHne, nojiy-^θηηοθ corjiacHo IIpHMepy 1. CTpyKTypH eoeaHHeHHtf noflTBepjftiaiOTCH c πομομ aHajW3a HMP, MacccneKTpoB μ βλθμθητηογο aHajm3a. Roraa aaiOTCH to^kh njiaBJie-HHH, OHH flBJIHIOTCH HeCKOPpeKTMpOBaHHfcJMM. ΠρΗΜβΡ 1 4-/4( π-φτορφθΗΚΗΐ) 6yrnji/-1-(2- impuanJi) imnepa3iiH^yMapaT. 6,0 r /0.0323 mojih/ 4-/π-φτορφθΗΐυι/6yTHJix Jiopnaa, 5,3 r /0.0323 mojih/ nnpHj[MJinHnepa3HHa, 5,2 r KapāoHaTa HaTpMH h 0,1 r žofla HarpeBaJiocB βμθοτθ c 25 mji KCHJiojia npw 150°C (TeMnepa-Typ MacjiHHOž CaHH) b τθ^θημθ 20 qacoB. ·
Docjie 0XJia3KfleHHH peaKUMOHHož cmpcm ao npnāJM3iiTejii>H0 100° 0, aoāaBJisjiocī) 50 mji TOJiyojia, h CMecb $MJH>TpoBajiacii. K (jMJītTpa-Ty aodaBJiHJiocb 25 mji npocToro 3φκρ3. OpraHEraecKHū pacTBop npo-MbiBajicH tph pa3a 25 mhjijihjihtpaMH Boaa, h HaKOHep oanH pa3 25 MJI-MH HaCbmeHHOrO paCTBOpa XJIOpHCTOrO HaTpHH. - 10 - ynapwBaHMe pacTBopuTejieft flaBajio ηθο^μιρηηοθ ocHOBaHMe, κοτοροβ KpHCTajuiM30Bajiocb c wcnojii>30BaHHeM UHKJioreKcaHa. To^Ka nJiaBJieHHfl nojijnjeHHoro cBoāoflHoro οοηοββημη cocīaBJiHeT 57-58°C. CBOČOflHOe OCHOBaHMe 3aTeM paCTBOpfīJIOCb B CMeCH 3Ta-HOJl/npOCTOŽ 3<J)Hp, H C ΠΟΜΟΠφΚ) H36bITKa <£yMapOBOft KMCJIOTbl B 3Ta-HOJie ocajKflajicH $yMapaT.
IlepeKpMCTajiJiH3amīH m STaHOJia saBajia 4,8 r ue-neBoro coe-ίΙΗΗβΗΗΗ /1:1/, Τ.ΠΧ 160-161° C. IIpKMep 2 ŪHXJioprHflpaT 4- /4- (π- φτορφθnm) 6yTH ji/- 1 -/2- (3- KapāaMHJimī-PHflHJl) /nnnepH3HHa. 5,9 r /0,025 mm/ 1-/4-(π-φτορφθΗΐυι)6yTHJi/nHnepM3HHa, 3,9 r /0,025 mm/ amm 2-xjiophhkgtmhobok khcjioth k 3,1 r KapāoHaTa ηβτρηη HarpeBajmcb c oāpaTHUM χολοζιμλβηηκομ βμθοτθ c 20 mji TOJiyojia b Te^eHHe 20 qaeoB. · nocjiel pxjiajiifleHMH nojiymīiaei> TBepflas cMect, KOTopaa pacT-Bopsjiacb c Mcnoji£>30BaHneM STHJianeTaTa η βολή. Tojiyoji /aTMJiape-TaTHan $a3a OTKejrajiacB, a saīeM npoMbiBajiacb boaoh w pacTBopoM x.nopncToro HaTpMH, a 3aT6M cymnjiacb cyjib$aTOM ηβτρηη.
BbinapHBaHHe pacTBopHTejieft flaBano ηθο^ηπιθηηοθ eBoāojtHoe ocHOBaHMe, κοτοροβ nepeKpncTajLnn30BbiBajiocb m TOJiyojia. IIojiy- o ^eHHoe CBoāoflHoe ocHOBaHMe njiaBHJiocL· npH 135-136 C. 5 Γ CBOČOflHOrO OCHOBaHHSĪ paCTBOpHJIOCb B STaHOJie, H HSČUT-kom cojihhož khcjiotu b STaHOJie ocajKaancfl anxJioprMflpaT. Πβρβκ-pncTajuiH3auHH aasajia 3,0 r uejieBoro coeHHHeHMH /2:1/, t.īijl 210-213° C. - 11 - LV10265 ΠρΗ HCII0JIi>30BaHHH B OCHOBHOM ΤΟΪΪ jKB ΠρΟΙίΘΗΥΡΗ nOJiyqaiOTCH ♦ cJieflyK)inne coeflHHeHHH (Bhme JieHHbie μ οπμιιι,θηηειθ c πομοιικιο mtho-
BeHHOft XpOMaTOrpa0MM B BHfle MHCTOrO OCHOBaHHH HJIH B BMfle COOT- ΒβΤΟΤΒγίΟΙΙίΗΧ COJieŽ) M3 COOTBeTCTByiOII]JIX hcxoothx MaTepnajioB. 2: 2 4-/3-( π-φτορφθΗΟΚΟΗ) προπηλ/-1-/6-χλορ-2-πηρηληλ/πη-
nepa3HH-xjiopri!j[paT, τ. πλ. 185-186°C 2:3 nojiyrimpaT XJfopriiflpaTa 4-/3-(π-φτορφΘΗθκοΜ)προπΗ.π/-
l-/2-nHpHMMflMJi/niinepa3HHa3 τ. nx 208-210° C 2:4 iHXJioprnflpaT 4-/3-(π-φτορφθΗθΚθΗ)προπΜ/-1-/2-πΐφΗ- o
flHJī/nHnepa3KHa, τ. πλ. 240-242 C 2:6 xjioprnflpaT 4-/4-( π-φτορφθΗΐυι)6γτίυι/-1-/2-πΐφΗΜΗΛΐϋϊ/ nHnepa3HHa, τ. πχ 197-198° C
2:7 $yMapaT 4-/4-( π-φτορφβΗΡυι) 6yTHJi/-l-/2-nMpMflMJi/nnne-pa3HHa, τ. itjī. 160-161° C 2:8 xjioprHflpaT 4-/3-( π-φτορφβΗΟΚΟΜ) προπΜ/-1-/3- ΗΗτρο- 0
-2-nnpn«MJi/-nHnepa3HHa} τ. πχ 182-183 C 2: 9 xjīopmflpaT 4-/4-(π-φτορφθΗΜ) 6yTHJi/-l-/6-xjiop-2-nH-
PHflMJi/nHnepasHHa, τ. πχ 150-151° C 2:10 (£yMapaT 4-/3-( π-φτορφΘΗοκοιΟπροπίϋΐ/-1-/6-μθτοκοη-2- © nHpnaiui/-nHnepa3HHa, τ. πχ 185-186 C 2:11 oKcajiaT 4-/3-(n-(J)Top(jpeHOKCM)nponnji/-l-/3-Kap5aMMJi-2 -nHpHflHx/-/l, 4 flHa3aiļHKJiorenTaHa/, τ. πχ 148-150 C /ocHOBaHHe, τ. πχ 140-141° 0/
2:12 nojiyH3onponaHOJi-nojiyrHapaT EHXJiopnmpaTa 4-/4-(π-$Top(|)eHHJi)-6yTHJi/-l-/3-3TOKCH-2-niipHflHJi/nHnepa3HHaJ τ.πχ. 168-169° C 2:13 l,5-$yMapaT 4-/3-(n-$Top$eHOKCn)nponnx/-l-/3-Kap6a- 12 -
Mmi-2-nHpnfliiJi/-2,5-TpaHCflMMeTHJinMiiepa3HHa, τ. πλ. 172-173 C /ocHOBaHMe, T. njl. 115-116°C / 2:14 (§yMapaT 4-/4-(n-(|)Top(i)eHO)6yTHJi/-l-/6-MeTKJi-2-impM-^PiJi/nHnepasHHa, τ. ilu. 172-173° C 2:15 jiHXJioprMj[paT 4-/3-(n-flM$Top$eHOKCH)nporoiJi/-l-/6-Me-THJi-2-nHpHflHJi/nHnepa3HHa, pa3Ji. 230°C 2:15 1,5 xjioprnapaT 4-/3-( π-ΑΗφτορφβΗοκοΐϊ) nponHJi/-1-/3-/ N-M6THJiKapāaMiiJi/-2-nnpMflMJi/nMnepa3MHaJ τ. iijl 211-213°C 2:17 flnxjioprHflpaT 4-/3-(n-$Top$eHOKCM)nporoiJi/-l-/3-riīfl-poKCH-2-nHpHflHJi/nHnepa3K[Ha, τ. πχ 240°C /ocHOBaHMe τ. īiji. 105° C/ 2:18 xjioprMflpaT 4-/3-( π-φτορφθΗΟΚΟΗ)προπΗΛ/-1-/327τρΗφτορ- · MeTHJi-6-xjiop-2-nHpHflHJ[/nHnepa3HHa, τ. nji. 190°C 2:19 OTJioprHflpaT 4-/3-(π-φτορτΗοφΘΗΟκοΐί)npormJi/-l-/3-Kap-6aMHJi-2-nHpHflHJi/nHnepa3iiHa, τ. m. 205°C 2:20 ļ[HXJioprHflpaT 4-/3-(π-φτορτΜθφΘΗθκθΗ)προπιυι/-1-/2-ΠΗ-pHflHJi/nirinepa3WHa, τ. nji. 150°C 2:21 4-/3-( π-φτορφβΗοκοΗ) nponiiJi/-l-/5-Mop$ojiiiHOKap6oHHJi-2
- nHPOT JI./nffiiepa3HH
2: 22 4-/4-(π-φτορφθΗΐυι)6yTMJi/-l-/3-nwnepHflHHOKap(5oHiiJi-2-impHflHJi/nHnepasHH ΠρΗΜβρ 3
CpoflCTso k 5-HTj, peuenTOpaM AHaJiHS CES3bIBaHHH ocymeeTBJifleTCH B OCHOBHOM, KaK OnHCaHO aBTopaMM Leysen et. al./Mat. Pharmacol. 21, 301-14, 1982/ e ηοπολβ30Β3ημθμ ’^Η-KeTaHcepnHa b Ka^ecTBe JiMraHfla. - 13 - LV10265
TaGaupa 1
CoenHHeHHe
Ki /Hm/ 2:9 7 2:10 11 2:19 7
CoeflHHeHHH, nepe^HCJieHHbie b TačJiime 1, saiorcH He c pejijbio OrpaHH^eHHH HMH flaHHOIO Η3θ6ρΘΤΘΗΗΗ, a flJIH HJUUOCTpaiBiH ΙφΗΜβ-POB n0Jie3H0Ž $apMaKOJIOrwqeCKOŽ aKTHBHOCTH COeSHHeHMH, OXBaTH-BaeMbK ΟδΐβΜΟΜ φορΜΥΛΗ /1/. ĪIPHMep 4 C'JiefljriomHe mm npenapaTHBHue φορωω hbjihiotch xapaKTe phhmh npe^CTaBHTejiHMii ajia Bcex $apMaKOJioriiqecKn aKTHBHUx coeflHHeHHft SaHHoro H3o6peT6HMH. ΠρκΜβρ īiqmoww$i KancyjmHOK npenapaTMB-HOŪ φορΜΗ:
Ha Kancyjiy, mt
Akthbhhā MHrpaflueHT b βη^θ cojih JīaKT03a KpaxMaji CTeapaT MarHHH Bcero 10 250 120 5 385 B cjiyqae Gojibinero KOJnraecTBa βκτηβηηχ ηηγpafluehtob kojm-qecTBo jiaKT03H μοαθτ čutb οηιβκθηο. ĪIpHMep noflxoi[flmež npenapaTHBHOft φορΜΗ b BMfle TaāJieTOK: - 14 -
Ha Kancyjiy, mt AKTHBHblft HHrpajlHeHT B BHfle COJIH 10 ^ρΤΟφβΛΒΗΜΖ KpaXMaJI 90 KOJIJIOMitHaH 5ByOKHCi) KPeMHHS 10
TanBK 20 CīeapaT MarHHff 2 5% ΒΟίΗΗή pacTBop JKBJiaTHHa 25
Bcero · 157
PacTBopH flJiH napaHTepaJiLHoro πρημθηθηηη c πομοπιβκ) ηηϊ>θκ-um MOryT npHrOTaBJIHBaTBCH B BOflHOM paCTBOpe paCTBOpHMOŽ B Bo^e $apMaueBTHqecKH npHeMJteMOft cojih aKTHBHoro BemecTBa npefl-no^THTejtbHO b KomjeHTpamin npHMepHO ot 0,5% flo 5% no Becy. 3th pacTBopu MoryT TaKJKe coaepjfjaTL CTa6miH3Hpyioinne areHTbi h/hjih 6y$epnpyKimne areHTbi h Moryr y,zio<5HO npeflocTaBJiHTbCH b pa3jmmibix fl03npoBaHHbix aMnyjiax. - 15 -LV 10265
ΦΟΡΜΥΛΑ M30BPETEHMH 1. Ηοβηθ coeflHHeHHH, HMeroimae oāmyio φορΜ?^ /1/
N—A (1) rae Rf npescTaBJiiīeT coāoft rajioreH hjim Boaopofl, h npescTaBJineT co6oft rajioreH; X npescTaBJisieT coGoft hjih KHCJiopoa, mh cepy hjim ΜβτΗΛβΗ; H R^ HBJIHIOTCfl OJ[MHaKOBtIMH HJIM pa3JIHHHHMH H BHāHpaiGTCiī H3 BOflopofla h HH3niero ajirama; n npejiCTaBJifleT co6ož 2 mm 3;
A BhldupaH M3 CJieHyKDIH,HX IIMpMMHHM JLb HhIX HJIM nMpHHHJrbHbK rpynn:
me R^BHāpaH H3 BOflopofla, HH3niero ajiKHJia mjih rajioreHa;
Rg H Rj HBJIHIOTCH OflHHaKOBbIMM HJIM paSJIH^HHMH H BblČMpaiOTCH H3 Bojiopofla, rajioreHa, HH3inero aJiKHJia, 3JieKTpoHo-,noHopHHX rpynn, Τ3ΚΗΧ KaK aJIKOKCH HJIM rHflpOKCH, 3JieKTp0H0-aKUenT0pHbIX - 16 - rpynn, τβκηχ KaK ijHaHO, ΗΗτρο, τρκφτορΜΘΤΗΛ, COORRj., CONR^R^ hjih CO-B; rse R^> npeflCTasjiseT cočofī Bouopon hm ΗΗ3ΐιΐΗή suhkhji; H R HBJISIIOTCH OflHHaKOBbIMH HJIH pa3JIHHHbIMH H BblČHpaiOTCfl H3 BO" jļoņona, HH3mero aJiKHJia h ijHKJīoajiKHJia; B npe^cTaBJineT cočofl rpynny, Bbi6paHHyio H3
0 me m npeflCTaBjračT cočoft 1, 2, 3 hjih 4, R// BblāpaH H3 BOflOpOfla HJIH ΗΗ3ΙΠΘΓΟ anKHJia, H HX ģapMarcojio-γη^θοκη npHeMJieMbie cojih. 2. CoeflHHeHHH, no n.lf b KOTopbK Ry npeflCTaBJiHeT coāoii bo-flopoi, a R npejicTaBJineT ranoreH, npeflno^THTejibHO, φτορ. 3. CoejiHHeHHH no n.l h 2, b κοτορυχ n=2. 4. ΟΟΘΑΗΗΘΗΗΗ ΠΟ Π. 1 HJIH 2, Β ΚΟΤΟΡΗΧ Rj H Ry- npeflCTaBJIH-iOT C000H BOJIOpOJI HJIH MeTHJI, npeflnOHTHTeJIBHO BOflOpOfl.
5. CoenHHeHHH no n. 1,2 hjih 3, b KOTopbix A npencTaBJineT coGoii
- 17 - LV10265 6. Οοθβηηθηηη no π. 4 ο τ ί h tj a io nu e c η τθμ, ^to R6
npe^cTaBJineT codotf bobopob, amm, τρΗφτορΜβτΜΛ, anKOKcn, aMHfl, rnapoKcn, KapāoKcn, hhtpo hjim unaHO, h R^ npencTaBJineT BOJIOpOfl, aJIKHJI, aJIKOKCH, ΓΗ,ΚΡΟΚΟΗ, HHTpO, raJIOreH, KapČOKCM, nnaHo mjih aMMflHjno rpynny. 7. Οοθβηηθηηη no juodOMy M3 n. n. 1-6, b κοτορπχ X npe^cTaB-jiaeT coooh khcjiopob mm ΜβΤΗΛβΗ. 8. ΟοβΛΗΗβΗΗΗ no π. 5, b κοτορΗχ R$ npeacTaBJiHeT codoiī bo-flOpOfl, aJIKHJT Μ.Ή* ΤρΗφΤΟρΜΟΤΜ, R? npOBCTaBJIHeT aJIKOKCH, BOflO-ροΒ, ΓΜΒροκοΗ, ΗΜτρο, rajioreH, iinaHo hjih aMHflHyjo rpynny h R pacnojio;fieH b S-nojio^eHini. 9. 0θθ£ΗΗΘΗΗΗ ΠΟ JIK3ČOMy H3 ΠΠ. 1-8, B KOTOpbIX 'X npeflCTaB- jineT coooii raicjiopoa. 10. CoefljffleHHH no n.6, b KOTopbix R6 npeflCTaBJiHeT codoft ΒΟΒοροΒ, h R? npeBCTaBjmeT codotf bobopob, nnaHo, hhtpo, ajiKOK-CH, aJIKHJI, rHflpOKCH HJIM aMHflHhlft 3aM8CTHT6JLb. 11. Οοθβηηθηηη no n. 7, b κοτορπχ R^ npencTaBJiHeT codoft aMHB, ΓΗΒΡΟΚΟΗ, BOBOPOB, MCTHJI, UMaHO HJIH ΜΘΤΟΚΟΜ 3aMeCTMTeJIi>. 12. Cnocod nojiyneHHfl coejtHHeHHiī, ημθιοιιιμχ odniyio $opMyjiy /1/
R^ Λ - 18 - rjļe Rj npeacTaBJiHeT cočoft ranoreH hjih bojiopoji, h npeflCTaBJiHeT coāotf rajioreH;
Rj H R^ HBJIHIOTCfl OflHHaKOBbIMH HJIH pa3JIH*JHbIMH H BblfiUpaiOTCH m BOflopojta η HH3uiero ajiKHJia; n npe^CTaBJiHeT co6ož 2 hjih 3; A BblČUpaH H3 CJieiīyiOmHX IIHpHMHilHJIBHbK HJIH IIHpHJIHJIbHbDC rpynn:
rjie R^ Bbičp'aH H3 Bojiopojia, HH3inero ajiKHJia hjih rajioreHa; Rč- H R^ HBJIHiOTCfl OJIMHaKOBblMH HJIH paSJIH^HblMH H BbIČHpaHbl H3 BOflOpOfla, rajioreHa, ΗΗ3ΙΠΘΓ0 aJIKHJia, 3JieKTp0H0-H0H0pHbIX rpynn, TaKHx KaK ajiKOKCH hjih γηζιροκοη, 3JieKTp0H0-aKiienT0pHhix rpynn, TaKHX KaK iinaHO, ΗΗτρο, τρπφτορΜβτρυι, COORR^, CONf^ R/0 hjih CO-B; rae Rj npejļCTaBJiHeT coāoft Boaopoji hjih HH3iiiHft anKHJi; R^ H Ri0 HBJIHKDTCH OflHHaKOBbIMH HJIH pa3JIHHHbIMH H BblČHpaHbl H3 BO~ «opojia, HH3iuero aJiKHJia h UHKJioajiKHJia; B BHČpaK H3: *41
R
H
- 19 - Λ LV10265 rfle m'npeflCTaBjraeT co6o$ 1, 2, 3 vum 4, R,t BbiāpaH M3 Bonopojia μη HH3mero anKHJia, h mx (JiapMaKOjio-nraecrai θκτμβηηχ cojietf, OTJiH^aioniificH tģ.m, <ito -coe-ΛΗΗθΗΜθ, MMeromee o6myio φορΜγζγ /11/
R R,
II b κοτορο# R^ m μμθιοτ 3HayeHm, onpeaejieHHbie Bbime, η Y npene-TaBJiaeT coGofl yaajiHeMp3 rpynny, nojtBepraioT B3aHMOfle#cTBKio c coeflHHeHJieM, HMeramnM o6myio (i»pMyjiy /111/
III - 20 - rite Rj, R^r, η η A μμθιοτ sHa^eHHH, onpejiejieHHbie βηιιιθ; mjim coe-Βμηθημθ, MMeioinee o6inyio $opMyjiy /IV/
rzie R/ . % , R, , μ η μμθιοτ 3Η8ΜΘημη, οπρθλθλθηηηθ paHee, nOflBepraiOTCH BSaMMOfleMCTBHIO C ΘΟΘβΜΗΘΗΜΘΜ, ΜΜΘΙΟΠΙΜΜ (jOpMyJiy /V/, /VI/ mjim /VII/:
V VI VII Γββ Rj-, R^ h R^ μμθιοτ 3HaweHHH, onpe^eJieHHbie paHee, μ Z npej*-cTaBJineT co6om y,qajiHeMyio rpynny.
13. ^apMaueBTMMecKaH κομπο3μημη, OTO^aioiiascH
*S LV 10265 - 21 - τθμ, ήο 0Ha co,iiep»HT b Ka^ecTBe βκτμβηογο HHrpaflueHTa οληο jmim 6ojiee coeOTHeHHtf, MMeioimix o<5myio ($opMyjiy /1/, npejpio^TH-τθλβηο BMecTe c t&apMapeBTimecKM npneMJieMbiM HocHTejieM, h, ecjiM Heo6xoflHMo, flpyrwM $apMaKOJiorM^ecKH aKTMBHbie areHTti. 14. Cnocoā jieqeHHH jKMBbDc cymecTB, eTpaaaiomiix ot ncxxmec-khx paccTpoiicTB, oTO'iaioiiiHiica τθμ, ήό yKa3aHH0My jKHBOTHOMy Ha3HaqaKDT mh npneMa οοθαμηθηηθ, HMeromee o6myio φορ-Myjiy /1/. - 22 - LV10265 ΡΕΦΕΡΑΤ
HacToamee H3o6peTeHHe KacaeTcn ηοβηχ οοθαπηθημη oOineft Φορμυλη
r;n;e R/ - ranoreH hjih Boaopofl, hR^- rajioreH; X - hjih KHCjiopofl, hjih cepa, hjih μθτηλθη, 1¾ H Ry HBJĪHHjTCH OJJHHaKOBblMH HJIH paSJIHHHblMH H BbldpaHbl H3 Bojtopoia h HHsmero ajiKHJia; n npeflCTaBJHieT cočoū 2 hjih 3;
A BblānpaH H3 CJiejiyiOIIIHX' ΠΗρΗΜΗί(ΜΒΗΗΧ HJIH ITHPHZIHJLb HbIX rpynn:
rne R^- BbīdpaH H3 Bonopozta, HH3iuero ajiKHJia hjih rajioreHa; Rč M R^ HBJIHIOTCH OflHHaKOBbIMH HJIH pa3JIHHHbIMH H BblCHpaHbl H3 BOflopofla, rajioreHa, HM3tuero ajiKHJia, 3JieKTpoHO-noHopHbix - 23 - rpyrm, TaKHX KaK HiranmĀ anKOKCH hjih γηπροκοη, 3JieκτροΗθ-aKueπ-το ρηηχ rpynn, TaKMX KaK unaHO, ηητρο, τρΗφτορΜβτΗΛ, COORR^, CONR^R^ hjih CO-B; rne R^ npejicTaBJiHeT cočoft BOflopofl hjih HH3iimfi aJIKHJI; Re, H Rf0 HBJIHIOTCH OHHHaKOBblMH HJIH paSJIHHHhIMH H BblGHpaHhl H3 BOflOpona, ΗΗ3ΙΙΙ6ΓΟ aJIKHJia H JļHKJIOaJIKHJia; B BbīGpaH H3:
R // /
—N \ 0 rae m npeflCTaBJiHeT cočoii 1, 2, 3 hjih 4. R// BblOpaH H3 BOJIOpOfla HJIH ΗΗ3ΙΠΘΓ0 aJIKHJia, Η HX $apMaKOJIO-γη^θοκη aKTHBHbix cojieiī. Ηοββιθ οοθπηηθηηη nojie3Hbi hjih jie^eHHH ποηχη^θοκηχ paccT-poiĪCTB.
Claims (14)
- LV10265 IZGUDROJUMA FORMULA PIRIDIL - UN PIRMIDIL-ATVASINĀJUMI, TO IEGŪŠANAS PAŅĒMIENS, FARMACEITISKĀ KOMPOZĪCIJA UN ĀRSTĒŠANAS METODE 1. Jaunie savienojumi ar vispārēju formulu IN-A kur R-j ir halogēns vai ūdeņradis, un R2 ir halogēns; X ir skābeklis, vai sērs, vai metilēngrupa; R3 un R4 ir vienādi vai dažādi un ir izvēlēti no ūdeņraža un zemākās alkilgrupas; n ir 2 vai 3; A izvēlēts no sekojošām pirimidila vai piridila grupām:kur R5 izvēlēts no ūdeņraža, zemākās alkilgrupas vai halogēna; Rg un R7 ir vienādi vai dažādi un tiek izvēlēti no ūdeņraža, halogēna, zemākās alkilgrupas, elektronu-donoru grupām, tādām kā alkoksi- vai hidroksigrupa, elektronu-akceptoru grupām, tādām kā ciano,- nitro,- trifluormetilgrupa vai - COORg, - CONRgRļg vai CO-B, kur Rg ir ūdeņradis vai zemākā alkilgrupa; Rg un Rļo 'r vienādi vai dažādi un ir izvēlēti no ūdeņraža, zemākās alkil- un cikloalkilgrupas; B ir grupa, kas izvēlēta noN (CHa)m — NOkur m ir 1, 2, 3, vai 4, / 2 Rļ ļ izvēlēts no ūdeņraža vai zemākās alkilgrupas, un to farmakoloģiski pieņemami sāļi.
- 2. Savienojumi, pēc 1. p-ta, kuros Rļ ir ūdeņradis, bet R2 ir halogēns, dodot priekšroku fluoram.
- 3. Savienojums pēc 1. un 2. p-ta, kur n=2.
- 4. Savienojums, pēc 1. un 2. p-ta, kuros R3 un R4 ir ūdeņradis vai metilgrupa, dodot priekšroku ūdeņradim.
- 5. Savienojumi pēc 1., 2. vai 3. p-ta, kuros A atbilst formulai N R.
- 6. Savienojumi, pēc 4. p-ta atšķiras ar to, ka Rg ir ūdeņradis, alkil-, trifluormetil-, alkoksi-, amīd-, hidroksi-, karboksi-, nitro- vai cianogrupa, un R7 ir ūdeņradis, alkil-, alkoksi-, hidroksi-, nitro-, halogēn-, karboksi-, ciano- vai amīda grupa.
- 7. Savienojumi, pēc jebkāda no p-tiem 1-6, kuros X ir skābeklis vai metilēngrupa.
- 8. Savienojumi, pēc 5. p-ta, kuros Rg ir ūdeņradis, alkil- vai trifluormetilgrupa, un R7 ir ūdeņradis, hidroksi-, karboksi-, nitro-, halogēn-, ciano- vai amīda grupa, un R7 ir izvietots 3-stāvoklī.
- 9. Savienojumi, pēc jebkura no p-tiem 1-8, kuros X ir skābeklis.
- 10. Savienojumi, pēc 6. p-ta, kuros Rg ir ūdeņradis, un R7 ir ūdeņradis, ciano-, nitro-, alkoksi-, alkil-, hidroksi- vai amīda aizvietotājs.
- 11. Savienojumi, pēc 7. p-ta, kuros R7 ir amīd-, hidroksigrupa, ūdeņradis, metil-, ciano- vai metoksi- aizvietotājs.
- 12. Savienojumu, ar vispārējo formulu (I) kur Rļ ir ūdeņradis vai halogēns, un R2 ir halogēns; R3 un R4 ir vienādi vai dažādi un tiek izvēlēti no ūdeņraža un zemākās alkilgrupas; n ir 2 vai 3; A izvēlēts no sekojošā piramidila vai piridila grupām: 3 LV10265‘7 β kur R5 izvēlēts no ūdeņraža, zemākās alkilgrupas vai halogēna: Rg un R7 ir vienādi vai dažādi un izvēlēti no ūdeņraža, halogēna, zemākās alkilgrupas, elektronu-donoru grupām, tādām kā zemākā alkoksi- vai hidroksigrupa, elektronu-akceptoru grupām, tādām kā ciano-, nitro-, trifluormetilgrupa, - COORg, -CONRgRļo vai CO-B; kur Rg ir ūdeņradis vai zemākā alkilgrupa; Rg un Rj q ir vienādi vai dažādi un izvēlēti no ūdeņraža, zemākās alkil- un cikloalkilgrupas; B izvēlēts no-N (CH2)m —NO kur m ir 1, 2, 3 vai 4, R-ļ 1 izvēlēts no ūdeņraža vai zemākās alkilgrupas, un to farmakoloģiski aktīvo sāļu iegūšanas paņēmiens atšķiras ar to, ka savienojumi ar vispārējo formulu (II)kurā Rļ un R2 ir augšminētās nozīmes, un Y ir atdalāmā grupa, pakjauj savstarpējai iedarbībai ar savienojumu, kurai vispārēja formula (II)HNN-A 4 kur R3, R4, n un A ir augšminētās nozīmes, vai savienojumu, kuram vispārēja formula (IV) r3 R, R2/A xch2ch2ch2-n nh kur Rļ, R2, R3, R4 un n ir augšminētās nozīmes, pakļauj savstarpējai iedarbībai ar savienojumu, kuram ir formula (V), (VI) un (VIII):kur R5, Rg un R7 ir agrāk minētās nozīmes un Z nozīmē atdalāmo grupu.
- 13. Farmaceitiskā kompozīcija atšķiras ar to, ka tā satur kā aktīvo ingradientu vienu vai vairākus savienojumus, kuriem vispārējā formula (I), dodot priekšroku kopā ar farmaceitiski pieņemamu nesēju, un, nepieciešamības gadījumā, ar citu farmaceitiski aktīvu aģentu.
- 14. Dzīvo būtņu ārstēšanas paņēmiens, kuras cieš no psihiskiem traucējumiem, atšķiras ar to, ka dotā dzīvnieka ārstēšanai nozīmē savienojumu ar vispārējo formulu (I).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8803429A SE8803429D0 (sv) | 1988-09-28 | 1988-09-28 | Novel pyridyl- and pyrimidyl derivatives |
| HU895103A HU203232B (en) | 1988-09-28 | 1989-09-28 | Process for producing new pyridyl and pyrimidinyl derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LV10265A LV10265A (lv) | 1994-10-20 |
| LV10265B true LV10265B (en) | 1995-08-20 |
Family
ID=26317811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LVP-93-577A LV10265B (en) | 1988-09-28 | 1993-06-15 | Derivatives of pyridine and pyrimidine, their preparation, pharmaceutical composition and treating method |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US5034390A (lv) |
| EP (1) | EP0361271B1 (lv) |
| JP (1) | JP2857693B2 (lv) |
| KR (1) | KR930007413B1 (lv) |
| CN (1) | CN1028756C (lv) |
| AT (1) | ATE97665T1 (lv) |
| AU (1) | AU616307B2 (lv) |
| CA (1) | CA1337417C (lv) |
| DD (1) | DD290884A5 (lv) |
| DE (1) | DE68910922T2 (lv) |
| DK (1) | DK171133B1 (lv) |
| ES (1) | ES2060709T3 (lv) |
| FI (1) | FI94629C (lv) |
| HU (1) | HU203232B (lv) |
| IE (1) | IE62790B1 (lv) |
| IL (1) | IL91701A (lv) |
| LT (1) | LT3549B (lv) |
| LV (1) | LV10265B (lv) |
| NO (1) | NO174667C (lv) |
| NZ (1) | NZ230743A (lv) |
| PH (1) | PH27039A (lv) |
| PT (1) | PT91826B (lv) |
| RU (1) | RU2021269C1 (lv) |
| SE (1) | SE8803429D0 (lv) |
| ZA (1) | ZA897404B (lv) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5219855A (en) * | 1988-01-29 | 1993-06-15 | Mitsubishi Kasei Corporation | Anxiolytic drug |
| IE911774A1 (en) * | 1990-06-11 | 1991-12-18 | Akzo Nv | Pyridinylpiperazine derivatives |
| US5166148A (en) * | 1990-07-09 | 1992-11-24 | The Du Pont Merck Pharmaceutical Company | 2-amino-1,4-dihydropyridine derivatives with calcium agonist and alpha1 -antagonist activity |
| US5270312A (en) * | 1990-11-05 | 1993-12-14 | Warner-Lambert Company | Substituted piperazines as central nervous system agents |
| SE9201956D0 (sv) * | 1992-06-25 | 1992-06-25 | Kabi Pharmacia Ab | Novel nicotinicacid esters |
| PL180899B1 (pl) * | 1994-09-30 | 2001-04-30 | Pfizer | Nowe pochodne 2,7-podstawionej oktahydro-1H-pirydo[1,2-a]pirazyny i środek farmaceutyczny je zawierający |
| GB9517381D0 (en) * | 1995-08-24 | 1995-10-25 | Pharmacia Spa | Aryl and heteroaryl piperazine derivatives |
| DE19600934A1 (de) * | 1996-01-12 | 1997-07-17 | Basf Ag | Substituierte Aza- und Diazacycloheptan- und Cyclooctanverbindungen und deren Verwendung |
| SE9601708D0 (sv) * | 1996-05-06 | 1996-05-06 | Pharmacia Ab | Pyridyl- and pyrimidyl-piperazines in the treatment of substance abuse disorders |
| DE19728996A1 (de) | 1997-07-07 | 1999-01-14 | Basf Ag | Triazolverbindungen und deren Verwendung |
| BR9813279B1 (pt) | 1997-10-27 | 2010-11-16 | derivado de homopiperazina, composição farmacêutica, e, uso do derivado de homopiperazina. | |
| IL145741A0 (en) * | 1999-05-04 | 2002-07-25 | Schering Corp | Piperazine derivatives useful as ccrs antagonists |
| GB0224917D0 (en) * | 2002-10-25 | 2002-12-04 | Novartis Ag | Organic compounds |
| EP1608373A4 (en) | 2003-03-19 | 2010-09-29 | Exelixis Inc | TIE-2 MODULATORS AND USE METHOD |
| RU2436772C2 (ru) * | 2010-01-28 | 2011-12-20 | Закрытое акционерное общество "НПК ЭХО" | 4[(4'-никотиноиламино)бутироиламино]бутановая кислота, проявляющая ноотропную активность, и способ ее получения |
| WO2018148529A1 (en) * | 2017-02-10 | 2018-08-16 | Florida A&M University | Identification of agents displaying functional activation of dopamine d2 and d4 receptors |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2979508A (en) * | 1959-10-12 | 1961-04-11 | Paul A J Janssen | Heterocyclic derivatives of 1-phenyl-omega-(piperazine) alkanols |
| GB966493A (en) * | 1961-11-13 | 1964-08-12 | Soc Ind Fab Antibiotiques Sifa | Novel n,n-disubstituted piperazine compounds and their preparation |
| US4191765A (en) * | 1976-05-25 | 1980-03-04 | Hoechst Aktiengesellschaft | 1-Aryloxy-2-hydroxy-3-aminopropanes |
| US4339580A (en) * | 1979-06-26 | 1982-07-13 | Mitsubishi Chemical Industries, Limited | Piperazinylalkoxyindanes and acid addition salts thereof |
| CH659069A5 (en) * | 1983-11-02 | 1986-12-31 | Sandoz Ag | 2-Piperazino- or -homopiperazino-quinazoline derivatives, process for their preparation and pharmaceuticals containing them |
| US4701456A (en) * | 1984-09-19 | 1987-10-20 | Warner-Lambert Company | Aminoalkoxybenzopyranones as antipsychotic and anxiolytic agents |
| US4892943A (en) * | 1985-10-16 | 1990-01-09 | American Home Products Corporation | Fused bicyclic imides with psychotropic activity |
| GB8603120D0 (en) * | 1986-02-07 | 1986-03-12 | Pfizer Ltd | Anti-dysrhythmia agents |
| US4704390A (en) * | 1986-02-13 | 1987-11-03 | Warner-Lambert Company | Phenyl and heterocyclic tetrahydropyridyl alkoxy-benzheterocyclic compounds as antipsychotic agents |
| AR242678A1 (es) * | 1986-03-05 | 1993-04-30 | Gonzalez Jorge Alberto | Mejoras en instrumentos musicales de cuerda de arco. |
| MX174210B (es) * | 1987-02-17 | 1994-04-28 | Pfizer | Procedimiento para la preparacion de compuestos arilpiperazinil-alquilenfenil-p-heterociclicos |
| US4748240A (en) * | 1987-04-03 | 1988-05-31 | American Home Products Corporation | Psychotropic bicyclic imides |
| US4994455A (en) * | 1987-10-26 | 1991-02-19 | Pfizer Inc. | Anti-anxiety agents |
| JP2712222B2 (ja) * | 1988-01-29 | 1998-02-10 | 三菱化学株式会社 | 抗不安薬 |
| US4873331A (en) * | 1988-12-09 | 1989-10-10 | American Home Products Corporation | Noradamantyl-carboxylic acid piperazinoalkyl esters |
-
1988
- 1988-09-28 SE SE8803429A patent/SE8803429D0/xx unknown
-
1989
- 1989-09-19 EP EP89117262A patent/EP0361271B1/en not_active Expired - Lifetime
- 1989-09-19 DE DE89117262T patent/DE68910922T2/de not_active Expired - Fee Related
- 1989-09-19 IE IE299489A patent/IE62790B1/en not_active IP Right Cessation
- 1989-09-19 AT AT89117262T patent/ATE97665T1/de not_active IP Right Cessation
- 1989-09-19 ES ES89117262T patent/ES2060709T3/es not_active Expired - Lifetime
- 1989-09-20 IL IL91701A patent/IL91701A/xx not_active IP Right Cessation
- 1989-09-22 NZ NZ230743A patent/NZ230743A/xx unknown
- 1989-09-25 AU AU41737/89A patent/AU616307B2/en not_active Ceased
- 1989-09-25 CA CA000612932A patent/CA1337417C/en not_active Expired - Fee Related
- 1989-09-26 DD DD89332978A patent/DD290884A5/de not_active IP Right Cessation
- 1989-09-27 RU SU894742280A patent/RU2021269C1/ru not_active IP Right Cessation
- 1989-09-27 PT PT91826A patent/PT91826B/pt not_active IP Right Cessation
- 1989-09-27 DK DK477189A patent/DK171133B1/da not_active IP Right Cessation
- 1989-09-27 NO NO893853A patent/NO174667C/no unknown
- 1989-09-27 PH PH39294A patent/PH27039A/en unknown
- 1989-09-28 ZA ZA897404A patent/ZA897404B/xx unknown
- 1989-09-28 KR KR1019890013966A patent/KR930007413B1/ko not_active Expired - Fee Related
- 1989-09-28 CN CN89107600A patent/CN1028756C/zh not_active Expired - Fee Related
- 1989-09-28 HU HU895103A patent/HU203232B/hu not_active IP Right Cessation
- 1989-09-28 FI FI894604A patent/FI94629C/fi active IP Right Grant
- 1989-09-28 JP JP1250834A patent/JP2857693B2/ja not_active Expired - Fee Related
- 1989-09-28 US US07/414,114 patent/US5034390A/en not_active Expired - Lifetime
-
1993
- 1993-06-02 LT LTIP604A patent/LT3549B/lt not_active IP Right Cessation
- 1993-06-15 LV LVP-93-577A patent/LV10265B/lv unknown
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