NO326522B1 - Tricykliske og heterocykliske derivatforbindelser og farmasoytiske preparater inneholdende disse forbindelsene som den aktive bestanddel - Google Patents
Tricykliske og heterocykliske derivatforbindelser og farmasoytiske preparater inneholdende disse forbindelsene som den aktive bestanddel Download PDFInfo
- Publication number
- NO326522B1 NO326522B1 NO20032956A NO20032956A NO326522B1 NO 326522 B1 NO326522 B1 NO 326522B1 NO 20032956 A NO20032956 A NO 20032956A NO 20032956 A NO20032956 A NO 20032956A NO 326522 B1 NO326522 B1 NO 326522B1
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- Norway
- Prior art keywords
- methyl
- dihydro
- methoxyphenyl
- pyrazolo
- cyclopenta
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Description
Den foreliggende oppfinnelse vedrører tri-heterocykliske forbindelser med formel
(I)
hvor alle symboler er som definert i det etterfølgende, som er anvendbare som et legemiddel, og vedrører også et farmasøytisk preparat som inneholder dem som en aktiv bestanddel.
Kortikotropinfrigjørende faktor (CRF) var et peptid som omfattet 41 aminosyre-rester og ble isolert fra hypotalamus i sau i 1981. Det ble foreslått at CRF ble frigjort fra hypotalamus og kontrollerte en utskillelse av adrenokortikotropt hormon (ACTH) fra hypofyse [Science, 218,377-379(1982)].
En biologisk effekt er begynt fra CRF binder til CRF reseptor, som eksisterer på membranoverflaten til ACTH produserende celle i fremre hypofyse. To subtyper av CRF reseptorer er blitt identifisert, og hver av disse er fordelt i et forskjellig område av hjernen. En mengde av reseptor 1 er for eksempel fordelt i hypofyse, hypotalamus, cerebral korteks og en mengde av reseptor 2 er fordelt i septal av hjerne, hypothalamus nucleus paraventircularis. Dessuten er reseptorer også fordelt 1 perifere organer, for eksempel hjertet, mage/tarm, lunge, adrenal medulla, milt, lever, nyre, prostatakjertel. Konkret, eksisterer reseptor 1 i tarm eller milt, reseptor 2 eksisterer i magen og særlig reseptor 2(3 eksisterer i hjerte og skjelettmuskel.
ACTH, som frigjøres ved en stimulering av CRF, stimulerer en utskillelse av kortisol fra adrenal korteks, og vedrører en systemisk virkning for reproduksjon, vekst, gastrointestinal funksjon, inflammasjon, immunsystem, nervesystem osv. Følgelig mener man at CRF spiller en rolle som en regulator.av disse funksjoner.
Det ble rapportert at overskudd av CRF ble utskilt i hjernen til pasienter med depresjon og angstlidelser [Science, 226, 1342-1343 (1984); Neuroscience og Behavioral Reviews, 22, 635-651 (1998); J. Endocrinol, 160, 1-12 (1999)].
Dessuten ble en forbindelse mellom CRF og forskjellige lidelser rapportert, for eksempel spiseforstyrrelse [Science, 273, 1561-1564 (1996)], inflammasjon [Endocrinology, 137, 5747-5750 (1996)], irritabel tarm [Am. J. Physiol, 253, G582-G586 (1987)], rusmiddelavhengighet [Psychopharmacology 137, 184-190 (1998)] og iskemi [Soc Neurosci Abstr (Nov 4-9, New Orleans), 807.5 (2000)].
På den annen side er CRF inngående involvert i forbindelse med stress. Administrering av for eksempel CRF til hjernen utløste den samme opptreden og endokrine respons som hos et dyr under stressbetingelser [Nature, 297, 331 (1982)].
En sammenheng mellom CRF og en lidelse i sentralnervesystemet, nevropsykiatrisk lidelse eller en lidelse i perifere organer har som over fått oppmerksomhet.
Følgelig betraktes en antagonisme av CRF reseptor til å være anvendbar for en sykdom med unormal utskillelse av CRF, for eksempel forskjellige sykdommer som omfatter stress-relaterte lidelser. Den er for eksempel ment å være anvendbar for en forebygging og/eller behandling av depresjon, enkelt-episode depresjon, tilbakevendende depresjon, post-partum depresjon, depresjon indusert ved barnemishandling, angst, angstrelaterte lidelser (for eksempel panikktilstander, særlig fobier, frykt for å falle, sosiale fobier, obsessiv-kompulsiv lidelse), emosjonell lidelse, bipolar lidelse, posttraumatisk stresslidelse, peptisk ulcus, diaré, forstoppelse, irritabel tarm, inflammatorisk tarmsykdom (ulcerøs kolitt, Crohns sykdom), stress-indusert gastrointestinal forstyrrelse, nervøs emese, spiseforstyrrelse (for eksempel anorexia nervosa, bulimia nervosa), fedme, stress-indusert søvnlidelse, muskelfibersmerte-indusert søvnlidelse, stress-indusert immunsuppresjon, stress-indusert hodepine, stress-indusert feber, stress-indusert smerte, postoperativt stress, revmatoid artritt, osteoartritt, osteoporose, psoriasis, tyreoidea dysfunksjon, uveitt, astma, upassende anti-diaréhormonindusert lidelse, smerte, inflammasjon, allergisk sykdom, hodeskade, ryggmargskade, iskemisk nevron-skade, toksisitets-nevronskade, Cushings sykdom, slag, spasme, muskelspasme, epilepsi, iskemisk sykdom, Parkinsons sykdom, Huntington sykdom, urininkontinens, Alzheimers sykdom, senil demens av Alzheimertype, multi-infarkt demens, amyotrof lateralsklerose, hypoglykemi, kardiovaskulær eller hjerte-relatert sykdom (hypertensjon, takykardi, kongestiv hjertesvikt), narkotikaavhengighet eller alkoholavhengighet.
På den annen side, er de etterfølgende forbindelser med en CRF antagonisme-aktivitet kjente.
(1)1 en beskrivelse i WO 97/29109, var en forbindelse med formel (A)
hvor R<1A> er NR<4A>R<5A> eller OR<5A>,
R<2A> er alkyl, alkyloksy, alkyltio,
R<3A> er H, alkyl, alkylsulfonyl, alkylsulfoksy eller alkyltio,
R<4A> er H, alkyl, mono- eller di(cykloalkyl)metyl, cykloalkyl, alkenyl, hydroksyalkyl, alkylkarbonyloksyalkyl eller alkyloksyalkyl,
R<5A> er alkyl, mono- eller di(cykloalkyl)metyl, Ar1A-CH2, alkenyl, alkyloksyalkyl, hydroksyalkyl, tienylmetyl, furanylmetyl, alkyltioalkyl, morfolinyl osv.,
eller R<4>A og R5<A> kan sammen med nitrogenatomet hvortil de er bundet danne pyrrolidinyl, piperidinyl, homopiperidinyl eller morfolinyl, eventuelt substituert med alkyl, alkyloksyalkyl,
Ai^ er fenyl, fenyl substituert med 1, 2 eller 3 substituenter som uavhengig er valgt fra halo, alkyl, trifluormetyl, hydroksy, osv., pyridinyl, pyridinyl substituert med 1, 2 eller 3 substituenter som uavhengig er valgt fra halo, alkyl, trifluormetyl, hydroksy,
beskrevet som CRF reseptor antagonist.
(2) I en beskrivelse i WO 98/03510, var en forbindelse med formel (B)
hvor AB er N eller CR<B>,
Z<B> er N eller CR<2B>,
Ar<B> er valgt fra fenyl, naftyl, pyridyl, pyrimidinyl, triazinyl, furanyl, tienyl, benzo-tienyl, benzofuranyl, osv., hver ArB er eventuelt substituert med 1 til 5 R<4B>,
R<B> er H, alkyl, alkenyl, alkynyl, cykloalkyl, cykloalkylalkyl, halo, cyano eller haloalkyl,
R<1B> er H, alkyl, alkenyl, alkynyl, halo, cyano eller haloalkyl, hydroksyalkyl, osv., R er H, alkyl, alkenyl, alkynyl, cykloalkyl, cykloalkylalkyl, hydroksyalkyl osv., R<3B> er H, OR<7B>, SH, S(0)nR<13B>, COR<7B>, C02R<7B>, OC(0)R13B, NR<8B>COR<7B>, N(COR<7B>)2, NR<8B>CONR<6B>R<7B>, NR<8B>C02R<13B>, NR<6B>R<7B>, alkyl, alkenyl, alkynyl, cykloalkyl, cykloalkylalkyl, osv.,
R<4B> er alkyl, alkenyl, alkynyl, cykloalkyl, cykloalkylalkyl, N02, halo, cyano, haloalkyl, NR<6B>R<7B>, NR<8B>COR<7B>, osv.,
beskrevet som CRF reseptor antagonist.
(3) I en beskrivelse i WO 98/08847, var en forbindelse med formel (C)
hvor de prikkede linjer er eventuelle dobbeltbindinger,
Ac er nitrogen eller CR<7C>,
B<c> er NR,<C>R2C, CR<1C>R<2C>R<,0C>, C(<=>CR<2C>R<11C>)R,<C>, NHCR<1C>R<2C>R<10C>, OCR1CR<2C>R10C, SCR1CR2CR<10C>, CR<2C>R<10C>NHR<1C>, CR<2C>R<10>COR<1C>, CR<2C>R<10C>SR<1C> eller COR<2C>,
J og K er hver uavhengig nitrogen eller karbon og begge er ikke nitrogener,
D og E er hver uavhengig valgt fra nitrogen, CR , C=0, C=S, svovel, oksygen, CR4CR6C ogNR8C,
G er nitrogen eller karbon,
ringen som inneholder Dc, E<c>, G<c>, K<c> og J<c> kan være en mettet eller umettet 5-leddet ring og eventuelt substituert med en eller to dobbeltbindinger og kan eventuelt inneholde fra ett til tre heteroatomer i ringen og kan eventuelt ha en eller to C=0 eller C=S,
R er alkyl som eventuelt er substituert med en eller to substituenter som uavhengig er valgt fra hydroksy, fluor, klor, brom, jod, O-alkyl, CF3, C(=0)0-alkyl, OC(=0)alkyl, osv.,
R<2C> er alkyl som eventuelt kan inneholde fra en til tre dobbeltbindinger eller trippelbindinger, aryl eller arylalkyl, cykloalkyl, cykloalkylalkyl, osv.,
R<3C> er H, alkyl, O-alkyl, klor, fluor, brom, jod, alkylen-O-alkyl, alkylen-OH eller S-alkyl,
R4C er H, alkyl, fluor, klor, brom, jod, hydroksy, cyano, amino, alkylen-OH, CF3, osv.,
R er fenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl og hver gruppe er substituert med fra en til fire substituenter R , hvor en til tre av de nevnte substituenter uavhengig kan velges fra fluor, klor, alkyl og O-alkyl, og hvor en av de nevnte substituenter kan velges fra brom, jod, formyl, OH, alkylen-OH, alkylen-O-alkyl, cyano, CF3, nitro, amino, alkylamino, dialkylamino, osv.,
beskrevet som CRF reseptor antagonist.
Den foreliggende oppfinnelse vedrører tri-heterocykliske forbindelser. Mer spesielt vedrører oppfinnelsen forbindelser med formel (I)
hvor X og Y hver uavhengig er karbon eller nitrogen og hvor begge ikke samtidig er nitrogener;
W er karbon eller nitrogen;
U og Z er hver uavhengig CR , NR , nitrogen, oksygen, svovel, C=0 eller C=S; R<2> er
(i) hydrogen,
(ii) Cl-8 alkyl,
(iii) C2-8 alkenyl,
(iv) C2-8 alkynyl,
(v) halogenatom,
(vi) CF3,
(vii) cyano,
(viii) nitro,
(ix) NR9R<10> hvor R<9> og R<10> hver uavhengig er
(i) hydrogen,
(ii) Cl-4 alkyl,
(iii) C3-10 mono- eller bi-karbocyklisk ring,
(iv) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (v) Cl-4 alkyl substituert med C3-10 mono- eller bi-karbocyklisk ring eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer,
1-2 oksygenatomer og/eller 1-2 svovelatomer,
(x) OR<11> hvor R11 er
(i) hydrogen,
(ii) Cl-4 alkyl,
(iii) C5-6 karbocyklisk ring,
(iv) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (v) Cl-4 alkyl som er substituert med en C5-6 karbocyklisk ring eller en 5-eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom,
(xi) SH,
(xii) S(0)nR<12> hvor n er 0, 1 eller 2, R<12> er
(i) Cl-4 alkyl,
(ii) C5-6 karbocyklisk ring,
(iii) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (iv) Cl-4 alkyl substituert med en C5-6 karbocyklisk ring eller en 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom
og/eller 1 svovelatom,
(xiii) COR11,
(xiv) COOR<11>,
(xv) CONR9R10,
(xvi) C3-10 mono- eller bi-karbocyklisk ring,
(xvii) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller
(xviii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<u>, SH, S(0)nR<12>, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi- karbocyklisk ring og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
R<13> er
(i) hydrogen,
(ii) Cl-4 alkyl,
(iii) C2-4 alkenyl,
(iv) C2-4 alkynyl,
(v) C3-10 mono- eller bi-karbocyklisk ring,
(vi) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (vii) Cl-4 alkyl substituert med C3-10 mono- eller bi-karbocyklisk ring eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
'-^ er en enkeltbinding eller dobbeltbinding,
er C4-6 karbocyklisk ring eller 4-6-leddet heterocyklisk ring inneholdende
minst ett av et nitrogenatom, oksygenatom og svovelatom og hvor disse ringer er usubstituerte eller substituert med 1-3 substituenter valgt fra Cl-4 alkyl, Cl-4 alkoksy, halogenatom og CF3,
med den betingelse at når X, Y, Z og U er karbon og W er nitrogen, da er ring A ikke benzen,
R<1> er
(i) Cl-8 alkyl som er usubstituert eller substituert med 1-5 R<14>,
(ii) C2-8 alkenyl som er usubstituert eller substituert med 1-5 R<14>,
(iii) C2-8 alkynyl som er usubstituert eller substituert med 1-5 R<14>,
(iv) NR<4>R<5> hvor R4 og R<5> hver uavhengig er,
(i) hydrogen,
(ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>,
(iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R<17>,
(iv) C2-15 alkynyl som er usubstituert eller substituert med 1^5 R<17>,
(v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-15 leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert
eller substituert med 1-5 R<18>,
(v) OR<6> hvor R<6> er
(i) hydrogen,
(ii) Cl-10 alkyl,
(iii) C2-10 alkenyl,
(iv) C2-10 alkynyl,
(v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (vii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<H>, SH, S(0)nR12, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R 1 fi, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer
som er usubstituert eller substituert med 1-5 R 1 Q,
(vi) SH,
(vii) S(0)nR<7> hvor n er som definert i det foregående, R<7> er
(i) Cl-8 alkyl,
(ii) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (iii) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogen atomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (iv) Cl-4 alkyl substituert med C3-10 mono- eller bi- karbocyklisk ring, som er usubstituert eller substituert med 1-5 R<18> eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer
og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (viii) COR<6>,
(ix) COOR6,
(x) CONR<4>R<5>,
(xi) NR8COR6ahvorR6aer
(i) hydrogen,
(ii) C1-10 alkyl,
(iii) C2-10 alkenyl,
(iv) C2-10 alkynyl eller
(v) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R1<0>, OR,<la>, =N-OR<n>, SH, S(0)nR<12>, CO<R11>, COOR<11>
og CONR<9>R<10>,
(xii) NR<8>COOR<6> hvor R<6> er som definert i det foregående, R<8> er
(i) hydrogen,
(ii) Cl-8 alkyl,
(iii) C2-8 alkenyl,
(iv) C2-8 alkynyl,
(v) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-10-leddet mono-.eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18> eller (vii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<n>, SH, S(0)nR12, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer
som er usubstituert eller substituert med 1-5 R<18>,
(xiii) NR<8>CONR<4>R<5>,
(xiv) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15> eller
(xv) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>,
Rll<a> er (i) hydrogen, (ii) Cl-4 alkyl eller (iii) Cl-4 alkyl substituert med C5-6 karbocyklisk ring eller 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom,
R<14> er (a) halogenatom, (b) CF3, (c) OCF3, (d) cyano, (e) nitro, (f) NR<4>R<5>, (g) OR<6>, (h) =N-OR<6>, (j) SH, (k) S(0)nR7, (1) COR<6>, (m) COOR<6>, (n) CONR<4>R<5>, (o) NR<8>COR<6>, (p) NR<8>COOR<6>, (q) NR<8>CONR4R<5>, (r) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15> eller (s) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>, R<15> er (a) Cl-8 alkyl, (b) C2-8 alkenyl, (c) C2-8 alkynyl, (d) Cl-4 alkoksy(Cl-4)alkyl, (e) halogenatom, (f) CF3, (g) OCF3, (h) cyano, Q) nitro, (k) NR<4>R<5>, (1) OR<6>, (m) SH, (n) S(0)nR<7>, (o) COR<6>, (p) COOR<6>, (q) CONR<4>R<5>, (r) NR<8>COR<6>, (s) NR<8>COOR<6>, (t) NR<8>CONR<4>R<5>, (u) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<19>, (v) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<19> eller (w) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<4>R<5>, OR<6>, =N-OR<6>, SH, S(0)nR<7>, COR<6>, COOR<6>, CONR<4>R<5>, NR<8>COR<6>, NR<8>COOR<6>, NR<8>CONR<4>R<5>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<19>, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<19>,
R1<7> er (a) halogenatom, (b) CF3, (c) OCF3, (d) cyano, (e) nitro, (f) NR<9>R10, (g) OR<lla>, (h) =N-OR<n>, (j) SH, (k) S(0)nR<12>, (1) COR<11>, (m) COOR<11>, (n) CONR<9>R<10>, (o) NR<8>COR<11>, (p) NR<8>COOR<11>, (q) NR<8>CONR<9>R<10>, (r) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R 1 fin eller (s) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R18a,
R<18> er (a) Cl-4 alkyl, (b) C2-4 alkenyl, (c) C2-4 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) SH, (k) S(0)nR<12>, (1) NR<9>R10, (m) OR<11>, (n) COR<11>, (o) COOR<11>, (p) CONR<9>R<10>, (q) C5-6 karbocyklisk ring, (r) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (s) Cl-4 alkyl substituert med C5-6 karbocyklisk ring eller 5 eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom,
R<18a> er (a) Cl-4 alkyl, (b) C2-4 alkenyl, (c) C2-4 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) SH, (k) S(0)nR<12>, (1) NR9R10, (m) OR<l>la, (n) COR<11>, (o) COOR<11> eller (p) CONR<9>R10,
R<19> er Cl-4 alkyl, Cl-4 alkoksy, halogenatom, CF3, OCF3, cyano, nitro, amino, NH(Cl-4 alkyl) eller N(C 1-4 alkyl)2,
R<3> is (i) C5-10 mono- eller bi-karbocyklisk ring substituert med 1-5 R<16> eller
(ii) 5-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer substituert med 1-5 R<16>,
R<16> er (a) Cl-8 alkyl,
(b) C2-8 alkenyl,
(c) C2-8 alkynyl,
(d) halogenatom,
(e) CF3,
(f) OCF3,
(g) cyano,
(h) nitro,
G)NR<9>R<10>,
(k)OR<11>,
(1) SH,
(m) S(0)nR<12>, med unntak av fenyltio,
(n)COR<11>,
(o) COOR11,
(p) CONR<9>R<10>,
(q)NR<8>COR<11>,
OONR^OOR<11>,
(s) NR<8>CONR<9>R<10>,
(t) C3-10 mono- eller bi-karbocyklisk ring,
(u) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer, (v) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR11, =N-OR<n>, SH, S(0)nR<12>, COR<11>, COOR<11>, CONR<9>R<10>, NR<8>COR<u>, NR<8>COOR<n>, NR<8>CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
med den betingelse at (1) når hver av X og W er karbonatomer, hver av Y og Z er nitrogenatomer, U er CR<2> og R<1> er OR<6>, da er R<3> ikke fenyl substituert med 1 halogenatom, fenyl substituert med 1 trifluormetyl og fenyl substituert med trifluormetyl og nitro, (2) når hver av X, Y og Z er karbonatomer og hver av U og
W er nitrogenatomer, da er R C5-10 mono- eller bi-karbocyklisk ring substituert med 1-5 R<16>,
og et farmasøytisk aksepterbart salt derav eller et hydrat derav.
Oppfinnelsen vedrører også et farmasøytisk preparat som omfatter en forbindelse ifølge oppfinnelsen som CRF reseptorantagonist.
I beskrivelsen betyr Cl-4 alkyl metyl, etyl, propyl, butyl og isomere grupper derav.
I beskrivelsen betyr Cl-8 alkyl metyl, etyl, propyl, butyl, pentyl, heksyl, heptyl, oktyl og isomere grupper derav.
I beskrivelsen betyr Cl-15 alkyl metyl, etyl, propyl, butyl, pentyl, heksyl, heptyl, oktyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl og isomere grupper derav.
I beskrivelsen betyr Cl-4 alkoksy metoksy, etoksy, propoksy, butoksy og isomere grupper derav.
I beskrivelsen betyr C2-4 alkenyl vinyl, propenyl, butenyl og isomere grupper derav.
I beskrivelsen betyr C2-8 alkenyl etyl, propyl, butyl, pentyl, heksyl, heptyl, oktyl med 1-3 dobbeltbindinger og isomere grupper derav, for eksempel vinyl, propenyl, butenyl, pentenyl, heksenyl, heksadienyl, heptenyl, heptadienyl, oktenyl, oktadienyl.
I beskrivelsen betyr C2-15 alkenyl etyl, propyl, butyl, pentyl, heksyl, heptyl, oktyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl med 1-3 dobbeltbindinger og isomere grupper derav, for eksempel vinyl, propenyl, butenyl, pentenyl, heksenyl, heksadienyl, heptenyl, heptadienyl, oktenyl, oktadienyl, nonenyl, nonadienyl, decenyl, dekadienyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl.
I beskrivelsen betyr C2-4 alkynyl etynyl, propynyl, butynyl og isomere grupper derav.
I beskrivelsen betyr C2-8 alkynyl etyl, propyl, butyl, pentyl, heksyl, heptyl, oktyl med 1-3 trippelbindinger og isomere grupper derav, for eksempel etynyl, propynyl, butynyl, pentynyl, heksynyl, heksadiynyl, heptynyl, heptadiynyl, oktynyl, oktadiynyl.
I beskrivelsen betyr C2-15 alkynyl etyl, propyl, butyl, pentyl, heksyl, heptyl, oktyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl med 1-3 trippelbindinger og isomere grupper derav, for eksempel etynyl, propynyl, butynyl, pentynyl, heksynyl, heksadiynyl, heptynyl, heptadiynyl, oktynyl, oktadiynyl, nonynyl, decynyl, undecynyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl.
I beskrivelsen er halogenatom fluor, klor, brom og jod.
I beskrivelsen betyr Cl-4 alkoksy(Cl-4)alkyl metyl, etyl, propyl, butyl og isomere grupper derav substituert med en av metoksy, etoksy, propoksy, butoksy og isomere grupper derav.
I beskrivelsen er en C4-6 karbocyklisk ring C4-6 karbocyklisk aryl eller en delvis eller fullstendig mettet ring derav, for eksempel cyklobutan, cyklopentan, cykloheksan, cyklopenten, cykloheksen, cyklopentadien, cykloheksadien, benzen.
I beskrivelsen er C5-6 karbocyklisk ring C5-6 karbocyklisk aryl eller en delvis eller fullstendig mettet ring derav, for eksempel cyklopentan, cykloheksan, cyklopenten, cykloheksen, cyklopentadien, cykloheksadien, benzen.
I beskrivelsen er C3-10 mono- eller bi-karbocyklisk ring C3-10 mono- eller bi-karbocyklisk aryl eller en delvis eller fullstendig mettet ring derav, for eksempel cyklopropan, cyklobutan, cyklopentan, cykloheksan, cykloheptan, cyklopenten, cykloheksen, cyklopentadien, cykloheksadien, benzen, pentalen, inden, naftalen, azulen, perhydropentalen, indan, perhydroinden, tetrahydronaftalen, perhydronaftalen, perhydroazulen.
I beskrivelsen er C3-15 mono- eller bi-karbocyklisk ring 3-15 mono- eller bi-karbocyklisk aryl eller en delvis eller fullstendig mettet ring derav eller en bro-dannet bi-karbocyklisk ring, for eksempel cyklopropan, cyklobutan, cyklopentan, cykloheksan, cykloheptan, cyklopenten, cykloheksen, cyklopentadien, cykloheksadien, benzen, pentalen, inden, naftalen, azulen, heptalen, perhydropentalen, indan, perhydroinden, tetrahydronaftalen, perhydronaftalen, perhydroazulen, perhydro-heptalen, bicyklo[3.1.1]heptan.
I beskrivelsen er C5-10 mono- eller bi-karbocyklisk ring C5-10 mono- eller bi-karbocyklisk aryl eller en delvis eller fullstendig mettet ring derav, for eksempel cyklopentan, cykloheksan, cykloheptan, cyklopenten, cykloheksen, cyklohepten, cyklopentadien, cykloheksadien, cykloheptadien, benzen, pentalen, inden, naftalen, azulen, perhydropentalen, indan, perhydroinden, tetrahydronaftalen, perhydronaftalen, perhydroazulen.
I beskrivelsen er den 4-6-leddede heterocykliske ring som inneholder minst ett nitrogen, oksygen og svovel 4-6-leddet heterocyklisk aryl inneholdende minst ett nitrogen, oksygen og svovel eller en delvis eller fullstendig mettet ring derav, for eksempel azetidin, pyrrolidin, pyrrolin, pyrrol, tetrahydrofuran, dihydrofuran, furan, tetrahydrotiofen, dihydrotiofen, tiofen, piperidin, dihydropyridin, pyridin, tetrahydropyran, dihydropyran, pyran, tetrahydrotiopyran, dihydrotiopyran, tiopyran.
I beskrivelsen er en 5- eller 6-leddet heterocyklisk ring som inneholder 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom 5- eller 6-leddet heterocyklisk aryl inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller en delvis eller fullstendig mettet ring derav, for eksempel pyrrol, imidazol, pyrazol, pyridin, pyrazin, pyrimidin, pyridazin, furan, pyran, tiofen, tiain (tiopyran), oksazol, isoksazol, tiazol, isotiazol, pyrrolin, pyrrolidin, piperidin, imidazolin, imidazolidin, pyrazolin, pyrazolidin, piperazin, perhydropyrimidin, perhydropyridazin, dihydrofuran, tetrahydrofuran, tetrahydropyran, dihydrotiofen, tetrahydrotiofen, tetrahydrotiain, morfolin, tiomorfolin.
I beskrivelsen er en 3-10-leddet mono- eller bi-heterocyklisk ring som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer 3-10-leddet mono-eller bi-heterocyklisk aryl som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller en delvis eller fullstendig mettet ring derav. En 3-10-leddet mono- eller bi-heterocyklisk aryl inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer er for eksempel pyrrol, imidazol, pyrazol, triazol, tetrazol, pyridin, pyrazin, pyrimidin, pyridazin, azepin, diazepin, furan, pyran, oksepin, tiofen, tiain (tiopyran), tiepin, oksazol, isoksazol, oksadiazol, oksazin, oksadiazin, oksazepin, oksadiazepin, tiazol, isotiazol, tiadiazol, tiazin, tiadiazin, tiazepin, tiadiazepin, indol, isoindol, indolizin, benzofuran, isobenzofuran, benzotiofen, isobenzotiofen, indazol, kinolin, isokinolin, kinolizin, ftalazin, naftyridin, kinoksalin, kinazolin, cinnolin, benzoksazol, benzoksadiazol, benzotiazol, benzimidazol, benzofurazan, benzotiadiazol, benzotriazol.
Den ovennevnte delvis eller fullstendig mettede 3-10-leddede mono- eller bi-heterocykliske aryl inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer er for eksempel aziridin, azetin, azetidin, pyrrolin, pyrrolidin, imidazolin, imidazolidin, pyrazolin, pyrazolidin, triazolin, triazolidin, tetrazolin, tetrazolidin, piperidin, piperazin, dihydropyridin, tetrahydropyridin, dihydropyrazin, tetrahydropyrazin, dihydropyrimidin, tetrahydropyrimidin, perhydropyrimidin, dihydropyridazin, tetrahydropyridazin, perhydropyridazin, dihydroazepin, tetrahydroazepin, perhydroazepin, dihydrodiazepin, tetrahydrodiazepin, perhydrodiazepin, oksiran, oksetan, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrooksepin, tetrahydrooksepin, perhydrooksepin, tiiran, tietan, dihydrotiofen, tetrahydrotiofen, dihydrotiain (dihydrotiopyran), tetrahydrotiain (tetrahydrotiopyran), dihydrotiepin, tetrahydrotiepin, perhydrotiepin, oksazolin (dihydrooksazol), oksazolidin (tetrahydrooksazol), dihydroisoksazol, tetrahydroisoksazol, oksadiazolin (dihydrooksadiazol), oksadiazolidin (tetrahydrooksadiazol), tiazolin (dihydrotiazol), tiazolidin (tetrahydrotiazol), dihydroisotiazol, tetrahydroisotiazol, morfolin, tiomorfolin, indolin, isoindolin, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzotiofen, perhydrobenzotiofen, dihydroisobenzotiofen, perhydroisobenzotiofen, dihydroindazol, perhydroindazol, dihydrokinolin, tetrahydrokinolin, perhydrokinolin, dihydroisokinolin, tetrahydroisokinolin, perhydroisokinolin, dihydroftalazin, tetrahydroftalazin, perhydrotfalazin, dihydronatfyridin, tetrahydronaftyridin, perhydronaftyridin, dihydrokinoksalin, tetrahydrokinoksalin, perhydrokinoksalin, dihydrokinazolin, tetrahydrokinazolin, perhydrokinazolin, dihydrocinnolin, tetrahydrocinnolin, perhydrocinnolin, dihydrobenzoksazol, perhydrobenzoksazol, dihydrobenzotiazol, perhydrobenzotiazol, dihydrobenzimidazol, perhydrobenzimidazol, dioksolan, dioksan, dioksazin, dioksaindan, kroman, isokroman.
I beskrivelsen er en 3-15-leddet mono- eller bi-heterocyklisk ring som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer en 3-15-leddet mono- eller bi-heterocyklisk aryl inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller en delvis eller fullstendig mettet ring derav. Det 3-15-leddede mono- eller bi-heterocykliske aryl som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer er for eksempel pyrrol, imidazol, pyrazol, triazol, tetrazol, pyridin, pyrazin, pyrimidin, pyridazin, azepin, diazepin, furan, pyran, oksepin, tiofen, tiain (tiopyran), tiepin, oksazol, isoksazol, oksadiazol, oksazin, oksadiazin, oksazepin, oksadiazepin, tiazol, isotiazol, tiadiazol, tiazin, tiadiazin, tiazepin, tiadiazepin, indol, isoindol, indolizin, benzofuran, isobenzofuran, benzotiofen, isobenzotiofen, indazol, kinolin, isokinolin, kinolizin, ftalazin, naftyridin, kinoksalin, kinazolin, cinnolin, benzoksazol, benzoksadiazol, benzotiazol, benzimidazol, benzazepin, benzodiazepin, benzotriazol, benzoksazepin, benzoksadiazepin, benzotiazepin, benzotiadiazol, benzotiadiazepin, benzofurazan.
Den ovennevnte delvis eller fullstendig mettede 3-15-leddede mono- eller bi-heterocykliske aryl som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer er for eksempel aziridin, azetin, azetidin, pyrrolin, pyrrolidin, imidazolin, imidazolidin, pyrazolin, pyrazolidin, triazolin, triazolidin, tetrazolin, tetrazolidin, piperidin, piperazin, dihydropyridin, tetrahydropyridin, dihydropyrazin, tetrahydropyrazin, dihydropyrimidin, tetrahydropyrimidin, perhydropyrimidin, dihydropyridazin, tetrahydropyridazin, perhydropyridazin, dihydroazepin, tetrahydroazepin, perhydroazepin, dihydrodiazepin, tetrahydrodiazepin, perhydrodiazepin, oksiran, oksetan, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrooksepin, tetrahydrooksepin, perhydrooksepin, tiiran, tietan, dihydrotiofen, tetrahydrotiofen, dihydrotiain (dihydrotiopyran), tetrahydrotiain (tetrahydrotiopyran), dihydrotiepin, tetrahydrotiepin, perhydrotiepin, oksazolin (dihydrooksazol), oksazolidin (tetrahydrooksazol), dihydroisoksazol, tetrahydroisoksazol, oksadiazolin (dihydrooksadiazol), oksadiazolidin (tetrahydrooksadiazol), tiazolin (dihydrotiazol), tiazolidin (tetrahydrotiazol), dihydroisotiazol, tetrahydroisotiazol, morfolin, tiomorfolin, indolin, isoindolin, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzotiofen, perhydrobenzotiofen, dihydroisobenzotiofen, perhydroisobenzotiofen, dihydroindazol, perhydroindazol, dihydrokinolin, tetrahydrokinolin, perhydrokinolin, dihydroisokinolin, tetrahydroisokinolin, perhydroisokinolin, dihydroftalazin, tetrahydroftalazin, perhydrotfalazin, dihydronaftyridin, tetrahydronaftyridin, perhydronaftyridin, dihydrokinoksalin, tetrahydrokinoksalin, perhydrokinoksalin, dihydrokinazolin, tetrahydrokinazolin, perhydrokinazolin, dihydrocinnolin, tetrahydrocinnolin, perhydrocinnolin, dihydrobenzoksazol, perhydrobenzoksazol, dihydrobenzotiazol, perhydrobenzotiazol, dihydrobenzimidazol, perhydrobenzimidazol, dihydrobenza-zepin, tetrahydrobenzazepin, dihydrobenzodiazepin, tetrahydrobenzodiazepin, dihydrobenzoksazepin, tetrahydrobenzoksazepin, dioksolan, dioksan, dioksazin, dioksaindan, kroman, isokroman.
I beskrivelsen er en 5-10-leddet mono- eller bi-heterocyklisk ring som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer et 5-10-leddet mono- eller bi-heterocyklisk aryl som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller en delvis eller fullstendig mettet ring derav. En 5-10-leddet mono- eller bi-heterocyklisk aryl som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer er for eksempel pyrrol, imidazol, pyrazol, triazol, tetrazol, pyridin, pyrazin, pyrimidin, pyridazin, azepin, diazepin, furan, pyran, oksepin, tiofen, tiain (tiopyran), tiepin, oksazol, isoksazol, oksadiazol, oksazin, oksadiazin, oksazepin, oksadiazepin, tiazol, isotiazol, tiadiazol, tiazin, tiadiazin, tiazepin, tiadiazepin, indol, isoindol, indolizin, benzofuran, isobenzofuran, benzotiofen, isobenzotiofen, indazol, kinolin, isokinolin, kinolizin, ftalazin, naftyridin, kinoksalin, kinazolin, cinnolin, benzoksazol, benzoksadiazol, benzotiazol, benzimidazol, benzofurazan, benzotiadiazol, benzotriazol.
Den ovennevnte delvis eller fullstendig mettede 5-10-leddede mono- eller bi-heterocykliske aryl som inneholder 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer er for eksempel pyrrolin, pyrrolidin, imidazolin, imidazolidin, pyrazolin, pyrazolidin, triazolin, triazolidin, tetrazolin, tetrazolidin, piperidin, piperazin, dihydropyridin, tetrahydropyridin, dihydropyrazin, tetrahydropyrazin, dihydropyrimidin, tetrahydropyrimidin, perhydropyrimidin, dihydropyridazin, tetrahydropyridazin, perhydropyridazin, dihydroazepin, tetrahydroazepin, perhydroazepin, dihydrodiazepin, tetrahydrodiazepin, perhydrodiazepin, oksiran, oksetan, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrooksepin, tetrahydrooksepin, perhydrooksepin, tiiran, tietan, dihydrotiofen, tetrahydrotiofen, dihydrotiain (dihydrotiopyran), tetrahydrotiain (tetrahydrotiopyran), dihydrotiepin, tetrahydrotiepin, perhydrotiepin, oksazolin (dihydrooksazol), oksazolidin (tetrahydrooksazol), dihydroisoksazol, tetrahydroisoksazol, oksadiazolin (dihydrooksadiazol), oksadiazolidin (tetrahydrooksadiazol), tiazolin (dihydrotiazol), tiazolidin (tetrahydrotiazol), dihydroisotiazol, tetrahydroisotiazol, morfolin, tiomorfolin, indolin, isoindolin, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzotiofen, perhydrobenzotiofen, dihydroisobenzotiofen, perhydroisobenzotiofen, dihydroindazol, perhydroindazol, dihydrokinolin, tetrahydrokinolin, perhydrokinolin, dihydroisokinolin, tetrahydroisokinolin, perhydroisokinolin, dihydroftalazin, tetrahydroftalazin, perhydroftalazin, dihydronaftyridin, tetrahydronaftyridin, perhydronaftyridin, dihydrokinoksalin, tetrahydrokinoksalin, perhydrokinoksalin, dihydrokinazolin, tetrahydrokinazolin, perhydrokinazolin, dihydrocinnolin, tetrahydrocinnolin, perhydrocinnolin, dihydrobenzoksazol, perhydrobenzoksazol, dihydrobenzotiazol, perhydrobenzotiazol, dihydrobenzimidazol, perhydrobenzimidazol, dioksolan, dioksan, dioksazin, dioksaindan, kroman, isokroman.
I forbindelsen med formel (I) ifølge oppfinnelsen er
en mettet, delvis mettet eller umettet 5-leddet karbocyklisk ring eller heterocyklisk ring. X og Y i ringen kan være alle kombinasjoner hvor X er karbon og Y er nitrogen, X er nitrogen og Y er karbon og både X og Y er karboner. De etter-følgende kombinasjoner er foretrukne. (i) X er karbon, Y er nitrogen, hver av U og Z er karbon eller nitrogen og W er karbon, (ii) X er nitrogen, Y er karbon, hver av U og Z er karbon eller nitrogen og W er karbon, (iii) hver av X og Y er karbon, hver av U og W er karbon eller nitrogen og Z er karbon, (iv) hver av X og Y er karbon, U er nitrogen og Z er oksygen eller svovel, U er oksygen eller svovel, Z er nitrogen og W er karbon, eller (v) hver av X og Y er karbon, hver av Z og W er nitrogen og U er C=0 eller C=S.
Mer foretrukne kombinasjoner er
(i-l) hver av X, U og W er karbon, og hver av Y og Z er nitrogen,
(i-2) hver av X, Z og W er karbon, og hver av Y og U er nitrogen,
(i-3) hver av X, Z, U og W er karbon og Y er nitrogen,
(ii-1) hver av X, Z og U er nitrogen, og hver av Y og W er karbon,
(ii-2) hver av X og Z er nitrogen, og hver av Y, U og W er karbon,
(ii-3) hver av X og U er nitrogen, og hver av Y, Z og W er karbon,
(ii-4) X er nitrogen, og hver av Y, Z, U og W er karbon,
(iii-1) hver av X, Y og Z er karbon, og hver av U og W er nitrogen,
(iii-2) hver av X, Y, Z og U er karbon og W er nitrogen,
(iv-1) hver av X, Y og W er karbon, Z er oksygen og U er nitrogen,
(iv-2) hver av X, Y og W er karbon, Z er svovel og U er nitrogen,
(iv-3) hver av X, Y og W er karbon, Z er nitrogen og U er oksygen,
(iv-4) hver av X, Y og W er karbon, Z er nitrogen og U er svovel,
(v-1) hver av X og Y er karbon, hver av Z og W er nitrogen og U er C=0, eller (v-2) hver av X og Y er karbon, hver av Z og W er nitrogen og U er C=S.
I forbindelsene med formel (I) ifølge oppfinnelsen, er de etterfølgende forbindelser med formler (I-i) - (I-xxvi) vist som konkrete forbindelser. I forbindelsene med formel (I-i) - (I-xxvi), er de etterfølgende forbindelser foretrukne. I forbindelsene med formel (I) ifølge oppfinnelsen, er en C4-6 karbocyklisk ring eller 4-6-leddet heterocyklisk ring inneholdende minst ett nitrogen, oksygen og svovel som angitt ved
C4-6 karbocyklisk aryl eller en delvis eller fullstendig mettet ring derav, eller 4-6-leddet heterocyklisk aryl inneholdende minst ett nitrogen, oksygen og svovel eller en delvis eller fullstendig mettet ring derav.
De etterfølgende er foretrukne som ring A:
hvor G er O, S eller NH, Rx er Cl-4 alkyl, Cl-4 alkoksy, halogenatom eller CF3, m er 0-3.
I forbindelsene med formel (I) ifølge oppfinnelsen er R<1> foretrukket
(i) Cl-8 alkyl som er usubstituert eller substituert med 1-5 R<14>,
(ii) C2-8 alkenyl som er usubstituert eller substituert med 1-5 R<14>,
(iii) C2-8 alkynyl som er usubstituert eller substituert med 1-5 R<14>,
(iv) NR4R5,
(v) OR<6>,
(vi) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15> eller (vii) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>.
En foretrukket kombinasjon av R<4> og R<5> i NR<4>R<5> i ovennevnte foretrukne R<1> er
(a) R<4> er (i) hydrogen og R5 er (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R , (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R<17>, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R151 eller (vi) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18> eller (b) R<4>er (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R 1*7, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R 1 *7 eller (v-1) C3-6 mono-karbocyklisk ring og R<5> er (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R<17>, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R<17>, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R 1 fi eller (vi) 3-15-leddet mono-eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R .
Det er foretrukket at den 3-15-leddede mono- eller bi-heterocykliske ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15> i ovennevnte foretrukne R<1>, binder gjennom et nitrogenatom i ringen. Det vil si gruppen: som er usubstituert eller substituert med 1-5 R<15>, og denne gruppe er en 3-15-leddet mono- eller bi-heterocyklisk ring som nødvendigvis inneholder ett nitrogen, og som eventuelt videre inneholder ett nitrogen, oksygen eller svovel. Konkret, er der de etterfølgende heterocykliske ringer som er usubstituert eller substituert med 1-5 R<15>.
Som spesifikk forbindelser ifølge oppfinnelser er der forbindelser som beskrevet i de etterfølgende eksempler og et farmasøytisk aksepterbart salt derav.
Dersom annet ikke er spesifikt angitt, er alle isomerer inkludert i den foreliggende oppfinnelse. Alkyl, alkoksy, alkylen og alkynyl inkluderer for eksempel rettkjedede og forgrenede isomerer. Isomerer basert på dobbeltbinding, ring, kondensert ring (E, Z, cis, trans), isomerer resulterende fra tilstedeværelsen av ett eller flere asym-metriske karbonatomer (R-konfigurasjon, S-konfigurasjon, a-konfigurasjon, (5-konfigurasjon, enantiomerer, diastereoisomerer), optisk aktive forbindelser med optisk rotasjon (D, L, d, 1-konfigurasjon), polare forbindelser oppnådd ved kromato-grafiske separasjoner (høypolar forbindelse, mindre polar forbindelse), likevekts-forbindelser, blandingene eksisterer i fritt forhold, racemiske blandinger er inkludert i den foreliggende oppfinnelse.
Salt
Forbindelsen ifølge oppfinnelsen med formel (I) kan omdannes til et tilsvarende farmasøytisk aksepterbart salt ved hjelp av kjente metoder. I forbindelse med den foreliggende oppfinnelse er farmasøytisk aksepterbare salter, salter av alkalimetaller, salter av jordalkalimetaller, ammoniumsalter, aminsalter, syreaddisjonssalter.
Ikke-toksiske vannoppløselige salter er foretrukne. Passende salter er salter av alkalimetaller som kalium, natrium, salter av jordalkalimetaller som kalsium, magnesium, ammoniumsalter, farmasøytisk aksepterbare organiske aminer som tetrametylammonium, trietylamin, metylamin, dimetylamin, cyklopentylamin, benzylamin, fenetylamin, piperidin, monoetanolamin, dietanolamin, tris(hydroksy-metyl)metylaminometan, lysin, arginin, N-metyl-D-glukamin. Et alkalimetallsalt er foretrukket.
Ikke-toksiske og vannoppløselige syreaddisjonssalter er foretrukne. Passende syreaddisjonssalter er salter av uorganiske syrer som hydroklorid, hydrobromid, sulfat, fosfat, nitrat, salter av organiske syrer som acetat, trifluoracetat, laktat, tartrat, oksalat, fumarat, maleat, citrat, benzoat, metansulfonat, etansulfonat, benzensulfo-nat, toluensulfonat, isetionat, glukuronat, glukonat.
Forbindelsen med formel (I) ifølge oppfinnelser og saltene derav kan omdannes til de tilsvarende hydrater ved hjelp av konvensjonelle metoder.
Fremstilling av forbindelsen ifølge oppfinnelsen
Den foreliggende forbindelse med formel (I) kan for eksempel fremstilles ved hjelp av den etterfølgende metode. (A) I forbindelsen med formel (I) kan forbindelsen hvor R<1> er OH, og R<2> og R<3> er ikke OH, cyano, =N-OR<n> eller en gruppe inneholdende OH, cyano eller =N-OR ,
dvs. forbindelsen med formel (I-A)
hvor hver av Z<a>, U<a> og R<3>"<a> har den samme betydning som Z, U og R<3>, med den betingelse at de ikke er OH, cyano, =N-OR<n> eller en gruppe inneholdende OH, cyano eller =N-OR<n>, og hvor de andre symboler er som definert i det foregående, fremstilles ved å reagere forbindelsen med formel (II-1)
hvor alle symboler er som definert i det foregående,
med forbindelsen med (III-1)
hvor Aa ringen er en mettet eller delvis mettet C4-6 karbocyklisk ring eller 4-6 - leddet heterocyklisk ring, Et er etyl, de andre symboler er som definert i det foregående,
eller underkastes suksessivt for oksidativ reaksjon.
Den ovennevnte reaksjon av forbindelsen med formel (II) og forbindelsen med formel (III) er for eksempel kjent, den gjennomføres i et organisk løsningsmiddel (for eksempel eddiksyre) ved fra romtemperatur til tilbakeløpstemperatur.
Oksidativ reaksjon er for eksempel kjent, den gjennomføres i et organisk løsnings-middel (for eksempel difenyleter), ved anvendelse av en metallkatalysator (for eksempel palladium-karbon, palladium, palladiumhydroksyd, palladiumacetat, palladium-sort), ved 0 °C ~ 250 °C.
(B) I forbindelsen med formel (I), kan forbindelsen hvor R<1> ikke er OH, og cyano, =N-OR<6> er en gruppe inneholdende cyano eller =N-OR<n>, og C3-10 mono- eller bi-karbocyklisk ring, 3-10-leddet mono- eller bi- heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og /eller 1-2 svovelatomer, R<2> og R<3> er ikke OH, cyano, =N-ORu eller en gruppe inneholdende OH, cyano eller =N-OR<11>, dvs. forbindelsen med formel (I-B)
hvor R<1>"<3> har den samme betydning som R<1>, med den betingelse at den ikke er OH, og cyano, =N-OR<6> eller en gruppe inneholdende cyano eller =N-OR<n>, og C3-10 mono- eller bi-karbocyklisk ring, C3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer, hvor de andre symboler er som definert i det foregående,
fremstilles ved å reagere forbindelsen med formel (IV)
hvor X er et halogenatom og de andre symbolene er som definert i det foregående, med en forbindelse med formel (V-1)
hvor R<1_ab> har den samme betydning som R<1>, med den betingelse at den ikke er OH, og cyano, =N-OR<6> eller en gruppe inneholdende cyano eller =N-OR<6>, og C3-10 mono- eller bi-karbocyklisk ring, 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer, eller underkastes suksessivt for en oksidativ reaksjon, eller
med forbindelsen med formel (V-2)
hvorR'"<ac>er C3-10 mono- eller bi-karbocyklisk ring, 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
eller underkastes suksessivt for en oksidativ reaksjon.
Den ovennevnte reaksjon av forbindelsen med formel (IV) og forbindelsen med formel (V-1) er kjent og gjennomføres for eksempel i et organisk løsningsmiddel (for eksempel isopropylalkohol, toluen, etanol, tetrahydrofuran) eller uten et løsningsmiddel, eventuelt i nærvær av en base (for eksempel natriumhydroksyd, natriumetoksyd) ved 0 ~ 200 °C.
Den ovennevnte reaksjon av forbindelsen med formel (IV) og forbindelsen med formel (V-2) er kjent og gjennomføres for eksempel i et organisk løsningsmiddel (for eksempel dimetoksyetan, dimetylformaid), i nærvær av en katalysator (for eksempel palladiumacetat) ved anvendelse av en fosfinforbindelse (for eksempel trifenylfosfin) ved 20°C ~ tilbakeløpstemperatur.
Oksidativ reaksjon gjennomføres ved hjelp av den ovennevnte metode.
På den annen side, i forbindelsen med formel (I-B), kan forbindelsen hvor R<1>"<3> er Cl-4 alkyl substituert med 1-2 OR<6> eller CONR<4>R<5>, dvs. forbindelsen (I-B-l)
hvor R<1>"<3>"<1> er Cl-4 alkyl substituert med 1-2 OR<6> eller CONR<4>R5 og hvor de andre symboler er som definert i det foregående,
også fremstilles ved å underkaste forbindelsen med formel (I-B-2)
hvor R<1>"<3>"<2> er Cl-4 alkyl substituert med 1-2 COOR<6> og hvor de andre symboler er som definert i det foregående, for en reduktiv reaksjon,
eller etter en reduktiv reaksjon, ved å reagere med forbindelsen med formel (VI)
X-R<6-3-2> (VI)
hvor R<6>"<3>"<2> er (i) Cl-10 alkyl, (ii) C2-10 alkenyl, (iii) C2-10 alkynyl, (iv) C3-15 mono- eller bi-karbocyklisk ring som er substituert med 1-5 R<18> eller er usubstituert, (v) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er substituert med 1-5 R<18> eller er usubstituert, eller (vi) Cl-4 alkyl substituert med 1-2 av gruppene valgt fra C3-10
mono- eller bi-karbocyklisk ring som er substituert med 1-5 R<18> eller er usubstituert og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er substituert med 1-5 R<18> eller er usubstituert,
eller med forbindelsen med formel (VII)
HNR<9>R<10>(VII)
hvor alle symbolene er som definert i det foregående.
Reduktiv reaksjon er kjent og gjennomføres for eksempel i et organisk løsningsmid-del (for eksempel dietyleter, metylenklorid, toluen) ved anvendelse av et reduksjonsmiddel (for eksempel diisopropylaluminumhydrid) ved -78 °C ~ 50 °C.
Reaksjonen av forbindelsen (VI) og forbindelsen etter reduktiv reaksjon av forbindelsen med formel (I-B-2) er kjent og gjennomføres for eksempel i et organisk løsningsmiddel (for eksempel dimetylformamid), ved anvendelse av en base (for eksempel natriumhydrid) ved 0 °C ~ 50 °C.
Reaksjonen av forbindelsen (VII) og forbindelsen etter reduktiv reaksjon av forbindelsen med formel (I-B-2) er kjent og gjennomføres for eksempel i et organisk løsningsmiddel (for eksempel metanol, etanol, isopropanol) ved 0 °C ~ 100 °C.
På den annen side, i forbindelsen med formel (I-B), kan forbindelsen hvor R<1> er NR<4>R<5> og R<4> og R<5> er hver uavhengig Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, og R<2> og R<3> er ikke OH, cyano, =N-ORu eller en gruppe inneholdende OH, cyano eller =N-OR<u>, dvs. forbindelsen (I-B-3)
hvor R<4b>"<3> og R<5b>"<3> hver uavhengig er Cl-15 alkyl som er substituert med 1-5 R eller er usubstituert og hvor de andre symbolene er som definert i det foregående, også fremstilles i henhold til det etterfølgende reaksjonsskjema (1).
I reaksjonsskjema (1), er R<4b>"<6> Cl-14 alkyl som er substituert med 1-5 R17 eller er usubstituert, R<5b>"<4> er Cl-14 alkyl som er substituert med 1-5 R17 eller er usubstituert og de andre symbolene er som definert i den foregående.
Amideringsreaksjon er kjent og gjennomføres for eksempel i et organisk løsnings-middel (f.eks. kloroform, metylenklorid, dietyleter, tetrahydrofuran) eller uten et løsningsmiddel ved anvendelse av acylhalogenid ( for eksempel oksalylklorid eller tionylklorid osv.) ved -20°C ~ tilbakeløpstemperatur, og det oppnådde acylhalo-genidderivat kan deretter reageres med amin i et organisk løsningsmiddel (for eksempel kloroform, metylenklorid, dietyleter, tetrahydrofuran), i nærvær av et tertiært amin (for eksempel pyridin, trietylamin, dimetylanilin, dimetylamino-pyridin) ved 0-40°C. Reaksjonen kan gjennomføres under en inert gass (for eksempel argon, nitrogen) for å unngå vann for å oppnå et foretrukket resultat.
Reduktiv reaksjon er kjent og gjennomføres for eksempel i et organisk løsnings-middel (for eksempel tetrahydrofuran) ved anvendelse av et reduksjonsmiddel (for eksempel borandimetylsulfidkompleks, litiumaluminumhydrid) ved 0 °C ~ til-bakeløpstemperatur.
Forbindelsen med formel (I-B-7) kan fremstilles ved å reagere forbindelsen med
hvor alle symbolene er som definert i det etterfølgende,
med en forbindelse med formel (III-2)
hvor alle symbolene er som definert i det etterfølgende,
eller underkastes suksessivt oksidativ reaksjon.
Den ovennevnte reaksjon av forbindelsen med formel (II-2) og forbindelsen med formel (III-2) er kjent og gjennomføres for eksempel i et organisk løsningsmiddel (for eksempel benzen, toluen) ved anvendelse av en syre (for eksempel p-toluen-sulfonsyre eller hydrat derav) ved fra romtemperatur til tilbakeløpstemperatur og deretter i et organisk løsningsmiddel (for eksempel tetrahydrofuran) ved anvendelse av en base (for eksempel litiumisopropylamid) ved -10 ~ 50 °C.
(C) I forbindelsen med formel (I) kan forbindelsen hvor minst av R og R er OH eller en gruppe inneholdende OH, dvs. forbindelsen med formel (I-C)
hvor hver Z<c>, Uc og R<3>"<c> har den samme betydning som Z, U og R3, med den betingelse at minst en av dem er OH eller en gruppe inneholdende OH og de andre symboler er som definert i det foregående, også fremstilles ved å underkaste, for demetylering, forbindelsen hvor minst en av R 2 og R 3 er metoksy eller en gruppe inneholdende metoksy i ■ forbindelsen med formel (I-B), dvs. forbindelsen med formel (I-B-8)
hvor hver Z<b>"<8>, Ub"8 og R<3>"<b>"<8> har den samme betydning som Z, U og R<3>, med den. betingelse at minst en av dem er metoksy eller en gruppe inneholdende metoksy og de andre symboler som definert i det foregående.
Demetyleringsreaksjon er kjent og gjennomføres for eksempel i et organisk løs-ningsmiddel (for eksempel metylenklorid, etylacetat, kloroform), ved anvendelse av Lewis syre (for eksempel bortribromid), ved -80 °C ~ 80 °C.
(D) I forbindelsen med formel (I), kan forbindelsen hvor minst en av R',R'ogR<J> er en gruppe inneholdende =N-OR<6> eller =N-OR<u>, dvs. forbindelsen med formel (I-D)
hvor hver R<1>"<d>, Z<d>, Ud og R<3>"<d> har den samme betydning som R<1>, Z, U og R<3>, med den betingelse at minst en av dem er en gruppe inneholdende =N-OR<6> eller =N-OR<n >og de andre symbolene er som definert i det foregående, fremstilles (1) ved å underkaste, for deacetalisering, forbindelsen hvor minst en av R , R og R<3> er en gruppe inneholdende -CH (O-Cl-4 alkyl)2 i forbindelsen med formel (I-B), dvs. forbindelsen med formel (I-B-9) (2) ved å underkaste, for oksidativ reaksjon, forbindelsen hvor R<1>"<8> er en gruppe inneholdende OH i forbindelsen med formel (I-B), eller forbindelsen med formel (I-C), dvs. forbindelsen med formel (I-B-10)
hvor hver R1"13"10, Zb<A0>, Ub_10 og R<3_b-10> har den samme betydning som R<1>, Z, U og R<3>, med den betingelse at R<1>^<10> er OH eller minst en av Zb-10, Ub_1° og R3*'™ er en gruppe inneholdende OH og de andre symboler er som definert i det foregående, og deretter for oksim-dannelsesreaksjon.
Deacetaliseringsreaksjon er kjent, og gjennomføres for eksempel i et organisk løsningsmiddel (for eksempel eddiksyre, dioksan), ved anvendelse av en syre (for eksempel saltsyre, svovelsyre) ved 0 ~ 100 °C.
Oksidativ reaksjon er kjent og gjennomføres for eksempel i et organisk løsnings-middel (for eksempel metylenklorid) eller uten et løsningsmiddel i nærvær av en base (for eksempel trietylamin, diisopropyletylamin), ved anvendelse av dimetyl-sulfoksyd og svoveltrioksydpyridinkompleks, dicykloheksylkarbodiimid eller oksalylklorid ved 0-50 °C.
Oksim-dannelsesreaksjon er kjent og gjennomføres for eksempel i et organisk løs-ningsmiddel (for eksempel pyridin), ved anvendelse av H2N-0-R<6> eller H2N-0-R<n>, ved 0-50 °C.
(E) I forbindelsen med formel (I), kan forbindelsen hvor minst en av R',R^ogR<J> er cyano eller en gruppe inneholdende cyano, dvs. forbindelsen med formel (I-E)
hvor hver R<1>"<6>, Ze, Ue og R3"<e> har den samme betydning som R<1>, Z, U og R<3>, med den betingelse at minst en av R<1>"<6>, Ze, U<e> og R<3>"<e> er cyano eller en gruppe inneholdende cyano og de andre symboler er som definert i det foregående,
fremstilles ved å underkaste, for dehydratiseringsreaksjon, forbindelsen hvor minst en av R<1>, R2 og R3 er en gruppe inneholdende =N-OH i forbindelsen med formel (I-D), dvs. forbindelsen (I-D-l)
hvor hver R<1>"""<1>, Z<d>"\ U<*>"<1> og R<3>"<1>"<1> har den samme betydning som R<1>, Z, U og R<3>, med den betingelse at minst en av R<1>"<*1>"<1>, Zd"\ Ud~ l og R3"d_1 er en gruppe inneholdende =N-OH og de andre symboler er som definert i det foregående.
Dehydratiseringsreaksjon er kjent og gjennomføres for eksempel i et organisk løs-ningsmiddel (for eksempel metylenklorid), i nærvær av en base (for eksempel trietylamin, diisopropyletylamin), ved anvendelse av vannfri trifluormetansulfon-syre eller triklormetylklorkarbonat ved 0 ~ 50 °C.
Forbindelsen med formel (IV) kan fremstilles ved å underkaste, for halogenerings-reaksjon, forbindelsen med formel (I-A).
Forbindelsen med formel (II), (III), (V), (VI) og (VII) kan være kjent per se, eller kan fremstilles ved hjelp av kjente metoder. Forbindelsen med formel (II)
hvor R har den samme betydning som R , med den betingelse at den ikke er OH, cyano, =N-OR'<1> eller en gruppe inneholdende OH, cyano eller =N-OR<u>, og R<3>"<a> er som definert i det foregående, kan f.eks. fremstilles ved å reagere forbindelsen med formel (VIII)
hvor alle symbolene er som definert i det foregående,
med hydradin. Dessuten, i forbindelsen med formel (III), er cyklopentanon-2-karboksylsyreetylester kommersielt tilgjengelig. I forbindelsen med formel (VI), er 1-cyano-l-(2-metyl-4-metoksyfenyl)propan-2-on beskrevet i dokumentet Bioorganic & Med. Chem., 8, 181-189 (2000).
Utgangsmaterialene og reagensene i det foreliggende oppfinnelse kan være kjente per se eller de kan fremstilles ved hjelp av kjente metoder.
I hver reaksjon i den foreliggende beskrivelse, kan reaksjonsprodukter renses ved konvensjonelle renseteknikker, for eksempel ved destillasjon under atmosfæretrykk eller redusert trykk, ved høytrykksvæskekromatografi, ved tynnsjiktskromatografi eller ved kolonnekromatografi ved anvendelse av silikagel eller magnesiumsilikat, eller ved vasking eller ved rekrystallisering. Rensing kan gjennomføres etter hver reaksjon eller etter en serie av reaksjoner.
Kort beskrivelse av tegningene
Figur 1 viser en grafisk fremstilling av tiden som rotter tilbrakte i de åpne armer og som fikk administrert 1,3, 10 og 30 mg/kg av den foreliggende forbindelse. Figur 2 viser en grafisk fremstilling av det antallet intredener inn i de åpne armer som rotter utførte som fikk administrert lj 3, 10 og 30 mg/kg av den foreliggende forbindelse.
Farmakologiske aktiviteter
Forbindelsen ifølge oppfinnelsen med formel (I) utviser CRF reseptor antagonistisk aktivitet, og en slik effekt av forbindelsen ifølge oppfinnelsen ble for eksempel bekreftet ved hjelp av de etterfølgende tester.
(1) Bindingsassay
cellemembranfremstilling
Etter at cellelinjen som uttrykte human CRFl reseptor (uttrykt cellelinje: CHO-K1 celler) var dyrket til den hadde nådd konfluens, ble cellene høstet med en skraper. Høstede celler ble vasket to ganger med PBS før de suspenderes i bindingsanalysebuffer (Tris-HCl (50 mM, pH 7,0), EDTA (2 mM, pH8,0), MgCl2 (10 mM)) avkjølt med is. Suspenderte celler ble homogenisert med en Downs-type homogenisator og underkastet sentrifugering ved 10 000 g for å samle membranfraksjonen. Den høstede cellemembranfraksjon ble resuspendert med en liten mengde av bindings-analysebufferen, og ble ytterligere fortynnet med nevnte buffer til 1 mg/ml. Membranfraksjonen som således ble oppnådd ble anvendt for bindingsanalyse.
Bindingsanalyse
50 ul [<125>I] h/r CRF fremstilt til 0,5 nM med bindingsanalysebuffer ble tilsatt til silikoniserte 1,5 ml rør. 1 ul av forbindelser fortynnet i passende multipler, DMSO (for anvendelse ved total binding), eller h/r CRF oppløsning (100 uM, for anvendelse ved ikke-spesifikk binding) ble tilsatt til rørene. Prøver på 50 ul av hvert av membranfraksjonspreparatene ble tilsatt til rørene for å initiere reaksjonen (slutt-konsentrasjon av [ 1 0 SI] h/r CRF: 0,25 nM), blandingen ble deretter inkubert i 2 timer ved romtemperatur. Etter terminering av reaksjonen, ble rørene underkastet sentrifugering ved 15 000 g for å samle membranfraksjonen. Supernatanten ble fjernet og pelleten ble vasket to ganger med avkjølt PBS (-) inneholdende 0,01% Triton X-100. Radioaktivitetsverdier for de respektive rør ble målt med en y-teller.
Den spesifikke binding ble utledet ved å subtrahere verdien for den ikke-spesifikke binding fra hver bindingsverdi.
Resultatene indikerte at disse forbindelser ifølge oppfinnelsen utviste potent affinitet på CRF1 reseptor (IC50: < 1 uM).
(2) Måling av en antifryktaktivitet ved anvendelse av en plussformet labyrint
("elevated plus-maze")
To armer (åpne og lukkede) av lik bredde og lengde (50 cm x 10 cm), som var anbrakt i en rett vinkel for å danne en plussformet labyrint var hevet til en høyde på 50 cm over bakkenivået. Den lukkede arm hadde en vegg på 40 cm. Belysning av begge ender i den åpne arm ble opprettholdt med konstant lys. Tretti minutter etter administrering av forskjellige doser av testforbindelser (5 ml/kg), ble SD hannrotter anbrakt i sentrum av den plussformede labyrint. Tiden som ble tilbrakt i de åpne armer og antallet inntredener inn i de respektive armer ble målt i løpet av en 5 minutters periode. Undersøkelsespersonalet for å måle indeksene var plassert på et fast sted under forløpet av forsøket.
Resultatene er vist i figur 1 og 2. Disse figurer indikerer at tiden tilbrakt i de åpne armer var signifikant forlenget og antallet inntredener inn i de åpne armer økte signifikant ved administrering av 3 og 10 mg/kg av forbindelsen i eksempel 2(78) ifølge oppfinnelsen, og dette viser således en anti-frykt effekt.
Toksisitet
Toksisiteten til forbindelsene ifølge oppfinnelsen er svært lav og det er derfor bekreftet at disse forbindelser er sikre for anvendelse som en medisin.
Industriell anvendbarhet
Anvendelse i farmasøytika
Forbindelsene ifølge oppfinnelsen med formel (I) er anvendbare for å utvise CRF reseptor antagonistisk aktivitet, for forebygging og/eller behandling av sykdommer indusert ved ekstraordinær sekresjon av CRF, for eksempel depresjon, enkeltepisode depresjon, tilbakevendende depresjon, post partum depresjon, depresjon indusert ved barnemishandling, angst, angstrelaterte lidelser (for eksempel panikklidelser, særlig fobier, frykt for å falle, sosiale fobier, obsessiv-kompulsiv lidelse), emosjonell lidelse, bipolar lidelse, posttraumatisk stresslidelse, peptisk ulcus, diaré, konstipasjon, irritabel tarm, inflammatorisk tarmsykdom (ulcerøs kolitt, Crohns sykdom), stress-indusert gastrointestinal forstyrrelse, nervøs emese, spiseforstyrrelse (for eksempel anorexia nervosa, bulimia nervosa), obesitas, stress-indusert søvnfor-styrrelse, søvnforstyrrelse indusert ved muskelfibersmerte, stress-indusert immun-suppresjon, stress-indusert hodepine, stress-indusert feber, stress-indusert smerte, postoperativt stress, revmatoid artritt, osteoartritt, osteoporose, psoriasis, tyreoidea dysfunksjon, uveitt, astma, upassende antidiaréhormonindusert lidelse, smerte, inflammasjon, allergisk sykdom, hodeskade, ryggmargskade, iskemisk nevron-skade, toksisitets-nevronskade, Cushings sykdom, slag, spasme, muskulær spasme, epilepsi, iskemisk sykdom, Parkinsons sykdom, Huntington sykdom, urininkonti-nenSj Alzheimers sykdom, senil demens av Alzheimer type, multi-infarkt demens, amyotrof lateralsklerose, hypoglykemi, kardiovaskulær eller hjerte-relatert sykdom (hypertensjon, takykardi, kongestiv hjertesvikt), narkotikaavhengighet eller alkoholavhengighet.
For de formål som er beskrevet over, kan forbindelsene med formel (I) ifølge oppfinnelsen, ikke-giftige salter derav, syreaddisjonssalter derav eller hydrater derav normalt administreres systemisk eller topisk, vanligvis ved oral eller parenteral administrering.
Dosene som skal administreres bestemmes avhengig av for eksempel alder, kropps-vekt, symptom, den ønskede terapeutiske effekt, administreringsruten og varigheten av behandlingen osv. I voksne personer, er dosene pr. person generelt fra 1 mg til 1000 mg ved oral administrering opp til flere ganger pr. døgn, og fra 0,1 mg til 100 mg ved parenteral administrering, foretrukket ved intravenøs administrering opp til flere ganger pr. døgn, eller ved kontinuerlig administrering mellom 1 og 24 timer pr. døgn inn i en vene.
Som nevnt over, vil de anvendte doser avhenge av forskjellige betingelser. Der er derfor tilfeller hvor doser som er lavere eller større enn de angitte områder kan anvendes.
Forbindelsene ifølge oppfinnelsen kan administreres i form av for eksempel faste preparater, flytende preparater eller andre preparater for oral administrering, injeksjoner, linimenter eller stikkpiller for parenteral administrering.
Faste preparater for. oral administrering inkluderer komprimerte tabletter, piller, kapsler, dispergerbare pulvere og granuler. Kapsler inkluderer harde kapsler og . myke kapsler.
I slike faste former kan en eller flere av de aktive forbindelser blandes med vehikler som laktose, mannitol, glukose, mikrokrystallinsk cellulose, stivelse, bindemidler som hydroksypropylcellulose, polyvinylpyrrolidon eller magnesiummetasilikat-aluminiat, desintegrerende midler som cellulosekalsiumglykolat, smøremidler som magnesiumstearat, stabiliseringsmidler og oppløsnings-hjelpestoffer som glutaminsyre eller asparginsyre, og fremstilles i henhold til metoder som er vel kjent innenfor normal farmasøytisk praksis. De faste former kan om ønsket belegges med beleg-ningsmidler som sukker, gelatin, hydroksypropylcellulose- eller hydroksypropyl-metylcelluloseftalat, eller kan belegges med to eller flere filmer. Et hvilket som helst ytterligere overtrekk kan inkludere inneslutting i kapsler av absorberbare materialer som gelatin.
Flytende former for oral administrering inkluderer farmasøytisk aksepterbare opp-løsninger, suspensjoner og emulsjoner, siruper og eliksirer. I slike former kan en eller flere av de aktive forbindelser være oppløst, suspendert eller emulgert i ett eller flere fortynningsmidler som er vanlig anvendt innen teknikken, som renset vann, etanol eller en blanding derav. Dessuten kan slike flytende former også inneholde enkelte tilsetningsstoffer som fuktemidler, suspensjonsmidler, emulgeringsmidler, søtningsstoffer, aromastoffer, preserveringsmidler eller buffere.
Injeksjoner for parenteral administrering inkluderer sterile vandige suspensjoner, emulsjoner og faste former som er oppløst eller suspendert i ett eller flere løsnings-midler for injeksjon umiddelbart før bruk. I injeksjoner kan en eller flere av de aktive forbindelser oppløses, suspenderes eller emulgeres i ett eller flere løsnings-midler. Løsningsmidlene kan inkludere destillert vann for injeksjon, fysiologisk saltoppløsning, vegetabilsk olje, propylenglykol, polyetylenglykol, alkohol, for eksempel etanol, eller en blanding derav. Injeksjoner kan inneholde enkelte tilsetningsstoffer som stabiliseringsmidler, oppløsnings-adjuvanser som glutaminsyre, asparginsyre eller POLYSORBATE80 (handelsnavn), suspensjonsmidler, emulgeringsmidler, lindrende middel, buffere, preserveringsmidler. De kan steriliseres i et sluttrinn, eller kan fremstilles og korrigeres i henhold til sterile metoder. De kan også fremstilles i form av sterile faste former, for eksempel frysetørkede produkter, som kan oppløses i sterilt vann eller annet fortynningsmiddel for injeksjon umiddelbart før bruk.
Andre former for parenteral administrering inkluderer væske for ekstern bruk, salver og endermatiske linimenter, inhalasjonspreparater, sprayer, stikkpiller og pessarer for vaginal administrering som inneholder en eller flere av de aktive forbindelsene og som kan fremstilles ved hjelp av kjente metoder. Spraypreparater kan inneholde ytterligere substanser annet enn fortynningsmidler, som stabiliseringsmidler, som natriumsulfat, isotoniske buffere som natriumklorid, natriumcitrat eller sitronsyre. For fremstilling av slike sprayer kan for eksempel metoden som beskrevet i US patenter nr. 2 868 691 eller 3 095 355 anvendes.
De etterfølgende referanseeksempler og eksempler illustrerer oppfinnelsen. Løsningsmidlene i parenteser viser utviklings- eller elueringsløsningsmidlene og forholdene for de anvendte løsningsmidler er uttrykt i volum i de kromatiske separasjoner og TLC (tynnsjiktkromatografi).
NMR dataene er vist med løsningsmiddelet anvendt i målingene, i parenteser.
Referanseeksempel 1
2-metyl-4-metoksyfenylacetonitril
Under en argonatmosfære, ble en blanding av N-bromsuccinimid (17,8 g) og 2, 2'-azobisisobutyronitril (492 mg) tilsatt til en oppløsning av l,2-dimetyl-4-metoksy-benzen (13,6 g) i karbontetraklorid (200 ml). Blandingen ble oppvarmet med tilbakeløp i 6,5 timer. Reaksjonsblandingen ble avkjølt med et isbad. En uopp-løselig substans ble fjernet ved filtrering og vasket med karbontetraklorid. Et kombinert filtrat ble konsentrert. Resten ble oppløst i N, N-dimetylformamid (100 ml) og natriumcyanid (9,86 g) ble tilsatt til blandingen. Blandingen ble omrørt over natten ved romtemperatur. Reaksjonsblandingen ble helt inn i vann, og blandingen ble ekstrahert med dietyleter. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (etylacetat: n-heksan =1:6
- > 1 : 4) til å gi tittelforbindelsen (11,78 g) med de følgende fysiske data.
TLC: Rf 0.20 (n-heksan : etylacetat = 9:1);
NMR (300MHz, CDC13) : 87.24 (d, J = 8.0Hz, 1H), 6.78-6.72 (m, 2H), 3.79 (s, 3H), 3.60 (s, 2H), 2.32 (s, 3H).
Referanseeksempel 2
1 -cyano-1 -(2-metyl-4-metoksyfenyl)propan-2-on
Under en argonatmosfære, ble det til en oppløsning av forbindelsen fremstilt i referanseeksempel 1 (11,7 g) i etylacetat (60 ml), tilsatt metallisk natrium (2,3 g) i stort antall. Blandingen ble omrørt i 2 timer ved 50 °C. Etylacetat (40 ml) ble tilsatt til reaksjonsblandingen, og blandingen ble oppvarmet med tilbakeløp i 2,5 timer og deretter omrørt over natten ved romtemperatur. En presipitert substans ble samlet ved filtrering og vasket med dietyleter. Den oppnådde krystall ble oppløst i vann (300 ml). Oppløsningen ble innstilt til pH 4 ved å tilsette 2N saltsyre, og ekstrahert med etylacetat. Det organiske laget ble tørket over vannfritt natriumsulfat og konsentrert til å gi tittelforbindelsen (12,06 g) med de følgende fysiske data.
TLC: Rf 0.45 (n-heksan : etylacetat =1:1).
Referanseeksempel 3
2-klor-4-metoksyborsyre
En oppløsning av 3-klor-4-bromanisol (2,14 g) i vannfritt tetrahydrofuran (10 ml) ble avkjølt til -78°C. 1,56 M n-butyllitium/heksan (6,5 ml) ble dryppet inn i oppløsningen og blandingen ble omrørt i 30 minutter. Triisopropylborate (2,3 ml) ble dryppet inn i reaksjonsblandingen, og blandingen ble omrørt i 2 timer ved
-78°C. En mettet vandig oppløsning av ammoniumklorid ble tilsatt til reaksjonsblandingen, og blandingen ble ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Et oppnådd faststoff ble vasket med t-butylmetyleter
(4 ml), filtrert og tørket til å gi tittelforbindelsen (681 mg) med de etterfølgende fysiske data.
TLC: Rf 0.55 (metylenklorid : metanol = 19 : 1);
NMR (300MHz, CDC13): 87.22 (d, J = 8.4Hz, 1H), 6.93 (d, J = 2.4Hz, 1H), 6.86 (dd, J = 8.4, 2.4Hz, 1H), 3.79 (s, 3H).
Referanseeksempel 4
4-(2-klor-4-metoksyfenyl)-5-metylisoksazol
Til en suspensjon av forbindelsen fremstilt i referanseeksempel 3 (644 mg), 4-jod-5-metylisoksazol (658 mg) og natriumbikarbonat (791 mg) i dimetoksyetan (2,5 ml)/vann (2,5 ml), ble tetrakis (trifenylfosfin) palladium (36 mg) tilsatt. Blandingen ble omrørt i 16 timer ved 80°C. Til reaksjonsblandingen som var avkjølt til romtemperatur ble vann og etylacetat tilsatt. En oppløselig substans ble fjernet ved filtrering. Et organisk lag ble separert fra filtratet, det ble vasket med en mettet vandig natriumkloridoppløsning, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (n-heksan : etylacetat = 19 : 1 —> 15 : 1) til å gi tittelforbindelsen (637 mg) med de etterfølgende fysiske data. TLC: Rf 0.44 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 8.29 (brs, 1H), 7.16 (d, J = 8.4Hz, 1H), 7.04 (d, J = 2.4Hz, 1H), 6.87 (dd, J = 8.4,2.4Hz, 1H), 3.84 (s, 3H), 2.41 (brs, 3H).
Referanseeksempel 5
1 -cyano-1 -(2-klor-4-metoksyfenyl)propan-2-on
Til en oppløsning av forbindelsen fremstilt i referanseeksempel 4 (623 mg) i metanol (2,8 ml), ble 1,5M natriummetoksyd/metanol (2,8 ml) tilsatt og blandingen ble omrørt i 4 timer. Reaksjonsblandingen ble fortynnet med vann, og vasket med heksan/t-butylmetyleter (10 ml, 1:1). Vannlaget ble innstilt til pH 5 ved å tilsette 4N saltsyre (1 ml), og ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumbikarbonat og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert til å gi tittelforbindelsen (497 mg) med de etterfølgende fysiske data.
TLC: Rf 0.13 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 87.38 (d, J = 8.4Hz, 1H), 7.00 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 8.4, 2.4Hz, 1H), 5.11 (s, 1H), 3.83 (s, 3H), 2.29 (s, 3H).
Referanseeksempel 6
5-amino-3-metyl-4-(2-metyl-4-metoksyfenyl)pyrazol
Til en oppløsning av forbindelsen fremstilt i referanseeksempel 2 (8,63 g) i toluen (200 ml), ble eddiksyre (8,0 ml) og hydrazinonhydrat (4,5 ml) tilsatt. Blandingen ble oppvarmet med tilbakeløp i 5,5 timer og omrørt over natten ved romtemperatur. Reaksjonsblandingen ble konsentrert. 6N saltsyre ble tilsatt til en rest og oppløs-ningen ble ekstrahert med etylacetat/n-heksan (30 ml/30 ml). Et vannlag ble gjort basisk ved å tilsette konsentrert vandig ammoniakk, og ekstrahert med etylacetat. Det organiske laget ble tørket over vannfritt natriumsulfat og konsentrert til å gi tittelforbindelsen (8,38 g) med de etterfølgende fysiske data.
TLC: Rf 0.30 (kloroform : metanol = 9:1);
NMR (300MHz, CDC13) : 87.08 (d, J = 8.0Hz, 1H), 6.84 (d, J = 2.5Hz, 1H), 6.77 (dd, J = 8.0, 2.5Hz, 1H), 4.10 (brs, 3H), 3.83 (s, 3H), 2.18 (s, 3H), 2.07 (s, 3H).
Eksempel 1
8-hydroksy-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Til en oppløsning av forbindelsen fremstilt i referanseeksempel 6 (500 mg) i eddiksyre (3 ml), ble etylcyklopentanon-2-karboksylat (0,40 ml) tilsatt. Blandingen ble oppvarmet med tilbakeløp i 3 timer. Etter at reaksjonsblandingen var avkjølt til romtemperatur, ble dietyleter/n-heksan (10 ml, 2 : 1) tilsatt til blandingen. En presipitert krystall ble samlet ved filtrering og krystallen ble vasket med dietyleter/n-heksan (10 ml, 2 : 1), og tørket til å gi tittelforbindelsen (480 mg) med de etterfølgende fysiske data.
TLC: Rf 0.47 (kloroform : metanol = 9:1);
NMR (300MHz, DMSO-d6): 611.90 (brs, 1H), 7.10 (d, J = 8.0Hz, 1H), 6.93 (d, J = 3.0Hz, 1H), 6.83 (dd, J = 8.0, 3.0Hz, 1H), 3.78 (s, 3H), 2.81 (t, J = 7.5Hz, 2H), 2.66 (t, J = 7.5Hz, 2H), 2.07 (s, 3H), 2.05 (s, 3H), 2.03 (rn, 2H).
Referanseeksempel 7
8-klor-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Til en suspensjon av forbindelsen fremstilt i eksempel 1 (400 mg) i toluen (4 ml), ble fosforoksyklorid (0,60 ml) og dietylanilin (0,25 ml) tilsatt. Blandingen ble oppvarmet med tilbakeløp i 1 time. Reaksjonsblandingen ble avkjølt og helt inn i en avkjølt vandig oppløsning av natriumbikarbonat. Blandingen ble omrørt i 10 minutter for å nedbryte overskudd av fosforoksyklorid. Reaksjonsblandingen ble ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (etylacetat: n-heksan =1:3 —> 1 : 2) til å gi tittelforbindelsen (411 mg) med de etterfølgende fysiske data. TLC: Rf 0.52 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 87.15 (d, J = 8.5Hz, 1H), 6.88 (d, J = 2.5Hz, 1H), 6.81 (dd, J = 8.5,2.5Hz, 1H), 3.83 (s, 3H), 3.09-3.00 (m, 4H), 2.40 (s, 3H), 2.23 (m, 2H), 2.15 (s, 3H).
Eksempel 2
8-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
En blanding av forbindelsen fremstilt i referanseeksempel 7 (150 mg) og 3-pentylamin (0,6 ml) ble omrørt i 1 time ved 140 °C. Reaksjonsblandingen ble avkjølt og renset ved kolonnekromatografi på silikagel (etylacetat: n-heksan =1:3) til å gi tittelforbindelsen (169 mg) med de etterfølgende fysiske data.
TLC: Rf 0.57 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 87.15 (d, J = 8.5Hz, 1H), 6.85 (d, J = 3.0Hz, 1H), 6.78 (dd, J = 8.5, 3.0Hz, 1H), 6.21 (d, J = 10.5Hz, 1H), 3.82 (s, 3H), 3.81 (m, 1H), 3.08 (t, J = 7.0Hz, 2H), 2.89 (t, J = 8.0Hz, 2H), 2.30 (s, 3H), 2.19 (s, 3H), 2.14 (m, 2H), 1.69 (m4H), 1.02 (m, 6H).
Eksempel 2(1) - 2(365)
De etterfølgende forbindelser ble oppnådd ved å anvende en tilsvarende forbindelse i stedet for l,2-dimetyl-4-metoksybenzen, ved den samme prosedyre som en serie av reaksjoner av Referanseeksempel 1 -» Referanseeksempel 2 -» Referanseeksempel 6 -> Eksempel 1 ved anvendelse av en tilsvarende forbindelse i stedet for etylcyklo-pentanon-2-karboksylat -» Referanseeksempel 7 -> Eksempel 2 ved anvendelse av en tilsvarende forbindelse i stedet for 3-pentylamin, eller ved anvendelse av forbindelsen fremstilt i Referanseeksempel 5 eller en tilsvarende forbindelse, ved den samme prosedyre som en serie av reaksjoner av Referanseeksempel 6 —> Eksempel 1 -» Referanseeksempel 7 -> Eksempel 2, eller ved en kjent metode for å oppnå et salt av forbindelsen.
Eksempel 2(1)
8-(N-etyl-N-n-butylamino)-2-metoksymetyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihy dro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.43 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.22 (d, J = 8.7Hz, 1 H), 6.84 (d, J = 2.7Hz, 1 H), 6.77 (dd, J = 8.7,2.7Hz, 1 H), 4.49 (m, 2 H), 3.81 (s, 3 H), 3.67 (q, J = 7.2Hz, 2 H), 3.61 (t, J = 7.2Hz, 2 H), 3.33 (s, 3 H), 2.97 (t, J = 7.2Hz, 2 H), 2.91 (t, J = 7.8Hz, 2 H), 2.19 (s, 3 H), 2.13 (m, 2 H), 1.55 (m, 2 H), 1.35 (m, 2 H), 1.17 (t, J = 7.2Hz, 3 H), 0.89 (t, J = 7.2Hz, 3 H).
Eksempel 2(2) 8-(N-propyl-N-(2-hydroksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyf^ dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.80 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 57.14 (d, J = 8.4Hz, 1 H), 6.86 (d, J = 2.7Hz, 1 H), 6.79 (dd, J = 8.4, 2.7Hz, 1 H), 3.90 (t, J = 4.8Hz, 2 H), 3.83 (s, 3 H), 3.64 (m, 2 H), 3.43 (m, 2 H), 2.98 (t, J = 7.2Hz, 2 H), 2.92 (t, J = 7.8Hz, 2 H), 2.31 (s, 3 H), 2.17 (s, 3 H), 2.15 (m, 2 H), 1.58 (m, 2 H), 0.95 (t, J = 7.2Hz, 3 H).
Eksempel 2(3)
8-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-tieno[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.51 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.15 (d, J = 8.5Hz, 1H), 6.86 (d, J = 2.5Hz, 1H), 6.79 (dd, J = 8.5, 2.5Hz, 1H), 6.44 (d, J = 10.0Hz, 1H), 4.32 (brs, 2H), 4.14 (brs, 2H), 3.82 (s, 3H), 3.76 (m, 1H), 2.32 (s, 3H), 2.18 (s, 3H), 1.84-1.57 (m 4H), 1.03 (t, J = 7.0Hz, 6H).
Eksempel 2(4)
9-(3-pentylamino)-6-metyl-5-(2-metyl-4-metoksyfenyl)-2,3-dihydro-tieno[3,2-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.40 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.5Hz, 1H), 6.85 (d, J = 3.0Hz, 1H), 6.79 (dd, J = 8.5, 3.0Hz, 1H), 6.17 (d, J = 10.0Hz, 1H), 3.99 (m, 1H), 3.82 (s, 3H), 3.36-3.20 (m, 4H), 2.30 (s, 3H), 2.18 (s, 3H), 1.82-1.56 (m 4H), 1.03 (t, J = 7.5Hz, 6H).
Eksempel 2(5)
8-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.33 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.5Hz, 1H), 6.86 (d, J = 2.5Hz, 1H), 6.79 (dd, J = 8.5, 2.5Hz, 1H), 6.32 (d, J = 10.0Hz, 1H), 5.29 (s, 2H), 4.90 (brs, 2H), 3.82 (s, 3H), 3.24 (m, 1H), 2.33 (s, 3H), 2.18 (s, 3H), 1.84-1.56 (m 4H), 1.02 (t, J = 7.5Hz, 6H).
Eksempel 2(6)
9-(3-pentylamino)-6-metyl-5-(2-metyl-4-metoksyfenyl)-2,3-dihydro-furo[3,2-d]pyrazolo[ 1,5 -a]pyrimidin
TLC: Rf 0.43 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.31 (brs, 1H), 7.12 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.4, 2.7Hz, 1H), 4.76 (t, J = 9.0Hz, 2H), 4.30 (m, 1H), 3.83 (s, 3H), 3.74 (t, J = 9.0Hz, 2H), 2.34 (s, 3H), 2.19 (s, 3H), 1.90-1.70 (m, 4H), 1.04 (m,6H).
Eksempel 2(7)
9-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5, 6,7, 8-tetrahydro-pyrazolo[3,2-b]kinazolinhydroklorid
TLC: Rf 0.45 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 13.04 (brs, 1H), 7.91 (brs, 1H), 7.15 (d, J = 8.5Hz, 1H), 6.96 (d, J = 2.5Hz, 1H), 6.87 (dd, J = 8.5, 2.5Hz, 1H), 5.65 (brs, 1H), 3.79 (s, 3H), 2.75 (m, 2H), 2.58 (m, 2H), 2.19 (s, 3H), 2.05 (s, 3H), 1.88-1.64(m, 8H), 0.91 (t, J = 7.5Hz, 6H).
Eksempel 2(8)
6-metyl-5-(2-metyl-4-metoksyfenyl)-9-[(2S, 4R)-4-metoksy-2-metoksymetylpyrolidin-l-yl]-2, 3-dihydro-furo[3,2-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.24 (n-heksan : etylacetat =1:1);
NMR (300MHz, DMSO-d6): 8 7.09 (d, J = 7.5Hz, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 7.5, 2.4Hz, 1H), 5.07 (brs, 1H), 4.66 (dt, J = 9.0, 9.0Hz, 1H), 4.56 (dt, J = 9.0, 9.0Hz, 1H), 4.24 (dd, J = 12.6, 3.6Hz, 1H), 4.05 (brs, 1H), 3.85 (d, J = 12.6Hz, 1H), 3.77 (s, 3H), 3.42 (dd, J = 10.2, 3.9Hz, 1H), 3.33 (dd, J = 10.2, 5.1Hz, 1H), 3.22 (dd, J = 9.0, 9.0Hz, 2H), 3.21 (s, 3H), 3.18 (s, 3H), 2.18 (s, 3H), 2.07 (s, 3H), 2.30-1.95 (m, 2H).
Eksempel 2(9)
9-(3-pentylamino)-6-metyl-5-(2-metyl-4-metoksyfenyl)-2,3-dihydro-pyrrolo[3,2-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.37 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): § 7.16 (d, J = 8.4Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 2.7, 8.4Hz, 1H), 5.86 (d, J = 10.5Hz, 1H), 4.07 (m, 1H), 3.82 (s, 3H), 3.58 (t, J = 8.1Hz, 2H), 3.06 (t, J = 8.1Hz, 2H), 2.30 (s, 3H), 2.19 (s, 3H), 1.52-1.82 (m, 4H), 1.01 (m,6H).
Eksempel 2(10)
2-metyl-3-(2-metyl-4-metoksyfenyl)-8-[(2S, 4R)-4-metoksy-2-metoksymetylpyrolidin-l-yl]-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a] pyrimidinhydroklorid
TLC: Rf 0.30 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.15 og 7.07 (d, J = 8.4Hz, to konformerer, 1H), 6.89 og 6.87 (d, J = 2.7Hz, to konformerer, 1H), 6.83 og 6.80 (dd, J = 8.4,2.7Hz, to konformerer, 1H), 5.65 (brs, 1H), 4.32-4.10 (m, 3H), 3.82 (s, 3H), 3.50-3.40 (m, 4H), 3.367 og 3.361 (s, to konformerer, 3H), 3.29 og 3.28 (s, to konformerer, 3H), 3.23-2.99 (m, 2H), 2.42 (m, 1H), 2.30-2.10 (m, 3H), 2.245 og 2.240 (s, to konformerer, 3H), 2.22 og 2.14 (s, to konformerer, 3H).
Eksempel 2(11)
2-metyl-3-(2-metyl-4-metoksyfenyl)-8-[(2S, 4R)-4-metoksy-2-metoksymetyl-pyrolidin-l-yl]-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.22 (n-heksan : etylacetat =1:1);
NMR (300MHz, DMSO-d6) 7.10 (brs, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 8.1, 2.4Hz, 1H), 5.33 (d, J = 10.8Hz, 1H), 5.25 (brs, 1H), 5.15 (d, J = 10.8Hz, 1H), 4.85 (d, J = 14.4Hz, 1H), 4.75 (d, J = 14.4Hz, 1H), 4.10-3.85 (m, 3H), 3.77 (s, 3H), 3.39 (dd, J = 9.9, 4.5Hz, 1H), 3.28 (dd, J = 9.9, 5.1Hz, 1H), 3.22 (s, 3H), 3.15 (s, 3H), 2.25 (m, 1H), 2.21 (s, 3H), 2.15-2.00 (m, 4H).
Eksempel 2(12)
6-metyl-5-(2-metyl-4-metoksyfenyl)-9-[(2S, 4R)-4-metoksy-2-metoksymetylpyrolidin-l-yl]-2, 3-dihydro-pyrrolo[3,2-d]pyrazolo[l,5-a] pyrimidin
TLC: Rf 0.43 (kloroform : metanol = 20 : 1) ;
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 2.7, 8.4Hz, 1H), 4.71 (m, 1H), 4.20 (m, 1H), 4.06 (m, 1H), 3.82 (s, 3H), 3.60 (t, J = 7.8Hz, 2H), 3.54 (m, 1H), 3.48 (dd, J = 4.5, 9.6Hz, 1H), 3.39 (m, 1H), 3.34 (s, 3H), 3.28 (s, 3H), 3.09 (m, 2H), 2.24-2.40 (m, 4H), 2.18 (s, 3H), 2.01 (m, 1H).
Eksempel 2(13)
8-isopropylamino-2-me1yl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d] pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.34 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.15 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.4, 2.7Hz, 1H), 6.39 (d, J = 9.6Hz, 1H), 5.32 (s, 2H), 4.90 (s, 2H), 3.82 (s, 3H), 3.74 (m, 1H), 2.32 (s, 3H), 2.16 (s, 3H), 1.41 (d, J = 6.6Hz, 6H).
Eksempel 2(14)
8-[(2S)-1,1 -dimetoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.26 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 8.1, 2.4Hz, 1H), 6.57 (brd, J = 11.1Hz, 1H), 5.36 (d, J = 9.9Hz, 1H), 5.26 (d, J = 9.9Hz, 1H), 4.90 (s, 2H), 4.33 (d, J = 3.9Hz, 1H), 3.82 (s, 3H), 3.50 (s, 3H), 3.48 (s, 3H), 3.39 (m, 1H), 2.32 (s, 3H), 2.17 (s, 3H), 1.88 (m, 1H), 1.68 (m, 1H), 1.04 (brs, 3H).
Eksempel 2(15)
8-[(2S)-1,1 -dimetoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.15 (d, J = 8.1Hz, 1H), 6.85 (d, J = 3.0Hz, 1H), 6.77 (dd, J = 8.1, 3.0Hz, 1H), 6.47 (brd, J= 11.8Hz, 1H), 4.34 (brs, 1H), 4.01 (m, 1H), 3.81 (s, 3H), 3.49 (s, 6H), 3.19-3.00 (m, 2H), 2.89 (t, J = 7.8Hz, 2H), 2.30 (s, 3H), 2.18 (s, 3H), 2.13 (m, 2H), 1.86 (m, 1H), 1.65 (m, 1H), 1.04 (brs, 3H).
Eksempel 2(16)
8-(l, 3-dimetoksypropan-2-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.42 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.14 (d, J = 8.1Hz, 1H), 6.87 (brd, J = 8.1Hz, 1H), 6.85 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 8.1,2.4Hz, 1H), 5.33 (s, 2H), 4.89 (s, 2H), 3.81 (s, 3H), 3.75 (m, 1H), 3.62 (d, J = 4.8Hz, 4H), 3.42 (s, 6H), 2.33 (s, 3H), 2.16 (s, 3H).
Eksempel 2(17)
8-bis(2-metoksyetyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.24 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.1Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.1, 2.7Hz, 1H), 5.22 (s, 2H), 4.89 (s, 2H), 3.88 (t, J = 6.0Hz, 4H), 3.82 (s, 3H), 3.55 (t, J = 6.0Hz, 4H), 3.30 (s, 6H), 2.33 (s, 3H), 2.16 (s, 3H).
Eksempel 2(18)
8-(l, 3-dimetoksypropan-2-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.53 (n-heksan : etylacetat = 1:1);
NMR (300MHz, CDC13): 8 7.01 (d, J = 8.4Hz, 1H), 6.72 (d, J = 2.7Hz, 1H), 6.64 (dd, J = 8.4, 2.7Hz, 1H), 6.60 (d, J = 9.9Hz, 1H), 4.14 (m, 1H), 3.69 (s, 3H), 3.50 (d, J = 5.4Hz, 4H), 3.30 (s, 6H), 2.99 (t, J = 7.2Hz, 2H), 2.76 (t, J = 7.8Hz, 2H), 2.18 (s, 3H),2.04 (s, 3H),2.01 (m, 2H).
Eksempel 2(19)
8-bis(2-metoksyetyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.41 (n-heksan : etylacetat = 1:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.4, 2.7Hz, 1H), 3.88 (t, J = 5.7Hz, 4H), 3.82 (s, 3H), 3.52 (t, J = 5.7Hz, 4H), 3.30 (s, 6H), 3.00 (t, J = 6.9Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H),2.14(m, 2H).
Eksempel 2(20)
(5RS)-8-(3-pentylamino)-2, 5-dimetyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.44 (n-heksan : etylacetat = 2:1);
NMR (300MHz, DMSO-d6): 8 8.71 (brs, 1H), 7.15 (d, J = 8.5Hz, 1H), 6.93 (d, J = 2.5Hz, 1H), 6.85 (dd, J = 8.5,2.5Hz, 1H), 5.70 (brs, 1H), 5.25 (dd, J = 10.0, 2.0Hz, 1H), 5.17 (d, J = 10.0Hz, 1H), 5.11 (m, 1H), 3.79 (s, 3H), 3.26 (m, 1H), 2.26 (s, 3H), 2.10 (s, 3H), 1.83-1.57 (m 4H), 1.41 (d, J = 5.5Hz, 3H), 0.93-0.83 (m, 6H).
Eksempel 2(21)
8-(3-pentylamino)-2-metyl-3-(2,4-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.50 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.50 (d, J = 2.0Hz, 1H), 7.35 (d, J = 8.5Hz, 1H), 7.29 (dd, J = 8.5, 2.0Hz, 1H), 6.23 (d, J = 10.5Hz, 1H), 3.81 (m, 1H), 3.09 (t, J = 7.5Hz, 2H), 2.91 (t, J = 7.5Hz, 2H), 2.34 (s, 3H), 2.15 (m, 2H), 1.82-1.55 (m 4H), 1.01 (t, J = 7.5Hz, 6H).
Eksempel 2(22)
8-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-pyrrolo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.48 (kloroform : metanol = 10 : 1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.1H, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 2.7, 8.1Hz, 1H), 6.29 (d, J = 10.2Hz, 1H), 4.43 (s, 2H), 4.10 (s, 2H), 3.82 (s, 3H), 3.49 (m, 1H), 2.32 (s, 3H), 2.18 (s, 3H), 1.55-1.84 (m, 4H), 1.02 (m, 6H).
Eksempel 2(23) 8-dietylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.67 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.4, 2.7Hz, 1H), 3.82 (s, 3H), 3.66 (q, J = 7.2Hz, 4H), 2.99 (t, J = 7.5Hz, 2H), 2.91 (t, J = 7.5Hz, 2H), 2.33 (s, 3H), 2.19 (s, 3H), 2.13 (m, 2H), 1.18 (t, J = 7.2Hz, 6H).
Eksempel 2(24)
8-(N-etyl-N-n-butylamino)-2-metyl-3-(2,4-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.78 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 5 7.17 (d, J = 8.4Hz, 1H), 6.86 (d, J = 3.0Hz, 1H), 6.79 (dd, J = 8.4, 3.0Hz, 1H), 3.82 (s, 3H), 3.70-3.56 (m, 4H), 2.97 (t, J = 6.9Hz, 2H), 2.91 (t, J = 7.7Hz, 2H), 2.33 (s, 3H), 2.19 (s, 3H), 2.13 (m, 2H), 1.55 (m, 2H), 1.32 (m, 2H), 1.17 (t, J = 7.2Hz, 3H), 0.90 (t, J = 7.2Hz, 3H).
Eksempel 2(25)
8-dicyklopropylmetylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.40 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.15 (d, J = 8.1Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.1,2.7Hz, 1H), 6.36 (d, J = 10.2Hz, 1H), 3.82 (s, 3H), 3.41 (m, 1H), 3.01 (t, J = 7.2Hz, 2H), 2.87 (t, J = 8.1Hz, 2H), 2.31 (s, 3H), 2.19 (s, 3H), 2.10 (m, 2H), 1.20-1.08 (m, 2H), 0.66-0.32 (m, 8H).
Eksempel 2(26)
8-(N-propyl-N-(2-hydroksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.26 (n-heksan : etylacetat =1:2);
NMR (300MHz, CDC13): 87.14 (d, J = 8.4Hz, 1 H), 6.87 (d, J = 2.7Hz, 1 H), 6.80 (dd, J = 8.4, 2.7Hz, 1 H), 6.54 (brs, 1 H), 5.21 (s, 2 H), 4.89 (s, 2 H), 3.96 (brt, J = 4.8Hz, 2 H), 3.83 (s, 3 H), 3.80 (m, 2 H), 3.29 (t, J = 7.5Hz, 2 H), 2.33 (s, 3 H), 2.17 (s, 3 H), 1.63 (m, 2 H), 1.00 (t, J = 7.5Hz, 3 H).
Eksempel 2(27)
8-(3-pentylamino)-2-metoksymetyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.27 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.19 (d, J = 8.5Hz, 1H), 6.85 (d, J = 2.5Hz, 1H), 6.78 (dd, J = 8.5,2.5Hz, 1H), 6.32 (d, J = 10.5Hz, 1H), 4.54-4.40 (m, 2H), 3.82 (s, 3H), 3.81 (m, 1H), 3.37 (s, 3H), 3.10 (t, J = 7.0Hz, 2H), 2.91 (t, J = 8.0Hz, 2H), 2.20 (s, 3H), 2.14 (m, 2H), 1.80-1.53 (m, 4H), 1.08-0.94 (m, 6H).
Eksempel 2(28)
8-(3-pentylamino)-2-metyl-3-(l, 3-dioksaindan-5-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.61 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.22 (d, J = 1.5Hz, 1H), 7.10 (dd, J = 1.5, 8.1Hz, 1H), 6.89 (d, J = 8.1Hz, 1H), 6.20 (br d, J = 10.5Hz, 1H), 5.96 (s, 2H), 3.80 (m, 1H), 3.08 (t, J = 7.5Hz, 2H), 2.94 (t, J = 8.1Hz, 2H), 2.52 (s, 3H), 2.15 (m, 2H), 1.51-1.80 (m, 4H), 1.00 (t, J = 7.5Hz, 6H).
Eksempel 2(29)
8-(3-pentylamino)-2-metyl-3-(3,4-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.56 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 2.1Hz, 1H), 7.19 (dd, J = 2.1, 8.1Hz, 1H), 6.96 (d, J = 8.1Hz, 1H), 6.20 (br d, J = 10.5Hz, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.80 (m,lH), 3.09 (t, J = 7.2Hz, 2H), 2.94 (t, J = 7.5Hz, 2H), 2.55 (s, 3H), 2.16 (m, 2H), 1.53-1.81 (m, 4H), 1.00 (t, J = 7.2Hz, 6H).
Eksempel 2(30) 8-cyklopropylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.33 (n-heksan : etylacetat = 3:2);
NMR (300MHz, CDC13): 5 7.14 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.1, 2.7Hz, 1H), 6.62 (brs, 1H), 5.54 (brs, 2H), 4.91 (brs, 2H), 3.82 (s, 3H), 2.89 (m, 1H), 2.30 (s, 3H), 2.15 (s, 3H), 0.98-0.84 (m, 4H).
Eksempel 2(31)
8-(3-pentylamino)-2-cyklobutyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.62 (benzen : etylacetat =5:1);
NMR (300MHz, CDC13): 8 7.09 (d, J = 8.1Hz, 1H), 6.83 (d, J = 2.7Hz, 1H), 6.75 (dd, J = 8.1, 2.7Hz, 1H), 6.35 (d, J = 10.5Hz, 1H), 3.82 (s, 3H), 3.81 (m, 1H), 3.53 (m, 1H), 3.08 (t, J = 7.5Hz, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.41 (m, 2H), 2.28-2.06 (m, 4H), 2.15 (s, 3H), 2.01-1.58 (m, 6H), 1.05 (t, J = 7.5Hz, 3H), 1.02 (t, J = 7.8Hz, 3H).
Eksempel 2(32)
8-(3-pentylamino)-2-etyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.59 (benzen : etylacetat =5:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.1Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.77 (dd, J = 8.1, 2.7Hz, 1H), 6.27 (d, J = 10.5Hz, 1H), 3.82 (s, 3H), 3.80 (m, 1H), 3.08 (t, J = 7.5Hz, 2H), 2.89 (t, J = 7.8Hz, 2H), 2.67 (m, 2H), 2.17 (s, 3H), 2.13 (m, 2H), 1.81-1.52 (m, 4H), 1.16 (t, J = 7.2Hz, 3H), 1.04 (t, J = 7.5Hz, 3H), 1.01 (t,J = 7.8Hz, 3H).
Eksempel 2(33)
8-(3-pentylamino)-2-isopropyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.60 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.28 (m, 1H), 7.09 (d, J = 8.4Hz, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 8.4, 2.4Hz, 1H), 3.99 (m, 1H), 3.84 (s, 3H), 3.49 (m, 2H), 3.12 (t, J = 7.2Hz, 2H), 2.99 (m, 1H), 2.28 (m, 2H), 2.20 (s, 3H), 1.85 (m, 2H), 1.74 (m, 2H), 1.24 (d, J = 6.9Hz, 3H), 1.19 (d, J = 7.2Hz, 3H), 1.08 (t, J = 7.5Hz, 3H), 1.06 (t, J = 7.5Hz, 3H).
Eksempel 2(34)
8-(2-etylbutylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.55 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.46 (m, 1H), 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 8.4, 2.4Hz, 1H), 3.83 (s, 3H), 3.74 (t, J = 6.0Hz, 2H), 3.49 (t, J = 7.8Hz, 2H), 3.21 (t, J = 7.5Hz, 2H), 2.28 (s, 3H), 2.26 (m, 2H), 2.19 (s, 3H), 1.68 (m, 1H), 1.53 (m, 4H), 1.00 (t, J = 7.5Hz, 6H).
Eksempel 2(35)
8-(3-pentylamino)-2-metyltiometyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.31 (n-heksan : etylacetat = 3:1); NMR (300MHz, CDC13): 8 7.31 (brd, J = 10.8Hz, 1H), 7.16 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.80 (dd, J = 8.4, 2.4Hz, 1H), 4.00 (brs, 1H), 3.83 (s, 3H), 3.70 (d, J = 13.5Hz, 1H), 3.60 (d, J = 13.5Hz, 1H), 3.50 (m, 2H), 3.14 (t, J = 7.2Hz, 2H), 2.29 (m, 2H), 2.32 (s, 3H), 2.04 (s, 3H), 1.95-1.65 (m, 4H), 1.07 (t, J = 7.2Hz, 3H), 1.05 (t, J = 7.5Hz, 3H). Eksempel 2(36) 8-(N-metyl-N-cyklopropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.16 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.14 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.1, 2.7Hz, 1H), 5.47 (brs, 2H), 4.90 (brs, 2H), 3.82 (s, 3H), 3.45 (s, 3H), 2.80 (m, 1H), 2.33 (s, 3H), 2.16 (s, 3H), 0.84 (d, J = 6.0Hz, 4H).
Eksempel 2(37)
8-(3-pentylamino)-2-metyl-3-(2, 4-dimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.50 (benzen : etylacetat = 10 : 1);
NMR (300MHz, CDC13): 8 7.13 (d, J = 7.5Hz, 1H), 7.11 (brs, 1H), 7.03 (m, 1H), 6.21 (d, J = 10.8Hz, 1H), 3.80 (m, 1H), 3.08 (t, J = 6.9Hz, 2H), 2.89 (t, J = 7.5Hz, 2H), 2.34 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H), 2.13 (m, 2H), 1.56-1.82 (m, 4H), 1.02 (m, 6H).
Eksempel 2(38)
8-(3-pentylamino)-2-metyl-3-(2, 5-dimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.54 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.31 (br d, J = 10.2Hz, 1H), 7.24 (d, J = 7.5Hz, 1H), 7.15 (br dd, J = 1.2, 7.5Hz, 1H), 7.01 (brs, 1H), 3.99 (m, 1H), 3.49 (t, J = 7.5Hz, 2H), 3.14 (t, J = 6.9Hz, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.29 (m, 2H), 2.18 (s, 3H), 1.64-1.94 (m, 4H), 1.07 (t, J = 7.5Hz, 3H), 1.06 (t, J = 7.2Hz, 3H).
Eksempel 2(39)
8-cyklobutylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.36 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.14 (d, J = 8.7Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.77 (dd, J = 8.7, 2.7Hz, 1H), 6.50 (brd, J = 8.4Hz, 1H), 4.46 (m, 1H), 3.81 (s, 3H), 3.12 (t, J = 7.2Hz, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.43 (m, 2H), 2.30 (s, 3H), 2.23-2.08 (m, 4H), 2.16 (s, 3H), 1.90-1.70 (m, 2H).
Eksempel 2(40)
8-(N-etyl-N-cyklobutylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.38 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.12 (d, J = 8.7Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.7,2.7Hz, 1H), 4.74 (m, 1H), 3.99 (m, 2H), 3.83 (s, 3H), 3.48 (t, J = 7.5Hz, 2H), 2.98 (t, J = 7.5Hz, 2H), 2.20-2.10 (m, 6H), 2.30 (s, 3H), 2.17 (s, 3H), 1.90-1.70 (m, 2H), 1.16 (t, J = 7.2Hz, 3H).
Eksempel 2(41)
8-(propan-1,3-diol-2-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-
dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.44 (kloroform : metanol = 9:1);
NMR (300MHz, CDC13): 8 7.17 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.1, 2.7Hz, 1H), 6.73 (d, J = 10.2Hz, 1H), 4.12 (m, 1H), 3.98-3.83 (m, 4H), 3.82 (s, 3H), 3.05 (t, J = 7.2Hz, 2H), 2.87 (t, J = 8.1Hz, 2H), 2.30 (s, 3H), 2.16 (s, 3H),2.11 (m, 2H).
Eksempel 2(42)
8-(3-penytlamino)-2-(2-furyl)-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.33 (n-heksan : "etylacetat = 4:1);
NMR (300MHz, CDC13): 8 7.47 (m, 1H), 7.21 (d, J = 8.1Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.1, 2.7Hz, 1H), 6.38-6.30 (m, 2H), 6.05 (m, 1H), 3.84 (s, 3H), 3.82 (m, 1H), 3.11 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.15 (m, 2H), 2.10 (s, 3H), 1.70 (m, 4H), 1.04 (t, J = 7.2Hz, 3H), 1.01 (t, J = 7.2Hz, 3H).
Eksempel 2(43)
8-(3-pentylamino)-2-fenyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.41 (n-heksan : etylacetat = 4:1);
NMR (300MHz, CDC13): 6 7.59-7.54 (m, 2H), 7.45-7.19 (m, 5H), 6.88-6.82 (m, 2H), 4.04 (m, 1H), 3.85 (s, 3H), 3.55 (t, J = 7.8Hz, 2H), 3.17 (t, J = 7.8Hz, 2H), 2.32 (m, 2H), 2.05 (s, 3H), 1.97-1.55 (m, 4H), 1.10 (t, J = 6.9Hz, 3H), 1.07 (t, J = 7.2Hz, 3H).
Eksempel 2(44)
8-(2-dimetylaminoetyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (metylenklorid : metanol =19:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.4Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.77 (dd, J = 8.4, 2.7Hz, 1H), 6.71 (t, J = 5.7Hz, 1H), 3.82 (s, 3H), 3.75 (dt, J = 5.7, 6.3Hz, 2H), 3.19 (t, J = 7.5Hz, 2H), 2.88 (t, J = 7.5Hz, 2H), 2.63 (t, J = 6.3Hz, 2H), 2.33 (s, 6H), 2.31 (s, 3H), 2.17 (s, 3H), 2.12 (m, 2H).
Eksempel 2(45)
8-(N-metyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidindihydroklorid
TLC: Rf 0.46 (metylenklorid : metanol = 9:1);
NMR (300MHz, pyridin-d5 0.5ml + CDC13 O.lml): 8 7.42 (d, J = 8.4Hz, 1H), 7.04 (d, J = 2.7Hz, 1H), 6.96 (dd, J = 8.4, 2.7Hz, 1H), 4.21 (t, J = 7.5Hz, 2H), 3.85 (t, J = 7.5Hz, 2H), 3.75 (s, 3H), 3.14 (s, 3H), 3.00 (s, 6H), 2.90 (t, J = 7.5Hz, 2H), 2.80 (t, J = 7.5 HZ, 2H), 2.41 (s, 3H), 2.36 (s, 3H), 1.90 (m, 2H).
Eksempel 2(46)
8-(N-etyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.46 (metylenklorid : metanol = 9:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.4Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.4, 2.7Hz, 1H), 3.82 (s, 3H), 3.80 (t, J = 7.2Hz, 2H), 3.64 (q, J = 7.2Hz, 2H), 2.99 (t, J = 7.5Hz, 2H), 2.90 (t, J = 7.5Hz, 2H), 2.56 (t, J = 7.2Hz, 2H), 2.31 (s, 3H), 2.25 (s, 6H), 2.17 (s, 3H), 2.12 (m, 2H), 1.17 (t, J = 7.2Hz, 3H).
Eksempel 2(47)
8-(4-heptylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.50 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.27 (brd, J = 9.6Hz, 1H), 7.11 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.4,2.7Hz, 1H), 4.12 (m, 1H), 3.82 (s, 3H), 3.49 (t, J = 7.5Hz, 2H), 3.11 (t, J = 7.5Hz, 2H), 2.32-2.20 (m, 2H), 2.28 (s, 3H), 2.20 (s, 3H), 1.82-1.60 (m, 4H), 1.60-1.36 (m, 4H), 0.99 (t, J = 7.2Hz, 3H), 0.98 (t, J = 7.2Hz, 3H).
Eksempel 2(48) 8-(2-butylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-aJpyrimidinhydroklorid
TLC: Rf 0.40 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.36 (brd, J = 9.9Hz, 1H), 7.12 og 7.11 (d, J = 8.4Hz, to konformerer, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.4, 2.7Hz, 1H), 4.18 (m, 1H), 3.83 (s, 3H), 3.48 (t, J = 7.5Hz, 2H), 3.16 (t, J = 7.5Hz, 2H), 2.40-2.20 (m, 2H), 2.28 (s, 3H), 2.19 og 2.18 (s, to konformerer, 3H), 1.80 (m, 2H), 1.48 og 1.47 (d, J = 6.6Hz, to konformerer, 3H), 1.09 og 1.08 (t, J = 7.2Hz, to konformerer, 3H).
Eksempel 2(49)
8-(N-propyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.42 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.13 (m, 1H), 6.88 (brs, 1H), 6.82 (m, 1H), 3.88 (m, 2H), 3.83 (brs, 3H), 3.77 (brs, 2H), 3.37 (m, 2H), 3.06 (m, 2H), 2.29 (s, 3H), 2.24 (m, 2H), 2.19 (s, 3H), 1.73 (m, 2H), 1.12 (m, 1H), 0.96 (m, 3H), 0.62 (m, 2H), 0.26 (brs, 2H).
Eksempel 2(50)
8-(3-pentylamino)-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.46 (n-heksan : etylacetat = 3:1);
NMR (300MHz, DMSO-d6): 89.25 (m, 1H), 8.31 (s, 1H), 7.23 (d, J = 8.1Hz, 1H), 6.95 (d, J = 2.4Hz, 1H), 6.86 (dd, J = 2.4, 8.1Hz, 1H), 3.99 (m, 1H), 3.78 (s, 3H), 3.15 (m, 2H), 3.02 (t, J = 7.8Hz, 2H), 2.20 (s, 3H), 2.18 (m, 2H), 1.60-1.88 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(51)
8-[(2R)-l-metoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.21 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.63 (brd, J = 8.4Hz, 1H), 7.09 (d, J = 8.7Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.7, 2.7Hz, 1H), 4.19 (m, 1H), 3.81 (s, 3H), 3.65-3.53 (m, 2H), 3.45 (t, J = 8.1Hz, 2H), 3.43 og 3.41 (s, to konformerer, 3H), 3.26-3.01 (m, 2H), 2.30-2.20 (m, 2H), 2.28 (s, 3H), 2.18 (s, 3H), 1.96-1.58 (in, 2H), 1.08 og 1.07 (t, J = 7.5Hz, to konformerer, 3H).
Eksempel 2(52)
8-[(2S)-l-metoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.21 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.59 (brd, J = 10.2Hz, 1H), 7.11 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 8.4, 2.7Hz, 1H), 4.19 (m, 1H), 3.83 (s, 3H), 3.66-3.53 (m, 2H), 3.48 (t, J = 8.1Hz, 2H), 3.44 og 3.42 (s, to konformerer, 3H), 3.26-3.02 (m, 2H), 2.30-2.20 (m, 2H), 2.29 (s, 3H), 2.20 (s, 3H), 1.98-1.69 (m, 2H), 1.09 og 1.08 (t, J = 7.5Hz, to konformerer, 3H).
Eksempel 2(53)
8-cyklopentylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.7Hz, 1H), 6.84 (d, J = 2.7Hz, 1H), 6.77 (dd, J = 8.7, 2.7Hz, 1H), 6.34 (brd, J = 9.0Hz, 1H), 4.38 (m, 1H), 3.82 (s, 3H), 3.15 (t, J = 7.2Hz, 2H), 2.89 (t, J = 7.8Hz, 2H), 2.30 (s, 3H), 2.17 (s, 3H), 2.18-2.00 (m, 4H), 1.95-1.65 (m,6H).
Eksempel 2(54)
8-(3-pentylamino)-2-metyl-3-(2,4-difluorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.57 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.50 (ddd, J = 6.6, 8.4, 8.4Hz, 1H), 6.86-6.99 (m, 2H), 6.23 (d, J = 10.8Hz, 1H), 3.80 (m, 1H), 3.09 (t, J = 7.2Hz, 2H), 2.92 (t, J =8.1Hz, 2H), 2.39 (d, J = 1.5Hz, 3H), 2.15 (m, 2H), 1.53-1.81 (m, 4H), 1.01 (t, J =7.2Hz, 6H).
Eksempel 2(55)
8-(3-pentylamino)-2-trifluormetyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.42 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.33 (br d, J = 10.2Hz, 1H), 7.13 (d, J = 8.7Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 2.4, 8.7Hz, 1H), 4.04 (m, 1H), 3.83 (s, 3H), 3.56 (m, 2H), 3.20 (m, 2H), 2.33 (m, 2H), 2.19 (s, 3H), 1.70-2.22 (m, 4H), 1.08 (m, 6H).
Eksempel 2(56)
8-(N-etyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.20 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.4, 2.7Hz, 1H), 4.34-4.17 (m, 2H), 3.91 (q, J = 7.2Hz, 2H), 3.83 (s, 3H), 3.68 (t, J = 5.1Hz, 2H), 3.47 (t, J = 7.8Hz, 2H), 3.32 (s, 3H), 3.06 (t5 J = 7.2Hz, 2H), 2.28 (s, 3H), 2.30-2.20 (m, 2H), 2.18 (s, 3H), 1.38 (t, J = 7.2Hz, 3H).
Eksempel 2(57)
8-cykloheksylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.1Hz, 1H), 6.84 (d, J = 2.7Hz, 1H), 6.77 (dd, J = 8.1, 2.7Hz, 1H), 6.34 (brd, J = 9.6Hz, 1H), 3.81 (s, 3H), 3.80 (m, 1H), 3.10 (t, J = 7.2Hz, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.30 (s, 3H), 2.17 (s, 3H), 2.18-2.00 (m, 4H), 1.90-1.80 (m, 2H), 1.75-1.60 (m, 1H), 1.50-1.20 (m, 5H).
Eksempel 2(58)
8-(N-propyl-N-(3-pentyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.43 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.14 (d, J = 8.1Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.1, 2.7Hz, 1H), 4.20 (m, 1H), 3.83 (s, 3H), 3.60 (m, 2H), 3.38 (t, J = 7.5Hz, 2H), 2.97 (t, J = 7.5Hz, 2H), 2.30-2.15 (m, 2H), 2.27 (s, 3H), 2.20 (s, 3H), 2.00-1.70 (m, 4H), 1.42 (m, 2H), 0.98 (t, J = 7.5Hz, 6H), 0.90 (t, J = 7.5Hz, 3H).
Eksempel 2(59)
8-(3-pentylamino)-2-metyl-3-(4-metoksyfenyl)-6J7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.57 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.60 (d, J = 9.0Hz, 2H), 6.99 (d, J = 9.0Hz, 2H), 6.10 (br d, J = 10.5Hz, 1H), 3.84 (s, 3H), 3.81 (m, 1H), 3.08 (t, J = 7.2Hz, 2H), 2.94 (t, J = 7.8Hz, 2H), 2.53 (s, 3H), 2.15 (m, 2H), 1.53-1.82 (m, 4H), 1.00 (t, J = 7.2Hz, 6H).
Eksempel 2(60)
8-(3-pentylamino)-2-isopropyl-3-(4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.54 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.48 (d, J = 8.7Hz, 2H), 6.97 (d, J = 8.7Hz, 2H), 6.29 (br d, J = 10.5Hz, 1H), 3.84 (s, 3H), 3.80 (m, 1H), 3.32 (sept, J = 6.9Hz, 1H), 3.07 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.5Hz, 2H), 2.13 (m, 2H), 1.63-1.83 (m, 4H), 1.33 (d, J = 6.9Hz, 6H), 1.01 (t, J = 7.5 HZ, 6H).
Eksempel 2(61)
8-t-butylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.35 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.15 (brd, J = 8.7Hz, 1H), 6.97 (brs, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.7,2.7Hz, 1H), 3.81 (s, 3H), 3.15 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.5Hz, 2H), 2.30 (s, 3H), 2.18 (s, 3H), 2.11 (m, 2H), 1.57 (s, 9H).
Eksempel 2(62)
8-(3-pentylamino)-3-(2,4, 6-trimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.58 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.91 (s, 1H), 7.39 (brd, J = 10.2Hz, 1H), 6.99 (s, 2H), 4.03 (m, 1H), 3.52 (t, J = 7.8Hz, 2H), 3.17 (t, J = 7.2Hz, 2H), 2.32 (s, 3H), 2.31 (m, 2H), 2.13 (s, 6H), 1.67-1.96 (m, 4H), 1.07 (t, J = 7.5Hz, 6H).
Eksempel 2(63)
8-(l-cyklobutyletyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.28 (n-heksan : etylacetat = 3:1);
NMR (300MHz, pyridin-d5 0.5ml + CDC13 O.lml) : 5 7.46 (d, J = 8.1Hz, 1H), 7.06 (d, J = 2.7Hz, 1H), 6.97 (dd, J = 8.1, 2.7Hz, 1H), 6.80 (d, J = 10.2Hz, 1H), 3.96 (m, 1H), 3.74 (s, 3H), 2.97 (ddd, J = 14.1, 7.2, 7.2Hz, 2H), 2.86 (t, J = 7.5Hz, 2H), 2.50-2.36 (m, 1H), 2.47 (s, 3H), 2.39 (s, 3H), 2.05-1.65 (m, 8H), 1.15 (d, J = 6.3Hz, 3H).
Eksempel 2(64)
8-(3-pentylamino)-2-metyl-3-(2, 3-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.37 (benzen : etylacetat = 10 : 1);
NMR (300MHz, CDC13): 6 7.08 (d, J = 8.1Hz, 1H), 6.78 (d, J = 8.1Hz, 1H), 6.21 (d, J = 10.8Hz, 1H), 3.84 (s, 3H), 3.81 (m, 1H), 3.08 (t, J = 6.6Hz, 2H), 2.88 (t, J = 8.1Hz, 2H), 2.29 (s, 3H), 2.21 (s, 3H), 2.13 (m, 2H), 2.10 (s, 3H), 1.56-1.82 (m, 4H), 1.03 (t, J = 7.5Hz, 3H), 1.01 (t, J= 6.9Hz, 3H).
Eksempel 2(65)
8-(3-pentylamino)-2-metyl-3-(2, 5-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.43 (benzen : etylacetat = 10 : 1);
NMR (300MHz, CDC13): 8 6.99 (s, 1H), 6.76 (s, 1H), 6.20 (d, J = 10.5Hz, 1H), 3.84 (s, 3H), 3.82 (m, 1H), 3.08 (t, J = 6.9Hz, 2H), 2.89 (t, J = 7.2Hz, 2H), 2.31 (s, 3H), 2.19 (s, 3H), 2.17 (s, 3H), 2.14 (m, 2H), 1.54-1.80 (m, 4H), 1.01 (m, 6H).
Eksempel 2(66)
8-(N-(2, 2, 2-trifluoretyl)-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.62 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.17 (d, J = 8.1Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.1,2.7Hz, 1H), 4.64 (q, J = 9.6Hz, 2H), 3.82 (s, 3H), 3.41 (d, J = 6.6Hz, 2H), 2.98 (t, J = 6.9Hz, 2H), 2.94 (t, J = 7.5Hz, 2H), 2.34 (s, 3H), 2.21-2.09 (m, 2H), 2.18 (s, 3H), i:03 (m, 1H), 0.57 (m, 2H), 0.21 (m, 2H).
Eksempel 2(67)
8-(2,2, 2-trifluoretyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.22 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.14 (d, J = 8.1Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.1, 2.7Hz, 1H), 6.75 (brt, J = 7.8Hz, 1H), 4.22 (dq, J = 7.8, 7.8Hz, 2H), 3.82 (s, 3H), 3.12 (t, J = 7.5Hz, 2H), 2.92 (t, J = 7.8Hz, 2H), 2.31 (s, 3H), 2.23-2.09 (m, 2H),2.17(s, 3H).
Eksempel 2(68)
8-[(2R)-l-metoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.25 (n-heksan : etylacetat = 2:1);
NMR (300MHz, pyridin-d5 0.5ml + CDC13 O.lml): 8 7.39 (d, J = 8.1Hz, 1H), 7.37 (brd, J = 9.3Hz, 1H), 7.03 (d, J = 2.7Hz, 1H), 6.95 (dd, J = 8.1, 2.7Hz, 1H), 5.45 (d, J = 9.9Hz, 1H), 5.35 (d, J = 9.9Hz, 1H), 4.98 (brs, 2H), 3.74 (s, 3H), 3.63-3.48 (m, 3H), 3.26 (s, 3H), 2.41 (s, 3H), 2.34 (s, 3H), 1.82-1.60 (m, 2H), 0.97 (t, J = 7.5Hz, 3H).
Eksempel 2(69)
8-[(2R)-1 -metoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-2, 3-dihydro-furo[3,2-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.29 (n-heksan : etylacetat = 2:1);
NMR (300MHz, pyridin-d5 0.5ml + CDC13 O.lml): 8 7.40 (d, J = 8.4Hz, 1H), 7.03 (brs, 1H), 6.95 (dd, J = 8.4, 2.4Hz, 1H), 6.80 (brd, J = 9.3Hz, 1H), 4.47 (m, 1H), 4.47 (t, J = 8.4Hz, 2H), 3.74 (s, 3H), 3.56 (d, J = 4.8Hz, 2H), 3.28 (s, 3H), 3.12 (t, J = 8.4Hz, 2H), 2.43 (s, 3H), 2.35 (s, 3H), 1.87-1.46 (m, 2H), 1.00 (t, J = 7.5Hz, 3H).
Eksempel 2(70)
8-(3-pentylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.33 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.90 (s, 1H), 7.39 (br d, J = 10.2Hz, 1H), 6.72 (s, 2H), 4.02 (m, 1H), 3.81 (s, 3H), 3.53 (t, J = 7.8Hz, 2H), 3.17 (t, J = 6.9Hz, 2H), 2.32 (m, 2H), 2.14 (s, 6H), 1.66-1.96 (m, 4H), 1.08 (t, J = 7 .2Hz, 6H).
Eksempel 2(71)
8-(3-pentylamino)-3-(4, 6-dimetyl-2-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
\ HC1
cCxj
N I
CH,
TLC: Rf 0.33 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.99 (s, 1H), 7.37 (br d, J = 10.8Hz, 1H), 6.75 (s, 1H), 6.70 (s, 1H), 4.01 (m, 1H), 3.85 (s, 3H), 3.57 (t, J = 7.8Hz, 2H), 3.16 (t, J = 7.2Hz, 2H), 2.36 (s, 3H), 2.31 (m, 2H), 2.23 (s, 3H), 1.63- 1.92 (m, 4H), 1.06 (t, J = 7.2Hz, 6H).
Eksempel 2(72)
8-(3-pentylamino)-2-metyl-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
n
H jC
OCHj
TLC: Rf 0.33 (benzen : etylacetat = 10 : 1);
NMR (300MHz, CDC13): 86.68 (s, 2H), 6.21 (d, J = 10.5Hz, 1H), 3.81 (m, 1H), 3.80 (s, 3H), 3.09 (t, J = 7.2Hz, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.19 (s, 3H), 2.13 (m, 2H), 2.04 (s, 6H), 1.55-1.83 (m, 4H), 1.03 (t, J = 7.5Hz, 6H).
Eksempel 2(73)
8-(3-pentylamino)-2-metyl-3-(4, 6-dimetyl-2-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.33 (benzen : etylacetat =10:1);
NMR (300MHz, CDC13): 86.75 (m, 1H), 6.62 (s, 1H), 6.21 (d, J = 10.5Hz, 1H), 3.80 (m, 1H), 3.71 (s, 3H), 3.06 (m, 2H), 2.87 (m, 2H), 2.34 (s, 3H), 2.24 (s, 3H), 2.12 (m, 2H), 2.09 (s, 3H), 1.53-1.80 (m, 4H), 1.03 (t, J = 7.2Hz, 3H), 1.00 (t, J = 7.5Hz, 3H).
Eksempel 2(74)
8-(3-mety lpentan-3 -y l)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.36 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 88.01 (brs, 1 H), 7.12 (d, J = 8.1Hz, 1 H), 6.89 (d, J = 2.7Hz, 1 H), 6.82 (dd, J = 8.1,2.7Hz, 1 H), 3.83 (s, 3 H), 3.52 (t, J = 7.8Hz, 2 H), 3.16 (t, J = 7.2Hz, 2 H), 2.28 (s, 3 H), 2.24 (m, 2 H), 2.20 (s, 3 H), 2.00-1.85 (m, 4 H), 1.55 (s, 3 H), 1.03 (t, J = 7.5Hz, 6 H).
Eksempel 2(75)
8-(3-pentylamino)-2-metyl-3-(5-klor-l, 3-dioksaindan-6-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.44 (benzen : etylacetat =10:1);
NMR (300MHz, CDC13): 86.96 (s, 1H), 6.85 (s, 1H), 6.22 (br d, J = 10.5Hz, 1H), 5.99 (s, 2H), 3.80 (m, 1H), 3.08 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.34 (s, 3H), 2.16 (m,2H), 1.53-1.81 (m, 4H), 1.01 (t, J = 7.2Hz, 6H).
Eksempel 2(76)
8-(N-etyl-N-benzylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.43 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 87.26-7.43 (m, 5H), 7.13 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.4Hz, 1H), 5.21 (s, 2H), 3.87 (q, J = 6.9Hz, 2H), 3.83 (s, 3H), 3.47 (t, J = 7.2Hz, 2H), 3.03 (t, J = 7.2Hz, 2H), 2.29 (s, 3H), 2.22 (m, 2H), 2.19 (s, 3H), 1.39 (t, J = 6.9Hz, 3H).
Eksempel 2(77)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-trifluormetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.52 (n-heksan : etylacetat = 3:1); NMR (300MHz, pyriden-d5(0.5ml),CDCl3(0.1ml)): 87.71 (d, J = 8.4Hz, 1H), 7.57 (m, 1H), 7.28 (m, 1H), 6.77 (d, J = 10.5Hz, 1H), 3.74 (m, 1H), 2.95 (t, J = 7.5Hz, 2H), 2.85 (t, J =7.8Hz, 2H), 2.46 (s, 3H), 1.98 (m, 2H), 1.64-1.48 (m, 4H), 0.92 (t, J = 7.5Hz, 6H).
Eksempel 2(78) 8-(3-penytlamino)-2-metyl-3-(2-kloM cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.20 (n-heksan : etylacetat = 3:1);
NMR (300MHz, pyriden-d5(0.5ml),CDCl3(0.1ml)): 87.59 (d, J = 8.4Hz, 1H), 7.24 (d, J = 2.4Hz,lH), 6.98 (dd, J = 8.4,2.4Hz, 1H), 6.78 (d, J = 10.5Hz, 1H), 3.74 (m, 1H), 3.69 (s, 3H), 2:94 (t, J = 7.2Hz, 2H), 2.85 (t, J = 7.8Hz, 2H), 2.51 (s, 3H), 1.96 (m, 2 H), 1.64-1.48 (m, 4H), 0.91 (t, J = 7.5Hz, 6H).
Eksempel 2(79)
8-(N-benzyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.24 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.34 - 7.44 (m, 3H), 7.27 - 7.34 (m, 2H), 7.13 (d, J = 8.4Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.4Hz, 1H), 5.11 (s, 2H), 4.14 (t, J = 4.8Hz, 2H), 3.84 (s, 3H), 3.64 (t, J = 4.8Hz, 2H), 3.49 (t, J =7.8Hz, 2H), 3.29 (s, 3H), 3.07 (t, J = 7.2Hz, 2H), 2.31 (s, 3H), 2.23 (m, 2H), 2.19 (s, 3H).
Eksempel 2(80)
8-(l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.15 (d, J = 8.1Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.78 ( dd, J = 2.7, 8.1Hz, CDC13), 5.97 (m, 1H), 5.83 (m, 1H), 4.21 (m, 2H), 3.85 (m, 2H), 3.82 (s, 3H), 3.07 (t, J = 7.2Hz, 2H), 2.89 (t, J = 7.5H z, 2H), 2.41 (m, 2H), 2.32 (s, 3H),2.16(s, 3H),2.11 (m,2H).
Eksempel 2(81)
8-(3-pentylamino)-2-metyl-3-(2-metoksy-4,5-dimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.29 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.29 (brd, J = 10.2Hz, 1 H), 7.04 (s, 1 H), 6.83 (s, 1 H), 3.95 (m, 1 H), 3.90 (s, 3 H), 3.56 (t, J = 7.8Hz, 2 H), 3.12 (t, J = 7.5Hz, 2 H), 2.42 (s, 3 H), 2.31 (s, 3 H), 2.28 (m, 2 H), 2.24 (s, 3 H), 1.90 - 1.62 (m, 4 H), 1.04 (t, J = 7.5Hz, 6 H).
Eksempel 2(82)
8-( 1,2, 3,4-tetrahydroisokinolin-2-yl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyfimidin
TLC: Rf 0.24 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.23 - 7.18 (m, 3 H), 7.16 (d, J = 8.4Hz, 1 H), 7.11 (m, 1 H), 6.86 (d, J = 2.4Hz, 1 H), 6.79 (dd, J = 8.4,2.4Hz, 1 H), 4.86 (s, 2 H), 4.09 (t, J = 5.7Hz, 2 H), 3.82 (s, 3 H), 3.08 (t, J = 5.7Hz, 2 H), 2.97 (t, J = 7.2Hz, 2 H), 2.89 (t, J = 7.8Hz, 2 H), 2.33 (s, 3 H), 2.17 (s, 3 H), 2.08 (m, 2 H).
Eksempel 2(83)
8-fenylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.35 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 8.01 (br, 1H), 7.45 - 7.38 (m, 2H), 7.33 - 7.17 (m, 4H), 6.87 (d, J = 2.4Hz, 1H), 6.80 (dd, J = 8.1, 2.4Hz, 1H), 3.83 (s, 3H), 2.89 (t, J = 7.8Hz, 2H), 2.35 (s, 3H), 2.30 (t, J = 7.5Hz, 2H), 2.21 (s, 3H), 2.02 - 1.90 (m, 2H).
Eksempel 2(84)
8-(2-metylfenyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.37 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.76 (br, 1H), 7.32 - 7.17 (m, 5H), 6.87 (d, J = 2.4Hz, 1H), 6.80 (dd, J = 8.4, 2.4Hz, 1H), 3.83 (s, 3H), 2.85 (t, J = 7.5Hz, 2H), 2.36 (s, 6H), 2.22 (s, 3H), 2.13 (t, J = 7.5Hz, 2H), 1.96 - 1.85 (m, 2H).
Eksempel 2(85)
8-(3-metylfenyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.38 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.96 (br, 1H), 7.32 - 7.26 (m, 1H), 7.19 (d, J = 8.4Hz, 1H), 7.12 - 7.01 (m, 3H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 2.88 (t, J = 7.8Hz, 2H), 2.40 (s, 3H), 2.35 (s, 3H), 2.31 (t, J = 6.9Hz, 2H), 2.21 (s, 3H), 2.02-1.91 (m,2H).
Eksempel 2(86)
8-(4-metylfenyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.33 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.93 (br, 1H), 7.23 - 7.11 (m, 5H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 2.86 (t, J = 7.5Hz, 2H), 2.40 (s, 3H), 2.35 (s, 3H), 2.29 (t, J = 7.5Hz, 2H), 2.21 (s, 3H), 2.00 - 1.88 (m, 2H).
Eksempel 2(87)
8-(N-fenyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.48 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.31 - 7.24 (m, 2H), 7.21 (d, J = 8.4Hz, 1H), 6.99 - 6.87 (m, 4H), 6.81 (dd, J = 8.4, 2.7Hz, 1H), 4.15 - 4.07 (m, 2H), 3.84 (s, 3H), 2.92 (t, J = 7.5Hz, 2H), 2.36 (s, 3H), 2.31 (t, J = 7.5Hz, 2H), 2.22 (s, 3H), 2.05 - 1.94 (m, 2H), 1.82 - 1.68 (m, 2H), 0.96 (t, J = 7.2Hz, 3H).
Eksempel 2(88)
8-(N-benzyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.63 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.33 - 7.21 (m, 5H), 7.19 (d, J = 8.4Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.4, 2.7Hz, 1H), 4.86 (s, 2H), 3.83 (s, 3H), 3.42 - 3.34 (m, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.81 (t, J = 7.1Hz, 2H), 2.36 (s, 3H), 2.20 (s, 3H), 2.11-1.98 (m, 2H), 1.67 - 1.54 (m, 2H), 0.88 (t, J = 7.5Hz, 3H).
Eksempel 2(89)
8-(N, N-diallylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.46 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J =2,7Hz, 1H), 6.82 (dd, J = 2.7, 8.4Hz, 1H), 6.03 (m, 2H), 5.40 (d, J = 10.5Hz, 2H), 5.35 (d, J = 18Hz, 2H), 4.49 (d, J = 6.0Hz, 4H), 3.83 (s, 3H), 3,47 (t, J = 7.8Hz, 2H), 3.08 (t, J = 7.2Hz, 2H), 2.28 (s, 3H), 2.23 (m, 2H), 2.18 (s, 3H).
Eksempel 2(90) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-dime1ylam^ cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
<y>— CH 3
H3C' VCH3
TLC: Rf 0.17 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.11 (d, J = 8.1Hz, 1 H), 6.70 (d, J = 2.7Hz, 1 H), 6.64 (dd, J = 8,1, 2.7Hz, 1 H), 6.19 (d, J = 10.2Hz, 1 H), 3.80 (m, 1 H), 3.08 (t, J = 7.5Hz, 2 H), 2.95 (s, 6 H), 2.89 (t, J = 7.5Hz, 2 H), 2.32 (s, 3 H), 2.18 (s, 3 H), 2.18 - 2.08 (m, 2 H), 1.80 - 1.56 (m, 4 H), 1.01 (brs, 6 H).
Eksempel 2(91)
8-( 1 -feny lpropy lamino)-2-mety 1-3 -(2-metyl-4-metoksy feny l)-6,7-dihy dro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.83 (d, J = 8.7Hz, 1H), 7.27 - 7.48 (m, 5H), 7.12 (d, J = 8.4Hz, 1H), 6.88 (m, 1H), 6.81 (dd, J = 2.7, 8.4Hz, 1H), 5.10 (m, 1H), 3.82 (s, 3H), 3.41 (m, 2H), 3.16 (m, 1H), 2.83 (m, 1H), 2.32 (s, 3H), 2.20 og 2.19 (s, totalt 3H), 2.12 (m, 4H), 1.12 og 1.01 (t, J = 7.2Hz, totalt 3H).
Eksempel 2(92)
8-(N-(2-fenyletyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
</V>^<V><HCI>
OCH,
TLC: Rf 0.35 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.23 - 7.05 (m,.6H), 6.90 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 8.4, 2.4Hz, 1H), 4.33 (t, J = 6.6Hz, 2H), 3.84 (s, 3H), 3.71 (t, J = 6.9Hz, 2H), 3.37 (t, J = 7.5Hz, 2H), 2.98 (t, J = 7.2Hz, 2H), 2.77 (t, J = 7.5Hz, 2H), 2.32 (s, 3H), 2.20 (s, 3H), 2.20 - 2.06 (m, 2H), 1.81-1.68 (m, 2H), 0.97 (t, J = 7.5Hz, 3H).
Eksempel 2(93)
8-(N-(3-fenylpropyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
r<^V'CHs
OCHj
TLC: Rf 0.40 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.26 - 7.05 (m, 6H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 3.66 - 3.53 (m, 4H), 2.88 (t, J = 7.5Hz, 2H), 2.87 (t, J = 7.5Hz, 2H), 2.62 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.19 (s, 3H), 2.15 - 2.04 (m, 2H), 1.95 - 1.83 (m, 2H), 1.61 - 1.49 (m, 2H), 0.88 (t, J = 7.2Hz, 3H).
Eksempel 2(94)
8-(N-(4-fenylbutyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.48 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.25 - 7.05 (m, 6H), 6.86 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.1, 2.7Hz, 1H), 3.83 (s, 3H), 3.63 (t, J = 6.6Hz, 2H), 3.57 - 3.49 (m, 2H), 2.90 (t,
J = 7.5Hz, 2H), 2.88 (t, J = 7.5Hz, 2H), 2.57 (t, J = 6.9Hz, 2H), 2.32 (s, 3H), 2.19 (s, 3H), 2.15 - 2.05 (m, 2H), 1.66 - 1.49 (m, 6H), 0.88 (t, J = 7.5Hz, 3H).
Eksempel 2(95)
8-(l-fenyl-2-butyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: RI 0.41 (heksan : etylacetat = 2:1);
NMR (300MHz, DMSO-d6): 8 9.24 (m, 1H), 7.04 - 7.30 (m, 6H), 6.95 (brs, 1H), 6.86 (dd, J =2.7, 8.4Hz, 1H), 4.20 (brs, 1H), 3.78 (s, 3H), 2.87 - 3.17 (m, 3H), 2.64 - 2.87 (m, 3H), 2.26 (s, 3H), 1.82-2.18 (m, 5H), 1.63 - 1.82 (m, 2 H), 0.93 (br t, J = 6.9Hz, 3H).
Eksempel 2(96)
8-(l-fenyl-3-pentyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.43 (heksan : etylacetat = 2:1);
NMR (300MHz, DMSO-d6): 8 8.53 (m, 1H), 7.09 - 7.28 (m, 6H), 6.96 (d, J = 3.0Hz, 1H), 6.85 (dd, J = 3.0, 8.4Hz, 1H), 4.10 (m, 1H), 3.82 (s, 3H), 2.89 - 3.02 (m, 3H), 2.68 - 2.85 (m, 3H), 2.25 (s, 3H), 2.00 - 2.22 (m, 7H), 1.79 (m, 2H), 0.93 (t, J = 7.5Hz, 3H).
' Eksempel 2(97)
8-(N-(4-metylfenyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.43 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.27 (d, J =8.1Hz, 2H), 7.13 - 7.22 (m, 3H), 6.90 (d, J = 2.4Hz, 1H), 6.84 (dd, J = 2.4, 8.7Hz, 1H), 4.46 (m, 2H), 3.84 (s, 3H), 3.35 (m, 2H), 2.43 (s, 3H), 2.31 (s, 3H), 2.22 (s, 3H), 1.77 - 1.97 (m, 6H), 0.98 (t, J = 7.5Hz, 3H).
Eksempel 2(98)
8-(N-(4-metylfenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-alpyrimidinhydroklorid
TLC: Rf 0.45 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.11 - 7.21 (m, 5H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.7Hz, 1H), 5.13 (s, 2H), 3.84 (s, 3H), 3.72 (t, J = 7.5Hz, 2H), 3.48 (t, J = 8.1Hz, 2H), 3.01 (t, J = 6.9Hz, 2H), 2.36 (s, 3H), 2.29 (s, 3H), 2.22 (m, 2H), 2.19 (s, 3H), 1.77 (m, 2H), 0.94 (t, J = 7.5Hz, 3H).
Eksempel 2(99)
8-(N-(3-metylfenyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-aJpyrimidinhydroklorid
TLC: Rf 0.41 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 5 7.36 (m, 1H), 7.06 - 7.24 (m, 4H), 6.91 (d, J = 2.4Hz, 1H), 6.84 (dd, J = 2.4, 8.1Hz, 1H), 4.46 (m, 2H), 3.84 (s, 3H), 3.36 (m, 2H), 2.42 (s, 3H), 2.32 (s, 3H), 2.23 (s, 3H), 1.77 - 2.00 (m, 6H), 0.99 (t, J = 7.2Hz, 3H).
Eksempel 2(100)
8-(N-(4-metoksyfenyl)métyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.18 (d, J = 8.7Hz, 2H), 7.13 (d, J = 8.4Hz, 1H), 6.90(d, J = 8.7Hz, 2H), 6.90 (d, J = 3.0Hz, 1H), 6.83 (dd, J = 3.0, 8.4Hz, 1H), 5.10 (s, 2H), 3.84 (s, 3H), 3.82 (s, 3H), 3.70 (t, J = 7.5Hz, 2H), 3.49 (t, J = 8.1Hz, 2H), 3.01 (t, J = 6.9Hz, 2H), 2.30 (s, 3H), 2.22 (m, 2H), 2.19 (s, 3H), 1.75 (m, 2H), 0.93 (t, J= 7.2Hz, 3H).
Eksempel 2(101)
8-(N-(4-klorfenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.37 (d, J = 8.7Hz, 2H), 7.24 (d, J = 8.7Hz, 2H), 7.12 (d, J = 8.4Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.4Hz, 1H), 5.15 (s, 2H), 3.83 (s, 3H), 3.68 (m, 2H), 3.50 (t, J =7.8Hz, 2H), 3.02 (t, J= 7.2Hz, 2H), 2.29 (s, 3H), 2.25 (m, 2H), 2.19 (s, 3H), 1.74 (m, 2H), 0.93 (t, J = 7.2Hz, 3H).
Eksempel 2(102)
8-(N-(2-metylfenyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.46 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.27 - 7.45 (m, 4H), 7.16 (d, J = 8.4Hz, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.84 (dd, J = 2.4, 8.4Hz, 1H), 4.53 (m, 1H), 4.37 (m, 1H), 3.84 (s, 3H), 3.34 (m, 2H), 2.31 (s, 3H), 2.23 (s, 3H), 2.10 (s, 3H), 1.50 - 2.07 (m, 6H), 0.97 (t, J = 7.5Hz, 3H).
Eksempel 2(103)
8-((3S)-3-metoksymetyl-l, 2, 3, 4-tetrahydroisokinolin-2-yl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.56 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.30 - 7.05 (m, 5H), 6.90 - 6.75 (m, 2H), 5.48 (m, 1H), 5.03 (d, J = 15.6Hz, 1H), 4.72 (dd, J = 15.6, 3.9Hz, 1H), 3.82 (s, 3H), 3.33 og 3.32 (s, 3H), 3.87 - 3.05 (m, 7H), 2.82 (d, J = 15.6Hz, 1H), 2.40 - 2.10 (m, 2H), 2.29 (s, 3H), 2.25 og 2.11 (s, 3H).
Eksempel 2(104)
8-(3-pentylamino)-2-metyl-3-(2-dimetylamino-4-metylpyridin-5-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidindihydroklorid
TLC: Rf 0.42 (kloroform : metanol = 20 : 1);
NMR (300MHz, CDC13): 8 8.01 (s, 1H), 7.32 (d, J = 10.2Hz, 1H), 6.85 (s, 1H), 4.00 (m, 1H), 3.41 (s, 6H), 3.40 (m, 2H), 3.17 (m, 2H), 2.37 (s, 3H), 2.33 (m, 2H), 2.32 (s, 3H), 1.65 - 1.95 (m, 4H), 1.07 (t, J = 7.5Hz, 3H), 1.06 (t, J = 7.2Hz, 3H).
Eksempel 2(105)
8-((2S)-l-metoksy-3-feny l-2-propyl)amino-2-mety 1-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.77 (m, 1H), 7.25 - 7.36 (m, 3H), 7.16 - 7.23 (m, 2H), 7.11 (m, 1H), 6.88 (m, 1H), 6.80 (m, 1H), 4.44 (m, 1H), 3.82 (s, 3H), 3.53 - 3.68 (m, 2H), 3.47 og 3.46 (s, 3H), 3.38 (m, 2H), 3.11 (t, J = 7.2Hz, 2H), 3.08 (m, 1H), 2.81 (m, 1H), 2.31 (s, 3H), 2.20 og 2.17 (s, 3H), 2.15 (m, 2H).
Eksempel 2(106)
8-(N-(4-metyltiofenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-alpyrimidinhydroklorid
TLC: Rf 0.50 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.25 (d, J = 8.4Hz, 2H), 7.18 (d, J = 8.4Hz, 2H), 7.13 (d, J = 8.1Hz, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 2.4, 8.1Hz, 1H), 5.13 (s, 2H), 3.84 (s, 3H), 3.70 (m, 2H), 3.50 (t, J = 7.8Hz, 2H), 3.01 (t, J = 6.9Hz, 2H), 2.50 (s, 3H), 2.29 (s, 3H), 2.23 (m, 2H), 2.19 (s, 3H), 1.75 (m, 2H), 0.93 (t, J = 7.5Hz, 3H).
Eksempel 2(107)
8-(4-fenylpiperazin-l-yl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidindihydroklorid
TLC: Rf 0.30 (heksan : etylacetat = 2:1);
NMR (300MHz, DMSO-d6): 8 7.30 - 7.38 (m, 2H), 7.21 - 7.29 (m, 2H), 7.12 (d, J = 8.4Hz, 1H), 7.00 (brd, J = 6.9Hz, 1H), 6.95 (d, J = 2.7Hz, 1H), 6.86 (dd, J = 2.7, 8.4Hz, 1H), 4.22 (brs, 4H), 3.79 (s, 3H), 3.53 (brs, 4H), 3.14 (m, 2H), 2.97 (t, J = 7.8Hz, 2H), 2.21 (s, 3H), 2.15 (m, 2H), 2.06 (s, 3H).
Eksempel 2(108)
8-(4-(2-klorfenyl)piperazin-l-yl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.38 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.41 (dd, J = 1.5,7.8Hz, 1H), 7.28 (m, 1H), 7.16 (d, J = 8.1Hz, 1H), 7.15 (d, J = 8.7Hz, 1H), 7.03 (m, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 2.7, 8.1Hz, 1H), 3.90 (m, 4H), 3.82 (s, 3H), 3.33 (t, J = 4.8H, 4H), 3.16 (t, J = 7.5Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.33 (s, 3H), 2.17 (s, 3H), 2.14 (m, 2H).
Eksempel 2(109)
8-(N, N-dibutylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidirihydroklorid
TLC: Rf 0.57 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.12 (d, J = 7.8Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 2.4, 7.8Hz, 1H), 3.90 (t, J = 7.5Hz, 4H), 3.83 (s, 3H), 3.48 (m, 2H), 3.02 (m, 2H), 2.27 (s, 3H), 2.25 (m, 2H), 2.19 (s, 3H), 1.71 (m, 4H), 1.38 (m, 4H), 0.97 (t, J = 6.9Hz, 6H).
Eksempel 2(110)
8-(N-metyl-N-butylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.36 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.1Hz, 1H), 6.88 (d, J = 3.0Hz, 1H), 6.81 (dd, J = 3.0, 8.1Hz, 1H), 3.97 (m, 2H), 3.83 (s, 3H), 3.51 (s, 3H), 3.45 (t, J = 8.1Hz, 2H), 3.12 (t, J= 6.9Hz, 2H), 2.26 (s, 3H), 2.23 (m, 2 H), 2.18 (s, 3H), 1.85 (m, 2H), 1.40 (m, 2H), 0.99 (t, J = 7.2Hz, 3H).
Eksempel 2(111)
8-(N-(4-metylfenyl)metyl-N-butylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cykIopenta[d]pyrazblo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.53 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.10 - 7.21 (m, 5H), 6.89 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 2.4, 8.1Hz, 1H), 5.13 (s, 2H), 3.83 (s, 3H), 3.77 (t, J = 7.2Hz, 2H), 3.48 (t, J = 7.8Hz, 2H), 3.01 (t, J = 6.9Hz, 2H), 2.36 (s, 3H), 2.29 (s, 3H), 2.21 (m, 2H), 2.19 (s, 3H), 1.73 (m, 2H), 1.34 (m, 2H), 0.93 (t, J= 7.2Hz, 3H).
Eksempel 2(112)
8-(N-(4-metylfenyl)metyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.23 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.25 - 7.05 (m, 5H), 6.98 - 6.78 (m, 2H), 5.06 (s, 2H), 4.22 - 4.03 (m, 2H), 3.84 (s, 3H), 3.75 - 3.58 (m, 2H), 3.58 - 3.38 (m, 2H), 3.30 (s, 3H), 3.20 - 2.90 (m, 2H), 2.36 (s, 3H), 2.30 (s, 3H), 2.21 (m, 2H), 2.19 (s, 3H).
Eksempel 2(113)
8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.35 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.25 - 6.95 (m, 5H), 6.95 - 6.73 (m, 2H), 5.40 - 5.15 (m,
2H), 3.83 (s, 3H), 3.65 - 3.30 (m, 2H), 3.30 - 2.95 (m, 2H), 2.35 (s, 3H), 2.31 (s, 3H), 2.30 - 2.10 (m, 3H), 2.19 (s, 3H), 1.10 - 0.80 (m, 4H).
Eksempel 2(114) 8-(N-cyklopropylme1yl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-m metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidirmydroklorid
TLC: Rf 0.37 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.30 - 7.00 (m, 5H), 7.00 - 6.75 (m, 2H), 5.24 (s, 2H), 3.84 (s, 3H), 3.80 - 3.60 (m, 2H), 3.60 - 3.35 (m, 2H), 3.20 - 2.90 (m, 2H), 2.34 (s, 3H), 2.29 (s, 3H), 2.22 (s, 2H), 2.11 (s, 3H), 1.38 - 1.05 (m, 1H), 0.75 - 0.50 (m, 2H), 0.35-0.10 (m, 2H).
Eksempel 2(115)
8-(N, N-dipropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.59 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.17 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 2.4, 8.4Hz, 1H), 3.82 (s, 3H), 3.56 (m, 4H), 2.95 (t, J = 7.2Hz, 2H), 2.90 (t, J = 7.8Hz, 2H), 2.33 (s, 3H), 2.19 (s, 3H), 2.13 (m, 2H), 1.58 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(116)
8-(N-(4-metylfenyl)metyl-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.33 (d, J= 8.1Hz, 2H), 7.19 (d, J = 8.1Hz, 2H), 7.11 (d, J = 8.7Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.7Hz, 1H), 5.27 (d, J = 15.0Hz, 1H), 5.24 (d, J = 15.0Hz, 1H), 4.41 (m, 2H), 3 .83 (s, 3H), 3.51 (t, J = 7.5Hz, 2H), 3.22 (t, J = 6.9Hz, 2H), 2.37 (s, 3H), 2.28 (s, 3H), 2.25 (m, 2H), 2.17 (s, 3H), 1.91 (t, J = 2.4Hz, 3H).
Eksempel 2(117)
8-(N-propyl-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.55 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 2.7, 8.1Hz, 1H), 4.40 (m, 2H), 3.82 (s, 3H), 3.55 (m, 2H), 3.11 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.13 (m, 2H), 1.81 (t, J = 2.4Hz, 3H), 1.66 (m, 2H), 0.95 (t, J= 7.5Hz, 3H).
Eksempel 2(118)
8-(5-nonylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.58 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.33 (brd, J = 10.5Hz, 1H), 7.12 (d, J = 8.7Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 2.7, 8.7Hz, 1H), 4.10 (m, 1H), 3.83 (s, 3H), 3.49 (t, J = 8.1Hz, 2H), 3.12 (t, J = 6.6Hz, 2H), 2.29 (s, 3H), 2.27 (m, 2H), 2.20 (s, 3H), 1.61-1.88 (m, 4H), 1.30 - 1.53 (m, 8H), 0.94 (m, 6H).
Eksempel 2(119)
8-(N-cyklopentyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.38 (heksan : etylacetat = 2:1);
NMR (300MHz, CD3OD): 87.20 - 6.98 (m, 5H), 6.93 (d, J = 2.4Hz, 1H), 6.85 (dd, J = 8.6, 2.4Hz, 1H), 5.20 (d, J = 16.5Hz, 1H), 5.09 (d, J = 16.5Hz, 1H), 5.02 - 4.70 (m, 1H), 3.81 (s, 3H), 3.17 (t, J = 7.2Hz, 2H), 2.98 (t, J = 7.8Hz, 2H), 2.29 (s, 3H), 2.22 (s, 3H), 1.98 (s, 3H), 2.40 - 1.60 (m, 10H).
Eksempel 2(120)
8-(N-cyklopropylmetyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.85 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 5 7.28 - 7.16 (m, 5H), 6.87 (d, J = 3.0Hz, 1H), 6.79 (dd, J = 3.0, 8.4Hz, 1H), 4.89 (s, 2H), 3.83 (s, 3H), 3.38 (d, J = 6.9Hz, 2H), 2.96 (t, J = 7.2Hz, 2H), 2.89 (t, J = 7.2Hz, 2H), 2.47 (s, 3H), 2.36 (s, 3H), 2.19 (s, 3H), 2.09 (kvint, J = 7;2Hz, 2H), 1.10 - 0.95 (m, 1H), 0.52 - 0.42 (m, 2H), 0.10 - 0.05 (m, 2H).
Eksempel 2(121)
8-(N-(4-fluorfenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.87 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 5 7.28 - 7.16 (m, 3H), 7.03 - 6.95 (m, 2H), 6.87 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 2.4, 8.4Hz, 1H), 4.80 (s, 2H), 3.83 (s, 3H), 3.40 - 3.32 (m, 2H), 2.89 (t, J = 7.5Hz, 2H), 2.81 (t, J = 7.5Hz, 2H), 2.36 (s, 3H), 2.20 (s, 3H), 2.07 (kvint, J = 7.5Hz, 2H), 1.62 - 1.50 (m, 2H), 0.88 (t, J = 7.2Hz, 3H).
Eksempel 2(122)
8-(N-cyklobutyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.48 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.19 (d, J = 8.4Hz, 1H), 7.02 (d, J = 7.5Hz, 2H), 6.89 (d, J = 7.5Hz, 2H), 6.87 (d, J = 3.0Hz, 1H), 6.80 (dd, J = 8.4, 3.0Hz, 1H), 4.90 - 4.70 (m, 2H), 4.08 (m, 1H), 3.83 (s, 3H), 2.84 (t, J = 7.5Hz, 2H), 2.61 (m, 2H), 2.39 (s, 3H), 2.30 (s, 3H), 2.19 (s, 3H), 2.20 - 2.06 (m, 4H), 1.96 (m, 2H), 1.80 - 1.60 (m, 2H).
Eksempel 2(123)
8-(N-etyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.69 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.19 (d, J = 8.1Hz, 1H), 7.14 - 7.06 (m, 4H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 2.7, 8.1Hz, 1H), 4.81 (s, 2H), 3.87 (s, 3H), 3.47 (q, J = 6.9Hz, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.81 (brt, J = 7.8Hz, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.20 (s, 3H), 2.04 (kvint, J = 7.8Hz, 2H), 1.18 (t, J = 6.9Hz, 3H).
Eksempel 2(124)
8-(N-propyl-N-(4-trifluormetylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.79 (heksan : etylacetat =1:1); NMR (300MHz, CDC13): 5 7.57 (brd, J = 8.1Hz, 2H), 7.44 (brd, J = 8.1Hz, 2H), 7.18 (d, J = 8.7Hz, 1H), 6.87 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 2.4, 8.7Hz, 1H), 4.91 (s, 2H), 3.83 (s, 3H), 3.49 - 3.25 (m, 2H), 2.90 (t, J = 7.8Hz, 2H), 2.87 (t, J = 7.8Hz, 2H), 2.35 (s, 3H), 2.19 (s, 3H), 2.18 - 2.00 (m, 2H), 1.62 - 1.50 (m, 2H), 0.88 (t, J = 7.5Hz, 3H). Eksempel 2(125) 8-(N-propyl-N-(tetrahydrofuran-2-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.31 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 6 7.16 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.78 (dd, J= 2.7, 8.1Hz, 1H), 3.84 - 4.06 (m, 2H), 3.82 (s, 3H), 3.64 - 3.80 (m, 3H), 3.50 - 3.64 (m, 2H), 2.99 (t, J = 7.2Hz, 2H), 2.91 (t, J = 8.1Hz, 2H), 2.32 (s, 3H), 2.19 (s, 3H), 2.13 (m, 2H), 1.74 - 2,00 (m, 3H), 1.42 - 1.65 (m, 3H), 0.89 (t, J= 7.5Hz, 3H).
Eksempel 2(126)
8-(N-butyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (heksan : etylacetat = 2:1); NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 2.7, 8.4Hz, 1H), 3.92 (t, J = 5.7Hz, 2H), 3.82 (s, 3H), 3.57 (m, 2H), 3.50 (t, J= 5.7Hz, 2H), 3.28 (s, 3H), 2.98 (t, J = 7.8Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.13 (m, 2H), 1.55 (m, 2H), 1.33 (m, 2H), 0.90 (t, J= 7.2Hz, 3H). Eksempel 2(127) 8-(N-propyl-N-cyklopropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.1Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.1,2.7Hz, 1H), 3.85 (m, 2H), 3.82 (s, 3H), 3.19 (t, J = 7.5Hz, 2H), 3.07 (m, 1H), 2.92 (t, J = 7.5Hz, 2H), 2.31 (s, 3H), 2.18 (s, 3H), 2.12 (m, 2H), 1.62 (m, 2H), 0.89 (t, J = 7.2Hz, 3H), 0.80 - 0.68 (m, 4H).
Eksempel 2(128)
8-(N-cyklobutylmetyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.57 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.17 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 2.7, 8.4Hz, 1H), 3.82 (s, 3H), 3.82 (t, J = 6.0Hz, 2H), 3.64 (d, J = 7.5Hz, 2H), 3.49 (t, J = 6.0Hz, 2H), 3.28 (s, 3H), 2.96 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.62 - 2.50 (m, 1H), 2.32 (s, 3H), 2.18 (s, 3H), 2.20 - 2.05 (m, 2H), 2.06 - 1.58 (m, 6H).
Eksempel 2(129)
8-(3-etoksykarbonyl-l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.27 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.27 (m, 1H), 7.09 (d, J = 8.1Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 2.7, 8.1Hz, 1H), 4.62 (m, 2H), 4.27 (q, J = 6.9Hz, 2H), 4.20 (t, J = 5.7Hz, 2H), 3.83 (s, 3H), 3.47 (t, J = 7.2Hz, 2H), 3.16 (t, J = 6.0Hz, 2H), 2.85 (m, 2H), 2.27 (s, 3H), 2.26 (m, 2H), 2.17 (s, 3H), 1.34 (t, J= 6.9 HZ, 3H).
Eksempel 2(130)
8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-turo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.68 (heksan : etylacetat = 1:1);
NMR (300MHz, CDC13): 8 7.21 (d, J = 7.8Hz, 2H), 7.16 (d, J = 7.8Hz, 2H), 7.13 (d, J= 8.4Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.4Hz, 1H), 5.41 (brs, 2H), 5.27 (m, 2H), 5.22 (brs, 2H), 3.83 (s, 3H), 3.74 (m, 2H), 2.37 (s, 3H), 2.31 (s, 3H), 2.20 (s, 3H), 1.24 (m, 1H), 0.67 (m, 2H), 0.24 (m, 2H).
Eksempel 2(131)
8-(3-(3-metyl-l, 2, 4-oksadiazol-5-yl)-l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.18 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.29 (m, 1H), 7.15 (d, J= 8.7Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 2.7, 8.7Hz, 1H), 4.57 (m, 2H), 3.94 (m, 2H), 3.82 (s, 3H), 3.09 (t, J = 7.5Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.71 (m, 2H), 2.42 (s, 3H), 2.32 (s, 3H), 2.17 (s,3H), 2.14 (m,2H).
Eksempel 2(132)
8-(4-heptylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.48 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.37 (d, J = 8.7Hz, 1H), 7.07 (d, J = 2.4Hz, 1H), 6.97 (dd, J = 2.4, 8.7Hz, 1H), 4.13 (m, 1H), 3.85 (s, 3H), 3.35 - 3.66 (m, 2H), 3.13 (t, J = 7.5Hz, 2H), 2.34 (s, 3H), 2.29 (m, 2H), 1.60 - 1.84 (m, 4 H), 1.34 - 1.60 (m, 4H), 1.00 (t, J = 7.2Hz, 3H), 0.99 (t, J = 7.5Hz, 3H).
Eksempel 2(133)
8-(N-cyklopropylmetyl-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.73 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.1, 2.7Hz, 1H), 4.54 (brs, 2H), 3.82 (s, 3H), 3.53 (d, J = 6.9Hz, 2H), 3.13 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.33 (s, 3H), 2.17 (s, 3H), 2.17 - 2.08 (m, 2H), 1.81 (t, J = 2.7Hz, 3H), 1.20 -1.16 (m, 1H), 0.60 - 0.52 (m, 2H), 0.36 - 0.28 (m, 2H).
Eksempel 2(134)
8-(N-(2-metoksyetyl)-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.13 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.4, 2.7Hz, 1H), 4.44 - 4.39 (m, 2H), 3.92 (t, J = 6.0Hz, 2H), 3.82 (s, 3H), 3.65 (t, J = 6.0Hz, 2H), 3.34 (s, 3H), 3.13 (t, J = 7 .2Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.17 (s, 3H), 2.17 - 2.08 (m, 2H), 1.81 (t, J = 2.7Hz, 3H).
Eksempel 2(135)
8-(2-butyrylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.80 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.4Hz, 1H), 6.85 (d, J = 2.4Hz, 1H), 6.78 (dd, J = 8.4, 2.4Hz, 1H), 6.53 (t, J = 6.9Hz, 1H), 4.36 - 4.30 (m, 2H), 3.82 (s, 3H), 3.25 (t, J = 7.2Hz, 2H), 2.90 (t, J = 7.8Hz, 2H), 2 .31 (s, 3H), 2.18 (s, 3H), 2.20 - 2.08 (m, 2H), 1.83 (t, J = 2.1Hz, 3H).
Eksempel 2(136) .
8-(4-(4-klorfenyl)-l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.10 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.42 - 7.30 (m, 4H), 7.16 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 8.1, 2.4Hz, 1H), 6.22 - 6.18 (m, 1H), 4.50 - 4.32 (m, 2H), 4.10 - 3.90 (m, 2H), 3.82 (s, 3H), 3.10 (t, J = 6.9Hz, 2 H), 2.91 (t, J = 7.5Hz, 2H), 2.82 - 2.69 (m, 2H), 2.33 (s, 3H), 2.17 (s, 3H), 2.17 - 2.08 (m, 2H).
Eksempel 2(137)
8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.53 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.36 (d, J = 8.4Hz, 1H), 7.18 (d, J = 8.1Hz, 2H), 7.15 (d, J = 8.1Hz, 2H), 7.08 (d, J = 2.7Hz, 1H), 6.97 (dd, J = 8.4,2.7Hz, 1H), 5.25 (d, J = 15.9Hz, 1H), 5.21 (d, J = 15.9Hz, 1H), 3.85 (s, 3H), 3.70 (m, 2H), 3.36 - 3.62 (m, 2H), 3.07 (t, J = 7.2Hz, 2H), 2.36 (s, 3H), 2.35 (s, 3H), 2.23 (m, 2H), 1.23 (m, 1H), 0.63 (m, 2H), 0.18 (m, 2H).
Eksempel 2(138)
8-(N-propyl-N-(4-trifluorme1yloksyfenyl)me1ylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.55 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.32 (brd, J = 8.7Hz, 2H), 7.18 (d, J = 8.4Hz, 1H), 7.15 (brd, J = 8.7Hz, 2H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.4, 2.7Hz, 1H), 4.84 (s, 2H), 3.83 (s, 3H), 3.41 - 3.35 (m, 2H), 2.89 (t, J = 7.5Hz, 2H), 2.83 (t, J = 7.8Hz, 2H), 2.36 (s, 3H), 2.19 (s, 3H), 2.19 - 2.00 (m, 2H), 1.66 - 1.54 (m, 2H), 0.88 (t, J = 7.5Hz, 3H).
Eksempel 2(139)
8-(N-(2-butyryl)-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.40 (heksan : etylacetat =3:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 8.7Hz, 1H), 7.05 (d, J = 2.4Hz, 1H), 6.88 (dd, J = 8.7, 2.4Hz, 1H), 4.54 (q, J = 2.1Hz, 2H), 3.83 (s, 3H), 3.52 (d, J = 6.6Hz, 2H), 3.13 (t, J = 7.5Hz, 2H), 2.92 (t, J = 7.5Hz, 2H), 2.37 (s, 3H), 2.13 (kvint, J = 7.5Hz, 2H), 1.81 (t, J = 2.1Hz, 3H), 1.16-1.02 (m, 1H), 0.60 - 0.52 (m, 2H), 0.32 - 0.26 (m, 2H).
Eksempel 2(140)
8-(N-propyl-N-(3-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.52 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.27 (m, 1H), 7.15 (m, 1H), 7.13 (d, J = 8.1Hz, 1H), 7.05 (m, 2H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.1Hz, 1H), 5.14 (s, 2H), 3.83 (s, 3H), 3.74 (m, 2H), 3.49 (t, J = 7.2Hz, 2H), 3.02 (t, J = 6.9Hz, 2H), 2.36 (s, 3H), 2.29 (s, 3H), 2.22 (m, 2H), 2.20 (s, 3H), 1.77 (m, 2H), 0.94 (t, J = 7.2Hz, 3H).
Eksempel 2(141)
8-(N-propyl-N-(2-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.52 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.18 - 7.30 (m, 4H), 7.13 (d, J = 8.1Hz, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 2.4, 8.1Hz, 1H), 5.13 (s, 2H), 3.83 (s, 3H), 3.78 (m, 2H), 3.49 (t, J = 6.9Hz, 2H), 3.00 (t, J = 6.9Hz, 2H), 2.28 (s, 3H), 2.24 (s, 3H), 2.21 (m, 2H), 2.19 (s, 3H), 1.79 (m, 2H), 0.94 (t, J = 7.2Hz, 3H).
Eksempel 2(142)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-etoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.34 (d, J = 8.7Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.95 (dd, J = 2.4, 8.7Hz, 1H), 4.07 (m, 2H), 3.99 (m, 1H), 3.34 - 3.65 (m, 2H), 3.13 (t, J = 7.8Hz, 2H), 2.35 (s, 3H), 2.29 (m, 2H), 1.62 - 1.93 (m, 4H), 1.42 (t, J = 6.9Hz, 3H), 1.06 (t, J= 7.5Hz, 3H), 1.05 (t, J = 7.2Hz, 3H).
Eksempel 2(143)
8-(3-pentylammo)-2-metyl-3-(2-klor-4-etoksyfenyl)-5,7-dihydro-furo[3,4-d] pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.52 (brd, J = 10.2Hz, 1H), 7.32 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.4Hz, 1H), 6.95 (dd, J = 2.4, 8.4Hz, 1H), 5.49 (d, J = 16.5Hz, 1H), 5.39 (d, J = 16.5Hz, 1H), 5.28 (brs, 2H), 4.07 (m, 2H), 3.40 (m, 1H), 2.40 (s, 3H), 1.68 - 1.98 (m, 4H), 1.43 (t, J = 6.9Hz, 3H), 1.07 (t, J = 7.2Hz, 3H), 1.06 (t, J = 7.2Hz, 3H).
Eksempel 2(144)
8-(N-metyl-N-heksylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.09 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 8.4, 2.4Hz, 1H), 4.01 - 3.95 (m, 2H), 3.83 (s, 3H), 3.51 (s, 3H), 3.51 - 3.42 (m, 2H), 3.18 - 3.06 (m, 2H), 2.26 (s, 3H), 2.26 - 2.18 (m, 2H), 2.18 (s, 3H), 1.96 - 1.80 (m, 2H), 1.44 - 1.25 (m, 6H), 0.90 (brt, J = 6.6Hz, 3H).
Eksempel 2(145)
8-(N-metyl-N-(3-pentyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (m, 1H), 4.55 (m, 1H), 3.83 (s, 3H), 3.46 (t, J = 7.8Hz, 2H), 3.27 (s, 3H), 3.10 (t, J = 6.9Hz, 2H), 2.26 (s, 3H), 2.45 (m, 2H), 2.19 (s, 3H), 1.76 - 1.98 (m, 4H), 1.01 (t, J = 7.2Hz, 6H).
Eksempel 2(146)
8-(N-metyl-N-(4-heptyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.51 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 3.0Hz, 1H), 6.82 (dd, J = 3.0, 8.4Hz, 1H), 4.80 (m, 1H), 3.83 (s, 3H), 3.47 (t, J = 7.5Hz, 2H), 3.27 (s, 3H), 3.09 (t, J = 7.5Hz, 2H), 2.25 (s, 3H), 2.24 (m, 2H), 2.19 (s, 3H), 1.64 - 1.94 (m, 4H), 1.28- 1.58 (m,4H), 0.97 (t, J = 7.2Hz, 6H).
Eksempel 2(147) 8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[lJ5-a]pyrimidm^
TLC: Rf 0.54 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.4Hz, 1H), 7.11 (d, J = 7.8Hz, 2H), 7.09 (d, J = 2.4Hz, 1H), 7.02 (d, J = 7.8Hz, 2H), 6.94 (dd, J = 2.4, 8.4Hz, 1H), 5.18 - 5.30 (m, 4H), 5.15 (s, 2H), 3.85 (s, 3H), 2.67 (m, 1H), 2.41 (s, 3H), 2.33 (s, 3H), 0.85 - 1.00 (m, 4H).
Eksempel 2(148)
8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.58 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.35 (d, J = 8.4Hz, 1H), 7.19 (d, J = 8.1Hz, 2H), 7.17 (d, J = 8.1Hz, 2H), 7.08 (d, J = 2.7Hz, 1H), 6.96 (dd, J = 2.7, 8.4Hz, 1H), 5.10 - 5.50 (m, 6H), 3.85 (s, 3H), 3.69 (m, 2H), 2.37 (s, 3H), 2.36 (s, 3H), 1.21 (m, 1H), 0.65 (m, 2H), 0.22 (m, 2H).
Eksempel 2(149)
8-(N-cyklobutyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.45 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.17 (,d J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.1, 2.7Hz, 1H), 4.35 (kvint, J = 7.5Hz, 1H), 3.82 (s, 3H), 3.69 - 3.10 (m, 2H), 2.94 (t, J = 6.9Hz, 2H), 2.90 (t, J = 7.8Hz, 2H), 2.33 (s, 3H), 2.22 - 2.02 (m, 9H), 1.78 - 1.58 (m, 2H), 1.39 (sekst, J = 7.8Hz, 2H), 0.84 (t, J = 7.8Hz, 3H).
Eksempel 2(150)
8-(N-isobutyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidindihydroklorid
TLC: Rf 0.63 (etylacetat: eddiksyre : vann = 3:1:1);
NMR (300MHz, DMSO-d6) : 8 7.11 (d, J = 8.4Hz, 1H), 6.91 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.4,2.7Hz, 1H), 4.08 - 3.98 (m, 2H), 3.78 (s, 3H), 3.50 - 3.42 (m, 2H), 3.42 - 3.32 (m, 2H), 3.01 (brt, J = 6.9Hz, 2H), 2.87 (brt, J = 7.8Hz, 2H), 2.79 (s, 3H), 2.77 (s, 3H), 2.25 (s, 3H), 2.18 - 2.00 (m, 2H), 2.08 (s, 3H), 1.80 - 1.64 (m, 1H), 0.83 (d, J = 6.6Hz, 6H).
Eksempel 2(151)
8-(N-propyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.34 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 8.7Hz, 1H), 7.28 - 7.24 (m, 2H), 7.08 (d, J = 3.0Hz, 1H), 7.05 - 6.97 (m, 2H), 6.90 (dd, J = 8.7, 3.0Hz, 1H), 5.09 (s, 2H), 4.91 (s, 2H), 4.89 (s, 2H), 3.84 (s, 3H), 3.33 - 3.27 (m, 2H), 2.40 (s, 3H), 1.63 (sekst, J = 7.8Hz, 2H), 0.39 (t, J = 7.8Hz, 3H).
Eksempel 2(152)
8-(N-propyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihy dro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.36 (heksan : etylacetat = 3 : 1);
NMR (300MHz, CDC13): 8 7.32 (d, J = 8.4Hz, 1H), 7.28 - 7.20 (m, 2H), 7.07 (d, J = 2.7Hz, 1H), 7.02 - 6.94 (m, 2H), 6.89 (dd, J = 8.4, 2.7Hz, 1H), 4.80 (s, 2H), 3.84 (s, 3H), 3.36 (brt, J = 7.5Hz, 2H), 2.90 (t, J = 7.5Hz, 2H), 2.82 (t, J = 7.5Hz, 2H), 2.39 (s, 3H), 2.07 (kvint, J = 7.5Hz, 2H), 1.68 - 1.48 (m, 2H), 0.87 (t, J = 7.5Hz, 3H).
Eksempel 2(153)
8-(N-cyklopropylmetyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.67 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.35 (d, J = 8.4Hz, 1H), 7.27 (d, J = 8.4Hz, 2H), 7.22 (d, J = 8.4Hz, 2H), 7.09 (d, J = 2.7Hz, 1H), 6.97 (dd, J = 2.7, 8.4Hz, 1H), 5.48 (d, J = 16.5Hz, 1H), 5.37 (d, J = 16.5Hz, 1H), 5.33 (d, J = 15.9Hz, 1H), 5.24 (s, 2H), 5.24 (d, J = 15.9Hz, 1H), 3.85 (s, 3H), 3.69 (m, 2H), 2.50 (s, 3H), 2.36 (s, 3H), 1.19 (m, 1H), 0.69 (m, 2H), 0.24 (m, 2H).
Eksempel 2(154)
8-(N, N-dipropylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.69 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.33 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.96 (dd, J = 2.4, 8.7Hz, 1H), 5.48 (td, J = 1.8, 16.8Hz, 1H), 5.36 (td, J = 1.8,16.8Hz, 1H), 5.21 (t, J = 1.8Hz, 2H), 3.85 (m, 4H), 3.85 (s, 3H), 2.35 (s, 3H), 1.83 (m, 4H), 1.02(t,J = 7.2Hz, 6H).
Eksempel 2(155)
8-(N, N-dibutylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.74 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.96 (dd, J = 2.4, 8.4Hz, 1H), 5.47 (d, J = 16.5Hz, 1H), 5.36 (d, J = 16.5Hz, 1H), 5.21 (s, 2H), 3.88 (m, 4H), 3.85 (s, 3H), 2.34 (s, 3H), 1.79 (m, 4H), 1.42 (m, 4H), 1.00 (t, J = 7.2Hz, 6H).
Eksempel 2(156)
8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.27 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13) : 8 7.33 - 7.26 (m, 3H), 7.06 (d, J = 2.7Hz, 1H), 7.01 - 6.95 (m, 2H), 6.88 (dd, J = 8.4, 2.7Hz, 1H), 4.88 (s, 2H), 3.84 (s, 3H), 3.38 (d, J = 6.9Hz, 2H), 2.96 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.2Hz, 2 H), 2.39 (s, 3H), 2.10 (kvint, J = 7.2Hz, 2H), 1.10 - 0.98 (m, 1H), 0.49 - 0.42 (m, 2H), 0.08 - 0.02 (m, 2H).
Eksempel 2(157)
8-(N-propyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.43 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.33 (d, J = 8.7Hz, 1H), 7.19 (d, J = 8.1Hz, 2H), 7.13 (d, J = 8.1Hz, 2H), 7.08 (d, J = 2.7Hz, 1H), 6.95 (dd, J = 2.7, 8.1Hz, 1H), 5.28 (m, 2H), 5.13 (m, 2H), 5.08 (m, 2H), 3.85 (s, 3H), 3.64 (m, 2 H), 2.37 (s, 3H), 2.36 (s, 3H), 1.80 (m, 2H), 0.95 (t, J = 7.5Hz, 3H).
Eksempel 2(158) 8-(3-pentylamino)-2-metyl-3-(3-klor-5-trifluormetylpyridin-2-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin dihydroklorid
TLC: Rf 0.19 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 8.91 (s, 1H), 8.12 (s, 1H), 3.99 (m, 1H), 3.50 (m, 2H), 3.15 (m, 2H), 2.47 (s, 3H), 2.32 (m, 2H), 1.94 - 1.64 (m, 4H), 1.06 (brt, J = 6.9Hz, 6H).
Eksempel 2(159)
8-(N-butyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.21 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.1Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.96 (dd, J = 8.1, 2.4Hz, 1H), 5.47 og 5.35 (ABd, J = 16.5Hz, 2H), 5.21 (brs, 2H), 4.00 - 3.75 (m) og 3.85 (s) totalt 7H, 2.34 (s, 3H), 1.90 - 1.75 (m, 4H), 1.42 (sekst, J = 7.2Hz, 2H), 1.05 - 0.98 (m, 6H).
Eksempel 2(160)
8-(N-butyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.33 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.12 (d, J = 8.7Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 8.7, 2.4Hz, 1H), 3.95 - 3.80 (m) og 3.83 (s) totalt 7H, 3.48 (t, J = 7.5Hz, 2H), 3.02 (t, J = 7.5Hz, 2H), 2.30 - 2.18 (m) og 2.27 (s) totalt 5H, 2.19 (s, 3H), 1.80
- 1.65 (m, 4H), 1.38 (sekst, J = 7.2Hz, 2H), 0.96 (t, J = 7.2Hz, 6H).
Eksempel 2(161)
8-(4-heptylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]-pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.54 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.52 (d, J = 10.2Hz, 1H), 7.34 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.97 (dd, J = 2.4, 8.7Hz, 1H), 5.49 (brd. J = 16.8Hz, 1H), 5.39 (d, J = 16.8Hz, 1H), 5.28 (m, 2H), 3.85 (s, 3H), 3.53 (m, 1H), 2.39 (s, 3H), 1.75 (m, 4H), 1.47 (m, 4H), 1.00 (t, J = 7.2Hz, 6H).
Eksempel 2(162)
8-(N-butyl-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-
iuro[3,4-d]pyrazolo[l,5-a]pyrirnidirihydroklori(l
TLC: Rf 0.48 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.33 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.96 (dd, J = 2.4, 8.7Hz, 1H), 5.46 (m, 1H), 5.35 (m, 1H), 5.23 (t, J = 1.5Hz, 2H), 3.80 - 4.00 (m, 4H), 3.85 (s, 3H), 2.34 (s, 3H), 1.80 (m, 2H), 1 .46 (t, J= 7.2Hz, 3H), 1.44 (m, 2H), 1.01 (t, J = 7.2Hz, 3H).
Eksempel 2(163)
8-(N-cyklopropyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.80 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13) : 8 7.32 (d, J = 8.4Hz, 1H), 7.17 - 7.09 (m, 2H), 7.07 (d, J = 2.7Hz, 1H), 6.96 - 6.93 (m, 2H), 6.90 (dd, J = 8.4,2.7Hz, 1H), 5.01 (s, 2H), 3.84 (s, 3H), 2.97 - 2.86 (m, 4H), 2.75 (m, 1H), 2.39 (s, 3H), 2.03 (m, 2H), 0.80 - 0.68 (m, 4H).
Eksempel 2(164)
8-(N-propyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.85 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.24 - 7.12 (m, 2H), 7.19 (d, J = 8.1Hz, 1H), 7.06 - 6.97 (m, 2H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.1,2.7Hz, 1H), 5.00 - 4.92 (m, 2H), 3.83 (s, 3H), 3.42 - 3.36 (m, 2H), 2.86 (t, J = 7.5Hz, 2 H), 2.75 (t, J = 7.5Hz, 2H), 2.37 (s, 3H), 2.19 (s, 3H), 2.02 (kvintett, J = 7.5Hz, 2H), 1.68 - 1.46 (m, 2H), 0.90 (t, J = 7.2Hz, 3H).
Eksempel 2(165)
8-(N-propyl-N-(3-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.86 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.30 - 7.22 (m, 1H), 7.18 (d, J = 8.4Hz, 1H), 7.08 - 7.01 (m, 2H), 6.98 - 6.90 (m, 1H), 6.87 (d, J = 2.4Hz, 1H), 6.80 (dd, J = 8.4,2.4Hz, 1H), 4.85 (s, 2H), 3.83 (s, 3H), 3.42 - 3.36 (m, 2H), 2.89 (t, J = 7.5Hz, 2H), 2.86 (t, J = 7.5Hz, 2H), 2.36 (s, 3H), 2.19 (s, 3H), 2.09 (kvintett, J = 7.5Hz, 2H), 1.68 - 1.52 (m, 2H), 0.88 (t, J = 7.5Hz, 3H).
Eksempel 2(166)
8-dicyklopropylmetylamino-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.39 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 8.7Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 2.4, 8.7Hz, 1H), 6.48 (brd, J = 9.9Hz, 1H), 5.22 (brs, 2H), 4.89 (brs, 2H), 3.83 (s, 3H), 2.87 (m, 1H), 2.37 (s, 3H), 1.15 (m, 2H), 0.61 (m, 4H), 0.42 (m, 4H).
Eksempel 2(167)
8-dicyklopropylmetylamino-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.40 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 8.4Hz, 1H), 7.04 (d, J = 2.4Hz, 1H), 6.87 (dd, J = 2.4, 8.4Hz, 1H), 6.37 (brd, J = 9.9Hz, 1H), 3.82 (s, 3H), 3.40 (m, 1H), 3.01 (t, J = 6.9Hz, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.35 (s, 3H), 2.11 (m, 2H), 1.14 (m, 2H), 0.50 - 0.66 (m, 4H), 0.35 - 0.50 (m, 4H).
Eksempel 2(168)
8-(N-butyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.52 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.40 - 7.30 (m, 1H), 7.08 (s, 1H), 7.00 - 6.90 (m, 1H), 4.00 - 3.80 (m) og 3.85 (s) totalt 7H, 3.65 - 3.30 (m, 2H), 3.10 - 2.95 (m, 2H), 2.40 - 2.20 (m) og 2.33 (s) totalt 5H, 1.80 - 1.65 (m, 4H), 1.43 - 1.30 (m, 2H), 0.97 (t, J = 6.6Hz, 6H).
Eksempel 2(169)
8-(N-cyklopropylmetyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.54 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.31 (d, J = 8.4Hz, 1H), 7.05 (d, J = 2.7Hz, 1H), 6.88 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 3.64 - 3.58 (m, 2H), 3.53 (d, J = 6.9Hz, 2H), 3.01 (t, J = 7.2Hz, 2H), 2.92 (t, J = 7.2Hz, 2H), 2.36 (s, 3H), 2.14 (kvintett, J = 7.2Hz, 2H), 1.65 - 1.55 (m, 2H), 1.05 - 0.90 (m, 1H), 0.91 (t, J = 7.5Hz, 3H), 0.50 - 0.40 (m, 2H), 0.15 - 0.05 (m, 2H).
Eksempel 2(170)
8-(N-cyklopropylmetyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.42 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.30 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 8.4, 2.7Hz, 1H), 5.23 (s, 2H), 4.91 (s, 2H), 3.83 (s, 3H), 3.65 - 3.50 (m, 4H), 2.38 (s, 3H), 1.63 (kvintett, J = 7.2Hz, 2H), 1.10 - 0.98 (m, 1H), 0.94 (t, J = 7.2Hz, 3H), 0.56 - 0.46 (m, 2H), 0.15 (dd, J = 10.8, 5.1Hz, 2H).
Eksempel 2(171)
8-(N-(2-butynyl)-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.44 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.7Hz, 1H), 7.08 (d, J = 1.8Hz, 1H), 6.96 (brd, J = 8.7Hz, 1H), 4.56 (d, J = 2.1Hz, 2H), 4.05 - 3.80 (m) og 3.85 (s) totalt 5H, 3.65 - 3.30 (m, 2H), 3.25 - 3.10 (m, 2H), 2.40 - 2.20 (m) og 2.33 (s) totalt 5H, 1.95 - 1.80 (m) og 1.89 (s) totalt 5H, 1.01 (t, J = 7.2Hz, 3H).
Eksempel 2(172)
8-(N-(2-butynyl)-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.36 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.28 (d, J = 8.7Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.90 (dd, J = 8.7,2.7Hz, 1H), 5.32 (s, 2H), 4.91 (s, 2H), 4.45 (q, J = 2.1Hz, 2H), 3.84 (s, 3H), 3.55 - 3.45 (m, 2H), 2.38 (s, 3H), 1.82 (t, J = 2.1Hz, 3H), 1.72 (sekstett, J = 7.2Hz, 2H), 0.98 (t, J = 7.2Hz, 3H).
Eksempel 2(173)
8-(N-butyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.34 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.35 (d, J = 7.8Hz, 1H), 7.08 (d, J = 2.1Hz, 1H), 6.97 (brd, J = 7.8Hz, 1H), 4.30 - 4.18 (m, 2H), 3.90 - 3.78 (m) og 3.85 (s) totalt 5H, 3.70
- 3.30 (m) og 3.64 (m) totalt 4H, 3.30 (s, 3H), 3.08 - 2.98 (m, 2H), 2.40 - 2.18 (m) og 2.33 (s) totalt 5H, 1.80 - 1.65 (m, 2H), 1.43 - 1.35 (m, 2H), 0.96 (t, J = 7.2Hz, 3H). Eksempel 2(174) 8-(N-butyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7- . dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.39 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.40 - 7.30 (m, 1H), 7.08 (brs, 1H), 7.05 - 6.95 (m, 1H), 5.60 - 5.35 (m, 2H), 5.30 - 5.15 (m, 2H), 4.40 - 4.20 (m, 2H), 3.90 - 3.70 (m) og 3.85 (s) totalt 7H, 3.35 (s, 3H), 2.35 (s, 3H), 1.85 - 1.70 (m, 2H), 1.50 - 1.38 (m, 2H), 0.99 (t, J = 6.9Hz, 3H).
Eksempel 2(175)
8-(N-propyl-N-(4-trifluormetyloksyfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.42 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.39 - 7.33 (m, 2H), 7.31 (d, J = 8.4Hz, 1H), 7.21-7.15 (m, 2H), 7.08 (d, J = 2.4Hz, 1H), 6.91 (dd, J = 8.4,2.4Hz, 1H), 5.12 (s, 2H), 4.95 (s, 2H), 4.90 (s, 2H), 3.84 (s, 3H), 3.36 - 3.28 (m, 2H), 2.40 (s, 3H), 1.70 - 1.54 (m, 2H), 0.89 (t, J = 7.5Hz, 3H).
Eksempel 2(176) 8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-2-m metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.28 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.33 - 7.26 (m, 2H), 7.18 (d, J = 8.4Hz, 1H), 7.03 - 6.94 (m, 2H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.4, 2.7Hz, 1H), 4.88 (s, 2H), 3.83 (s, 3H), 3.38 (d, J = 6.9Hz, 2H), 2.95 (t, J = 6.9Hz, 2H), 2.89 (t, J = 6.9Hz, 2H), 2.36 (s, 3H), 2.19 (s, 3H), 2.09 (kvintett, J = 6.9Hz, 2H), 1.01 (m, 1H), 0.58 - 0.42 (m, 2H), 0.20 - 0.01 (m, 2H).
Eksempel 2(177)
8-(3-pentylamino)-2-metyl-3-(3, 5-diklorpyridin-2-yl)-6,7-dihydro-5H-cyklopenta [d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.38 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 8.58 (d, J = 2.1Hz, 1H), 7.81 (d, J = 2.1Hz, 1H), 6.24 (brd, J = 11.1Hz, 1H), 3.80 (m, 1H), 3.08 (t, J = 7.5Hz, 2H), 2.93 (t, J = 7.5Hz, 2H), 2.41 (s, 3H), 2.15 (kvintett, J = 7.5Hz, 2H), 1.80 - 1.52 (m, 4H), 1.00 (t, J = 7.5Hz, 6H).
Eksempel 2(178)
8-(N-butyl-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.61 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.35 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.96 (dd, J = 2.7, 8.4Hz, 1H), 3.94 (m, 4H), 3.85 (s, 3H), 3.30 - 3.62 (m, 2H), 3.05 (m, 2H), 2.32 (s, 3H), 2.25 (m, 2H), 1.74 (m, 2H), 1.32 - 1.48 (m, 5H), 0.98 (t, J = 7.8Hz, 3H).
Eksempel 2(179)
8-(N-cyklopropylmetyl-N-(4-trifluoniietylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.54 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.65 (d, J = 8.4Hz, 2H), 7.47 (d, J = 8.4Hz, 2H), 7.13 (d, J = 8.7Hz, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 2.4, 8.7Hz, 1H), 5.37 (s, 2H), 3.83 (s, 3H), 3.66 (m, 2H), 3.52 (t, J = 7.5Hz, 2H), 3.11 (t, J = 7.2Hz, 2H), 2.29 (s, 3H), 2.27 (m, 2H), 2.19 (s, 3H), 1.14 (m, 1H), 0.65 (m, 2H), 0.17 (m, 2H).
Eksempel 2(180)
8-(3-pen1ylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]-pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.52 (brd, J = 10.2Hz, 1H), 7.35 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 6.96 (dd, J = 2.7, 8.7Hz, 1H), 5.50 (d, J = 16.5Hz, 1H), 5.39 (d, J = 16.5Hz, 1H), 5.29 (s, 2H), 3.85 (s, 3H), 3.39 (m, 1H), 2.40 (s, 3H), 1.68 - 1.98 (m, 4H),T.06 (m, 6H).
Eksempel 2(181)
8-(N-cyklopropylmetylamino-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.28 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.34 - 7.28 (m, 2H), 7.30 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 7.05 - 6.98 (m, 2H), 6.901 (dd, J = 8.4,2.7Hz, 1H), 5.21 (s, 2H), 4.93 (s, 2H), 4.90 (s, 2H), 3.84 (s, 3H), 3.38 (d, J = 6.9 H z,'2H), 2.40 (s, 3 H), 1.08 - 0.94 (m, 1H), 0.56 - 0.48 (m, 2H), 0.14 - 0.06 (m, 2H).
Eksempel 2(182)
8-(N-benzyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidindihydroklorid
TLC: Rf 0.60 (etylacetat: eddiksyre : vann = 3:1:1);
NMR (300MHz, CD3OD): 87.45 - 7.32 (m, 5H), 7.18 (d, J = 8.4Hz, 1H), 6.98 (d, J = 2.7Hz, 1H), 6.90 (dd, J = 8.4,2.7Hz, 1H), 5.20 (s, 2H), 4.40 (m, 2H), 3.84 (s, 3H), 3.75 (m, 2H), 3.16 (m, 2H), 3.06 (m, 2H), 2.96 (s, 6H), 2.35 (s, 3H), 2.38 - 2.18 (m, 2H),2.11 (s, 3H).
Eksempel 2(183)
8-(N-benzyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l ,5-a]pyrimidin dihydroklorid
TLC: Rf 0.80 (etylacetat: eddiksyre : vann = 3:1:1);
NMR (300MHz, CD3OD): 87.60 - 7.30 (m, 6H), 7.19 (d, J = 2.4Hz, 1H), 7.08 - 7.02 (m, 1H), 5.13 (s, 2H), 4.96 (s, 2H), 4.94 (s, 2H), 4.40 - 4.24 (m, 2H), 3.87 (s, 3H), 3.76 (m, 1H), 3.56 (m, 1H), 2.99 (s, 3H), 2.98 (s, 3H), 2 .44 (s, 3H).
Eksempel 2(184)
8-(N-benzyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidindihydroklorid
TLC: Rf 0.27 (kloroform : metanol = 9:1);
NMR (300MHz, CD3OD): 87.46 - 7.26 (m, 6H), 7.20 (d, J = 2.1Hz, 1H), 7.08 - 7.02 (m, 1H), 5.11 (brs, 2H), 4.34 - 4.20 (m, 2H), 3.87 (s, 3H), 3.76 - 3.64 (m, 2H), 3.34 - 2.86 (m) og 2.96 (s) totalt 10H, 2.41 (s, 3H), 2.26 - 2.10 (m, 2H).
Eksempel 2(185)
8-(N-(2-butynyl)-N-etylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.36 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.4Hz, 1H), 4.55 (q, J = 2.1Hz, 2H), 4.08 (m, 2H), 3.83 (s, 3H), 3.48 (t, J = 7.5Hz, 2H), 3.22 (t, J = 6.9Hz, 2H), 2.28 (s, 3H), 2.24 (m, 2H), 2.17 (s, 3H), 1.90 (t, J = 2.1Hz, 3H), 1.47 (t, J = 7.2Hz, 3H).
Eksempel 2(186)
8-(N-(2-butynyl)-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihy dro-furo [3,4-d]pyrazolo[ 1,5 -ajpyrimidinhy droklorid
TLC: Rf 0.26 (heksan : etylacetat = 2:1);
NMR (300MHz, CDCl3): 8 7.32 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.95 (dd, J = 2.4, 8.4Hz, 1H), 5.41 (s, 2H), 5.36 (m, 2H), 4.46 (m, 2H), 4.08 (m, 2H), 3.85 (s, 3H), 2.36 (s, 3H), 1.89 (t, J = 2.7Hz, 3H), 1.51 (t, J = 7.2Hz, 3H).
Eksempel 2(187)
8-(N-(2-butynyl)-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.32 (heksan : etylacetat = 2:1);
NMR (300Hz, CDC13) : 87.34 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.96 (dd, J = 2.7, 8.4Hz, 1H), 4.54 (m, 2H), 4.09 (m, 2H), 3.85 (s, 3H), 3.35 - 3.64 (m, 2H), 3.22 (t, J = 7.2Hz, 2H), 2.34 (S, 3H), 2.26 (m, 2H), 1.90 (t, J = 2.4Hz, 3H), 1.47 (t, J = 7.2Hz, 3H).
Eksempel 2(188)
8-(N, N-dipropylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.40 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.30 (d, J = 8.4Hz, 1H), 7.05 (d, J = 2.7Hz, 1H), 6.88 (dd, J = 2.7, 8.4Hz, 1H), 3.83 (s, 3H), 3.56 (m, 4H), 2.95 (t, J = 7.2Hz, 2H), 2.91 (t, J = 8.1Hz, 2H), 2.36 (s, 3H), 2.13 (m, 2H), 1.58 (m, 4H), 0.89 (t, J = 7.2Hz, 6H).
Eksempel 2(189)
8-(N-(2-butynyl)-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)
-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.50 (toluen : aceton =5:1);
NMR (300MHz, CDC13): 8 7.28 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.90 (dd, J = 8.4, 2.7Hz, 1H), 5.35 (s, 2H), 4.91 (s, 2H), 4.56 (m, 2H), 3.83 (s, 3H), 3.50 (m, 2H), 2.39 (s, 3H), 1.82 (t, J = 2.4Hz, 3H), 1.15 (m, 1H), 0.64 - 0.56 (m, 2H), 0.38 - 0.28 (m, 2H).
Eksempel 2(190)
8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.22 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.60 (brd, J = 8.1Hz, 2H), 7.47 (brd, J 8.1Hz, 2H), 7.17 (d, J = 8.7Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.7, 2.7Hz, 1H), 4.90 (s, 2H), 3.83 (s, 3H), 3.39 (m, 2H), 2.94 - 2.82 (m, 4H), 2.34 (s, 3H), 2.18 (s, 3H), 2.11 (m, 2H), 1.59 (m, 2H), 0.88 (t, J = 7.2Hz, 3H).
Eksempel 2(191)
8-(N-cyklopropyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.20 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.32 (d, J = 8.4Hz, 1H), 7.19 - 7.13 (m, 2H), 7.08 (d, J = 2.7Hz, 1H), 7.06 - 7.01 (m, 2H), 6.91 (dd, J = 8.4, 2.7Hz, 1H), 5.20 (s, 2H), 5.15 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 2.56 (m, 1H), 2.46 (s, 3H), 2.41 (s, 3H), 0.95 - 0.88 (m, 4H).
Eksempel 2(192)
8-(N-propyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.25 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 8.7Hz, 1H), 7.20 (s, 4H), 7.08 (d, J = 2.7Hz, 1H), 6.90 (dd, J = 8.7, 2.7Hz, 1H), 5.10 (s, 2H), 4.90 (s, 2H), 4.89 (s, 2H), 3.84 (s, 3H), 3.34 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 1.70 - 1.50 (m, 2H), 0.89 (t, J = 7.5Hz, 3H).
Eksempel 2(193)
8-(N-cyklopropyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.19 (heksan : etylacetat = 3:1); NMR (300MHz, CDC13): 8 7.32 (d, J = 8.4Hz, 1H), 7.14 - 7.04 (m, 3H), 7.02 - 6.94 (m, 2H), 6.92 (dd, J = 8.4, 2.4Hz, 1H), 5.19 (s, 2H), 5.16 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 2.55 (m, 1H), 2.41 (s, 3H), 0.90 - 0.76 (m, 4H), Eksempel 2(194) 8-(N-propyl-N-(3-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.48 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.33 (d, J = 8.4Hz, 1H), 7.26 - 7.15 (m, 2H), 7.07 (d, J = 2.4Hz, 1H), 7.05 - 6.98 (m, 2H), 6.89 (dd, J = 8.4,2.4Hz, 1H), 4.94 (s, 2H), 3.84 (s, 3H), 3.39 (m, 2H), 2.88 (t, J = 7.5Hz, 2H), 2.77 (t, J = 7.5Hz, 2H), 2.40 (s, 3H), 2.04 (kvintett, J = 7.5Hz, 2H), 1.63 (m, 2H), 0.90 (t, J = 7.5Hz, 3H).
Eksempel 2(195)
8-(N-propy l-N-(3 -fluorfenyl)metylamino)-2-metyl-3 -(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.46 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.32 (d, J = 8.4Hz, 1H), 7.28 - 7.16 (m, 2H), 7.08 (d, J = 2.4Hz, 1H), 7.07 - 6.99 (m, 2H), 6.91 (dd, J = 8.4, 2.4Hz, 1H), 5.07 (s, 2H), 5.04 (s, 2H), 4.88 (s, 2H), 3.84 (s, 3H), 3.13 (m, 2H), 2.41 (s, 3H), 1.68 (sekstett, J = 7.5Hz, 2H), 0.93 (t, J = 7.5Hz, 3H).
Eksempel 2(196)
8-dipropylamino-2-metyl-3-(2, 5-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.64 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.41 (d, J = 8.7Hz, 1H), 7.40 (d, J = 2.4Hz, 1H), 7.23 (dd, J = 8.7, 2.4Hz, 1H), 3.60 - 3.52 (m, 4H), 2.96 (t, J = 7.8Hz) og 2.93 (t, J = 7.8Hz) totalt 4H, 2.37 (s, 3H), 2.15 (kvintett, J = 7.8Hz, 2H), 1.65 - 1.50 (m, 4H), 0.89 (t, J = 7.2Hz, 6H).
Eksempel 2(197)
8-dipropylamino-2-metyl-3-(2,4-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolof 1,5-a]pyrimidin
TLC: Rf 0.57 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.51 (d, J = 2.4Hz, 1H), 7.35 (d, J = 8.1Hz, 1H), 7.29 (dd, J = 8.1, 2.4Hz, 1H), 3.65 - 3.50 (m, 4H), 2.96 (t, J = 7.2Hz) og 2.92 (t, J = 7.2Hz) totalt 4H, 2.36 (s, 3H), 2.14 (kvintett, J = 7.2Hz, 2H), 1.63 - 1.45 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(198)
8-dipropylamino-2-metyl-3-(4-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.58 (heksan : etylacetat = 3:1); NMR (300MHz, CDC13): 8 7.58 (d, J = 7.8Hz, 2H), 7.24 (d, J = 7.8Hz, 2H), 3.60 - 3.52 (m, 4H), 3.00 - 2.90 (m, 4H), 2.56 (s, 3H), 2.37 (s, 3H), 2.14 (kvintett, J = 7.5Hz, 2H), 1.64 - 1.48 (m, 4H), 0.87 (t, J = 7.2Hz, 6H). Eksempel 2(199) 8-dipropylamino-2-metyl-3-(3-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.61 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.50 (s) og 7.47 (d, J = 7.5Hz) totalt 2H, 7.32 (t, J = 7.5Hz, 1H), 7.06 (t, J = 7.5Hz, 1H), 3.60 - 3.52 (m, 4H), 2.96 (t, J = 7.8Hz, 4H), 2.57 (s, 3H), 2.41 (s, 3H), 2.15 (kvintett, J = 7.8Hz, 2H), 1.64 - 1.45 (m, 4H), 0.88 (t, J = 7.2Hz, 6H).
Eksempel 2(200)
8-dipropylamino-2-metyl-3-(2-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolof 1,5-a]pyrimidin
TLC: Rf 0.56 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.35 - 7.20 (m, 4H), 3.62 - 3.54 (m, 4H), 2.96 (t, J = 7.2Hz) og 2.90 (t, J = 7.2Hz) totalt 4H, 2.34 (s, 3H), 2.22 (s, 3H), 2.13 (kvintett, J = 7.2Hz, 2H), 1.63 - 1.50 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(201)
8-(N-propyl-N-(benz[d] 1,3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.31 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.18 (d, J = 8.1Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.77 - 6.83 (m, 2H), 6.67 - 6.75 (m, 2H), 5.94 (s, 2H), 4.74 (s, 2H), 3.83 (s, 3H), 3.37 (m, 2H), 2.89 (t, J = 7.8Hz, 2H), 2.85 (t, J = 7.5Hz, 2H), 2 .35 (s, 3H), 2.20 (s, 3H), 2.08 (m, 2H), 1.58 (m, 2H), 0.88 (t, J= 7.2Hz, 3H).
Eksempel 2(202)
8-(N-propyl-N-(benz[d] 1,3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.38 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.36 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 6.97 (dd, J = 8.4, 2.7Hz, 1H), 6.70 - 6.82 (m, 3H), 6.00 (s, 2H), 5.07 (s, 2H), 3.85 (s, 3H), 3.71 (m, 2H), 3.36 - 3.64 (m, 2H), 3.03 (t, J = 7.4Hz, 2H), 2.35 (s, 3H), 2.24 (m, 2H), 1.74 (m, 2H), 0.93 (t, J = 7.5Hz, 3H).
Eksempel 2(203)
8-(3-pentylamino)-2-metyl-3-(2-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.39 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.30 - 7.18 (m, 4H), 6.23 (d, J = 10.5Hz, 1H), 3.90 - 3.75 (m, 1H), 3.09 (t, J = 7.2Hz, 2H), 2.90 (t, J = 7.2Hz, 2H), 2.32 (s, 3H), 2.22 (s, 3H), 2.14 (kvint, J = 7.2Hz, 2H), 1.80 - 1.58 (m, 4H), 1.08 - 0.96 (m, 6H).
Eksempel 2(204)
8-(3-pentylamino)-2-metyl-3-(3-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.45 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.50 (s, 1H), 7.46 (d, J = 7.8Hz, 1H), 7.31 (t, J = 7.8Hz, 1H), 7.05 (d, J = 7.8Hz, 1H), 6.21 (d, J = 10.8Hz, 1H), 3.86 - 3.74 (m, 1H), 3.08 (t, J = 7.2Hz, 2H), 2.95 (t, J = 7.2Hz, 2H), 2.55 (s, 3H), 2.41 (s, 3H), 2.15 (kvintett, J = 7.2Hz, 2H), 1.82 - 1.55 (m, 4H), 1.01 (t, J = 7.5Hz, 6H).
Eksempel 2(205)
8-(3-pentylamino)-2-metyl-3-(4-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.47 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.57 (d, J = 7.8Hz, 2H), 7.24 (d, J = 7.8Hz, 2H), 6.20 (10.5Hz, 1H), 3.83 - 3.75 (m, 1H), 3.08 (t, J = 7.2Hz, 2H), 2.94 (t, J = 7.2Hz, 2H), 2.55 (s, 3H), 2.37 (s, 3H), 2.15 (kvintett, J = 7.2Hz, 2H), 1.80 - 1.52 (m, 4H), 1.00 (t, J = 7.2Hz, 6H).
Eksempel 2(206)
8-(3-pentylamino)-2-metyl-3-(2-metyltio-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.10 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.26 - 7.16 (m, 1H), 6.83 (m, 1H), 6.84 - 6.76 (m, 1H), 3.97 (m, 1H), 3.86 (s, 3H), 3.48 (m, 2H), 3.12 (m, 2H), 2.44 (s, 3H), 2.33 (s, 3H), 2.28 (m, 2H), 1.95 - 1.44 (m, 4H), 1.11 - 0.99 (m, 6H).
Eksempel 2(207)
8-(N-propyl-N-(benz[d] 1,3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-klor-4-
metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1 s5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 6.95 (dd, J = 2.7, 8.7Hz, 1H), 6.78 - 6.83 (m, 2H), 6.72 (m, 1H), 5.99 (s, 2H), 5.28 (m, 2H), 5.16 (s, 2H), 5.04 (m, 2H), 3.85 (s, 3H), 3.60 (m, 2H), 2.38 (s, 3H), 1.77 (m, 2H), 0.95 (t, J = 7.2Hz, 3H).
Eksempel 2(208)
8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.58 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.25 - 7.43 (m, 5H), 7.13 (d, J = 7.8Hz, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 2.4, 7.8Hz, 1H), 5.28 (s, 2H), 3.84 (s, 3H), 3.69 (m, 2H), 3.48 (t, J = 8.1Hz, 2H), 3.07 (t, J = 7.2Hz, 2H), 2.30 (s, 3H), 2.24 (m, 2H), 2.19 (s, 3H), 1.16 (m, 1H), 0.63 (m, 2H), 0.18 (m, 2H).
Eksempel 2(209)
8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.56 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.25 - 7.43 (m, 6H), 7.09 (d, J = 2.7Hz, 1H), 6.96 (dd, J = 2.7, 8.4Hz, 1H), 5.27 (m, 2H), 3.85 (s, 3H), 3.68 (m, 2H), 3.48 (m, 2H), 3.07 (t, J = 6.9Hz, 2H), 2.35 (s, 3H), 2.23 (m, 2H), 1.16 (m, 1H), 0.64 (m, 2H), 0.18 (m, 2H).
Eksempel 2(210)
8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.26 - 7.45 (m, 6H), 7.09 (d, J = 2.4Hz, 1H), 6.96 (dd, J = 2.4, 8.1Hz, 1H), 5.36 (m, 2H), 5.28 (m, 2H), 5.23 (s, 2H), 3.85 (s, 3H), 3.69 (m, 2H), 2.37 (s, 3H), 1.21 (m, 1H), 0.66 (m, 2H), 0.22 (m, 2H).
Eksempel 2(211)
8-(N-butyl-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.38 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.4, 2.7Hz, 1H), 4.40 (brs, 2H), 3.82 (s, 3H), 3.59 (m, 2H), 3.11 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.13 (m, 2H), 1.81 (t, J = 2.1Hz, 3H), 1.63 (m, 2H), 1.38 (m, 2H), 0.94 (t, J = 7.5Hz, 3H).
Eksempel 2(212)
8-(3-pentylamino)-2-metyl-3-(2-metyl-4-fluorfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[l ,5-a]pyrimidinhydroklorid
TLC: Rf 0.44 (heksan : etylacetat = 3:1);
NMR (300MHz, DMSO-d6): 87.34 - 7.24 (m, 2H), 7.20 - 7.10 (m, 1H), 4.03 - 3.85 (m, 1H), 3.14 (brt, J = 8.1Hz, 2H), 2.95 (brt, J = 8.1Hz, 2H), 2.25 (s, 3H), 2.25 - 2.10 (m) og 2.12 (s) totalt 5H, 1.85 - 1.60 (m, 4H), 0.95 - 0.85 (m, 6H).
Eksempel 2(213)
8-(3-pentylamino)-2-metyl-3-(2, 5-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.46 (heksan : etylacetat = 3:1);
NMR (300MHz, DMSO-d6): 87.68 (d, J = 8.4Hz, 1H), 7.62 - 7.55 (m) og 7.59 (s) totalt 2H, 4.03 - 3.85 (m, 1H), 3.14 (brt, J = 7.8Hz, 2H), 2.96 (brt, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.25 - 2.10 (m, 2H), 1.85 - 1.60 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(214)
8-(3-pentylamino)-2-metyl-3-(2,4-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
J^OCH,
OCH3
TLC: Rf 0.43 (heksan : etylacetat =1:1);
NMR (300MHz, DMSO-d6): 57.24 (d, J = 8.1Hz, 1H), 6.71 (d, J = 2.4Hz, 1H), 6.66 (dd, J = 8.1, 2.4Hz, 1H), 4.05 - 3.85 (m, 1H), 3.85 (s, 3H), 3.74 (s, H), 3.15 (brt, J = 8.1Hz, 2H), 2.99 (brt, J = 8.1Hz, 2H), 2.33 (s, 3H), 2.25 - 2.10 (m, 2H), 1.85 - 1.63 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(215)
8-(3-pentylamino)-2-metyl-3-(2-fluor-4-metylfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
( I V-CH,
fy
CHS
TLC: Rf 0.43 (heksan : etylacetat = 3:1);
NMR (300MHz, DMSO-d6): 69.20 - 9.00 (m, 1H), 7.39 (t, J = 7.8Hz, 1H), 7.22 (d, J = 11.1Hz, 1H), 7.17 (d, J = 7.8Hz, 1H), 4.05 - 3.60 (m, 1H, dekket med H20 i DMSO-d6), 3.14 (brt, J = 7.8Hz, 2H), 2.99 (brt, J = 7.8Hz, 2H), 2.40 (s, 3H), 2.37 (s, 3H), 2.18 (kvintett, J = 7.8Hz, 2H), 1.83 - 1.60 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(216)
8-(N-butyl-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.80 (heksan : etylacetat = 1:1); NMR (300MHz, CDC13): 8 7.29 (d, J = 8.7Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.88 (dd, J = 8.7, 2.4Hz, 1H), 4.39 (q, J = 2.1Hz, 2H), 3.83 (s, 3H), 3.59 (m, 2H), 3.11 (t, J = 7.5Hz, 2H), 2.93 (t, J = 7.5Hz, 2H), 2.36 ( s, 3H), 2.14 (kvintett, J = 7.5Hz, 2H), 1.81 (t, J = 2.1Hz, 3H), 1.68 - 1.54 (m, 2H), 1.39 (sekstett, J = 7.5Hz, 2H), 0.94 (t, J = 7.5Hz, 3H). Eksempel 2(217) 8-(N-butyl-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.78 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.28 (d, J = 8.7Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 8.7, 2.7Hz, 1H), 5.33 (s, 2H), 4.91 (s, 2H), 4.44 (q, J = 2.4Hz, 2H), 3.83 (s, 3H), 3.54 (m, 2H), 2.38 (s, 3H), 1.82 (t, J = 2.4Hz, 3H), 1.74-1.61 (m, 2H), 1.41 (sekstett, J = 7.5Hz, 2H), 0.96 (t, J = 7.5Hz, 3H).
Eksempel 2(218)
8-(3-metyl-2-butylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.36 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.45 (brd, J = 10.2Hz, 1H), 7.11 (dd J = 4.2, 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 2.4, 8.4Hz, 1H), 4.07 (m, 1H), 3.83 (s, 3H), 3.49 (m, 2H), 3.15 (t, J = 6.9Hz, 2H), 2.29 (m, 2H), 2 .28 (s, 3H), 2.20 og 2.19 (s, totalt 3H), 1.99 (m, 1H), 1.42 og 1.41 (d, J = 6.6Hz, totalt 3H), 1.05 -1.14 (m, 6H).
Eksempel 2(219)
8-(l-cykloheksyletylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.36 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.42 (brd, J = 10.5Hz, 1H), 7.11 og 7.10 (d, J = 8.1Hz, totalt 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 2.7, 8.1Hz, 1H), 4.03 (m, 1H), 3.82 (s, 3H), 3.48 (m, 2H), 3.12 (t, J = 7.5Hz, 2H), 2.28 (m, 2H), 2.28 (s, 3H), 2.20 og 2.18 (s, totalt 3H), 1.52 - 1.95 (m, 6H), 1.41 og 1.40 (d, J = 6.6Hz, totalt 3H), 1.01 - 1.37 (m, 5H).
Eksempel 2(220)
8-(2-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.36 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.34 (brd, J = 9.6Hz, 1H), 7.11 og 7.10 (d, J = 8.7Hz, totalt 1H), 6.89 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 2.7, 8.7Hz, 1H), 4.25 (m, 1H), 3.83 (s, 3H), 3.49 (m, 2H), 3.16 (t, J = 6.9Hz, 2H), 2.29 (m, 2H), 2.28 (s, 3H), 2.20 og 2.19 (s, totalt 3H), 1.70 - 1.80 (m, 2H), 1.44 - 1.58 (m, 2H), 1.47 og 1.46 (d, J = 6.6Hz, totalt 3H), 1.01 (m, 3H).
Eksempel 2(221)
8-(2-heptylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.43 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.32 (brd, J = 10.2Hz, 1H), 7.12 og 7.11 (d, J = 8.4Hz, totalt 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J= 2.7, 8.4Hz, 1H), 4.22 (m, 1H), 3.83 (s, 3H), 3.50 (m, 2H), 3.15 (t, J = 6.9Hz, 2H), 2.29 (m, 2H), 2.28 (s, 3H), 2.20 og 2.19 (s, totalt 3H), 1.71 - 1.81 (m, 2H), 1.30 - 1.55 (m, 9H), 0.92 (m, 3H).
Eksempel 2(222)
8-(l-metoksy-2-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.30 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.66 (brd, J = 8.4Hz, 1H), 7.11 og 7.10 (d, J = 8.7Hz, totalt 1H), 6.88 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 2.7, 8.7Hz, 1H), 4.46 (m, 1H), 3.82 (s, 3H), 3.64 (dd, J = 3.9, 9.9Hz, 1H), 3.42 - 3.58 (m, 3H), 3.46 og 3.45 (s, totalt 3H), 3.23 (m, 1H), 3.11 (m, 1H), 2.29 (m, 2H), 2.29 (s, 3H), 2.19 og 2.18 (s, totalt 3H), 1.49 (d, J = 6.6Hz,3H).
Eksempel 2(223)
8-(2-oktylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.60 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.33 (brd, J = 10.2Hz, 1H), 7.12 og 7.11 (d, J = 8.1Hz, totalt 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.1Hz, 1H), 4.23 (m, 1H), 3.83 (s, 3H), 3.50 (brt, J = 7.2Hz, 2H), 3.15 (t, J =.6.6H z, 2H), 2.29 (m, 2H), 2.28 (s, 3H), 2.20 og 2.19 (s, totalt 3H), 1.75 (m, 2H), 1.46 og 1.45 (d, J = 6.3Hz, totalt 3H), 1.26 - 1.45 (m, 8H), 0.90 (m, 3H).
Eksempel 2(224)
8-(l, 2, 3, 4-tetrahydronaftalen-l-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.16 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.44 (m, 1H), 7.27 - 7.14 (m, 4H), 6.85 (d, J = 2.7Hz, 1H), 6.78 (dd, J = 8.1, 2.7Hz, 1H), 6.69 (brd, J = 9.9Hz, 1H), 5.22 (m, 1H), 3.82 (s, 3H), 3.24 - 3.08 (m, 2H), 3.00 - 2.76 (m, 4H), 2.26 (s, 3H), 2.24 - 1.82 (m, 6H), 2.20 (s, 3H).
Eksempel 2(225)
8-((lS, 2S, 3S, 5R)-2, 6, 6-trimetylbicyklo[3.1.1]-3-heptyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.25 (heksan : etylacetat = 3:1); NMR (300MHz, CDC13): 8 7.16 (d, J = 8.1Hz, 1H), 6.85 (d, J = 2.4Hz, 1H), 6.78 (dd, J = 8.1, 2.4Hz, 1H), 6.35 (brd, J = 10.8Hz, 1H), 4.31 (m, 1H), 3.82 (s, 3H), 3.22 - 3.06 (m, 2H), 2.91 (t, J = 8.1Hz, 2H), 2.62 - 2.46 (m, 2H), 2.31 (s, 3H), 2.19 (s,
3H), 2.19 - 1.82 (m, 6H), 1.29 (s, 3H), 1.20 (d, J = 6.0Hz, 3H), 1.11-1.08 (m, 1H), 1.09 (s, 3H).
Eksempel 2(226)
8-(3-pentylamino)-2-metyl-3-(2-metyl-4-klorfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.41 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.38 - 7.32 (m, 2H), 7.26 - 7.10 (m, 2H), 4.04 - 3.90 (m, 1H), 3.60 - 3.30 (m, 2H), 3.13 (t, J = 6.6Hz, 2H), 2.39 (s, 3H), 2.35 (s, 3H), 2.28 (kvintett, J = 6.6Hz, 2H), 1.92 - 1.40 (m, 4H), 1.06 (t, J = 7.2Hz, 6H).
Eksempel 2(227)
8-(3-pentylamino)-2-metyl-3-(2, 5-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[l ,5-a]pyrimidinhydroklorid
TLC: Rf 0.52 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13) : 8 7.32 - 7.24 (m, 1H), 7.00 - 6.90 (m, 2H), 6.85 (d, J = 2.4Hz, 1H), 4.05 - 3.95 (m, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.56 (t, J = 7.8Hz, 2H), 3.12 (t, J = 7.8Hz, 2H), 2.43 (s, 3H), 2.29 (kvintett, J = 7.8Hz, 2H), 1.90 - 1.40 (m, 4H), 1.05 (t, J = 7.5Hz, 6H).
Eksempel 2(228)
8-(3-pentylamino)-2-metyl-3-(2-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.24 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.41 (t, J = 8.1Hz, 1H), 7.34 - 7.24 (m, 2H), 7.10 - 7.02 (m, 2H), 4.03 - 3.90 (m, 1H), 3.94 (s, 3H), 3.56 (t, J = 7.5Hz, 2H), 3.12 (t, J = 7.5Hz, 2H), 2.43 (s, 3H), 2.36 - 2.20 (m, 2H), 1.90 - 1.40 (m, 4H), 1.05 (t, J = 7.5Hz, 6H).
Eksempel 2(229)
8-dicyklopropylmetylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.46 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.87 (m, 1H), 7.11 (d, J = 8.7Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.7Hz, 1H), 5.37 (s, 2H), 5.19 (m, 2H), 3.83 (s, 3H), 2.90 (m, 1H), 2.36 (s, 3H), 2.20 (s, 3H), 1.26 (m, 2H), 0.66 - 0.85 (m, 4H), 0.47 (m, 4H).
Eksempel 2(230)
8-(N-butyl-N-etylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.7Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.7Hz, 1H), 5.40 (s, 2H),.5.23 (s, 2H), 3.85 - 4.00 (m, 4H), 3.83 (s, 3H), 2.29 (s, 3H), 2.19 (s, 3H), 1.82 (m, 2H), 1.46 (t, J = 6.9Hz, 3H), 1.44 (m, 2H), 1.02 (t, J = 6.9Hz, 3H).
Eksempel 2(231)
8-(N-butyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.54 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 2.4, 8.4Hz, 1H), 5.40 (s, 2H), 5.21 (s, 2H), 3.87 (m, 4H), 3.83 (s, 3H), 2.29 (s, 3H), 2.19 (s, 3H), 1.82 (m, 4H), 1.42 (m, 2H), 1.02 (t, J = 7.2Hz, 3H), 1.00 (t, J = 7.2Hz, 3H).
Eksempel 2(232)
8-(N, N-dipropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.51 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.4Hz, 1H), 6.89 (d, J = 3.0Hz, 1H), 6.82 (dd, J = 3.0, 8.4Hz, 1H), 5.39 (brs, 2H), 5.21 (brs, 2H), 3.85 (m, 4H), 3.83 (s, 3H), 2.29 (s, 3H), 2.19 (s, 3H), 1.83 (m, 4H), 1.02 (t, J = 7.2Hz, 6H).
Eksempel 2(233)
8-(N-etyl-N-(4-hydroksybutyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.29 (heksan : etylacetat =1:2);
NMR (300MHz, CDC13): 5 7.10 (d, J = 8.4Hz, 1H), 6.87 (d, J = 3.0Hz, 1H), 6.79 (dd, J = 3.0, 8.4Hz, 1H), 3.87 - 4.01 (m, 4H), 3.82 (s, 3H), 3.65 (t, J = 6.0Hz, 2H), 3.38 (t, J = 7.5Hz, 2H), 3.06 (t, J = 7.2Hz, 2H), 2 .27 (s, 3H), 2.24 (m, 2H), 2.17 (s, 3H), 1.86 (m, 2H), 1.61 (m, 2H), 1.38 (t, J = 7.2Hz, 3H).
Eksempel 2(234)
8-bis(2-metoksyetyl)amino-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.35 (heksan : etylacetat =1:2);
NMR (300MHz, CDC13): 8 7.33 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.96 (dd, J = 2.4, 8.4Hz, 1H), 5.40 (m, 1H), 5.33 (m, 1H), 5.25 (m, 2H), 4.15 (m, 4H), 3.85 (s, 3H), 3.71 (t, J = 5.1Hz, 4H), 3.35 (s, 6H), 2.35 (s, 3H).
Eksempel 2(235)
8-(3-pentylamino)-2-metyl-3-(2-metoksy-5-isopropylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.36 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.23 (dd, J = 8.4, 2.1Hz, 1H), 7.12 (d, J = 2.1Hz, 1H), 6.98 (d, J = 8.4Hz, 1H), 4.00 - 3.85 (m) og 3.91 (s) totalt 4H, 3.58 - 3.30 (m, 2H), 3.11 (t, J = 6.9Hz, 2H), 2.92 (m, 1H), 2.43 (s, 3H), 2.35 - 2.20 (m, 2H), 1.90 -1.50 (m, 4H), 1.26 (d, J = 6.9Hz, 6H), 1.04 (t, J = 7.5Hz, 6H).
Eksempel 2(236)
8-(3-pentylamino)-2-metyl-3-(2-metoksy-5-fluorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.20 - 6.95 (m, 4H), 4.04 - 3.80 (m) og 3.91 (s) totalt 4H, 3.52 - 3.40 (m, 2H), 3.12 (t, J = 7.2Hz, 2H), 2.43 (s, 3H), 2.27 (kvintett, J = 7.2Hz, 2H), 1.90 - 1.40 (m, 4H), 1.05 (t, J = 7.5Hz, 6H).
Eksempel 2(237)
8-(N-butyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13) : 8 7.44 - 7.20 (m, 3H), 7.14 - 6.90 (m, 4H), 5.03 (brs, 2H), 3.85 (s, 3H), 3.62 (m, 2H), 3.29 (m, 2H), 2.96 (m, 2H), 2.37 (s, 3H), 2.19 (m, 2H), 1.65 (m, 2H), 1.32 (m, 2H), 0.90 (m, 3H).
Eksempel 2(238) 8-(N-butyl-N-(4-lfuorfenyl)metylamino)-2-metyl-3-(2-klor-4-metok dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.20 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.40 - 7.26 (m, 3H), 7.12 (brd, J = 7.8Hz, 2H), 7.09 (d, J = 2.1Hz, 1H), 6.99 - 6.92 (m, 1H), 5.40 (m, 2H), 5.30 - 5.08 (m, 4H), 3.85 (s, 3H), 3.70 (m, 2H), 2.37 (s, 3H), 1.76 (m, 2H), 1.36 (m, 2H), 0 .94 (t, J = 7.5Hz, 3H).
Eksempel 2(239)
8-(N-butyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.28 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.29 (m, 2H), 7.18 - 7.04 (m, 3H), 6.89 (d, J = 2.1Hz, 1H), 6.85 - 6.78 (m, 1H), 5.23 (m, 2H), 5.15 (m, 2H), 5.11 (m, 2H), 3.83 (s, 3H), 3.58 (m, 2H), 2.33 (s, 3H), 2.20 (s, 3H), 1.71 (m, 2H), 1.35 (m , 2H), 0.95 - 0.84 (m, 3H).
Eksempel 2(240)
8-(3-pentylamino)-2-metyl-3-(2-metoksy-5-klorfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.33 (dd, J = 9.0, 3.0Hz, 1H), 7.25 - 7.05 (m) og 7.22 (d, J = 3.0Hz) totalt 2H, 6.98 (d, J = 9.0Hz, 1H), 4.03 - 3.85 (m) og 3.93 (s) totalt 4H, 3.55 - 3.40 (m, 2H), 3.13 (t, J = 7.2Hz, 2H), 2.43 (s, 3H), 2.28 (kvintett, J = 7.2Hz, 2H), 1.90 - 1.40 (m, 4H), 1.05 (t, J = 7.5Hz, 6H).
Eksempel 2(241)
8-(N-etyl-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.37 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.4Hz, 1H), 5.41 (s, 4H), 4.48 (m, 2H), 4.14 (m, 2H), 3.83 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H), 1.90 (t, J = 2.4Hz, 3H), 1.5 4 (t, J = 7.2Hz, 3H).
Eksempel 2(242)
8-(N-propyl-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.10 (d, J = 8.1Hz, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.1Hz, 1H), 5.41 (m, 2H), 5.39 (m, 2H), 5.42 (m, 2H), 3.98 (m, 2H), 3.83 (s, 3H), 2.31 (s, 3H), 2.18 (s, 3H), 1.94 (m, 2H), 1. 89 (t, J = 2.7Hz, 3H), 1.05 (t, J = 7.2Hz, 3H).
Eksempel 2(243)
8-(N-propyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5J-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 5 7.27 (d, J = 8.4Hz, 2H), 7.20 (d, J = 8.4Hz, 2H), 7.12
(d, J = 8.4Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.4Hz, 1H), 5.40 (s, 2H), 5.11 - 5.26 (m, 4H), 3.84 (s, 3H), 3.70 (m, 2H), 2.50 (s, 3H), 2.31 (s, 3H), 2.20
(s, 3H), 1.84 (m, 2H), 0.97 (t, J = 7.2Hz, 3H).
Eksempel 2(244)
8-(N-propyl-N-(benz[d] 1,3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 6 7.13 (d, J = 8.1Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.1Hz, 1H), 6.82 (d, J = 7.5Hz, 1H), 6.78 (d, J = 1.5Hz, 1H), 6.73 (dd, J = 1.5,7.5Hz, 1H), 6.01 (s, 2H), 5.39 (s, 2H), 5.17 (s, 2H), 5.11 (m, 2H), 3.84 (s, 3H), 3.69 (m, 2H), 2.32 (s, 3H), 2.21 (s, 3H), 1.81 (m, 2H), 0.96 (t, J = 7.2Hz, 3H).
Eksempel 2(245)
8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-fUro[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.34 - 7.46 (m, 3H), 7.26 - 7.33 (m, 2H), 7.13 (d, J = 8.7Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.84 (dd, J = 2.7, 8.7Hz, 1H), 5.42 (s, 2H), 5.33 (m, 2H), 5.24 (s, 2H), 3.84 (s, 3H), 3.73 (m, 2H), 2.31 (s, 3H), 2.20 (s, 3H), 1.24 (m, 1H), 0.69 (m, 2H), 0.24 (m, 2H).
Eksempel 2(246)
8-(N-cyklopropylmetyl-N-(4-tirfluormetylfenyl)metylamino)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.48 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.62 (brd, J = 7.8Hz, 2H), 7.48 (brd, J = 7.8Hz, 2H), 7.34 (brd, J = 8.1Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.90 - 6.88 (m, 1H), 5.19 (brs, 2H), 3.85 (s, 3H), 3.54 (m, 2H), 3.36 - 3.14 (m, 2H), 3.14 - 2.98 (m, 2H), 2.36 (s, 3H), 2.22 (m, 2H), 1.12 - 0.98 (m, 1H), 0.64 - 0.52 (m, 2H), 0.18 - 0.08 (m, 2H).
Eksempel 2(247)
8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dmydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.42 (heksan : etylacetat = 2:1); NMR (300MHz, CDC13): 8 7.65 (brd, J = 7.5Hz, 2H), 7.49 (brd, J = 7.5Hz, 2H), 7.33 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.95 (dd, J = 8.4,2.4Hz, 1H), 5.35 - 5.18 (m, 6H), 3.85 (s, 3H), 3.54 (d, J = 6.6Hz, 2H), 2.36 (s, 3H), 1.11 (m, 1H), 0.72 - 0.60 (m, 2H), 0.22 - 0.14 (m, 2H). Eksempel 2(248) 8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.42 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.68 (d, J = 7.8Hz, 2H), 7.49 (d, J = 7.8Hz, 2H), 7.12 (d, J = 8.4Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 8.4, 2.7Hz, 1H), 5.42 (m, 2H), 5.38 (s, 2H), 5.27 (s, 2H), 3.83 (s, 3H), 3.61 (m, 2H), 2.30 (s, 3H), 2.19 (s, 3H), 1.15 (m, 1H), 0.74 - 0.66 (m, 2H), 0.26 - 0.18 (m, 2H).
Eksempel 2(249)
8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dmydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.29 (heksan : etylacetat =2:1);
NMR (300MHz, CDC13): 8 7.66 (brd, J = 7.8Hz, 2H), 7.49 (brd, J = 7.8Hz, 2H), 7.15 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.4, 2.7Hz, 1H), 5.15 (brs, 2H), 5.09 (brs, 2H), 5.01 (brs, 2H), 3.83 (s, 3H), 3.37 (m, 2H), 2.33 (s, 3H), 2.18 (s, 3H), 1.74 - 1.60 (m, 2H), 0.91 (t, J = 6.9Hz, 3H).
Eksempel 2(250)
8-(N-cyklopropyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.32 (d, J = 8.4Hz, 1H), 7.16 - 7.07 (m, 3H), 7.02 - 6.94 (m 2H), 6.92 (dd, J = 8.4, 3.0Hz, 1H), 5.20 (s, 2H), 5.18 (s, 2H), 4.94 (s, 2H), 3.84 (s, 3H), 2.56 (m, 1H), 2.41 (s, 3H), 0.89 - 0.79 (m, 4H).
Eksempel 2(251)
8-(N-cyklopropyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.44 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.19 - 7.08 (m, 3H), 7.04 - 6.96 (m, 2H), 6.88 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.4,2.7Hz, 1H), 5.28 - 5.18 (m, 4H), 5.00 (s, 2H), 3.83 (s, 3H), 2.60 (m, 1H), 2.38 (s, 3H), 2.18 (s, 3H), 0.90 - 0.80 (m, 4H).
Eksempel 2(252)
8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 5 7.36 - 7.29 (m, 2H), 7.15 - 7.05 (m, 3H), 6.90 (d, J = 2.7Hz, 1H), 6.84 (dd, J = 8.1, 2.7Hz, 1H), 5.39 (s, 2H), 5.32 - 5.20 (m, 4H), 3.84 (s, 3H), 3.62 (m, 2H), 2.32 (s, 3H), 2.20 (s, 3H), 1.20 - 1.08 (m, 1H), 0.72 - 0.62 (m, 2H), 0.28-0.18 (m, 2H).
Eksempel 2(253)
8-(N-propyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.35 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.97 (dd, J = 8.7, 2.4Hz, 1H), 5.48 (d, J = 16.8Hz, 1H), 5.36 (d, J = 16.8Hz, 1H), 5.23 (s, 2H), 4.38 - 4.22 (m, 2H), 3.85 (s, 3H), 3.78 - 3.66 (m, 4H), 3.34 (s, 3H), 2.35 (s, 3H), 1.81 (sekstett, J = 7.5Hz, 2H), 1.01 (t, J = 7.5Hz, 3H).
Eksempel 2(254)
8-(N-propyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfeiryl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.33 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 8.4, 2.4Hz, 1H) 5.41 (s, 2H), 5.22 (s, 2H), 4.30 (m, 2H), 3.83 (s, 3H), 3.80 - 3.60 (m, 4H), 3.34 (s, 3H), 2.30 (s, 3H), 2.19 (s, 3H), 1.81 (sekstett, J = 7.5Hz, 2H), 1.01 (t,J = 7.5Hz, 3H).
Eksempel 2(255)
8-(3-pentylamino)-2-metyl-3-(2-metyl-4-cyanofenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.65 (s, 1H), 7.57 (d. J = 7.8Hz, 1H), 7.34 (d, J = 7.8Hz, 1H), 7.24 - 7.08 (m, 1H), 4.06 - 3.88 (m, 1H), 3.41 (brt, J = 7.2Hz, 2H), 3.15 (t, J = 7.2Hz, 2H), 2.40 - 2.20 (m) og 2.30 (s) totalt 8H, 1.90 - 1.40 (m, 4H), 1.06 (t, J = 6.6Hz, 6H).
Eksempel 2(256)
8-(N-propyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.46 (heksan : etylacetat = 2:1); NMR (300MHz, CDC13): 8 7.34 (brd, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.99 - 6.91 (m, 1H), 4.20 (m, 2H), 3.85 (s, 3H), 3.75 (m, 2H), 3.62 (m, 2H), 3.52 - 3.30 (m, 2H), 3.30 (s, 3H), 3.03 (m, 2H), 2.33 (s, 3H), 2.24 ( m, 2H), 1.72 (m, 2H), 0.96 (t, J = 7.5Hz, 3H). Eksempel 2(257) 8-(N-etyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.42 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.40 - 7.30 (m, 1H), 7.30 - 7.16 (m, 4H), 7.08 (d, J = 2.4Hz, 1H), 6.99 - 6.92 (m, 1H), 5.11 (brs, 2H), 3.85 (s, 3H), 3.78 (m, 2H), 3.42 (m, 2H), 3.00 (m, 2H), 2.50 (s, 3H), 2.35 (s, 3H), 2.21 (m, 2H), 1.34 (m, 3H).
Eksempel 2(258)
8-(N-etyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfeny0 dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.35 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.35 (d, J = 8.7Hz, 1H), 7.28 (brd, J = 8.1Hz, 2H), 7.21 (brd, J = 8.1Hz, 2H), 7.09 (d, J = 2.7Hz, 1H), 6.97 (dd, J = 8.7, 2.7Hz, 1H), 5.48 - 5.27 (m, 2H), 5.27 - 5.06 (m, 4H), 3.85 (s, 3H), 3.88 - 3.78 (m, 2H), 2.50 (s, 3H), 2.36 (s, 3H), 1.42 (t, J = 6.9Hz, 3H).
Eksempel 2(259)
8-(N-etyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.28 (brd, J = 8.4Hz, 2H), 7.22 (brd, J = 8.4Hz, 2H), 7.13 (d, J = 8.4Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.84 (dd, J = 8.4, 2.7Hz, 1H), 5.40 (brs, 2H), 5.22 - 5.08 (m, 4H), 3.86 (m, 2H), 3.84 (s, 3H), 2.50 (s, 3H), 2.31 ( s, 3H), 2.20 (s, 3H), 1.43 (t, J = 6.6Hz, 3H).
Eksempel 2(260)
8-(3-pentylamino)-2-metyl-3-(4-metyltiofenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolof 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.46 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.52 (d, J = 8.4Hz, 2H), 7.39 (d, J = 8.4Hz, 2H), 7.31 (d, J = 10.5Hz, 1H), 4.06 - 3.90 (m, 1H), 3.60 (t, J = 7.8Hz, 2H), 3.13 (t, J = 7.8Hz, 2H), 2.52 (s, 3H), 2.49 (s, 3H), 2.30 (kvintett, J = 7.8Hz, 2H), 1.94 - 1.64 (m, 4H), 1.05 (t, J = 7.2Hz,6H).
Eksempel 2(261)
8-(N-butyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.61 (heksan : etylacetat =1:2);
NMR (300MHz, CDC13) : 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 8.4, 2.4Hz, 1H), 5.40 (s, 2H), 5.22 (s, 2H), 4.29 (m, 2H), 3.83 (s, 3H), 3.78 (m, 2H), 3.72 (t, J = 5.1Hz, 2H), 3.34 (s, 3H), 2.3 0 (s, 3H), 2.19 (s, 3H), 1.77 (kvintet, J = 7.5Hz, 2H), 1.42 (sikstet, J = 7.5Hz, 2H), 1.00 (t, J = 7.5Hz, 3H).
Eksempel 2(262)
8-(3-pentylamino)-2-metyl-3-(4-dimetylaminofenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.57 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.72 (d, J = 7.8Hz, 2H), 7.60 - 7.40 (m, 2H), 6.88 - 6.75 (m, 1H), 3.98 - 3.85 (m, 1H), 3.35 - 3.25 (m, 2H), 3.15 - 3.05 (m) og 3.13 (s) totalt 8H, 2.52 (s, 3H), 2.25 (kvintett, J = 7.8Hz, 2H), 1.85 - 1.60 (m, 4H), 1.03 (t, J = 7.5Hz, 6H).
Eksempel 2(263)
8-(N-cyklopropylmetyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.55 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 8.4, 2.4Hz, 1H), 5.24 (s, 2H), 5.04 (s, 2H), 3.83 (s, 3H), 3.69 - 3.63 (m, 4H), 2.33 (s, 3H), 2.18 (s, 3H), 1.70 (sikst, J = 7.5Hz, 2H), 1.07 (m, 1H), 0.96 (t, J = 7.5Hz, 3H), 0.56 (m, 2H), 0.20 (m, 2H).
Eksempel 2(264)
8-(N-propyl-N-(5-metylmran-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 6.90 (dd, J = 2.7, 8.4Hz, 1H), 6.02 (d, J = 3.0Hz, 1H), 5.86 (m, 1H), 5.08 (s, 2H), 4.91 (s, 2H), 4.90 (s, 2H), 3.84 (s, 3H), 3.26 (m, 2H), 2. 41 (s, 3H), 2.23 (s, 3H), 1.66 (m, 2H), 0.94 (t, J = 7.2Hz, 3H).
Eksempel 2(265)
8-(N-propyl-N-(5-melylfuran-2-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.18 (d, J = 8.1Hz, 1H), 6.88 (d, J = 2.4Hz, 1H), 6.81 (d, J = 2.4, 8.1Hz, 1H), 6.01 (d, J = 3.0Hz, 1H), 5.86 (m, 1H), 5.07 (s, 2H), 4.91 (s, 2H), 4.88 (s, 2H), 3.83 (s, 3H), 3.25 (m, 2H), 2.3 7 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 1.67 (m, 2H), 0.94 (t, J = 7.5Hz, 3H).
Eksempel 2(266)
8-(N-cyklopropylmetyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.29 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.80 (dd, J = 8.1, 2.4Hz, 1H), 5.25 (s, 2H), 4.90 (s, 2H), 4.05 (t, J = 5.4Hz, 2H), 3.83 (s, 3H), 3.56 (t, J = 5.4Hz, 2H), 3.48 (d, J = 6.9 H z, 2H), 3.29 (s, 3H), 2.34 (s, 3H), 2.17 (s, 3H), 1.04 (m, 1H), 0.56 (m, 2H), 0.22 (m, 2H).
Eksempel 2(267)
8-(N-propyl-N-(4-trifluormetyloksyfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfeny l)-5,7-dihy dro-furo[3,4-d]pyrazolo[ 1,5 -a]pyrimidinhy droklorid
TLC: Rf 0.51 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.36 (brd, J = 8.1Hz, 2H), 7.18 (brd, J = 8.1Hz, 2H), 7.17 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 8.4, 2.4Hz, 1H), 5.13 (brs, 2H), 4.97 (brs, 2H), 4.92 (brs, 2H), 3.83 (s, 3H), 3.34 (m, 2H), 2.36 (s, 3H), 2.18 (s, 3H), 1.64 (m, 2H), 0.90 (t, J = 7.2Hz, 3H).
Eksempel 2(268)
8-(N-propyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.53 (heksan : etylacetat = 2:1);.
NMR (300MHz, CDC13): 8 7.32 - 7.22 (m, 2H), 7.17 (brd, J = 8.7Hz, 1H), 7.02 (m, 2H), 6.88 (d, J = 2.4Hz, 1H), 6.82 (brd, J = 8.7Hz, 1H), 5.11 (brs, 2H), 4.95 (brs, 4H), 3.83 (s, 3H), 3.34 (m, 2H), 2.36 (s, 3H), 2.19 (s, 3H), 1.65 (m, 2H), 0.90 (t, J = 6.9Hz, 3H).
Eksempel 2(269)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-metyltiofenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.64 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.40 - 7.34 (m, 2H), 7.33 - 7.24 (m, 2H), 3.99 (m, 1H), 3.66 - 3.35 (m, 2H), 3.13 (t, J = 7.5Hz, 2H), 2.52 (s, 3H), 2.35 (s, 3H), 2.30 (m, 2H), 1.94 - 1.64 (m, 4H), 1.10-1.00 (m, 6H).
Eksempel 2(270)
8-(N-cyklopropylmetyl-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)--5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.52 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.14 (d, J = 8.1Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.1, 2.7Hz, 1H), 5.37 (s, 2H), 5.05 (s, 2H), 4.58 (s, 2H), 3.83 (s, 3H), 3.62 (m, 2H), 2.35 (s, 3H), 2.17 (s, 3H), 1.84 (s, 3H), 1.20 (m, 1H), 0.63 (m, 2H), 0.36 (m, 2H).
Eksempel 2(271)
8-(N-(2-metoksyetyl)-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.29 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.13 (d, J = 8.1Hz, 1H), 6.87 (d, J = 2.4Hz, 1H), 6.81 (dd, J = 8.1, 2.4Hz, 1H), 5.39 (s, 2H), 5.06 (s, 2H), 4.42 (s, 2H), 4.06 (m, 2H), 3.83 (s, 3H), 3.81 (m, 2H), 3.37 (s, 3H), 2.33 (s, 3H), 2.17 (s, 3H), 1.85 (s, 3H).
Eksempel 2(272)
8-(N-(2-metoksyetyl)-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.39 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.28 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 8.4, 2.4Hz, 1H), 5.37 (s, 2H), 4.92 (s, 2H), 4.36 (m, 2H), 3.95 (t, J = 5.4Hz, 2H), 3.83 (s, 3H), 3.76 (t, J = 5.4Hz, 2H), 3.36 (s, 3H), 2.37 (s, 3H), 1.83 (s, 3H).
Eksempel 2(273)
8-(N-(2-metoksyetyl)-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.44 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.32 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.7Hz, 1H), 6.93 (dd, J = 8.4, 2.7Hz, 1H), 4.53 (m, 2H), 4.18 (m, 2H), 3.84 (s, 3H), 3.81 (t, J = 4.8Hz, 2H), 3.36 (s, 3H), 3.30 (m, 2H), 3.20 (t, J = 7.2Hz, 2H), 2.34 (s, 3H), 2.22 (kvintett, J = 7.2Hz, 2H), 1.86 (t, J = 2.4Hz, 3H).
Eksempel 2(274)
8-(N-propyl-N-(5-metylfuran-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.53 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.32 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 2.7, 8.4Hz, 1H), 5.99 (d, J = 3.0Hz, 1H), 5.85 (dd, J = 1.6, 3.0Hz, 1H), 4.78 (s, 2H), 3.84 (s, 3H), 3.35 (m, 2H), 2.90 (t, J = 7.5Hz, 2H), 2.81 (t, J = 7.2Hz, 2H), 2.39 (s, 3H), 2.22 (m, 3H), 2.07 (m, 2H), 1.62 (m, 2H), 0.91 (t, J = 7.5Hz, 3H).
Eksempel 2(275)
8-(N-benzyl-N-cyklopropylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.42 - 7.30 (m, 4H), 7.25 - 7.15 (m, 2H), 7.09 (d, J = 2.4Hz, 1H), 7.00 - 6.94 (m, 1H), 5.39 (d, J = 14.7Hz, 1H), 5.27 (d, J = 14.7Hz, 1H), 3.85 (s, 3H), 3.70 - 3.32 (m, 2H), 3.12 (m, 2H), 2.96 (m, 1H), 2.37 (s, 3H), 2.21 (m, 2H), 1.20-0.92 (m,4H).
Eksempel 2(276)
8-(N-benzyl-N-cyklopropylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo [3,4-d]pyrazolo [ 1,5-a]pyrimidinhy droklorid
TLC: Rf 0.42 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.32 (d, J = 8.4Hz, 1H), 7.30 - 7.26 (m, 3H), 7.15 - 7.09 (m, 2H), 7.08 (d, J = 2.4Hz, 1H), 6.91 (dd, J = 8.4,2.4Hz, 1H), 5.20 (s, 2H), 5.19 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 2.56 (m, 1H), 2.41 (s, 3H), 0.92 - 0.78 (m, 4H).
Eksempel 2(277)
8-(N-benzyl-N-cyklopropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 2:1); NMR (300MHz, CDC13): 8 7.33 - 7.19 (m, 3H), 7.19 (d, J = 8.1Hz, 1H), 7.14 - 7.08 (m, 2H), 6.88 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.1, 2,7Hz, 1H), 5.32 - 5.12 (m, 2H), 5.19 (s, 2H), 4.89 (s, 2H), 3.83 (s, 3H), 2.57 (m, 1H), 2.38 (s, 3H), 2.18 (s, 3H), 0.92 - 0.78 (m, 4H). Eksempel 2(278) 8-(N-cyklopropylmetyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-ifiro[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.30 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.33 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.94 (dd, J = 8.4, 2.4Hz, 1H), 5.30 (m) og 5.27 (s) totalt 4H, 4.32 (m, 2H), 3.84 (s, 3H), 3.72 - 3.67 (m, 4H), 3.31 (s, 3H), 2.36 (s, 3H), 1.11 (m, 1H), 0.71 (m, 2H), 0.36 (m, 2H).
Eksempel 2(279)
8-(N-cyklopropylmetyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.33 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.95 (dd, J = 8.4, 2.4Hz, 1H), 4.30 (m, 2H), 3.85 (s, 3H), 3.71 (d, J = 6.6Hz, 2H), 3.64 (t, J = 5.1Hz, 2H), 3.41 (m, 2H), 3.29 (s, 3H), 3.07 (t, J = 7.2Hz, 2H), 2.34 (s, 3H), 2.24 (kvintett, J = 7.2Hz, 2H), 1.09 (m, 1H), 0.65 (m, 2H), 0.31 (m, 2H).
Eksempel 2(280)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-bromfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.61 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.65 (d, J = 2.1Hz, 1H), 7.44 (dd, J = 2.1, 8.1Hz, 1H), 7.28 (d, J = 8.1Hz, 1H), 6.23 (br d, J = 10.5Hz, 1H), 3.81 (m, 1H), 3.09 (t, J = 7.2Hz, 2H), 2.90 (t, J = 7.8Hz, 2H), 2.34 (s, 3H), 2.1 5 (m, 2H), 1.60 - 1.82 (m, 4H), 1.01 (t, J = 7.5Hz, 6H).
Eksempel 2(281)
8-(3-pentylamino)-2-metyl-3-(2, 5-diklor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.65 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.40 (s, 1H), 7.06 (s, 1H), 6.22 (br d, J = 10.5Hz, 1H), 3.92 (s, 3H), 3.81 (m, 1H), 3.08 (t, J = 6.9Hz, 2H), 2.91 (t, J = 7.8Hz, lH), 2.33 (s, 3H), 2.15 (m, 2H), 1.58 - 1.82 (m, 4H), 1.01 (t, J = 7.5Hz, 6H).
Eksempel 2(282)
8-(3-pentylamino)-2-metyl-3-(2, 5-diklor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.61 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.39 (s, 1H), 7.07 (s, 1H), 6.34 (br d, J = 10.5Hz, 1H), 5.29 (m, 2H), 4.93 (m, 2H), 3.93 (s, 3H), 3.24 (m, 1H), 2.36 (s, 3H), 1.67 - 1.84 (m, 4H), 1.02 (t, J = 7.2Hz, 6H).
Eksempel 2(283)
8-(N-cyklopropyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.61 (d, J = 7.8Hz, 2H), 7.33 (d, J = 7.8Hz, 2H), 7.30 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 6.91 (dd, J = 8.7,2.7Hz, 1H), 5.27 (s, 2H), 5.25 (s, 2H), 4.93 (s, 2H), 3.84 (s, 3H), 2.58 (m, 1H), 2.40 (s, 3H), 0.84 (m, 4H).
Eksempel 2(284)
8-(N-cyklopropyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.24 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.61 (d, J = 7.8Hz, 2H), 7.33 (d, J = 7.8Hz, 2H), 7.17 (d, J = 8.1Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.1,2.7Hz, 1H), 5.40 - 5.20 (m, 2H), 5.25 (s, 2H), 4.91 (s, 2H), 3.83 (s, 3H), 2.58 (m, 1H), 2.36 (s, 3H), 2.17 (s, 3H), 0.84 (m, 4H).
Eksempel 2(285)
8-dibutylamino-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.66 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.35 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.1Hz, 1H), 6.94 (dd, J = 8.4, 2.1Hz, 1H), 3.84 (s og m, totalt 7H), 3.35 (m, 2H), 3.01 (t, J = 7.5Hz, 2H), 2.33 (s, 3H), 2.22 (kvintett, J = 7.5Hz, 2H), 1. 67 (kvintett, J = 7.5Hz, 4H), 1.36 (sekstett, J = 7.5Hz, 2H), 0.95 (t, J = 7.5Hz, 6H).
Eksempel 2(286)
8-dibutylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]-pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.63 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.11 (d, J = 8.4Hz, 1H), 6.89 (d, J = 2.4Hz, 1H), 6.83 (dd, J = 8.4, 2.4Hz, 1H), 5.43 (s, 2H), 5.21 (s, 2H), 3.88 (m, 4H), 3.83 (s, 3H), 2.29 (s, 3H), 2.20 (s, 3H), 1.78 (kvintett, J = 7.5Hz, 4H), 1.42 (sekstett, J = 7.5Hz, 4H), 1.00 (t, J = 7.5Hz, 6H).
Eksempel 2(287)
8-bis(2-metoksyetyl)amino-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-alpyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.35 (d, J = 9.0Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 6.96 (dd, J = 9.0, 2.7Hz, 1H), 4.15 (m, 4H), 3.85 (s, 3H), 3.64 (t, J = 5.4Hz, 4H), 3.53 (m, 1H), 3.45 (m, 1H), 3.31 (s, 6H), 3.05 (t, J = 7.2Hz, 2H), 2.34 (s, 3H), 2.22 (kvintett, J = 7.2Hz, 2H).
Eksempel 2(288)
8-(N-etyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.49 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 7.8Hz, 1H), 7.07 (d, J = 2.1Hz, 1H), 6.92 (m, 1H), 5.28 (s, 2H), 5.11 (s, 2H), 3.84 (s, 3H), 3.81 (m, 2H), 3.69 (m, 2H), 2.37 (s, 3H), 1.33 (s, 3H), 1.09 (m, 1H), 0.60 (m, 2H), 0.24 (m, 2H).
Eksempel 2(289)
8-(N-etyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.50 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.12 (m, 1H), 6.89 (s, 1H), 6.82 (m, 1H), 5.38 (m, 2H), 5.31 (m, 2H), 3.99 (m, 2H), 3.83 (s og m, totalt 5H), 2.3l(s, 3H), 2.20 (s, 3H), 1.44 (m, 3H), 1.19 (m, 1H), 0.72 (m, 2H), 0.36 (m, 2H).
Eksempel 2(290)
8-(N-etyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihy dro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.51 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.89 (dd, J =8.4, 2.4Hz, 1H), 3.84 (s, 3H), 3.77 (q, J = 7.2Hz, 2H), 3.59 (d, J = 6.6Hz, 2H), 3.04 (t, J = 7.5Hz, 4H), 2.36 (s, 3H), 2.16 (kvintett, J = 7.5Hz, 2H), 1.23 (t, J = 7.2Hz, 3H), 1.03 (m, 1H), 0.50 (m, 2H), 0.15 (m, 2H).
Eksempel 2(291)
8-(N-cyklopropyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.29 (heksan : etylacetat = 2:1);
NMR (300MHz, DMSO-d6): 57.83 - 7.76 (m, 2H), 7.54 - 7.48 (m, 2H), 7.30 (dd, J = 8.7, 1.2Hz, 1H), 7.16 (m, 1H), 7.02 - 6.96 (m, 1H), 5.12 (m, 2H), 3.82 (s, 3H), 3.06 (m, 2H), 2.94 - 2.78 (m, 3H), 2.25 (s, 3H), 2.05 (m, 2H), 0.79 - 0.70 (m, 2H), 0.61 (m, 2H).
Eksempel 2(292)
8-(N-cyklopropylmetyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.37 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.69 (brd, J = 7.2Hz, 2H), 7.49 (brd, J = 7.2Hz, 2H), 7.34 (brd, J = 8.4Hz, 1H), 7.09 (d, J = 2.1Hz, 1H), 6.96 (m, 1H), 5.33 (m, 2H), 3.85 (s, 3H), 3.60 (m, 2H), 3.48 (m, 2H), 3.10 (m, 2H), 2.3 3 (s, 3H), 2.28 (m, 2H), 1.18 - 1.02 (m, 1H), 0.70 - 0.58 (m, 2H), 0.22 - 0.10 (m, 2H).
Eksempel 2(293)
8-(N-cyklopropylmetyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.21 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.68 (d, J = 8.1Hz, 2H), 7.52 (d, J = 8.1Hz, 2H), 7.31 (d, J = 8.7Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.94 (dd, J = 8.7,2.4Hz, 1H), 5.26 (m, 4H), 5.14 (s, 2H), 3.84 (s, 3H), 3.45 (d, J = 6.6 H z, 2H), 2.36 (s, 3H), 1.05 (m, 1H), 0.68 - 0.56 (m, 2H), 0.18 - 0.10 (m, 2H).
Eksempel 2(294)
8-(N-cyklopropylmetyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.37 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.66 (d, J = 7.8Hz, 2H), 7.52 (d, J = 7.8Hz, 2H), 7.15 (d, J = 8.1Hz, 1H), 6.88 (d, J = 2.4Hz, 1H), 6.82 (dd, J = 8.1, 2.4Hz, 1H), 5.25 (s, 2H), 5.13 (s, 2H), 5.00 (s, 2H), 3.83 (s, 3H), 3.41 (d, J = 6.6Hz, 2H), 2.34 (s, 3H), 2.18 (s, 3H), 1.02 (m, 1H), 0.60 - 0.52 (m, 2H), 0.12 - 0.06 (m, 2H).
Eksempel 2(295)
8-(N-propyl-N-(tiofen-3-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.48 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 8.7Hz, 1H), 7.28 (m, 1H), 7.13 (m, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.98 (dd, J = 0.9, 4.8Hz, 1H), 6.90 (dd, J = 2.4, 8.7Hz, 1H), 5.08 (s, 2H), 4.96 (s, 2H), 4.89 (s, 2H), 3.84 (s, 3H), 3.32 (m, 2H), 2.41 (s, 3H), 1.64 (m, 2H), 0.90 (t, J = 7.5Hz, 3H).
Eksempel 2(296)
8-(N-propyl-N-(5-metyltiofen-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.50 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 8.7Hz, 1H), 7.07 (d, J = 2.4Hz, 1H), 6.90 (dd, J = 2.4, 8.7Hz, 1H), 6.66 (d, J = 3.3Hz, 1H), 6.56 (m, 1H), 5.02 - 5.17 (m, 4H), 4.90 (s, 2H), 3.84 (s, 3H), 3.27 (m, 2H), 2.44 (s, 3H), 2.42 (s, 3H), 1.64 (m, 2H), 0.92 (t, J = 7.5Hz, 3H).
Eksempel 2(297)
8-(N-butyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.61 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.31 (d, J = 8.7Hz, 1H), 7.06 (d, J = 2.1Hz, 1H), 6.89 (dd, J =8.7, 2.1Hz, 1H), 3.83 (s, 3H), 3.69 (t, J = 7.2Hz, 2H), 3.56 (d, J = 7.2Hz, 2H), 3.02 (m, 4H), 2.36 (s, 3H), 2.15 (kvintett, J = 7. 2Hz, 2H), 1.58 (kvintett, J = 7.5Hz, 2H), 1.34 (sekstett, J = 7.5Hz, 2H), 1.02 (m, 1H), 0.91 (t, J = 7.5Hz, 3H), 0.48 (m, 2H), 0.13 (m, 2H).
Eksempel 2(298)
8-(N-butyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.40 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.32 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.1Hz, 1H), 6.93 (dd, J =8.4, 2.1Hz, 1H), 5.25 (s, 2H), 5.17 (s, 2H), 3.84 (s, 3H), 3.77 (m, 2H), 3.71 (m, 2H), 2.37 (s, 3H), 1.70 (kvintett, J = 7.2Hz, 2H), 1.39 (sekstett, J = 7.2Hz, 2H), 1.10 (m, 1H), 0.96 (t, J = 7.2Hz, 3H), 0.62 (m, 2H), 0.25 (m, 2H).
Eksempel 2(299)
8-(N-butyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.7Hz, 1H), 6.88 (d, J = 2.1Hz, 1H), 6.81 (dd, J =8.7, 2.1Hz, 1H), 5.25 (s, 2H), 5.13 (s, 2H), 3.83 (s, 3H), 3.75 (m, 2H), 3.70 (m, 2H), 2.33 (s, 3H), 2.18 (s, 3H), 1.69 (m, 2H), 1 .39 (sekstett, J = 7.5Hz, 2H), 1.09 (m, 1H), 0.96 (t, J = 7.5Hz, 3H), 0.60 (m, 2H), 0.23 (m, 2H).
Eksempel 2(300)
8-(N-propyl-N-(tiofen-3-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.48 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.28 (dd, J = 2.7, 5.1Hz, 1H), 7.18 (d, J = 8.7Hz, 1H), 7.13 (m, 1H), 6.97 (dd, J = 1.5, 5.1Hz, 1H), 6.88 (d, J = 3.0Hz, 1H), 6.81 (dd, J = 3.0, 8.7Hz, 1H), 5.07 (s, 2H), 4.96 (s, 2H), 4.87 (s , 2H), 3.83 (s, 3H), 3.31 (m, 2H), 2.37 (s, 3H), 2.19 (s, 3H), 1.64 (m, 2H), 0.91 (t, J = 7.2Hz, 3H).
Eksempel 2(301)
8-(N-propyl-N-(5-metyltiofen-2-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.18 (d, J = 8.4Hz, 1H), 6.88 (d, J = 3.0Hz, 1H), 6.81 (dd, J = 3.0, 8.4Hz, 1H), 6.65 (d, J = 3.3Hz, 1H), 6.55 (m, 1H), 5.11 (s, 4H), 4.88 (s, 2H), 3.83 (s, 3H), 3.27 (m, 2H), 2.43 (s, 3H), 2. 38 (s, 3H), 2.19 (s, 3H), 1.65 (m, 2H), 0.92 (t, J = 7.5Hz, 3H).
Eksempel 2(302)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-eto cyklopenta[d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.56 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.21 (d, J = 1.5Hz, 1H), 8.08 (dd, J = 1.5,7.8Hz, 1H), 7.56 (d, J = 7.8Hz, 1H), 7.30 (brd, J = 10.8Hz, 1H), 4.38 (q, J = 6.9Hz, 2H), 4.00 (m, 1H), 3.34 - 3.64 (m, 2H), 3.15 (t, J = 6.9Hz, 2H), 2.35 (s, 3H), 2.31 (m, 2H), 1.65 - 1.96 (m, 4H), 1.41 (t, J = 6.9Hz, 3H), 1.07 (t, J = 7.5Hz, 3H), 1.06 (t, J = 7.5Hz, 3H).
Eksempel 2(303)
8-(N-propyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.52 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.35 (m, 2H), 7.10 - 6.92 (m, 5H), 5.16 (m, 2H), 3.85 (s, 3H), 3.70 (m, 2H), 3.60 - 3.34 (m, 2H), 3.03 (m, 2H), 2.35 (s, 3H), 2.26 (m, 2H), 1.75 (m, 2H), 0.94 (m, 3H).
Eksempel 2(304)
8-(N-propyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.48 - 7.33 (m, 2H), 7.13 - 7.04 (m, 4H), 6.97 (dd, J = 8.4, 2.4Hz, 1H), 5.50 - 5.15 (m, 4H), 5.17 (s, 2H), 3.85 (s, 3H), 3.74 - 3.60 (m, 2H), 2.37 (s, 3H), 1.82 (sekstett, J = 7.2Hz, 2H), 0.97 (t, J = 7.2Hz, 3H).
Eksempel 2(305)
8-(N-propyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.55 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.36 - 7.26 (m, 1H), 7.16 (d, J = 8.7Hz, 1H), 7.09 - 6.96 (m, 3H), 6.88 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.7,2.7Hz, 1H), 5.13 (s, 2H), 5.03 (s, 2H), 5.02 (s, 2H), 3.83 (s, 3H), 3.41 (m, 2H), 2.35 (s, 3H), 2.19 (s, 3H), 1.69 (sekstett, J = 7.2Hz, 2H), 0.92 (t, J = 7.2Hz, 3H).
Eksempel 2(306)
8-(N-propyl-N-(5-metyltiofen-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.57 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.32 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 2.7, 8.4Hz, 1H), 6.64 (d, J = 3.3Hz, 1H), 6.54 (m, 1H), 4.96 (s, 2H), 3.84 (s, 3H), 3.38 (m, 2H), 2.90 (t, J = 7.5Hz, 2H), 2.86 (t, J = 7.2Hz, 2H), 2.43 (s, 3H), 2.40 (s, 3H), 2.08 (m, 2H), 1.61 (m, 2H), 0.90 (t, J = 7.5Hz, 3H).
Eksempel 2(307)
8-(N-propyl-N-(tiofen-3-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0,53 (heksan : etylacetat = 3 :1);
NMR (300MHz, CDC13): 8 7.32 (d, J = 8.7Hz, 1H), 7.25 (m, 1H), 7.11 (m, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.95 (dd, J = 1.5, 5.1Hz, 1H), 6.89 (dd, J = 2.7, 8.7Hz, 1H), 4.85 (s, 2H), 3.84 (s, 3H), 3.39 (m, 2H), 2.90 (t, J = 7.5Hz, 2H), 2.81 (t, J = 7.2Hz, 2H), 2.39 (s, 3H), 2.07 (m, 2H), 1.60 (m, 2H), 0.89 (t, J = 7.2Hz, 3H).
Eksempel 2(308)
8-(N-etyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0,58 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.30 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.7Hz, 1H), 6.88 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 3.66 (q, J = 6.9Hz, 2H), 3.60 - 3.50 (m, 2H), 3.02 - 2.84 (m, 4H), 2.37 (s, 3H), 2.20 - 2.04 (m, 2H), 1.64 - 1.52 (m, 2H), 1.17 (t, J = 6.9Hz, 3H), 0.90 (t, J = 6.9Hz, 3H).
Eksempel 2(309)
8-(N-etyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.55 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.7Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.7, 2.7Hz, 1H), 5.20 (s, 2H), 4.89 (s, 2H), 3.82 (s, 3H), 3.67 (q, J = 7.2Hz, 2H), 3.60 - 3.48 (m, 2H), 2.34 (s, 3H), 2.18 (s, 3H), 1.72 - 1.56 (m, 2H), 1.23 (t, J = 7.2Hz, 3H), 0.93 (t, J = 7.2Hz, 3H).
Eksempel 2(310)
8-(N-etyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo [3,4-d]py razolo [1,5 -ajpyrimidin
TLC: Rf 0.51 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 8.7Hz, 1H), 7.06 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 8.7, 2.7Hz, 1H), 5.19 (s, 2H), 4.90 (s, 2H), 3.83 (s, 3H), 3.67 (q, J = 7.2Hz, 2H), 3.60 - 3.48 (m, 2H), 2.38 (s, 3H), 1.70 - 1.50 (m, 2H), 1.24 (t, J = 7.2Hz, 3H), 0.93 (t, J = 7.2Hz, 3H).
Eksempel 2(311)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-karbamoylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
N /~" CH'
rYcl
TLC: Rf 0.53 (metylenklorid : etylacetat = 10 : 1);
NMR (300MHz, CDC13) : 8 7.96 (d, J = 1.8Hz, 1H), 7.70 (dd, J = 8.1, 1.8Hz, 1H), 7.50 (d, J = 8.1Hz, 1H), 6.26 (d, J = 10.5Hz, 1H), 3.82 (m, 1H), 3.14 - 3.05 (m, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.36 (s, 3H), 2.22 - 2.10 (m, 2H), 1.85 - 1.50 (m, 4H), 1.02 (t, J = 7.5Hz, 6H).
Eksempel 2(312)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-(N-metylkarbamoyl)fenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.55 (metylenklorid : etylacetat = 10 : 1); NMR (300MHz, CDC13): 8 7.89 (d, J = 1.8Hz, 1H), 7.64 (dd, J = 7.8, 1.8Hz, 1H), 7.45 (d, J = 7.8Hz, 1H), 6.42 (brs, 1H), 6.26 (d, J = 10.2Hz, 1H), 3.82 (m, 1H), 3.14 - 3.05 (m, 2H), 3.01 (d, J = 4.5Hz, 3H), 2.91 (t, J = 7.8Hz, 2H), 2.35 (s, 3H), 2.22 - 2.09 (m, 2H), 1.82 - 1.55 (m, 4H), 1.02 (t, J = 7.5Hz, 6H).
Eksempel 2(313)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-(N, N-dimetylkarbamoyl)fenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.65 (metylenklorid : etylacetat =10:1);
NMR (300MHz, CDC13): 8 7.56 (d, J = 1.5Hz, 1H), 7.46 (d, J = 7.8Hz, 1H), 7.36 (dd, J = 7.8, 1.5Hz, 1H), 6.26 (d, J = 9.9Hz, 1H), 3.82 (m, 1H), 3.17 - 3.02 (m, 8H), 2.92 (t, J = 7.8Hz, 2H), 2.34 (s, 3H), 2.21 - 2.06 (m, 2H), 1.85 - 1.42 (m, 4H), 1.02 (t, J = 7.5Hz, 6H).
Eksempel 2(314)
8-(3-pentylamino)-2-metyl-3-(2, 6-dimetyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.29 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 6.69 (s, 2H), 6.32 (d, J = 10.8Hz, 1H), 5.29 (s, 2H), 4.88 (s, 2H), 3.80 (s, 3H), 3.30 - 3.18 (m, 1H), 2.22 (s, 3H), 2.04 (s, 6H), 1.83 - 1.55 (m, 4H), 1.03 (t, J = 7.2Hz, 6H).
Eksempel 2(315)
8-(N-etyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.30 - 7.22 (m, 2H), 7.18 (d, J = 8.1Hz, 1H), 7.06 - 6.94 (m, 2H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.1, 2.7Hz, 1H), 5.09 (s, 2H), 4.96 - 4.80 (m, 4H), 3.83 (s, 3H), 3.41 (q, J = 7.2Hz, 2H), 2.37 (s, 3H), 2.18 (s, 3H), 1.23 (t, J = 7.2Hz, 3H).
Eksempel 2(316)
8-(N-etyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.42 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.32 (d, J = 8.4Hz, 1H), 7.26 - 7.22 (m, 2H), 7.07 (d, J = 2.4Hz, 1H), 7.04 - 6.94 (m, 2H), 6.90 (dd, J = 8.4, 2.4Hz, 1H), 4.81 (s, 2H), 3.84 (s, 3H), 3.47 (q, J = 7.2Hz, 2H), 2.90 (t, J = 7.2Hz, 2H), 2.82 (t, J = 7.2Hz, 2H), 2.40 (s, 3H), 2.16-1.98 (m, 2H), 1.18 (t, J = 7.2Hz, 3H).
Eksempel 2(317)
8-(N-etyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.46 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.31 (d, J = 8.1Hz, 1H), 7.30 - 7.24 (m, 2H), 7.08 (d, J = 2.7Hz, 1H), 7.06 - 6.94 (m, 2H), 6.91 (dd, J = 8.1, 2.7Hz, 1H), 5.10 (s, 2H), 4.90 (s, 2H), 4.89 (s, 2H), 3.84 (s, 3H), 3.42 (q, J = 7.2Hz, 2H), 2.40 (s, 3H), 1.22 (t, J = 7.2Hz, 3H).
Eksempel 2(318)
8-(3-pentylamino)-2-metyl-3-(2-klor-4, 6-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.26 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 6.67 (d, J = 2.7Hz, 1H), 6.45 (d, J = 2.7Hz, 1H), 6.23 (d, J = 10.8Hz, 1H), 3.82 (s, 3H), 3.80 (m, 1H), 3.70 (s, 3H), 3.07 (m, 2H), 2.90 (m, 2H), 2.25 (s, 3H), 2.13 (m, 2H), 1.52 - 1.80 (m, 4H), 1.02 (t, J = 7.2Hz, 3H), 1.01 (t, J = 7.2Hz, 3H).
Eksempel 2(319)
8-(3-pentylamino)-2-metyl-3-(2-klor-4, 6-dimetoksyfenyl)-5,7-dihydro-furo[3,4-d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.22 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 6.68 (d, J = 2.7Hz, 1H), 6.47 (d, J = 2.7Hz, 1H), 6.34 (d, J = 10.8Hz, 1H), 5.28 (s, 2H), 4.92 (d, J = 13.5Hz, 1H), 4.90 (d, J = 13.5Hz, 1H), 3.83 (s, 3H), 3.71 (s, 3H), 3.23 (m, 1H), 2.28 (s, 3H), 1.53 - 1.82 (m, 4H), 1.02 (t, J = 7.5Hz, 3H), 1.01 (t, J = 7.5Hz, 3H).
Eksempel 2(320)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-aminofenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.22 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.82 (d, J = 2.1Hz, 1H), 6.63 (dd, J = 8.4, 2.1Hz, 1H), 6.21 (d, J = 10.2Hz, 1H), 3.87 - 3.62 (m, 3H), 3.12 - 3.03 (m, 2H), 2.95 - 2.86 (m, 2H), 2.34 (s, 3H), 2.20 - 2.07 (m, 2H), 1.85 - 1.50 (m, 4H), 1.01 (t, J = 7.5Hz, 6H).
Eksempel 2(321)
8-(4-heptylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]-pyrazolo[l ,5-a]pyrimidin
TLC: Rf 0.48 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.15 (d, J = 8.7Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.7, 2.7Hz, 1H), 6.32 (d, J = 10.8Hz, 1H), 5.29 (s, 2H), 4.90 (s, 2H), 3.82 (s, 3H), 3.40 (m, 1H), 2.32 (s, 3H), 2.18 (s, 3H), 1.78 - 1.38 (m, 8H), 0.95 (t, J = 7.2Hz, 6H).
Eksempel 2(322)
8-(3-pentylamino)-2-metyl-3-(2-klor-4-metylaminofenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.45 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13) : 8 7.18 (d, J = 8.4Hz, 1H), 6.73 (d, J = 2.4Hz, 1H), 6.56 (dd, J = 8.4, 2.4Hz, 1H), 6.21 (d, J = 10.5Hz, 1H), 3.88 - 3.70 (m, 2H), 3.12 - 3.02 (m, 2H), 2.95 - 2.80 (m, 2H), 2.85 (s, 3H), 2.34 (s, 3H), 2.20 - 2.05 (m, 2H), 1.80 - 1.50 (m, 4H), 1.01 (t, J = 7.2Hz, 6H).
Eksempel 2(323)
8-(3-pentylamino)-2-metyl-3-(2-formyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.26 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 9.85 (s, 1H), 7.55 (d, J = 2.7Hz, 1H), 7.38 (d, J = 8.4Hz, 1H), 7.22 (dd, J = 8.4, 2.7Hz, 1H), 6.23 (d, J = 9.6Hz, 1H), 3.93 - 3.74 (m) og 3.89 (s) totalt 4H, 3.09 (t, J = 7.5Hz, 2H), 2.88 (t, J = 7.5Hz, 2H), 2.39 (s, 3H), 2.14 (kvintett, J = 7.5Hz, 2H), 1.83 - 1.50 (m, 4H), 1.02 (t, J = 7.5Hz, 6H).
Eksempel 2(324)
8-(3-pentylamino)-2-metyl-3-(2-cyano-4-metoksyfenyl)-6,7-dihydro-5H-cyklo-penta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.54 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.46 (d, J = 9.0Hz, 1H), 7.24 (d, J = 2.4Hz, 1H), 7.18 (dd, J = 9.0, 2.4Hz, 1H), 6.24 (d, J = 10.5Hz, 1H), 3.88 - 3.73 (m) og 3.86 (s) totalt 4H, 3.09 (t, J = 7.2Hz, 2H), 2.92 (t, J = 7.2Hz, 2H), 2.43 (s, 3H), 2.15 (kvintett, J = 7.2Hz, 2H), 1.80 - 1.50 (m, 4H), 1.02 (t, J = 7.2Hz, 6H).
Eksempel 2(325)
8-(3-pentylamino)-2-metyl-3-(2-etyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklo-penta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.12 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.4Hz, 1H), 6.77 (dd, J = 8.4, 2.4Hz, 1H), 6.21 (d, J = 10.5Hz, 1H), 3.83 - 3.75 (m) og 3.83 (s) totalt 4H, 3.08 (t, J = 7.2Hz, 2H), 2.88 (t, J = 7.2Hz, 2H), 2.52 (q, J = 7.8Hz, 2H), 2.28 (s, 3H), 2.13 (kvintett, J = 7.2Hz, 2H), 1.83 - 1.50 (m, 4H), 1.10 - 0.98 (m, 9H).
Eksempel 2(326)
8-(4-heptylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.51 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 8.20 (s, 1H), 7.65 (d, J = 8.4Hz, 1H), 7.38 (d, J = 10.2Hz, 1H), 7.08 - 6.97 (m, 2H), 4.15 (m, 1H), 3.84 (s, 3H), 3.61 (m, 2H), 3.16 (m, 2H), 2.33 (m, 2H), 1.88 - 1.60 (m, 4H), 1.60 - 1.35 (m, 4H), 0.99 (t, J = 7.5Hz, 6H).
Eksempel 2(327)
8-(N, N-dipropylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.54 (heksan : etylacetat =3:1);
NMR (300MHz, CDC13): 8 8.32 (s, 1H), 7.78 (d, J = 8.7Hz, 1H), 7.03 (d, J = 2.7Hz, 1H), 6.91 (dd, J = 8.7, 2.7Hz, 1H), 3.83 (s, 3H), 3.57 (m, 4H), 2.97 (m, 4H), 2.17 (m, 2H), 1.66 - 1.50 (m, 4H), 0.88 (t, J = 7.5Hz, 6H).
Eksempel 2(328)
8-(N, N-dipropylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.58 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.35 (s, 1H), 7.72 (d, J = 9.0Hz, 1H), 7.04 (d, J = 2.4Hz, 1H), 6.91 (dd, J = 9.0, 2.4Hz, 1H), 5.20 (s, 2H), 4.94 (s, 2H), 3.82 (s, 3H), 3.57 (t, J = 7.5Hz, 4H), 1.72 - 1.46 (m, 4H), 0.90 (t, J = 7.2Hz, 6H).
Eksempel 2(329)
8-(N-cyklopropylmetyl-N-propylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.60 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.73 (d, J = 8.4Hz, 1H), 7.05 (d, J = 2.7Hz, 1H), 6.92 (dd, J = 8.4,2.7Hz, 1H), 5.25 (s, 2H), 4.96 (s, 2H), 3.83 (s, 3H), 3.64 - 3.50 (m, 4H), 1.72 - 1.56 (m, 2H), 1.04 (m, 1H), 0.93 (t, J = 7.5Hz, 3H), 0.58 - 0.44 (m, 2H), 0.20 - 0.08 (m, 2H).
Eksempel 2(330)
8-(N-benzyl-N-cyklopropylmetylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo [3,4-d]pyrazolo [ 1,5 -ajpyrimidin
9
°ccx)
OCHj
TLC: Rf 0.52 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 6 8.42 (s, 1H), 7.74 (d, J = 8.4Hz, 1H), 7.38 - 7.20 (m, 5H), 7.06 (d, J = 2.7Hz, 1H), 6.93 (dd, J = 8.4, 2.7Hz, 1H), 5.25 (s, 2H), 4.96 (s, 2H), 4.95 (s, 2H), 3.84 (s, 3H), 3.43 (d, J = 6.6Hz, 2H), 1.04 (m, 1H), 0.58 - 0.46 (m,2H), 0.16-0.04 (m,2H).
Eksempel 2(331)
8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.56 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.42 (s, 1H), 7.75 (d, J = 8.4Hz, 1H), 7.19 (d, J = 7.8Hz, 2H), 7.13 (d, J = 7.8Hz, 2H), 7.06 (d, J = 2.4Hz, 1H), 6.93 (dd, J = 8.4,2.4Hz, 1H), 5.24 (s, 2H), 4.95 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 3.42 (d, J = 6.3Hz, 2H), 2.33 (s, 3H), 1.04 (m, 1H), 0.58 - 0.46 (m, 2H), 0.18 - 0.04 (m, 2H).
Eksempel 2(332)
8-(N-propyl-N-(2-butynyl)amino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.41 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.71 (d, J = 8.7Hz, 1H), 7.05 (d, J = 2.7Hz, 1H), 6.92 (dd, J = 8.7, 2.7Hz> 1H), 5.34 (s, 2H), 4.97 (s, 2H), 4.44 (q, J = 2.4Hz, 2H), 3.83 (s, 3H), 3.52 (m, 2H), 1.82 (t, J = 2.4Hz,.3H), 1.80 - 1.62 (m, 2H), 0.98 (t, J = 7.2Hz, 3H).
Eksempel 2(333)
8-(3-pentylamino)-2-metyl-3-(2-metoksykarbonyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.26 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.70 (d, J = 2.7Hz, 1H), 7.34 (d, J = 8.4Hz, 1H), 7.30 - 7.16 (m) og 7.19 (dd, J = 8.4,2.7Hz) totalt 2H, 4.03 - 3.83 (m) og 3.89 (s) totalt 4H, 3.77 (s, 3H), 3.54 - 3.36 (m, 2H), 3.11 (t, J = 7.5Hz, 2H), 2.33 - 2.00 (m) og 2.25 (s) totalt 4H, 1.90 - 1.58 (m, 4H), 1.05 (t, J = 7.5Hz, 6H).
Eksempel 2(334)
8-(N-butyl-N-cyklopropylmetylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.45 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.74 (d, J = 9.0Hz, 1H), 7.05 (d, J = 2.7Hz, 1H), 6.91 (dd, J = 9.0, 2.7Hz, 1H), 5.25 (s, 2H), 4.96 (s, 2H), 3.83 (s, 3H), 3.66 - 3.52 (m, 4H), 1.66 - 1.48 (m, 2H), 1.44 - 1.22 (m, 2H), 1.04 (m, 1H), 0.91 (t, J = 7.2Hz, 3H), 0.60 - 0.44 (m, 2H), 0.22 - 0.08 (m, 2H).
Eksempel 2(335)
8-(3-pentylamino)-3-(2-klor-4-metota^
[l,5-a]pyrimidin
TLC: Rf 0.57 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 8.32 (s, 1H), 7.74 (d, J = 8.7Hz, 1H), 7.04 (d, J = 2.7Hz, 1H), 6.91 (dd, J = 8.7,2.7Hz, 1H), 6.42 (d, J = 10.8Hz, 1H), 5.31 (s, 2H), 4.97 (s, 2H), 3.83 (s, 3H), 3.28 (m, 1H), 1.84 - 1.54 (m, 4H), 1.01 (t, J = 7.2Hz, 6H).
Eksempel 2(336)
8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.41 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.41 (s, 1H), 7.74 (d, J = 9.0Hz, 1H), 7.38 - 7.24 (m, 2H), 7.12 - 6.96 (m, 3H), 6.92 (dd, J = 9.0,2.7Hz, 1H), 5.25 (s, 2H), 4.95 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 3.39 (d, J = 6.9Hz, 2H), 1.02 (m, 1H), 0.60 - 0.44 (m, 2H), 0.16- 0.02 (m, 2H).
Eksempel 2(337)
8-(N-cyklopropyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.41 (toluen : etylacetat = 10 : 1);
NMR (300MHz, CDC13): 5 7.32 (d, J = 8.4Hz, 1H), 7.23 (m, 1H), 7.13 - 6.97 (m, 3H), 7.06 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 8.4, 2.7Hz, 1H), 5.15 (brs, 2H), 3.84 (s, 3H), 2.98 - 2.86 (m, 4H), 2.83 (m, 1H), 2.40 (s, 3H), 2. 02 (m, 2H), 0.84 - 0.72 (m, 4H).
Eksempel 2(338)
8-(N-cyklopropylmetyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.49 (toluen : etylacetat =10:1);
NMR (300MHz, CDC13) : 8 7.32 (d, J = 8.7Hz, 1H), 7.35 - 7.16 (m, 2H), 7.06 (d, J = 2.4Hz, 1H), 7.08 - 6.97 (m, 2H), 6.89 (dd, J = 8.7Hz, 2.4Hz, 1H), 5.02 (s, 2H), 3.84 (s, 3H), 3.41 (d, J = 6.9Hz, 2H), 2.98 - 2.84 (m, 4H), 2.40 (s, 3H), 2.07 (m, 2H), 1.05 (m, 1H), 0.48 (m, 2H), 0.10 (m, 2H).
Eksempel 2(339)
8-(N-cyklopropylmetyl-N-propylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.76 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 8.32 (s, 1H), 7.78 (d, J = 8.7Hz, 1H), 7.03 (d, J = 2.7Hz, 1H), 6.91 (dd, J = 8.7, 2.7Hz, 1H), 3.83 (s, 3H), 3.68 - 3.58 (m, 2H), 3.52 (d, J = 6.9Hz, 2H), 3.06 - 2.90 (m, 4H), 2.26 - 2.08 (m, 2H), 1.66 - 1.46 (m, 2H), 1.01 (m, 1H), 0.90 (t, J = 7.2Hz, 3H), 0.52 - 0.42 (m, 2H), 0.16 - 0.04 (m, 2H).
Eksempel 2(340)
8-(N-propyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.61 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.79 (d, J = 9.0Hz, 1H), 7.18 - 7.07 (m, 4H), 7.04 (d, J = 2.7Hz, 1H), 6.92 (dd, J = 9.0, 2.7Hz, 1H), 4.79 (s, 2H), 3.83 (s, 3H), 3.45 - 3.36 (m, 2H), 2.96 (t, J = 7.8Hz, 2H), 2.89 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.20 - 2.04 (m, 2H), 1.66 - 1.46 (m, 2H), 0.87 (t, J = 7.2Hz, 3H).
Eksempel 2(341)
8-(N-benzyl-N-cyklopropylmetylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.67 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 8 8.38 (s, 1H), 7.79 (d, J = 8.7Hz, 1H), 7.38 - 7.18 (m, 5H), 7.05 (d, J = 2.4Hz, 1H), 6.92 (dd, J = 8.7, 2.4Hz, 1H), 4.92 (s, 2H), 3.83 (s, 3H), 3.40 (d, J = 6.9Hz, 2H), 3.01 (t, J = 7.2Hz, 2H), 2.97 (t, J = 7.8Hz, 2H), 2.22 - 2.06 (m, 2H), 1.02 (m, 1H), 0.54 - 0.42 (m, 2H), 0.12 - 0.02 (m, 2H).
Eksempel 2(342)
8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.71 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.79 (d, J = 8.4Hz, 1H), 7.20 (d, J = 8.1Hz, 2H), 7.11 (d, J = 8.1Hz, 2H), 7.05 (d, J = 2.7Hz, 1H), 6.92 (dd, J = 8.4, 2.7Hz, 1H), 4.88 (s, 2H), 3.83 (s, 3H), 3.39 (d, J = 6.6Hz, 2H), 3.01 (t, J = 7.2Hz, 2H), 2.97 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.22 - 2.06 (m, 2H), 1.02 (m, 1H), 0.54 - 0.42 (m, 2H), 0.14-0.02 (m,2H).
Eksempel 2(343)
8-(N-propyl-N-(4-fluorfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.54 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.79 (d, J = 8.7Hz, 1H), 7.30 - 7.22 (m, 2H), 7.05 (d, J = 2.4Hz, 1H), 7.04 - 6.96 (m, 2H), 6.92 (dd, J = 8.7, 2.4Hz, 1H), 4.78 (s, 2H), 3.83 (s, 3H), 3.46 - 3.34 (m, 2H), 2.97 (t, J = 7.8Hz, 2H), 2.89 (t, J = 7.2Hz, 2H), 2.20 - 2.04 (m, 2H), 1.66 - 1.48 (m, 2H), 0.87 (t, J = 7.5Hz, 3H).
Eksempel 2(344)
8-dicyklopropylmetylamino-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5 -ajpyrimidin
TLC: Rf 0.58 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.28 (s, 1H), 7.78 (d, J = 8.7Hz, 1H), 7.03 (d, J = 2.4Hz, 1H), 6.91 (dd, J = 8.7, 2.4Hz, 1H), 6.42 (d, J = 9.6Hz, 1H), 3.82 (s, 3H), 3.44 (m, 1H), 3.10 - 3.00 (m, 2H), 2.98 - 2.88 (m, 2H), 2.22 - 2.06 (m, 2H), 1.20 - 1.06 (m, 2H), 0.68 - 0.48 (m, 4H), 0.48 - 0.34 (m, 4H).
Eksempel 2(345)
8-(4-heptylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo-[l,5-a]pyrimidin
TLC: Rf 0.54 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.32 (s, 1H), 7.74 (d, J = 8.7Hz, 1H), 7.04 (d, J = 2.7Hz, 1H), 6.92 (dd, J = 8.7, 2.7Hz, 1H), 6.42 (d, J = 10.8Hz, 1H), 5.32 (s, 2H), 4.97 (s, 2H), 3.83 (s, 3H), 3.42 (m, 1H), 1.78 -1.26 (m, 8H), 0.95 (t, J = 7.2Hz, 6H).
Eksempel 2(346)
8-(N-propyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.53 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 8.41 (s, 1H), 7.75 (d, J = 8.7Hz, 1H), 7.16 - 7.08 (m, 4H), 7.06 (d, J = 2.4Hz, 1H), 6.92 (dd, J = 8.7, 2.4Hz, 1H), 5.14 (s, 2H), 4.95 (s, 2H), 4.88 (s, 2H), 3.84 (s, 3H), 3.42 - 3.28 (m, 2H), 2.33 (s, 3H), 1.72 - 1.50 (m, 2H), 0.89 (t, J = 7.5Hz, 3H).
Eksempel 2(347)
8-(N-propyl-N-(4-fluorfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.50 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 8.41 (s, 1H), 7.74 (d, J = 8.4Hz, 1H), 7.32 - 7.18 (m, 2H), 7.08 - 6.97 (m, 3H), 6.93 (dd, J = 8.4,2.4Hz, 1H), 5.15 (s, 2H), 4.95 (s, 2H), 4.88 (s, 2H), 3.84 (s, 3H), 3.40 - 3.26 (m, 2H), 1.70 - 1.48 (m, 2H), 0.89 (t, J = 7.2Hz, 3H).
Eksempel 2(348)
8-dicyklopropylmetylamino-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]-pyrazolo [ 1,5 -ajpyrimidin
TLC: Rf 0.47 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.33 (s, 1H), 7.73 (d, J = 8.7Hz, 1H), 7.04 (d, J = 2.7Hz, 1H), 6.91 (dd, J = 8.7, 2.7Hz, 1H), 6.55 (d, J = 9.6Hz, 1H), 5.25 (s, 2H), 4.94 (s, 2H), 3.83 (s, 3H), 2.92 (m, 1H), 1.22 - 1.06 (m, 2H), 0.70 - 0.48 (m, 4H), 0.48 - 0.30 (m, 4H).
Eksempel 2(349)
8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.42 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.41 (s, 1H), 7.73 (d, J = 8.4Hz, 1H), 7.60 (d, J = 8.1Hz, 2H), 7.50 (d, J = 8.1Hz, 2H), 7.06 (d, J = 2.7Hz, 1H), 6.93 (dd, J = 8.4, 2.7Hz, 1H), 5.27 (s, 2H), 5.02 (s, 2H), 4.96 (s, 2H), 3.84 (s, 3H), 3.40 (d, J = 6.6Hz, 2H), 1.02 (m, 1H), 0.60 - 0.46 (m, 2H), 0.16 - 0.04 (m, 2H).
Eksempel 2(350)
8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihy dro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.60 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.36 (s, 1H), 7.80 (d, J = 8.4Hz, 1H), 7.12 - 6.99 (m, 5H), 6.93 (dd, J = 8.4, 2.7Hz, 1H), 4.96 (s, 2H), 3.83 (s, 3H), 2.97 (t, J = 7.8Hz, 2H), 2.94 (t, J = 7.5Hz, 2H), 2.78 (m, 1H), 2.32 (s, 3H), 2.16 - 2.00 (m, 2H), 0.82 - 0.68 (m, 4H).
Eksempel 2(351)
8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.55 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.78 (d, J = 8.7Hz, 1H), 7.58 (d, J = 8.1Hz, 2H), 7.49 (d, J = 8.1Hz, 2H), 7.05 (d, J = 2.7Hz, 1H), 6.92 (dd, J = 8.7, 2.7Hz, 1H), 4.97 (s, 2H), 3.83 (s, 3H), 3.39 (d, J = 6.6Hz, 2H), 3.04 (t, J = 7.2Hz, 2H), 2.99 (t, J = 7.8Hz, 2H), 2.18 (m, 2H), 1.01 (m, 1H), 0.56-0.42 (m, 2H), 0.14-0.02 (m, 2H).
Eksempel 2(352)
8-(3-pentylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.53 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.27 (s, 1H), 7.79 (d, J = 8.7Hz, 1H), 7.03 (d, J = 2.4Hz, 1H), 6.91 (dd, J = 8.7,2.4Hz, 1H), 6.30 (d, J = 10.2Hz, 1H), 3.82 (s, 3H), 3.82 (m, 1H), 3.11 (t, J = 7.2Hz, 2H), 2.96 (t, J = 7.8Hz, 2H), 2.24-2.08 (m, 2H), 1.84-1.52 (m, 4H), 1.01 (t, J = 7.5Hz, 6H).
Eksempel 2(353)
8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.46 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.37 (s, 1H), 7.78 (d, J = 8.7Hz, 1H), 7.38-7.24 (m, 2H), 7.05 (d, J = 2.7Hz, 1H), 7.05-6.93 (m, 2H), 6.92 (dd, J = 8.7,2.7Hz, 1H), 4.87 (s, 2H), 3.83 (s, 3H), 3.37 (d, J = 6.9Hz, 2H), 3.01 (t, J = 7.5Hz, 2H), 2.97 (t, J = 7.5Hz, 2H), 2.22-2.06 (m, 2H), 1.00 (m, 1H), 0.54-0.40 (m, 2H), 0.12-0.02 (m, 2H).
Eksempel 2(354)
8-(3-pentylamino)-2-mety 1-3-(2-(l-metyl-1-hy droksyetyl)-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazo!o[ 1,5-a]pyrimidin
TLC: Rf 0.50 (heksan : etylacetat =1:2);
. NMR (300MHz, CDC13): 8 7.23 (d, J = 2.7Hz, 1H), 7.03 (d, J = 8.7Hz, lHj, 6.83 (dd, J = 8.7, 2.7Hz, 1H), 6.26 (d, J = 10.2Hz, 1H), 5.00-4.85 (m , 1H), 3.85-3.75 (m)
og 3.84 (s) totalt 4H, 3.06 (t, J = 6.9Hz, 2H), 2.85 (t, J = 6.9Hz, 2H), 2.29 (s, 3H),
. 2.11 (kvintett, J = 7.5Hz, 2H), 1.80-1.50 (m) og 1.64 (s) totalt 7H, 1.30 (s, 3H), 1.03 (t, J = 7.2Hz) og 1.00 (t, J = 7.2Hz) totalt 6H.
Eksempel 2(355) 8-(N-propyl-N-(4-trifluormetyloksyfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.52 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 5 7.32 (d, J = 9.0Hz, 2H), 7.32 (d, J = 8.4Hz, 1H), 7.15 (d, J = 9.0Hz, 2H), 7.07 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 8.4, 2.7Hz, 1H), 4.84 (s, 2H), 3.84 (s, 3H), 3.44-3.32 (m, 2H), 2.91 (t, J = 7.5Hz, 2H), 2.84 (t, J = 7.8Hz, 2H), 2.39 (s, 3H), 2.06-1.98 (m, 2H), 1.66-1.48 (m, 2H), 0.88 (t, J = 7.2Hz, 3H).
Eksempel 2(356)
8-(3-heksylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.44 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.30 (d, J = 8.7Hz, 1H), 7.05 (d, J = 2.4Hz, 1H), 6.88 (dd, J = 8.7, 2.4Hz, 1H), 6.22 (d, J = 10.8Hz, 1H), 3.84 (m, 1H), 3.83 (s, 3H), 3.08 (t, J = 7.5Hz, 2H), 2.90 (t, J = 7.8Hz, 2H), 2.34 (s, 3H), 2.20-2.04 (m, 2H), 1.80-1.32 (m, 6H), 1.00 (t, J = 6.9Hz, 3H), 0.95 (t, J = 6.9Hz, 3H).
Eksempel 2(357)
8-(3-pentylamino)-2-metyl-3-(2-metoksy-4-metylpyridin-5-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.23 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 8.00 (s, 1H), 6.69 (s, 1H), 6.23 (d, J = 10.5Hz, 1H), 3.94 (s, 3H), 3.82 (m, 1H), 3.08 (t, J = 7.5Hz, 2H), 2.89 (t, J = 7.8Hz, 2H), 2.32 (s, 3H), 2.20-2.06 (m, 2H), 2.18 (s, 3H), 1.82-1.54 (m, 4H), 1.02 (t, J = 7.2Hz, 6H).
Eksempel 2(358)
8-(N-butyl-N-cyklopropylmetylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.61 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 5 8.27 (s, 1H), 7.71 (d, J = 8.4Hz, 1H), 7.04 (d, J = 2.4Hz, 1H), 6.94 (m, 1H), 3.90-3.70 (m, 2H), 3.83 (s, 3H), 3.64 (d, J = 6.6Hz, 2H), 3.30-3.12 (m, 2H), 3.12-2.96 (m, 2H), 2.32-2.12 (m, 2H), 1.68-1.50 (m, 2H), 1.46-1.20 (m, 2H), 1.06 (m, 1H), 0.91 (t, J = 7.2Hz, 3H), 0.62-0.46 (m, 2H), 0.24-0.10 (m, 2H).
Eksempel 2(359)
8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidinhydroklorid
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 8.42 (s, 1H), 7.76 (d, J = 8.7Hz, 1H), 7.09 (d, J = 8.1Hz, 2H), 7.06 (d, J = 2.7Hz, 1H), 6.99 (d, J = 8.1Hz, 2H), 6.93 (dd, J = 8.7, 2.7Hz, 1H), 5.19 (s, 2H), 5.11 (s, 2H), 4.96 (s, 2H), 3.84 (s, 3H), 2.58 (m, 1H), 2.32 (s, 3H), 0.86-0.76 (m, 4H).
Eksempel 2(360)
8-(N-propyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.74 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.32 (d, J = 8.7Hz, 1H), 7.16-7.06 (m, 4H), 7.07 (d, J = 3.0Hz, 1H), 6.89 (dd, J = 8.7, 3.0Hz, 1H), 4.80 (s, 2H), 3.84 (s, 3H), 3.42-3.30 (m, 2H), 2.89 (t, J = 7.8Hz, 2H), 2.82 (t, J = 7.2Hz, 2H), 2.39 (s, 3H), 2.33 (s, 3H), 2.04-1.98 (m, 2H), 1.70-1.48 (m, 2H), 0.87 (t, J = 7.2Hz, 3H).
Eksempel 2(361)
8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyI)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.38 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.64 (d, J = 8.1Hz, 2H), 7.50 (d, J = 8.1Hz, 2H), 7.30 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.7Hz, 1H), 6.90 (d, J = 8.4, 2.7Hz, 1H), 5.14 (s, 2H), 5.01 (s, 2H), 4.91 (s, 2H), 3.84 (s, 3H), 3.36-3.22 (m, 2H), 2.38 (s, 3H), 1.70-1.50 (m, 2H), 0.89 (t, J = 7.2Hz, 3H).
Eksempel 2(362)
8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.46 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.61 (d, J = 7.8Hz, 2H), 7.47 (d, J = 7.8Hz, 2H), 7.31 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 8.4, 2.7Hz, 1H), 4.90 (s, 2H), 3.84 (s, 3H), 3.44-3.32 (m, 2H), 2.92 (t, J = 7.8Hz, 2H), 2.88 (t, J = 7.5Hz, 2H), 2.38 (s, 3H), 2.20-2.02 (m, 2H), 1.66-1.46 (m, 2H), 0.88 (t, J = 7.2Hz, 3H).
Eksempel 2(363)
8-(N-cyklopropylmetyl-N-metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.30 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.30 (d, J = 8.4Hz, 1H), 7.05 (d, J = 3.0Hz, 1H),6.88 (dd, J = 8.4, 3.0Hz, 1H), 3.83 (s, 3H),3.61 (d, J = 6.9Hz, 2H), 3.30 (s, 3H),3.12 (t, J = 7.2Hz, 2H), 2.92 (t, J = 7.5Hz, 2H),2.36 (s, 3H), 2.20-2.06 (m, 2H),1.09 (m, 1H), 0.60-0.46 (m, 2H),0.24-0.12 (m, 2H).
Eksempel 2(364)
8-(N-cyklopropylmetyl-N-metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.22 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.87 (d, J = 3.0Hz, 1H),6.80 (dd, J = 8.4, 3.0Hz, 1H), 5.35 (s, 2H),4.89 (s, 2H), 3.83 (s, 3H),3.72 (dd, J = 6.9, 1.5Hz, 2H), 3.27 (s, 3H),2.34 (s, 3H), 2.15 (s, 3H),1.10 (m, 1H), 0.60-0.48 (m, 2H),0.24-0.14 (m, 2H).
Eksempel 2(365)
8-(N-cyklopropylmetyl-N-metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.18 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 8.7Hz, 1H), 7.06 (d, J = 2.7Hz, 1H),6.88 (dd, J = 8.7,2.7Hz, 1H), 5.35 (s, 2H),4.91 (s, 2H), 3.83 (s, 3H),3.71 (d, J = 6.9Hz, 2H), 3.27 (s, 3H),2.38 (s, 3H), 1.10 (m, lH),0.62-0.50 (m, 2H), 0.26-0.16 (m, 2H).
Eksempel 2(366)
8-(4-heptylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[dj-pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.55 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.80 (s, 1H), 6.83 (s, 2H), 6.27 (d, J = 11.1Hz, 1H), 3.98 (m, 1H), 3.80 (s, 3H), 3.11 (t, J = 7.5Hz, 2H), 2.91 (t, J = 7.8Hz, 2H), 2.22-2.04 (m, 2H), 2.13 (s, 6H), 1.76-1.30 (m, 8H), 0.96 (t, J = 7.2Hz, 6H).
Eksempel 2(367)
8-dipropylamino-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[dj-pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.54 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.86 (s, 1H), 6.69 (s, 2H), 3.80 (s, 3H), 3.64-3.46 (m, 4H), 2.98 (t, J = 7.2Hz, 2H), 2.92 (t, J = 7.5Hz, 2H), 2.22-2.00 (m, 2H), 2.12 (s, 6H), 1.68-1.48 (m, 4H), 0.89 (t, J = 7.5Hz, 6H).
Eksempel 2(368)
8-(N-cyklopropylmetyl-N-propylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.51 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.86 (s, 1H), 6.69 (s, 2H), 3.80 (s, 3H), 3.68-3.58 (m, 2H), 3.54 (d, J = 6.6Hz, 2H), 3.03 (t, J = 7.5Hz, 2H), 2.93 (t, J = 7.5Hz, 2H), 2.04-2.00 (m, 2H), 2.12 (s, 6H), 1.68-1.50 (m, 2H), 1.02 (m, 1H), 0.91 (t, J = 7.5Hz, 3H), 0.54-0.40 (m, 2H), 0.18-0.04 (m, 2H).
Eksempel 2(369)
8-(N-benzyl-N-cyklopropylmetylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.49 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.93 (s, 1H), 7.42-7.08 (m, 5H), 6.70 (s, 2H), 4.94 (s, 2H), 3.81 (s, 3H), 3.41 (d, J = 6.6Hz, 2H), 3.02 (t, J = 7.5Hz, 2H), 2.92 (t, J = 7.8Hz, 2H), 2.22-2.04 (m, 2H), 2.13 (s, 6H), 1.03 (m, 1H), 0.54-0.38 (m, 2H), 0.12-0.01 (m, 2H).
Eksempel 2(370) .
8-(N-cyklopropylmetyl-N-(4-metylfenylmetyl)amino)-3-(2, 6-dimetyl-4-
metoksyfenyl)-6J-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.53 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.92 (s, 1H), 7.21 (d, J = 8.1Hz, 2H), 7.11 (d, J = 8.1Hz, 2H), 6.70 (s, 2H), 4.89 (s, 2H), 3.81 (s, 3H), 3.40 (d, J = 6.9Hz, 2H), 3.02 (t, J = 7.2Hz, 2H), 2.92 (t, J = 7.5Hz, 2H), 2.32 (s, 3H), 2.22-2.04 (m, 2H), 2.13 (s, 6H), 1.03 (m, 1H), 0.54-0.40 (m, 2H), 0.10-0.01 (m, 2H).
Eksempel 2(371)
8-(N-propyl-N-(4-fluorfenylmetyl)amino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.46 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.92 (s, 1H), 7.36-7.18 (m, 2H), 7.06-6.88 (m, 2H), 6.70 (s, 2H), 4.80 (s, 2H), 3.81 (s, 3H), 3.46-3.32 (m, 2H), 3.00-2.80 (m, 4H), 2.22-2.00 (m, 2H), 2.13 (s, 6H), 1.70-1.48 (m, 2H), 0.88 (t, J = 7.2Hz, 3H).
Eksempel 2(372)
8-dicyklopropylmetylamino-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
OCH,
TLC: Rf 0.45 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 5 7.81 (s, 1H), 6.68 (s, 2H), 6.40 (d, J = 9.9Hz, 1H), 3.80 (s, 3H), 3.46 (m, 1H), 3.05 (t, J = 7.5Hz, 2H), 2.89 (t, I = 7.8Hz, 2H), 2.22-2.02 (m, 2H), 2.13 (s, 6H), 1.20-1.06 (m, 2H), 0.68-0.36 (m, 8H).
Eksempel 2(373)
8-(N-butyl-N-cyklopropylmetylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
OCH,
TLC: Rf 0.61 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.87 (s, 1H), 6.69 (s, 2H), 3.80 (s, 3H), 3.76-3.60 (m, 2H), 3.53 (d, J = 6.9Hz, 2H), 3.03 (t, J = 7.2Hz, 2H), 2.93 (t, J = 7.5Hz, 2H), 2.22-2.00 (m, 2H), 2.12 (s, 6H), 1.64-1.46 (m, 2H), 1.42-1.22 (m, 2H), 1.02 (m, 1H), 0.90 (t, J = 7.2Hz, 3H), 0.56-0.38 (m, 2H), 0.18-0.02 (m, 2H).
Eksempel 2(374)
8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cykIopenta[d]pyrazolo[l,5-a]pyrimidin
ego
<HsC>^^<s?\>^<CH3>
OCHj
TLC: Rf 0.51 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.92 (s, 1H), 7.38-7.26 (m, 2H), 7.06-6.94 (m, 2H), 6.71 (s, 2H), 4.89 (s, 2H), 3.81 (s, 3H), 3.39 (d, J = 6.6Hz, 2H), 3.02 (t, J = 7.2Hz, 2H), 2.93 (t, J = 7.2Hz, 2H), 2.22-2.00 (m, 2H), 2.13 (s, 6H), 1.01 (m, 1H), 0.54-0.40 (m, 2H), 0.10-0.01 (m, 2H).
Eksempel 3
8-(N-etyl-N-n-butylamino)-2-hydroksymetyl-3-(2-metyl-4-hydroksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Til en oppløsning av forbindelsen fremstilt i eksempel 2(1) (506 mg) i metylenklorid (14 ml) som var avkjølt til -78 °C, ble IM bortribromid i metylenklorid (12 ml) tilsalt. Blandingen ble omrørt i 30 minutter ved -78 °C og i 5 timer ved -30 °C. Reaksjonsblandingen ble helt inn i en mettet vandig oppløsning av natriumbikarbonat og den oppnådde oppløsning ble ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (n-heksan : etylacetat =1:1 —> 2 : 3) til å gi tittelforbindelsen (303 mg) med de etterfølgende fysiske data.
TLC: Rf 0.14 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 9.41 (brs, 1 H), 6.90 (d, J = 9.0Hz, 1 H), 6.42 (m, 2 H), 4.71 (brs, 2 H), 3.70 (q, J = 7.5Hz, 2 H), 3.64 (t, J = 7.5Hz, 2 H), 3.01 (t, J = 7.8Hz, 4 H), 2.39 (brs, 1 H), 2.18 (m, 2 H), 2.01 (s, 3 H), 1.58 (m, 2 H), 1.35 (m, 2 H), 1.21 (t, J = 7.5Hz, 3 H), 0.91 (t, J = 7.5Hz, 3 H).
Eksempel 4
8-(N-etyl-N-n-butylamino)-2-hydroksymetyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin
Til en oppløsning av forbindelsen fremstilt i eksempel 3 (985 mg) i metylenklorid (10 ml) som var avkjølt til 0 °C, ble natriumhydrid (95 mg, 63,1 % dispersjon i olje) tilsatt. Blandingen ble omrørt i 30 minutter. Metyljodid (0,18 ml) ble tilsatt til reaksjonsblandingen og den oppnådde blanding ble omrørt i 2 timer ved 0 °C. En mettet vandig oppløsning av ammoniumklorid ble tilsatt til reaksjonsblandingen og den oppnådde oppløsning ble ekstrahert med etylacetat. Det organiske laget ble vasket påfølgende med IM vandig oppløsning av natriumhydroksyd og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (toluen : etylacetat = 5 : 1 —> 4 : 1 —> 7 : 2) til å gi tittelforbindelsen (947 mg) med de etterfølgende fysiske data.
TLC: Rf 0.35 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 87.19 (d, J = 8.4Hz, 1 H), 6.85 (d, J = 2.7Hz, 1 H), 6.78 (dd, J = 8.4, 2.7Hz, 1 H), 4.73 (d, J = 5.7Hz, 2 H), 3.82 (s, 3 H), 3.65 (q, J = 7.2Hz, 2 H), 3.59 (t, J = 7.2Hz, 2 H), 2.98 (t, J = 6.9Hz, 2 H), 2.92 (t, J = 7.8Hz, 2 H), 2.35 (m, 1 H), 2.19 (s, 3 H), 2.15 (m, 2 H), 1.55 (m, 2 H), 1.35 (m, 2 H), 1.18 (t, J = 7.2Hz, 3 H), 0.90 (t, J = 7.2Hz, 3 H).
Eksempel 5
8-(N-propyl-N-(2-metoksyiminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Til en oppløsning av forbindelsen fremstilt i eksempel 2(2) (186 mg) i dimetylsul-foksyd (5 ml), ble trietylamin (0,39 ml) og svoveltrioksydpyridinkompleks (225 mg) tilsatt. Blandingen ble omrørt i 2 timer ved romtemperatur. Reaksjonsblandingen ble helt inn i vann og ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Til en oppløsning av resten i pyridin (5 ml), ble o-metylhydroksylaminhydroklorid (28 mg) tilsatt. Blandingen ble omrørt i 15 timer ved romtemperatur. Reaksjonsblandingen ble konsentrert og fortynnet med etylacetat. Den fortynnede oppløsning ble vasket påfølgende med en mettet vandig oppløsning av natriumbikarbonat og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (n-heksan : etylacetat = 4:1 —> 3 : 1) til å. gi tittelforbindelsen (16 mg) med de etterfølgende fysiske data.
TLC: Rf 0.78 (n-heksan : etylacetat =1:1);
NMR (300MHz, CDC13) :
Vesentlig isomer
8 7.57 (t, J = 5.7Hz, 1H), 7.15 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 8.4, 2.4Hz, 1H), 4.35 (d, J = 6.0Hz, 2H), 3.86 (s, 3H), 3.82 (s, 3H), 3.49 (t, J = 7.8Hz, 2H), 2.99 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.5Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.14 (m, 2H), 1.58 (m, 2H), 0.90 (t, J = 7.2Hz, 3H)
Mindre vesentlig isomer
8 7.15 (d, J = 8.4Hz, 1H), 6.95 (t, J = 3.9Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 8.4, 2.4Hz, 1H), 4.47 (d, J = 4.2Hz, 2H), 3.90 (s, 3H), 3.82 (s, 3H), 3.54 (t, J = 7.8Hz, 2H), 2.99 (t, J = 7.2Hz, 2H), 2.91 (t, J = 7.5Hz, 2H), 2.32 (s, 3H), 2.18 (s, 3H), 2.14 (m, 2H), 1.58 (m, 2H), 0.92 (t, J = 7.2Hz, 3H).
Eksempel 5(l)-5(2)
De etterfølgende forbindelser ble oppnådd ved hjelp av den samme prosedyre som reaksjonen i eksempel 5 ved anvendelse av forbindelsen fremstilt i eksempel 2(26), eller forbindelsen fremstilt i eksempel 4 og hydroksylaminhydroklorid i stedet for o-metylhydroksylaminhydroklorid.
Eksempel 5(1)
8-(N-propyl-N-(2-metoksyiminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-ajpyrimidinhydroklorid
TLC: Rf 0.22 (n-heksan : etylacetat = 3:1);
NMR (300MHz, pyridin-d5 0,5 ml + CDC13 0,1 ml) :
Vesentlig isomer
5 7.87 (t, J = 5.4Hz, 1H), 7.38 (d, J = 8.4Hz, 1H), 7.03 (d, J = 2.7Hz, 1H), 6.95 (dd, J = 8.4, 2.7Hz, 1H), 5.27 (s, 2H), 4.97 (s, 2H), 4.59 (d, J = 5.4Hz, 2H), 3.86 (s, 3H), 3.74 (s, 3H), 3.38 (t, J = 7.5Hz, 2H), 2.44 (s, 3H), 2.31 (s, 3H), 1.65-1.50 (m, 2H), 0.81 (t, J = 7.5Hz,3H).
Mindre vesentlig isomer
8 7.38 (d, J = 8.4Hz, 1H), 7.31 (t, J = 4.2Hz, 1H), 7.03 (d, J = 2.7Hz, 1H), 6.95 (dd, J = 8.4, 2.7Hz, 1H), 5.25 (s, 2H), 4.95 (s, 2H), 4.71 (d, J = 4.2Hz, 2H), 3.92 (s, 3H), 3.74 (s, 3H), 3.43 (t, J = 7.2Hz, 2H), 2.43 (s, 3H), 2.31 (s, 3H), 1.65-1.50 (m, 2H), 0.84 (t, J = 7.2Hz, 3H). Eksempel 5(2) 8-(N-etyl-N-n-butylamino)-2-hydroksyiminometyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.19 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 8.15 (s, 1H), 7.96 (brs, 1H), 7.18 (d, J = 8.1Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.1, 2.7Hz, 1H), 3.82 (s, 3H), 3.67 (q, J = 7.2Hz, 2H), 3.61 (t, J = 7.5Hz, 2H), 2.99 (t, J = 7.2Hz, 2H), 2.92 (t, J = 7.8Hz, 2H), 2.18 (s, 3H), 2.16 (m, 2H), 1.55 (m, 2H), 1.33 (m, 2H), 1.18 (t, J = 7.2Hz, 3H), 0.89 (t, J = 7.5Hz, 3H).
Eksempel 6
8-[(2S)-l-hydroksyiminobutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Til en oppløsning av forbindelsen fremstilt i eksempel 2(15) (290 mg) i eddiksyre (4 ml), ble IM saltsyre (1,4 ml) tilsatt og blandingen ble omrørt i 1 time ved 80 °C. Reaksjonsblandingen ble helt inn i en mettet vandig oppløsning av natriumbikarbonat (100 ml) under avkjøling på et isbad, og den oppnådde blanding ble ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Hydroksylaminhydroklorid (52 mg) ble tilsatt til en oppløsning av resten i pyridin (3 ml), og blandingen ble omrørt i 15 timer ved romtemperatur. Reaksjonsblandingen ble konsentrert, og fortynnet med etylacetat. Den fortynnede oppløsningen ble vasket påfølgende med en mettet vandig oppløsning av natriumbikarbonat og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (n-heksan : etylacetat =1 : 1) til å gi tittelforbindelsen (143 mg) med de etterfølgende fysiske data som isomeriske blandinger.
TLC: Rf 0.32 (n-heksan : etylacetat = 1:1);
NMR (300MHz, CDC13):
Vesentlig isomer
8 7.80 (brs, 1 H), 7.47 (d, J = 6.0Hz, 1 H), 7.14 (d, J = 8.4Hz, 1 H), 6.84 (d, J = 2.7Hz, 1 H), 6.78 (dd, J = 8.4, 2.7Hz, 1 H), 6.53 (d, J = 9.6Hz, 1 H), 4.60 (m, 1 H), 3.82 (s, 3 H), 3.25-3.00 (m, 2 H), 2.88 (t, J = 7.5Hz, 2 H), 2.31 (s, 3 H), 2.17 (s, 3 H), 2.10 (m, 2 H), 1.90 (m, 2 H), 1.11 (t, J = 7.2Hz, 3 H)
Mindre vesentlig isomer
8 8.52 (brs, 1 H), 7.14 (d, J = 8.4Hz, 1 H), 6.84 (d, J = 2.7Hz, 1 H), 6.80 (m, 1 H), 6.78 (dd, J = 8.4, 2.7Hz, 1 H), 6.44 (d, J = 9.6Hz, 1 H), 5.23 (m, 1 H), 3.82 (s, 3 H), 3.25-3.00 (m, 2 H), 2.88 (t, J = 7.5Hz, 2 H), 2.31 (s, 3 H), 2.17 (s, 3 H), 2.10 (m, 2 H), 1.90 (m, 2 H), 1.11 (t, J = 7.2Hz, 3 H). Eksempel 6(1) 8-[(2S)-l -metoksy iminobutan-2-y 1] amino-2-metyl-3 -(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin
Tittelforbindelsen (128 mg) med de etterfølgende fysiske data ble oppnådd ved hjelp av den samme prosedyre som reaksjonen i eksempel 5, ved anvendelse av forbindelsen fremstilt i eksempel 2(14) (365 mg) og o-metylhydroksylaminhydroklorid i stedet for hydroksylaminhydroklorid.
TLC: Rf 0.20 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13):
Vesentlig isomer
5 7.36 (d, J = 6.0Hz, 1H), 7.14 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.4, 2.7Hz, 1H), 6.60 (d, J = 9.9Hz, 1H), 5.47 (d, J = 10.5Hz, 1H), 5.31 (d, J = 10.5Hz, 1H), 4.89 (s, 2H), 4.07 (m, 1H), 3.86 (s, 3H), 3.82 (s, 3H), 2.33 (s, 3H), 2.16 (s, 3H), 1.96-1.87 (m, 2H), 1.10 (t, J = 7.5Hz, 3H).
Mindre vesentlig isomer
5 7.14 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.4, 2.7Hz, 1H), 6.76 (m, 1H), 6.53 (d, J = 9.9Hz, 1H), 5.30 (m, 2H), 4.89 (s, 2H), 4.72 (m, 1H), 3.96 (s, 3H), 3.82 (s, 3H), 2.33 (s, 3H), 2.16 (s, 3H), 1.96-1.87 (m, 2H), 1.10 (t, J = 7.5Hz, 3H). Eksempel 7 8- [(1S)-1 -cy anopropylamino]-2-metyl-3 -(2-metyl-4-metoksyfeny l)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-ajpyrimidin
Til en oppløsning av forbindelsen fremstilt i eksempel 6 (137 mg) i metylenklorid (1 ■ ml) som var avkjølt til -78 °C, ble trietylamin (0,32 ml) og trifluormetansulfonsyre-anhydrid (0,13 ml) tilsatt. Blandingen ble omrørt i 2 timer ved romtemperatur. En mettet vandig oppløsning av natriumbikarbonat ble tilsatt til reaksjonsblandingen og den oppnådde oppløsning ble ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (n-heksan : etylacetat = 3:1 —>■ 2 : 1) til å gi tittelforbindelsen (100 mg) med de etterfølgende fysiske data.
TLC: Rf 0.27 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 6 7.15 (d, J = 8.1Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.79 (dd, J = 8.1, 2.7Hz, 1H), 6.50 (d, J = 9.6Hz, 1H), 4.78 (m, 1H), 3.82 (s, 3H), 3.33 (ddd, J = 14.4, 7.5, 6.3Hz, 1H), 3.11 (ddd, J = 14.4, 8.1, 6.3Hz, 1H), 2.93 (m, 2H), 2.31 (s, 3H), 2.25-2.10 (m, 7H), 1.29 (t, J = 7.5Hz, 3H).
Eksempel 7(1)
8-(N-etyl-N-n-butylamino)-2-cyano-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
Tittelforbindelsen (195 mg) med de etterfølgende fysiske data ble oppnådd ved hjelp av den samme prosedyre som reaksjonen i eksempel 7 ved anvendelse av forbindelsen fremstilt i eksempel 5(2) (211 mg).
TLC: Rf 0.34 (n-heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.28 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 3.65 (q, J = 6.9Hz, 2H), 3.58 (t, J = 7.5Hz, 2H), 3.00 (t, J = 7.2Hz, 2H), 2.96 (t, J = 7.8Hz, 2H), 2.29 (s, 3H), 2.18 (m, 2H), 1.57 (m, 2H), 1.33 (m, 2H), 1.20 (t, J = 6.9Hz, 3H), 0.91 (t, J = 7.2Hz, 3H).
Eksempel 8
9-(3-pentylamino)-6-me1yl-5-(2-metyl-4-metoksyfenyl)-furo[3,2-d]pyrazolo[l,5-a] pyrimidin
Til en oppløsning av forbindelsen fremstilt i eksempel 2(6) (215 mg) i difenyleter (3 ml), ble 10% palladium-karbon (150 mg) tilsatt og blandingen ble omrørt i 4 timer ved 250 °C. Etter at reaksjonsblandingen var avkjølt til romtemperatur ble den fortynnet med metanol (10 ml). Den fortynnede oppløsning ble filtrert gjennom celite (handelsnavn). Filtratet ble konsentrert og resten ble renset ved kolonnekromatografi på silikagel (n-heksan : aceton = 9 : 1) til å gi tittelforbindelsen (150 mg) med de etterfølgende fysiske data.
TLC: Rf 0.42 (n-heksan : etylacetat = 2:1);
NMR (300MHz, CDC13) : 8 7.76 (d, J = 2.4Hz, 1H), 7.20 (d, J = 8.1Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.1,2.7Hz, 1H), 6.78 (d, J = 2.4Hz, 1H), 6.28 (brd, J = 10.2Hz, 1H), 4.30 (m, 1H), 3.83 (s, 3H), 2.37 (s, 3H), 2.21 (s, 3H), 1.92-1.65 (m, 4H), 1.05 (m, 6H).
Eksempel 9
8-(3-pentyloksy)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta [d]pyrazolo[ 1,5-ajpyrimidin
3-pentanol (202 mg) ble dryppet inn i en oppløsning av natriumhydrid (92,0 mg, 60% i olje) i toluen, og blandingen ble omrørt i 2 minutter ved 80 °C. Forbindelsen fremstilt i referanseeksempel 7 (250 mg) ble tilsatt til denne blanding og den oppnådde blanding ble omrørt i 5 timer. Vann og etylacetat ble tilsatt til reaksjonsblandingen og omrørt. Det organiske laget ble separert. Imens ble vannlaget ekstrahert med etylacetat. Et kombinert organisk lag ble vasket med en mettet
vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 5 : 1) til å gi tittelforbindelsen (128 mg) med de etterfølgende fysiske data.
TLC: Rf 0.58 (toluen : aceton = 5:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 8.4, 2.4Hz, 1H), 5.05 (kvintett, J = 6.0Hz, 1H), 3.82 (s, 3H), 3.05 (t, J = 7.5Hz, 2H), 2.94 (t, J = 7.5Hz, 2H), 2.34 (s, 3H), 2.22 - 2.10 (m, 2H ), 2.16 (s, 3H), 1.92 - 1.78 (m, 4H), 1.05 (t, J = 7.5Hz, 6H).
Eksempel 9(1) - 9(5)
De etterfølgende forbindelser ble oppnådd ved den samme prosedyre som reaksjonen i eksempel 9 ved anvendelse av en tilsvarende forbindelse.
Eksempel 9(1)
8-(3-pentyloksy)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta-[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.50 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 8.4, 2.4Hz, 1H), 5.06 (kvintett, J = 6.0Hz, 1H), 3.83 (s, 3H), 3.05 (t, J = 7.2Hz, 2H), 2.95 (t, J = 7.2Hz, 2H), 2.38 (s, 3H), 2.1 6 (kvintett, J = 7.2Hz, 2H), 1.94 - 1.74 (m, 4H), 1.04 (t, J = 7.5Hz, 6H).
Eksempel 9(2)
8-(3-pentyloksy)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dmydro-furo[3,4-d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.25 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 5 7.28 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.7Hz, 1H), 6.90 (dd, J = 8.4, 2.7Hz, 1H), 5.29 (s, 2H), 4.93 (s, 2H), 4.56 (m, 1H), 3.84 (s, 3H), 2.41 (s, 3H), 1.99 - 1.80 (m, 4H), 1.05 (t, J = 7.5Hz, 6H).
Eksempel 9(3)
8-(4-heptyloksy)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolofl ,5-a]pyrimidin
TLC: Rf 0.85 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.29 (d, J = 8.7Hz, 1H), 7.06 (d, J = 2.7Hz, 1H), 6.89 (dd, J = 8.7, 2.7Hz, 1H), 5.22 (kvintett, J = 6.0Hz, 1H), 3.83 (s, 3H), 3.05 (t, J = 7.5Hz, 2H), 2.95 (t, J = 7.5Hz, 2H), 2.37 (s, 3H), 2. 16 (kvintett, J = 7.5Hz, 2H), 1.90 - 1.66 (m, 4H), 1.58 - 1.42 (m, 4H), 0.95 (t, J = 7.2Hz, 6H).
Eksempel 9(4)
8-isopropyloksy-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.36 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 5 7.29 (d, J = 8.4Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 8.4, 2.4Hz, 1H), 5.43 (sept, J = 6.3Hz, 1H), 3.83 (s, 3H), 3.06 (t, J = 7.5Hz, 2H), 2.96 (t, J = 7.5Hz, 2H), 2.38 (s, 3H), 2.16 (kvintett, J = 7.5Hz, 2H), 1.51 (d, J = 6.3Hz, 6H).
Eksempel 9(5)
8-(l, 6-heptadien-4-yl)oksy-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.58 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.29(d, J = 8.4Hz, 1H), 7.06 (d, J =2.7Hz, 1H), 6.89 (dd, J = 8.4, 2.7Hz, 1H), 5.90 (ddt, J = 17.1,10.2, 6.9Hz, 2H), 5.34 (kvintett, J = 6.3Hz, 1H), 5.17 (m, 2H), 5.11 (dd, m, 2H), 3.83 (s, 3H), 3.01 (t, J = 7.5Hz, 2H), 2.95 (t, J = 7.5Hz, 2H), 2.70 - 2.50 (m, 4H), 2.38 (s, 3H), 2.15 (kvintett, J = 7.5Hz, 2H).
Eksempel 10
8-(3-pentyltio)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]-pyrazolof 1,5-a]pyrimidinhydroklorid
3-acetyltiopentan (252 mg) og forbindelsen fremstilt i referanseeksempel 7 (300 mg) ble tilsatt til en oppløsning av natriumhydrid (68,9 mg, 60% i olje) i etanol (17 ml) ved 0 °C. Etter at blandingen var omrørt i 1 time ble reaksjonsblandingen konsentrert. Vann og etylacetat ble tilsatt til resten og omrørt. Det organiske laget
ble separert. Imens ble vannlaget ekstrahert med etylacetat. Et kombinert organisk lag ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på
silikagel (heksan : etylacetat = 5:1). 4N saltsyre - etylacetat (0,2 ml) ble tilsatt til den rensede substans og oppløsningen ble omrørt i 10 minutter og konsentrert til å gi tittelforbindelsen (271,1 mg) med de etterfølgende fysiske data.
TLC: Rf 0.57 (heksan : etylacetat = 2 : 1);
NMR (300MHz, CDC13): 5 7.29 (d, J = 8.7Hz, 1H), 7.07 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 8.7, 2.4Hz, 1H), 4.27 (kvintett, J = 6.3Hz, 1H), 3.84 (s, 3H), 3.05 (t, J = 7.5Hz, 2H), 3.00 (t, J = 7..5Hz, 2H), 2.40 (s, 3H), 2 .17 (kvintett, J = 7.5Hz, 2H), 1.72 - 1.64 (m, 4H), 1.02 (t, J = 7.5Hz, 6H).
Eksempel 11
8-(4-metylfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Til forbindelsen fremstilt i referanseeksempel 7 (300 mg) i dimetoksyetan (3 ml), ble 4-metylfenylborsyre (131 mg), palladiumacetat (11 mg), trifenylfosfin (48 mg) og en mettet vandig oppløsning av natriumkarbonat (2 ml) tilsatt og blandingen ble oppvarmet med tilbakeløp i 5 timer. Etter at reaksjonsblandingen var avkjølt ble den fortynnet med etylacetat. Den fortynnede oppløsning ble vasket med en mettet vandig oppløsning av natriumklorid og vann, tørket over vannfritt magnesiumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 5 : 1) til å gi tittelforbindelsen (222 mg) med de etterfølgende fysiske data.
TLC: Rf 0.41 (heksan : etylacetat = 3 : 1);
NMR (300MHz, CDC13): 8 7.72 (d, J = 8.1Hz, 2H), 7.36 (d, J = 8.1Hz, 2H), 7.19 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 2.7, 8.4Hz, 1H), 3.84 (s, 3H), 3.01 (t, J = 7.5Hz, 2H), 2.94 (t, J = 6.6Hz, 2H), 2. 45 (s, 3H), 2.30 (s, 3H), 2.20 (s, 3H), 2.14 (m, 2H).
Eksempel 11(1)- 11(5)
De etterfølende forbindelser ble oppnådd ved hjelp av den samme prosedyre som reaksjonen i eksempel 11 ved å anvende en tilsvarende forbindelse.
Eksempel 11(1)
8-(2, 4-diklorfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidinhydroklorid
Cl
fy
(I JL/~CHj
OCH,
TLC: Rf TLC: Rf 0.38 (heksan : etylacetat = 3:1);
NMR (300MHz, DMSO-d6): 8 7.91 (d, J = 1.8Hz, 1H), 7.70 (d, J = 8.4Hz, 1H), 7.64 (dd, J = 1.8, 8.4Hz, 1H), 7.11 (br d, J = 8.1Hz, 1H), 6.90 (d, J = 2.7Hz, 1H), 6.81 (dd, J =2.7, 8.4Hz, 1H), 3.77 (s, 3H), 2.94 (m, 2H), 2.68 (m, 2H), 2.14 (s, 3H), 2.12 (m, 2H), 2.09 (s, 3H).
Eksempel 11(2)
8-(3-trifluormetylfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.27 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 8.08 (brs, 1 H), 8.06 (brd, J = 8.1Hz, 1 H), 7.79 (brd, J = 7.8Hz, 1 H), 7.70 (brdd, J = 8.1, 7.8Hz, 1 H), 7.19 (d, J = 8.1Hz, 1 H), 6.89 (d, J = 2.7Hz, 1 H), 6.82 (dd, J = 8.1, 2.7Hz, 1 H), 3.84 (s, 3 H), 3.04 (t, J = 7.5Hz, 2 H), 2.94 (t, J = 7.5Hz, 2 H), 2.31 (s, 3 H), 2.20 (s, 3 H), 2.18 (m, 2 H).
Eksempel 11(3)
8-(4-metoksyfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidinhydroklorid
TLC: Rf 0.23 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.92 (d, J = 9.0Hz, 2 H), 7.16 (d, J = 9.0Hz, 2 H), 7.16 (d, J = 9.0Hz, 1 H), 6.92 (d, J = 2.7Hz, 1 H), 6.86 (dd, J = 9.0,2.7Hz, 1 H), 3.95 (s, 3 H), 3.85 (s, 3 H), 3.61 (t, J = 7.5Hz, 2 H), 3.09 (t, J = 7.5Hz, 2 H), 2.38 (s, 3 H), 2.30 (m, 2 H), 2.20 (s, 3 H).
Eksempel 11(4)
8-(3, 5-diklorfenyl)-2-metyi-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5 -ajpyrimidin
TLC: Rf 0.50 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.69 (d, J = 1.8Hz, 2H), 7.52 (t, J = 1.8Hz, 1H), 7.17 (d, J = 8.4Hz, 1H), 6.88 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.4Hz, 1H), 3.84 (s, 3H), 3.02 (t, J = 7.5Hz, 2H), 2.93 (t, J = 6.9Hz, 2H), 2. 32 (s, 3H), 2.19 (s, 3H), 2.17 (m, 2H).
Eksempel 11(5)
8-(2-metylfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.38 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.34 - 7.48 (m, 4H), 7.20 (m, 1H), 6.89 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 2.7, 8.1Hz, 1H), 3.84 (s, 3H), 3.04 (m, 2H), 2.81 (m, 1H), 2.62 (m, 1H), 2.27 (s, 3H), 2.20 (m, 3H), 2.17 (s, 3H), 2.15 (m, 2H).
Eksempel 12
8-bis(etoksykarbonyl)metyl-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-alpyrimidin
Dietylmalonat (880 mg) ble tilsatt til en suspensjon av natriumhydrid (210 mg, 63,1% i olje) i tetrahydrofuran (10 ml) og blandingen ble omrørt i 30 minutter ved romtemperatur. Forbindelsen fremstilt i referanseeksempel 7 (820 mg) ble tilsatt til reaksjonsblandingen og den oppnådde blanding ble oppvarmet med tilbakeløp i 4 timer. En mettet vandig oppløsning av ammoniumklorid (10 ml) ble tilsatt til reaksjonsblandingen og den ble ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 8 : 1 -> 7 : 1) til å gi tittelforbindelsen (1,10 g) med de etterfølgende fysiske data.
TLC: Rf 0.48 (heksan : etylacetat = 2:1);
NMR (300MHz, CDC13): 8 7.15 (d, J = 8.1Hz, 1 H), 6.87 (d, J = 3.0Hz, 1 H), 6.80 (dd, J = 8.1, 3.0Hz, 1 H), 6.02 (s, 1 H), 4.32 (m, 4 H), 3.82 (s, 3 H), 2.96 (t, J = 7.8Hz, 2 H), 2.91 (t, J = 7.8Hz, 2 H), 2.32 (s, 3 H), 2.21 - 2.09 (m, 2 H), 2.17 (s, 3 H), 1.32 (t, J = 7.2Hz,6H).
Eksempel 12(1) - 12(4)
De etterfølgende forbindelser ble oppnådd ved hjelp av den samme prosedyre som reaksjonen i eksempel 12 ved å anvende en tilsvarende forbindelse.
Eksempel 12(1)
8-(l-dimetylamino-l, 3-diokso-2-butyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
TLC: Rf 0.55 (etylacetat);
NMR (300MHz, CDC13): 8 7.14 (d, J = 8.1Hz, 1H), 6.87 (d, J = 1.8Hz, 1H), 6.83 - 6.74 (m, 1H), 6.29 (s, 1H), 3.83 (s, 3H), 3.05 (s, 3H), 3.05 - 2.60 (m, 6H), 2.41 (s, 3H), 2.30 (s, 3H), 2.16 (brs, 6H).
Eksempel 12(2)
8-(2, 4-diokso-3-pentyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin
TLC: Rf 0.34 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 16.93 (s, 1H), 7.19 (d, J = 8.4Hz, 1H), 6.89 (d, J = 3.0Hz, 1H), 6.83 (dd, J = 8.4, 3.0Hz, 1H), 3.84 (s, 3H), 3.04 (t, J = 7.2Hz, 2H), 2.81 (t, J = 7.2Hz, 2H), 2,33 (s, 3H), 2.20 (kvintett, J = 7 .2Hz, 2H), 2.18 (s, 3H), 1.95 (s, 6H).
Eksempel 12(3)
8-bis(etoksykarbonyl)metyl-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.18 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.28 (d, J = 8.4Hz, 1H), 7.07 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 8.4, 2.4Hz, 1H), 6.02 (s, 1H), 4.40 - 4.20 (m, 4H), 3.84 (s, 3H), 2.98 (t, J = 7.5Hz, 2H), 2.92 (t, J = 7.5Hz, 2H), 2.35 (s, 3H), 2.17 (kvintett, J = 7.5Hz, 2H), 1.31 (t, J = 7.2Hz, 6H).
Eksempel 12(4)
8-bis(etoksykarbonyl)metyl-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin
TLC: Rf 0.28 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.28 (d, J = 8.4Hz, 1H), 7.08 (d, J = 2.4Hz, 1H), 6.91 (dd, J = 8.4,2.4Hz, 1H), 6.12 (s, 1H), 5.11 (s, 2H), 4.95 (s, 2H), 4.41 - 4.20 (m, 4H), 3.84 (s, 3H), 2.39 (s, 3H), 1.33 (t, J = 7.2Hz, 6H ).
Eksempel 13
8-(l,3-hydroksy-2-propyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Under en argonatmosfære ble IM diisopropylaluminiumhydrid (3,94 ml, i heksan) dryppet inn i en oppløsning av forbindelsen fremstilt i eksempel 12 (355 mg) i vannfri dietyleter (7 ml) ved -78 °C. Blandingen ble oppvarmet ved 0 °C og omrørt i 4,5 timer. Metanol ble dryppet inn i blandingen og den ble deretter oppvarmet ved romtemperatur. IN saltsyre ble tilsatt til reaksjonsblandingen og blandingen ble ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløs-ning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat =3 : 1) til å gi tittelforbindelsen (260 mg) med de etterfølgende fysiske data.
TLC: Rf 0.50 (kloroform : metanol = 9:1);
NMR (300MHz, CDC13): 8 7.13 (brd, J = 8.7Hz, 1H), 6.87 (s, 1H), 6.80 (brd, J = 8.7Hz, 1H), 4.97 (m, 1H), 4.90 (m, 1H), 4.24 (m, 2H), 4.13 (m, 2H), 3.83 (s, 3H), 3.59 (m, 1H), 2.98 (brt, J = 7.2Hz, 4H), 2.31 (s, 3H), 2.28-2.00 (m, 5H).
Eksempel 14
8-( 1,3 -dimetoksy-2-propyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin
En oppløsning av forbindelsen fremstilt i eksempel 13 (120 mg) i DMF (2 ml) ble dryppet inn i en oppløsning av natriumhydrid (26,0 mg, 60% i olje) i DMF ved 0 °C. Metyljodid (81,0 ul) ble dryppet inn i blandingen og blandingen ble omrørt i 1 time. Vann og etylacetat ble tilsatt til reaksjonsblandingen og det organiske laget ble separert. Vannlaget ble ekstrahert med etylacetat. Et kombinert organisk lag ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert etter at benzen (5 ml) var tilsatt. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat =3 : 1) til å gi tittelforbindelsen (58,7 mg) med de etterfølgende fysiske data.
TLC: Rf 0.80 (etylacetat);
NMR (300MHz, CDC13) : 8 7.15 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.4Hz, 1H), 6.79 (dd, J = 8.4,2.4Hz, 1H), 4.28 - 4.16 (m, 1H), 4.14 - 4.06 (m, 2H), 3.96 - 3.86 (m, 2H), 3.83 (s, 3H), 3.35 (s, 6H), 3.06 (t, J = 7.5Hz, 2H), 2 .94 (t, J = 7.5Hz, 2H), 2.31 (s, 3H), 2.17 (s, 3H), 2.17 - 2.08 (m, 2H).
Eksempel 15
8-(N, N-dimetylkarbamoylmetyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin
Til en oppløsning av forbindelsen fremstilt i eksempel 12 (410 mg) i metanol (1 ml), ble en 50 % vandig dimetylaminooppløsning (491 mg) tilsatt ved 24 °C og blandingen ble omrørt i 20 timer ved 90 °C. Reaksjonsblandingen ble avkjølt til romtemperatur og vann og etylacetat ble tilsatt til blandingen og omrørt. Det organiske laget ble separert. I tillegg ble vannlaget ekstrahert med etylacetat. Det kombinerte organiske lag ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt natriumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 5 : 1) til å gi tittelforbindelsen (102,7 mg) med de etterfølgende fysiske data.
TLC: Rf 0.55 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 8 7.16 (d, J = 8.4Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 3.27 (d, J = 1.2Hz, 1H), 3.04 - 2.94 (m, 5H), 2.72 (s, 3H), 2.36 (s, 3H), 2.24 - 2.10 (m, 8H).
Referanseeksempel 8
2-klor-4-metoksybenzaldehyd
Til en suspensjon av natriumhydrid (2,6 g, 62,6% i olje) i dimetylformamid (80 ml), ble en oppløsning av 2-klor-4-hydroksybenzaldehyd (10,0 g) i dimetylformamid (50 ml) inndryppet i løpet av 15 minutter. Blandingen ble omrørt i 30 minutter. Metyljodid (4,2 ml) ble dryppet inn i reaksjonsblandingen i løpet av 10 minutter ved 0 °C og blandingen ble omrørt i 1 time. Reaksjonsblandingen ble helt inn i vann og ekstrahert med heksan/etylacetat (1 : 1). Det organiske laget ble vasket med vann og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert til å gi tittelforbindelsen (10,7 g) med de etterfølgende fysiske data.
TLC: Rf 0.61 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 10.33 (d, J = 0.6Hz, 1H), 7.90 (d, J = 9.0Hz, 1H), 6.94 (d, J = 2.4Hz, 1H), 6.89 (ddd, J = 9.0, 2.4, 0.6Hz, 1H), 3.89 (s, 3H).
Referanseeksempel 9
1 -(2, 2-dibrometenyl)-2-klor-4-metoksybenzen
Cl
<Br>vorH
OCHj
Karbontetrabromid (10,7 g) ble tilsatt til en oppløsning av forbindelsen fremstilt i referanseeksempel 8 (5,0 g) i metylenklorid. Trifenylfosfin (16,9 g) ble tilsatt i porsjoner til blandingen som ble holdt ved en innvendig temperatur på 5 grader eller lavere. Blandingen ble omrørt i 30 minutter ved 0 °C. En suspensjon av reaksjonsblandingen i heksan (500 ml) ble helt inn i silikagel (30 g) og deretter filtrert. Silikagelen ble vasket med heksan/etylacetat (10:1). Filtratet og vaskeløsningene ble kombinert og konsentert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 10 : 1) til å gi tittelforbindelsen (6,6 g) med de etterfølgende fysiske data.
TLC: Rf 0.82 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.62 (d, J = 9.0Hz, 1H), 7.51 (s, 1H), 6.94 (d, J = 2.1Hz, 1H), 6.83 (dd, J = 9.0, 2.1Hz, 1H), 3.81 (s, 3H).
Referanseeksempel 10
1 -(1 -propynyl)-2-klor-5-metoksybenzen
Til en oppløsning av forbindelsen fremstilt i referanseeksempel 9 (1,98 g) i tetrahydrofuran (20 ml), ble en 1,57M oppløsning av n-butyllitium i heksan (8,2 ml) tilsatt ved -78 °C. Blandingen ble omrørt i 30 minutter og 1 time ved 0 °C. Reaksjonsblandingen ble avkjølt til -78 °C, og metyljodid (0,46 ml) ble tilsatt og blandingen ble omrørt i 1 time ved 0 °C. Reaksjonsblandingen ble helt inn i vann og ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 10 : 1) til å gi tittelforbindelsen (0,89 g) med de etterfølgende fysiske data.
TLC: Rf 0.69 (heksan : etylacetat =5:1);
NMR (300MHz, CDC13): 8 7.34 (d, J = 8.7Hz, 1H), 6.91 (d, J = 2.7Hz, 1H), 6.73 (d, J = 8.7Hz, 2.7Hz, 1H), 3.79 (s, 3H), 2.10 (s, 3H).
Referanseeksempel 11
5-bis(trimetylsilyl)amino-2-cyano-3-metyl-4-(2-klor-4-metoksyfenyl)pyrrol
Under en argonatmosfære ble diisobutylaluminumhydrid (13,8 ml) sakte tilsatt til nikkelklorid (832 g), som var tørket med oppvarming i 30 minutter, og deretter ble blandingen omrørt i 15 minutter. Etter at en farge på blandingen var forandret til sort, ble forbindelsen fremstilt i referanseeksempel 10 (11,6 g) i trimetylsilylcyanid (46 ml) tilsatt i løpet av 25 minutter til reaksjonsblandingen. Blandingen ble oppvarmet og heksan ble avdestillert. Oppløsningen ble omrørt i 2,5 timer ved 130 °C. Reaksjonsblandingen ble avkjølt ved romtemperatur og fortynnet med metylenklorid. Den fortynnede oppløsning ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 10 : 1) til å gi tittelforbindelsen (9,5 g) med de etterfølgende fysiske data og 2-bis(trimetylsilyl)amino-5-cyano-3-metyl-4-(2-klor-4-metoksy-fenyl)pyrrol (5,2 g) som biprodukt.
TLC: Rf 0.34 (heksan : etylacetat = 10 : 1);
NMR (300MHz, CDC13): 8 7.76 (brs, 1H), 7.10 (d, J = 8.4Hz, 1H), 7.00 (d, J = 2.7Hz, 1H), 6.82 (dd, J = 8.4, 2.7Hz, 1H), 3.83 (s, 3H), 2.06 (s, 3H), 0.14 (s, 9H), - 0.14 (s, 9H).
Referanseeksempel 12
5 -amino-2-cy ano-3 -mety l-4-(2-klor-4-metoksy fenyl)pyrrol
Til en oppløsning av forbindelsen fremstilt i referanseeksempel 11 (6,27 g) i metanol (50 ml), ble en IN vandig oppløsning av natriumhydroksyd (15,4 ml) tilsatt ved romtemperatur. Blandingen ble oppvarmet med tilbakeløp i 1,5 timer. Etterat reaksjonsblandingen var avkjølt til romtemperatur ble blandingen helt inn i en vandig oppløsning av natriumkarbonat, og ekstrahert med etylacetat. Det organiske laget ble vasket med en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert til å gi tittelforbindelsen (4,78 g) med de etterfølgende fysiske data.
TLC: Rf 0.20 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 6 8.61 (brs, 1H), 7.14 (d, J = 8.7Hz, 1H), 7.03 (d, J = 2.4Hz, 1H), 6.86 (dd, J = 8.7,2.4Hz, 1H), 3.83 (s, 3H), 3.71 (brs, 2H), 2.04 (s, 3H).
Eksempel 16
l-cyano-2-metyl-8-hydroksy-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklo-penta[djpyrazolo[ 1,2-ajpyrimidin
Tittelforbindelsen (1,35 g) ble oppnådd ved den samme prosedyre som reaksjonen i eksempel 1, ved å anvende forbindelsen fremstilt i referanseeksempel 12 (4,15 g). TLC: Rf 0.15 (heksan : etylacetat = 1:1);
NMR (300MHz, DMSO-d6) : 812.25 (brs, 1H), 7.31 (d, J = 7.8Hz, 1H), 7.20 (d, J = 2.7Hz, 1H), 7.02 (dd, J = 7.8,2.7Hz, 1H), 3.83 (s, 3H), 2.83 (m, 2H), 2.66 (m, 2H), 2.06 (s, 3H), 2.03 (m, 2H).
Eksempel 17
l-cyano-2-metyl-8-(3-pentylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,2-a]pyrimidin
Tittelforbindelsen (112 mg) ble oppnådd ved hjelp av den samme prosedyre som reaksjonen i eksempel 2 ved å anvende l-cyano-2-metyl-8-klor-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrrolo[l,2-ajpyrimidin (180 mg) som ble fremstilt ved den samme prosedyre som reaksjonen i referanseeksempel 7 ved å anvende forbindelsen fremstilt i referanseeksempel 16.
TLC: Rf 0.36 (toluen : etylacetat = 9:1);
NMR (300MHz, CDC13): 5 7.25 (d, J = 8.4Hz, 1H), 7.05 (d, J = 2.4Hz, 1H), 6.88 (dd, J = 8.4, 2.4Hz, 1H), 5.94 (d, J = 9.0Hz, 1H), 3.83 (s, 3H), 3.82 (m, 1H), 3.04 (m, 2H), 2.87 (m, 2H), 2.29 (s, 3H), 2.11 (m, 2H), 1.82-1.60 (m, 4H), 1.04 (t, J = 7.5Hz, 3H), 1.03 (t, J = 7.5Hz, 3H).
Eksempel 17(1)
l-cyano-2-metyl-8-dipropylamino-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,2-a]pyrimidin
Tittelforbindelsen med de etterfølgende fysiske data ble oppnådd med den samme prosedyre som en serie av reaksjoner slik som Referanseeksempel 8 - > Referanseeksempel 9 -> Referanseeksempel 10 —> Referanseeksempel 11 ->■ Referanseeksempel 12 -> Eksempel 16 -> Eksempel 17, ved å anvende en tilsvarende forbindelse.
TLC: Rf 0.39 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.26 (d, J = 8.1Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 6.89 (dd, J = 8.1, 2.4Hz, 1H), 3.84 (s, 3H), 3.35-3.13 (m, 4H), 3.00-2.80 (m, 4H), 2.32 (s,
3H), 2.14 (m, 2H), 1.81-1.38 (m, 4H), 0.91 (t, J = 7.5Hz, 6H).
Referanseeksempel 13
5-amino-4-cyano-2, 3-dimetyl-l-(2-metyl-4-metoksyfenyl)pyrrol
Til en oppløsning av 2-metyl-4-metoksyanilin (10 g) i toluen (120 ml), ble acetoin og p-toluensulfonsyrehydrat (44 mg) tilsatt. Blandingen ble oppvarmet med til-bakeløp i 2 timer. Etter at reaksjonsblandingen ble avkjølt til romtemperatur ble malononitril (4,6 ml) tilsatt til reaksjonsblandingen og denne ble oppvarmet med tilbakeløp i 12 timer. Den avkjølte reaksjonsblandingen ble konsentrert. Resten ble fortynnet med eter og filtrert til å gi tittelforbindelsen (5,73 g) med de etterfølgende fysiske data.
TLC: Rf 0.65 (heksan : etylacetat = 1:1);
NMR (300MHz, CDC13): 8 7.07 (d, J = 8.4Hz, 1H), 6.87 (d, J = 3.0Hz, 1H), 6.82 (dd, J = 3.0, 8.4Hz, 1H), 3.84 (s, 3H), 3.71 (brs, 2H), 2.06 (s, 3H), 1.99 (s, 3H), 1.73 (s, 3H).
Eksempel 18
2, 3-dimetyl-4-amino-l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[ej-pyrrolo[2,3-b]pyridin
Til en oppløsning av forbindelsen fremstilt i referanseeksempel 13 (4,0 g) i benzen (40 ml), ble cyklopentanon (1,46 ml) og p-toluensulfonsyrehydrat (40 mg) tilsatt. Blandingen ble oppvarmet med tilbakeløp og dehydratisert i 12 timer. En uopp-løselig substans ble fjernet ved filtrering gjennom celite og filtratet ble konsentrert. Under en argonatmosfære, ble 2M litiumdiisopropylamid (15,7 ml, i THF) tilsatt til en oppløsning av resten i vannfritt tetrahydrofuran (80 ml) ved 0 °C, og deretter ble blandingen oppvarmet til romtemperatur og omrørt i 5 døgn. Vann ble tilsatt til reaksjonsblandingen og blandingen ble ekstrahert med etylacetat. Ekstrakten ble vasket påfølgende med vann og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (etylacetat) til å gi tittelforbindelsen (2,85 g) med de etterfølgende fysiske data.
TLC: Rf 0.51 (kloroform : metanol = 10 : 1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.4Hz, 1H), 6.85 (d, J = 3.0Hz, 1H), 6.80(dd, J = 3.0, 8.4Hz, 1H), 4.31 (s, 2H), 3.83 (s, 3H), 2.90 (m, 2H), 2.74 (m, 2H), 2.48 (s, 3H), 2.10 (m, 2H), 1.97 (s, 3H), 1.90 (s, 3H).
Eksempel 19
2,3-dimetyl-4-etylkarbonylamino-l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin
Til en oppløsning av forbindelsen fremstilt i eksempel 18 (600 mg) i THF (60 ml),
ble trietylamin (520 ul) og propionylklorid (180 ul) tilsatt. Blandingen ble omrørt i 2 timer. Reaksjonsblandingen ble fortynnet med etylacetat, og den fortynnede opp-løsning ble vasket påfølgende med en mettet vandig oppløsning av natriumbikarbonat og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert. Resten ble vasket med heksan til å gi tittelforbindelsen (451 mg) med de etterfølgende fysiske data.
TLC: Rf 0.60 (kloroform : metanol =10:1);
NMR (300MHz, CDC13): 8 7.30 (m, 1H), 7.08 (d, J = 8.4Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.83 (dd, J = 2.7, 8.4Hz, 1H), 3.84 (s, 3H), 2.98 (t, J = 7.2Hz, 2H), 2.87 (m, 2H), 2.51 (m, 2H), 2.37 (s, 3H), 2.09 (m, 2H), 2.02 (s, 3H), 1.88 (s, 3H), 1.33 (m, 3H).
Eksempel 20
2,3-dimetyl-4-propylamino-l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin
Til en oppløsning av forbindelsen fremstilt i eksempel 19 (451 mg) i THF (5,0 ml), ble 2M borandimetylsulfidkompleks (4,8 ml, i THF) tilsatt og blandingen ble oppvarmet med tilbakeløp i 5 timer. Metanol ble tilsatt til reaksjonsblandingen og deretter ble blandingen oppvarmet med tilbakeløp i 2 timer. Etter av reaksjonsblandingen var avkjølt ble blandingen fortynnet med etylacetat. Den fortynnede oppløsning ble vasket med vann og en mettet vandig oppløsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat =1 : 1) til å gi tittelforbindelsen (268 mg) med de etterfølgende fysiske data.
TLC: Rf 0.47 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13) : 8 7.09 (d, J = 8.7Hz, 1H), 6.85 (d, J = 2.7Hz, 1H), 6.80 (dd, J = 2.7, 8.7Hz, 1H), 3.83 (s, 3H), 3.43 (m, 2H), 3.05 (m, 2H), 2.84 (m, 2H), 2.48 (s, 3H), 2.04 (m, 2H), 1.97 (s, 3H), 1.90 (s, 3H), 1.65 (m, 2H), 1.02 (t, J = 7.5Hz, 3H).
Eksempel 21
2,3 -dimetyl-4-(N-ety lkarbonyl-N-propylamino)-1 -(2-mety 1-4-metoksyfeny l)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin
Under en argonatmosfære ble trietylamin (360 ul) og propionylklorid (134 ul) tilsatt til en oppløsning av forbindelsen fremstilt i eksempel 20 (234 mg) i metylenklorid (3,0 ml) ved 0 °C. Blandingen ble omrørt i 1 time. Reaksjonsblandingen ble fortynnet med etylacetat og den fortynnede oppløsning ble vasket påfølgende med en mettet vandig oppløsning av natriumbikarbonat, vann og en mettet vandig opp-løsning av natriumklorid, tørket over vannfritt magnesiumsulfat og konsentrert. Resten ble renset ved kolonnekromatografi på silikagel (heksan : etylacetat = 2:1) til å gi tittelforbindelsen (242 g) med de etterfølgende fysiske data.
TLC: Rf 0.57 (heksan : etylacetat =1:1);
NMR (300MHz, CDC13): 87.11 (m, 1H), 6.90 (d, J = 2.4Hz, 1H), 6.85 (dd, J = 2.4, 8.4Hz, 1H), 3.92 (m, 1H), 3.86 (s, 3H), 3.42 (m, 1H), 3.01 (t, J = 7.8Hz, 2H), 2.87 (m, 2H), 2.20 (s, 3H), 1.94-2.20 (m, 4H), 2.05 (s, 3H), 1.92 og 1.90 (s, totalt 3H), 1.63 (m, 2H), 0.99-1.10 (m, 3H), 0.85-0.94 (m, 3H).
Eksempel 22
2,3-dimetyl-4-dipropylamino-l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin
Tittelforbindelsen (182 mg) med de etterfølgende fysiske data ble oppnådd ved hjelp av den samme prosedyre som reaksjonen i eksempel 20, ved å anvende forbindelsen fremstilt i eksempel 21 (242 mg).
TLC: Rf 0.45 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.4Hz, 1H), 6.87 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.4, 2.7Hz, 1H), 3.84 (s, 3H), 3.17 (m, 4H), 2.95 (t, J = 7.5Hz, 2H), 2.88 (t, J = 7.5Hz, 2H), 2.44 (s, 3H), 2.05 (m, 2H), 2.01 (s, 3H), 1.92 (s, 3H), 1.52 (m, 4H), 0.85 (t, J = 7.2Hz, 6H).
Eksempel 22(1)
2,3-dimetyl-4-(N-etyl-N-pentylamino)-l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin
Tittelforbindelsen med de etterfølgende fysiske data ble oppnådd ved hjelp av den samme prosedyre som en serie av reaksjoner slik som Eksempel 19 -> Eksempel 20 - > Eksempel 21 ->• Eksempel 22 ved å anvende en forbindelse fremstilt i eksempel 18 og en tilsvarende forbindelse.
TLC: Rf 0.41 (heksan : etylacetat = 3:1);
NMR (300MHz, CDC13): 8 7.10 (d, J = 8.4Hz, 1H), 6.86 (d, J = 2.7Hz, 1H), 6.81 (dd, J = 8.4, 2.7Hz, 1H), 3.84 (s, 3H), 3.27 (q, J = 6.9Hz, 2H), 3.18 (m, 2H), 2.95 (t, J = 7.2Hz, 2H), 2.88 (t, J = 7.8Hz, 2H), 2.44 (s, 3H), 2.05 (m, 2H), 2.00 (s, 3H), 1.91 (s, 3H), 1.50 (m, 2H), 1.38-1.20 (m, 4H), 1.05 (t, J = 6.9Hz, 3H), 0.86 (t, J = 6.9Hz, 3H).
Formuleringseksempel
Formuleringseksempel 1
De etterfølgende komponenter ble blandet ved hjelp av en konvensjonell metode og stanset ut for å oppnå 100 tabletter som hver inneholdt 50 mg av aktiv bestanddel.
Formuleringseksempel 2
De etterfølgende komponenter ble blandet ved hjelp av en konvensjonell metode. Oppløsningen ble sterilisert på vanlig måte, anbrakt i 5 ml porsjoner i ampuller og frysetørket for å oppnå 100 ampuller som hver inneholdt 20 mg av den aktive bestanddel.
Claims (24)
1. Forbindelse,
karakterisert ved at den har formel (I)
hvor X og Y hver uavhengig er karbon eller nitrogen og hvor begge ikke samtidig er nitrogener;
W er karbon eller nitrogen;
U og Z er hver uavhengig CR , NR , nitrogen, oksygen, svovel, C=0 eller C=S; R<2> er (i) hydrogen, (ii) Cl-8 alkyl, (iii) C2-8 alkenyl, (iv) C2-8 alkynyl, (v) halogenatom, (vi) CF3, (vii) cyano, (viii) nitro, (ix) NR9R<10> hvor R<9> og R<10> hver uavhengig er (i) hydrogen, (ii) Cl-4 alkyl, (iii) C3-10 mono- eller bi-karbocyklisk ring, (iv) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (v) Cl-4 alkyl substituert med C3-10 mono- eller bi-karbocyklisk ring eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer, (x) OR<11> hvor R<11> er (i) hydrogen, (ii) Cl-4 alkyl, (iii) C5-6 karbocyklisk ring, (iv) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (v) Cl-4 alkyl som er substituert med en C5-6 karbocyklisk ring eller en 5-eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom, (xi) SH, (xii) S(0)nR<12> hvor n er 0, 1 eller 2, R<12> er (i) Cl-4 alkyl, (ii) C5-6 karbocyklisk ring, (iii) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (iv) Cl-4 alkyl substituert med en C5-6 karbocyklisk ring eller en 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom, (xiii) COR11, (xiv) COOR11, (xv) CONR9R10, (xvi) C3-10 mono- eller bi-karbocyklisk ring, (xvii) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (xviii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR11, =N-OR<n>, SH, S(0)nR<12>, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi- karbocyklisk ring og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
R<13> er (i) hydrogen, (ii) Cl-4 alkyl, (iii) C2-4 alkenyl, (iv) C2-4 alkynyl, (v) C3-10 mono- eller bi-karbocyklisk ring, (vi) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (vii) Cl-4 alkyl substituert med C3-10 mono- eller bi-karbocyklisk ring eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
'-^ er en enkeltbinding eller dobbeltbinding,
er C4-6 karbocyklisk rine eller 4-6-leddet heterocyklisk ring inneholdende minst ett av et nitrogenatom, oksygenatom og svovelatom og hvor disse ringer er usubstituerte eller substituert med 1-3 substituenter valgt fra Cl-4 alkyl, Cl-4 alkoksy, halogenatom og CF3,
med den betingelse at når X, Y, Z og U er karbon og W er nitrogen, da er ring A ikke benzen,
R<1> er (i) Cl-8 alkyl som er usubstituert eller substituert med 1-5 R<14>, (ii) C2-8 alkenyl som er usubstituert eller substituert med 1-5 R<14>, (iii) C2-8 alkynyl som er usubstituert eller substituert med 1-5 R<14>, (iv) NR<4>R<5> hvor R4 og R<5> hver uavhengig er, (i) hydrogen, (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R 1 7, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R<17>, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R<17>, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-15 leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1R, (v) OR6 hvor R<6> er (i) hydrogen, (ii) Cl-lO alkyl, (iii) C2-10 alkenyl, (iv) C2-10 alkynyl, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (vii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<n>, SH, S(0)nR12, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (vi) SH, (vii) S(0)nR 7 hvor n er som definert i det foregående, R 7 er (i) C1-8 alkyl, (ii) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (iii) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogen atomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1 ft, (iv) Cl-4 alkyl substituert med C3-10 mono- eller bi- karbocyklisk ring, som er usubstituert eller substituert med 1-5 R<18> eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (viii) COR<6>, (ix) COOR<6>, (x) CONR<4>R<5>, (xi) NR8COR6ahvorR6aer (i) hydrogen, (ii) Cl-10 alkyl, (iii) C2-10 alkenyl, (iv) C2-10 alkynyl eller (v) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR,<la>, =N-OR<n>, SH, S(0)nR12, COR<11>, COOR<11 >og CONR<9>R<10>, (xii) NR8COOR6 hvor R<6> er som definert i det foregående, R<8> er (i) hydrogen, (ii) Cl-8 alkyl, (iii) C2-8 alkenyl, (iv) C2-8 alkynyl, (v) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1 H eller (vii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<u>, SH, S(0)nR12, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R 1R, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1 fl, (xiii) NR<8>CONR<4>R5, (xiv) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15> eller (xv) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>,
Rll<a> er (i) hydrogen, (ii) Cl-4 alkyl eller (iii) Cl-4 alkyl substituert med C5-6 karbocyklisk ring eller 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom,
R<14> er (a) halogenatom, (b) CF3, (c) OCF3, (d) cyano, (e) nitro, (f) NR<4>R<5>, (g) OR<6>, (h) =N-OR<6>, (j) SH, (k) S(0)nR<7>, (1) COR<6>, (m) COOR<6>, (n) CONR<4>R<5>, (o) NR<8>COR6, (p) NR<8>COOR<6>, (q) NR<8>CONR<4>R<5>, (r) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15> eller (s) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>, R<15> er (a) Cl-8 alkyl, (b) C2-8 alkenyl, (c) C2-8 alkynyl, (d) Cl-4 alkoksy(Cl-4)alkyl, (e) halogenatom, (f) CF3, (g) OCF3, (h) cyano, (j) nitro, (k) NR<4>R<5>, (1) OR<6>, (m) SH, (n) S(0)nR<7>, (o) COR<6>, (p) COOR<6>, (q) CONR<4>R<5>, (r) NR<8>COR<6>, (s) NR<8>COOR<6>, (t) NR<8>CONR4R<5>, (u) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<19>, (v) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<19> eller (w) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro,
NR<4>R<5>, OR<6>, =N-OR<6>, SH, S(0)nR<7>, COR<6>, COOR<6>, CONR<4>R<5>, NR<8>COR<6>, NR<8>COOR<6>, NR<8>CONR<4>R<5>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<19>, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som eir usubstituert eller substituert med 1-5 R<19>,
R<17> er (a) halogenatom, (b) CF3, (c) OCF3, (d) cyano, (e) nitro, (f) NR<9>R<10>, (g) OR<1>,<a>, (h) =N-OR<1]>, (j) SH, (k) S(0)nR<12>, (1) COR<11>, (m) COOR<11>, (n) CONR<9>R<10>, (o) NR<8>COR<u>, (p) NR<8>COOR<H>, (q) NR<8>CONR<9>R10, (r) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18a> eller (s) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R18a,
R<18> er (a) Cl-4 alkyl, (b) C2-4 alkenyl, (c) C2-4 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) SH, (k) S(0)nR<12>, (1) NR<9>R10, (m) OR<11>, (n) COR<11>, (o) COOR<11>, (p) CONR<9>R<10>, (q) C5-6 karbocyklisk ring, (r) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (s) Cl-4 alkyl substituert med C5-6 karbocyklisk ring eller 5 eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom,
R18<a> er (a) Cl-4 alkyl, (b) C2-4 alkenyl, (c) C2-4 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) SH, (k) S(0)nR<12>, (1) NR<9>R<10>, (m) ORlla, (n) COR<11>, (o) COOR<11> eller (p) CONR<9>R10,
R<19> er Cl-4 alkyl, Cl-4 alkoksy, halogenatom, CF3, OCF3, cyano, nitro, amino, NH(Cl-4 alkyl) eller N(C 1-4 alkyl)2,
R<3> is (i) C5-10 mono- eller bi-karbocyklisk ring substituert med 1-5 R<16> eller (ii) 5-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer substituert med 1-5 R<16>,
R<16> er (a) C1-8 alkyl, (b) C2-8 alkenyl, (c) C2-8 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) NR9R10,
(k)OR<11>,
(1) SH, (m) S(0)nR<12>, med unntak av fenyltio, (n) COR11,
(o)COOR<11>, (p) CONR<9>R<10>,
(q)NR<8>COR<H>,
(r)NR<8>COOR<u, >
(s)NR<8>CONR<9>R<10>, (t) C3-10 mono- eller bi-karbocyklisk ring, (u) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer, (v) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<n>, SH, S(0)nR<12>, COR11, COOR<11>, CONR<9>R<10>, NR<8>COR<n>, NR<8>COOR<u>, NR<8>CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer,
1-2 oksygenatomer og/eller 1-2 svovelatomer,
med den betingelse at (1) når hver av X og W er karbonatomer, hver av Y og Z er nitrogenatomer, U er CR 9 og R 1 er OR f\ , da er R "\ ikke fenyl substituert med 1 halogenatom, fenyl substituert med 1 trifluormetyl og fenyl substituert med trifluormetyl og nitro, (2) når hver av X, Y og Z er karbonatomer og hver av U og W er nitrogenatomer, da er R<3> C5-10 mono- eller bi-karbocyklisk ring substituert med 1-5 R<16>,
og et farmasøytisk aksepterbart salt derav eller et hydrat derav.
2. Forbindelse som angitt i krav 1, hvor X er karbon, Y er nitrogen, hver av U og Z er karbon eller nitrogen og W er karbon, et farmasøytisk aksepterbart salt derav ellet et hydrat derav.
3. Forbindelse som angitt i krav 2, hvor hver av X, U og W er karbon, hver av Y og Z er nitrogen, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
4. Forbindelse som angitt i krav 2, hvor hver av X, Z, U og W er karbon, Y er nitrogen, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
5. Forbindelse som angitt i krav 1, hvor hver av X, Y, Z og U er karbon, W er nitrogen, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
6. Forbindelse som angitt i krav 1, hvor
er C4-6 karbocyklisk ring, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
7. Forbindelse som angitt i krav 1, hvor
er 4-6-leddet heterocyklisk ring inneholdende minst ett nitrogenatom, oksygenatom og svovelatom, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
8. Forbindelse som angitt i krav 1, hvor R<1> er (i) Cl-8 alkyl som er usubstituert eller substituert med 1-5 R<14>, (ii) C2-8 alkenyl som er usubstituert eller substituert med by 1-5 R<14>, (iii) C2-8 alkynyl som er usubstituert eller substituert med 1-5 R<14>, (iv) NR<4>R<5>, (v) OR<6>, (vi) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15>, eller (vii) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>, hvor R<1>4 og R1<5> er som definert i krav 1, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
9. Forbindelse med formel (I-i) som angitt i krav 1,
hvor alle symboler er som definert i krav 1, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
10. Forbindelse som angitt i krav 9, hvor
er C4-6 karbocyklisk ring, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
11. Forbindelse som angitt i krav 9, hvor
er 4-6-leddet heterocyklisk ring inneholdende minst ett nitrogenatom, oksygenatom og svovelatom, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
12. Forbindelse som angitt i krav 9, hvor R<1> er NR<4>R<5>, og (a) R<4> er (i) hydrogen-atom, (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R , (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R 1 7, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R<17>, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1 -5 R 1 fi eller (vi) 3-15-leddet mono-eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1 fi eller (b)R<4>er(ii)Cl-15alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R<17>, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R 17 eller (v-1) C3-6 mono-karbocyklisk ring og R<5> er (ii) C1-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R , (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R 17, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R eller (vi) 3-15-leddet mono-eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1 fi, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
13. Forbindelse med formel (I-ii) som angitt i krav 1,
hvor alle symbolene er som definert i krav 1, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
14. Forbindelse som angitt 13, hvor
er C4-6 karbocyklisk ring, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
15. Forbindelse som angitt i krav 13, hvor
er 4-6-leddet heterocyklisk ring inneholdende minst ett nitrogenatom, oksygenatom og svovelatom, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
16. Forbindelse som angitt i krav 13, hvor R<1> er NR<4>R<5>, og (a) R<4> er (i) hydrogen-atom, (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R 17, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R<17>, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R 1 8 eller (vi) 3-15-leddet mono-eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18> eller (b) R<4> er (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R<17>, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R 17 eller (v-1) C3-6 mono-karbocyklisk ring og R K er (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R 17, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R 1 7, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R<17>, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18> eller (vi) 3-15-leddet mono-eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, et farmasøytisk aksepterbart salt derav eller et hydrat derav.
17. Forbindelse som angitt i krav 1, som er valgt fra
(1) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(2) 8-(N-etyl-N-n-butylamino)-2-metoksymetyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(3) 8-(N-propyl-N-(2-hydroksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(4) 9-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5, 6,7, 8-tetrahydro-pyrazolo[3,2-b]kinazoline,
(5) 8-[(2S)-1, 1 -dimetoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(6) 8-( 1,3-dimetoksypropan-2-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(7) 8-bis(2-metoksyetyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(8) 8-(3-pentylamino)-2-metyl-3-(2, 4-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(9) 8-dietylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(10) 8-(N-etyl-N-n-butylamino)-2-metyl-3-(2, 4-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(11) 8-dicyklopropylmetylamino-2-metyl-3-(2-metyl-4-m 5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(12) 8-(3-pentylamino)-2-metoksymetyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 155-a]pyrimidin,
(13) 8-(3-pentylamino)-2-metyl-3-( 1, 3-dioksaindan-5-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(14) 8-(3-pentylamino)-2-metyl-3-(3, 4-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(15) 8-(3-pentylamino)-2-cyklobutyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H^ cyklopenta[d]pyrazolo[ 155-a]pyrimidin,
(16) 8-(3-pentylamino)-2-etyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(17) 8-(3-pentylairiino)-2-isopropyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(18) 8-(2-e1ylbutylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(19) 8-(3-pentylamino)-2-metyltiometyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-aJpyrimidin,
(20) 8-(3-pentylamino)-2-metyl-3-(2,4-dimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5 -ajpyrimidin,
(21) 8-(3-pentylamino)-2-metyl-3-(2, 5-dimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(22) 8-cyklobutylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(23) 8-(N-etyl-N-cyklobutylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(24) 8-(propan-l, 3-diol-2-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(25) 8-(3-pentylamino)-2-(2-furyl)-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(26) 8-(3-pentylamino)-2-fenyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(27) 8-(2-dimetylaminoetyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(28) 8-(N-metyl-N-(2-dimetylaminoetyl)arnino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-657-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(29) 8-(>^e1yl-N-(2-dimetylaminoetyl)amino)-2-m 6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(30) 8-(4-heptylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(31) 8-(2-butylamino)-2-me1yl-3-(2-metyl-4-metoksyfenyl)-657-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(3 2) 8-(N-propyl-N-cyklopropylmetylamino)-2-metyl-3 -(2-mety 1-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(33) 8-(3-pentylamino)-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(34) 8-[(2R)-l-metoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6J7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(35) 8-[(2S)-l-metoksybutan-2-yl]amino-^^ dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(36) 8-cyklopentylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(37) 8-(3-pentylamino)-2-metyl-3-(2, 4-difluorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(38) 8-(3-pentylamino)-2-trifluormetyl-3-(2-metyl-4-metoksyfenyl)-6,^ 5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(39) 8-(N-etyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metolcsyfenyl)-6,7 dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(40) 8-cykloheksylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(41) 8-(N-propyl-N-(3-pentyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(42) 8-(3-pentylamino)-2-metyl-3-(4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(43) 8-(3-pentylamino)-2-isopropyl-3-(4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(44) 8-t-butylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5 -ajpyrimidin,
(45) 8-(3-pentylamino)-3-(2,4, 6-trimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(46) 8-( 1 -cyklobutyletyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(47) 8-(3-pentylamino)-2-metyl-3-(2, 3-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5 -ajpyrimidin,
(48) 8-(3-pentylamino)-2-metyl-3-(2, 5-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(49) 8-(N-(2, 2,2-trifIuoretyl)-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(50) 8-(2,2,2-trifiuoretyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(51) 8-(3-pentylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5 -ajpyrimidin,
(52) 8-(3-pentylamino)-3-(4, 6-dimetyl-2-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(53) 8-(3-pentylamino)-2-metyl-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(54) 8-(3-pentylamino)-2-metyl-3-(4, 6-dimetyl-2-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(55) 8-(3-metylpentan-3-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(56) 8-(3-pentylamino)-2-metyl-3-(5-klor-l, 3-dioksaindan-6-yl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(57) 8-(N-etyl-N-benzylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(58) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-trifluormetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(59) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(60) 8-(N-benzyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-ajpyrimidin,
(61) 8-(3-pentylamino)-2-metyl-3-(2-metoksy-4,5-dimetylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(62) 8-fenylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-ajpyrimidin,
(63) 8-(2-metylfenyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(64) 8-(3-me1ylfenyl)amino-2-metyl-3-(2-me1yl-4-metoksyfenyl)-6 cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(65) 8-(4-metylfenyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(66) 8-(N-fenyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(67) 8-(N-benzyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(68) 8-(N, N-diallylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(69) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-dimetylaminofenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(70) 8-( 1 -fenylpropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(71) 8-(N-(2-fenyletyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(72) 8-(N-(3-fenylpropyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(73) 8-(N-(4-fenylbutyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(74) 8-( 1 -fenyl-2-butyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(75) 8-( 1 -fenyl-3-pentyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(76) 8-(N-(4-metylfenyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(77) 8-(N-(4-metylfenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-ajpyrimidin,
(78) 8-(N-(3-metylfenyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-ajpyrimidin,
(79) 8-(N-(4-metoksyfenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(80) 8-(N-(4-klorfenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(81) 8-(N-(2-metylfenyl)-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(82) 8-(3-pentylamino)-2-metyl-3-(2-dimetylamino-4-metylpyridin-5-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(83) 8-((2S)-l-metoksy-3-fenyl-2-propyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6J-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(84) 8-(N-(4-metyltiofenyl)metyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(85) 8-(N,N-dibutylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6J-d% cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(86) 8-(N-metyl-N-butylamino)-2-metyI-3-(2-metyl-4-metoksyfenyl)-6,7-dihy 5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(87) 8-(N-(4-metylfenyl)metyl-N-butylam^ 6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(88) 8-(N-(4-metylfenyl)metyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-m metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(89) 8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[lJ5-a]pyrimidin3
(90) 8-(N-cyklopropylmetyl-N-(4-me1ylfenyl)me1ylamino)-2-metyl-3-(2-mety metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(91) 8-(N, N-dipropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(92) 8-(N-(4-metylfenyl)metyl-N-(2-butynyl)amino)-2-metyl-3-(2-mety metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(93) 8-(N-propyl-N-(2-butynyl)amino>^ dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(94) 8-(5-nonylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(95) 8-(N-cyklopen1yl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(96) 8-(N-cyklopropylmetyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-metyl-4 metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(97) 8-(N-(4-fluorfenyl)metyl-N-propylammo)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(98) 8-(N-cyklobutyl-N-(4-metylfenyl)metylarnino)-2-metyl-3 -(2-metyl-4-metoksyfenyl)-6J-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(99) 8-(N-etyl-N-(4-metylfenyl)metylam 6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(100) 8-(N-propyl-N-(4-trifluoimetylfenyl)metylamino)-2-mety metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(101) 8-(N-propyl-N-(tetrahydromran-2-yl)metylamino)-2-mety metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(102) 8-(N-butyl-N-(2-metoksyetyl)amino)-2-mety^^ 6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(103) 8-(N-propyl-N-cyklopropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(104) 8-(N-cyklobutylmetyl-N-(2-metoksyetyl)amino)-2-metyl-3 -(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(105) 8-(4-heptylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(106) 8-(N-cyklopropylmetyl-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(107) 8-(N-(2-metoksyetyl)-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(108) 8-(2-butyrylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(109) 8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(110) 8-(N-propyl-N-(4-trifluormetyloksyfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(111) 8-(N-(2-butyryl)-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(112) 8-(N-propyl-N-(3-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(113) 8-(N-propyl-N-(2-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(114) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-etoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(115) 8-(N-metyl-N-heksylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(116) 8-(N-metyl-N-(3-pentyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(117) 8-(N-metyl-N-(4-heptyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(118) 8-(N-cyklobutyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyO dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(119) 8-(N-isobutyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopénta[d]pyrazolo[l,5-a]pyrimidin,
(120) 8-(N-propyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(121) 8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(122) 8-(3-pentylamino)-2-metyl-3-(3-klor-5-trifluormetylpyridin-2-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(123) 8-(N-butyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(124) 8-(N-cyklopropyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(125) 8-(N-propyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(126) 8-(N-propyl-N-(3-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(127) 8-dicyklopropylmetylamino-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(128) 8-(N-butyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(129) 8-(N-cyklopropylmetyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(130) 8-(N-(2-butynyl)-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(131) 8-(N-butyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(132) 8-(N-cyklopropylmetyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(133) 8-(3-pentylamino)-2-metyl-3-(3, 5-diklorpyridin-2-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(134) 8-(N-butyl-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(135) 8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(136) 8-(N-benzyl-N-(2-dimetylaminoetyl)amino)-2-m metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(137) 8-(N-benzyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(138) 8-(N-(2-butynyl)-N-etylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl^ dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(139) 8-(N-(2-butynyl)-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(140) 8-(N, N-dipropylamino)-2-metyl-3-(2-klor-4-meto^^ cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(141) 8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-mety 1-3-(2-mety 1-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(142) 8-(N-propyl-N-(3-lfuorfenyl)me1ylamino)-2-metyl-3-(2-klor-4-metoksyfen 6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(143) 8-dipropylamino-2-metyl-3-(2, 5-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(144) 8-dipropylamino-2-metyl-3-(2, 4-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(145) 8-dipropylamino-2-metyl-3-(4-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(146) 8-dipropylamino-2-metyl-3-(3-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(147) 8-dipropylamino-2-metyl-3-(2-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(148) 8-(N-propyl-N-(benz[d] 1, 3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(149) 8-(N-propyl-N-(benz[d] 1, 3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(150) 8-(3-pentylamino)-2-metyl-3-(2-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(151) 8-(3-pentylamino)-2-metyl-3-(3-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(152) 8-(3-pentylamino)-2-metyl-3-(4-metylfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(153) 8-(3-pentylamino)-2-metyl-3-(2-metyltio-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(154) 8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(155) 8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3 -(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(156) 8-(N-butyl-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfeny0 dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(157) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-fluorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(158) 8-(3-pentylamino)-2-metyl-3-(2, 5-diklorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(159) 8-(3-pentylamino)-2-metyl-3-(2, 4-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 155-a]pyrimidin,
(160) 8-(3-pentylamino)-2-metyl-3-(2-fluor-4-metylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(161) 8-(N-butyl-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(162) 8-(3-metyl-2-butylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7 5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(163) 8-( 1 -cykloheksyletylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(164) 8-(2-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5 -ajpyrimidin,
(165) 8-(2-heptylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(166) 8-( 1 -metoksy-2-propylamino)-2-metyl-3 -(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-ajpyrimidin,
(167) 8-(2-oktylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(168) 8-(l, 2, 3, 4-tetrahydronaftalen-l-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(169) 8-((lS, 2S, 3S, 5R)-2, 6, 6-trimetylbicyklo[3.1.1j-3-heptyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(170) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-klorfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(171) 8-(3-pentylamino)-2-metyl-3-(2, 5-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-ajpyrimidin,
(172) 8-(3-pentylamino)-2-metyl^ cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(173) 8-(N-etyl-N-(4-hydroksybutyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(174) 8-(3-pentylamino)-2-metyl-3-(2-metoksy-5-isopropylfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(175) 8-(3-pentylamino)-2-metyl-3-(2-metoksy-5-lfuorfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(176) 8-(N-butyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(177) 8-(3-pentylamino)-2-metyl-3-(2-metoksy-5-klorfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(178) 8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-2-metyl-3 -(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-ajpyrimidin,
(179) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-cyanofenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(180) 8-(N-propyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(181) 8-(N-etyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(182) 8-(3-pentylamino)-2-metyl-3-(4-metyltiofenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(183) 8-(3-pentylamino)-2-metyl-3-(4-dimetylaminofenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(184) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-metyltiofenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(185) 8-(N-(2-metoksyetyl)-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(186) 8-(N-propyl-N-(5-metylfuran-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(187) 8-(N-benzyl-N-cyklopropylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-ajpyrimidin,
(188) 8-(N-cyklopropylmetyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-ajpyrimidin,
(189) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-bromfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(190) 8-(3-pentylamino)-2-metyl-3-(2, 5-diklor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(191) 8-dibutylamino-2-metyl-3 -(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(192) 8-bis(2-metoksyetyl)amino-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(193) 8-(N-etyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(194) 8-(N-cyklopropyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6J-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(195) 8-(N-cyklopropylmetyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l55-a]pyrimidin,
(196) 8-(N-butyl-N-cyklopropylmetylamino)-2-metyl-3 -(2-klor-4-metoksyfeny 1)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(197) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-etoksykarbonylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(198) 8-(N-propyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(199) 8-(N-propyl-N-(5-metyltiofen-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(200) 8-(N-propyl-N-(tiofen-3-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(201) 8-(N-etyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(202) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-karbamoylfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(203) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-(N-metylkarbamoyl)fenyl)-6,7-dihy dro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(204) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-(N, N-dimetylkarbamoyl)fenyl))-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(205) 8-(N-etyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(206) 8-(3-pentylamino)-2-metyl-3-(2-klor-4, 6-dimetoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(207) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-aminofenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(208) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-metylam cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(209) 8-(3-pentylamino)-2-metyl-3-(2-formyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(210) 8-(3-pentylamino)-2-metyl-3-(2-cyano-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(211) 8-(3-pentylamino)-2-metyl-3-(2-etyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(212) 8-(4-heptylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(213) 8-(N, N-dipropylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(214) 8-(3 -pentylamino)-2-mety 1-3 -(2-metoksykarbonyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(215) 8-(N-cyklopropyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-ajpyrimidin,
(216) 8-(N-cyklopropylmetyl-N-(2-fiuorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-ajpyrimidin,
(217) 8-(N-cyklopropylmetyl-N-propylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(218) 8-(N-propyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(219) 8-(N-benzyl-N-cyklopropylmetylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(220) 8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(221) 8-(N-propyl-N-(4-fluorfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(222) 8-dicyklopropylmetylamino-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(223) 8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-3 -(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin, . (224) 8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin, (225) 8-(3-pentylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(226) 8-(N-cyklopropylmetyl-N-(4-lfuorfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(227) 8-(3-pentylamino)-2-metyl-3 -(2-( 1 -metyl-1 -hydroksyetyl)-4-metoksyfeny 1)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(228) 8-(N-propyl-N-(4-trifluormetyloksyfenyl)metylamino)-2-metyl-3 -(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(229) 8-(3-heksylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(230) 8-(3-pentylamino)-2-metyl-3-(2-metoksy-4-metylpyridin-5-yl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(231) 8-(N-butyl-N-cyklopropylmetylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(232) 8-(N-propyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(233) 8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(234) 8-(N-cyklopropylmetyl-N-metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(235) 8-(N-etyl-N-n-butylamino)-2-hydroksymetyl-3-(2-metyl-4-hydroksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(236) 8-(N-etyl-N-n-butylamino)-2-hydroksymetyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(237) 8-(N-propyl-N-(2-metoksyiminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(238) 8-(N-etyl-N-n-butylamino)-2-hydroksyiminometyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(239) 8-[(2S)-l-hydroksyiminobutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(240) 8-[( 1S)-1 -cyanopropylamino]-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(241) 8-(N-etyl-N-n-butylamino)-2-cyano-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(242) l-cyano-2-metyl-8-(3-pentylamino)-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,2-a]pyrimidin,
(243) l-cyano-2-metyl-8-dipropylamino-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,2-a]pyrimidin,
(244) 2, 3-dimetyl-4-amino- l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin,
(245) 2, 3-dimetyl-4-etylkarbonylamino-1 -(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin,
(246) 2, 3-dimetyl-4-propylamino-1 -(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin,
(247) 2, 3-dime1yl-4-(N-etylkarbonyl-N-propylamino)-l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin,
(248) 2, 3-dime1yl-4-dipropylamino-l-(2-me1yl-4-metoksyfenyl)-6J-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin,
(249) 8-(4-heptylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(250) 8-dipropylamino-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(251) 8-(N-cyklopropylmetyl-N-propylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(252) 8-(N-benzyl-N-cyklopropylmetylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(253) 8-(N-cyklopropylmetyl-N-(4-metylfenylmetyl)amino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(254) 8-(N-propyl-N-(4-fiuorfenylmetyl)amino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(255) 8-dicyklopropylmetylamino-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(256) 8-(N-butyl-N-cyklopropylmetylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(257) 8-(N-cyklopropylmetyl-N-(4-fiuorfenyl)metylamino)-3-(2, 6-dimetyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin og
(258) 2, 3-dimetyl-4-(N-etyl-N-pentylamino)-l-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[e]pyrrolo[2,3-b]pyridin,
et farmasøytisk aksepterbart salt derav eller et hydrat derav.
18. Forbindelse som angitt i krav 1, som er valgt fra
(1) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-tieno[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(2) 9-(3-pentylamino)-6-metyl-5-(2-metyl-4-metoksyfenyl)-2, 3-dihydro-tieno[3,2-d]pyrazolo[l ,5-ajpyrimidin,
(3) 8-(3-pentylamino)-2-metyl-3-(2-m d]pyrazolo[ 1,5-a]pyrimidin,
(4) 9-(3-pentylamino)-6-metyl-5-(2-metyl-4-metoksyfenyl)-2,3-dihydro-furo[3,2-d]pyrazolo[ 1,5-ajpyrimidin,
(5) 9-(3-pentylamino)-6-metyl-5-(2-metyl-4-metoksyfenyl)-2, 3-dihydro-pyrrolo[3,2-d]pyrazolo[ 1,5-a]pyrimidin,
(6) 8-isopropylamino-2-me1yl-3-(2-metyl-4-metoksyfenyl)-5J-dihydro-mro[ d]pyrazolo[ 1,5-ajpyrimidin,
(7) 8-[(2S)-1, 1 -dimetoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(8) 8-(l, 3-dimetoksypropan-2-yl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(9) 8-bis(2-metoksyetyl)amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(10) (5RS)-8-(3-pentylamino)-2,5-dimetyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo [3,4-d]pyrazolo[ 1,5 -ajpyrimidin,
(11) 8-(3-pentylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-pyrrolo[3,4-djpyrazolo[l,5-a]pyrimidin,
(12) 8-(N-propyl-N-(2-hydroksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(13) 8-cyklopropylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(14) 8-(N-metyl-N-cyklopropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(15) 8-[(2R)-1 -metoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(16) 8-[(2R)-1 -metoksybutan-2-yl]amino-2-metyl-3-(2-metyl-4-metoksyfenyl)-2, 3-dihydro-furo[3,2-d]pyrazolo[l,5-a]pyrimidin,
(17) 8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(18) 8-(3-pentylmino)-2-metyl-3-(2-klor-4-etoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(19) 8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(20) 8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(21) 8-(N-propyl-N-(4-lfuorfenyl)metylam 5,7-dihydro-mro[3,4-d]pyrazolo[l,5-a]pyrimidin,
(22) 8-(N-cyklopropylmetyl-N-(4-metyltiofenyl)me1ylamino)-2-metyl-3-(2-klor-4 metoksyfenyl)-5J-dihydro-mro[3,4-d]pyrazolo[l,5-a]pyrimidin,
(23) 8-(N, N-dipropylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(24) 8-(N,N-dibutylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(25) 8-(N-propyl-N-(4-metylfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(26) 8-(N-butyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(27) 8-(4-heptylamino)-2-metyl-3-(2^klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(28) 8-(N-butyl-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(29) 8-dicyklopropylmetylamino-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(30) 8-(N-cyklopropylmetyl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(31) 8-(N-(2-butynyl)-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(32) 8-(N-butyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-ajpyrimidin,
(33) 8-(N-propyl-N-(4-trifluormetyloksyfenyl)metylamino)-2-metyl-3 -(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(34) 8-(3-pentylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(35) 8-(N-cyklopropylmetylamino-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[ 1,5-ajpyrimidin,
(36) 8-(N-benzyl-N-(2-dimetylaminoetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(37) 8-(N-(2-butynyl)-N-etylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(38) 8-(N-(2-butynyl)-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(39) 8-(N-cyklopropyl-N-(4-metyltiofenyl)metylamino)-2-mety 1-3 -(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(40) 8-(N-propyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(41) 8-(N-cyklopropyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(42) 8-(N-propyl-N-(3 -fluorfenyl)metylamino)-2-metyl-3 -(2-klor-4-metoksyfeny 1)-SJ-dihydro-furotS^-dJpyrazolotljS-ajpyrimidin,
(43) 8-(N-propyl-N-(benz[d] 1, 3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-i\iro[3,4-d]pyrazolo[l,5-a]pyrimidin,
(44) 8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(45) 8-(N-butyl-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(46) 8-dicyklopropylmetylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(47) 8-(N-butyl-N-etylamino)-2-metyl-3-(2-me1yl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(48) 8-(N-butyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(49) 8-(N, N-dipropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(50) 8-bis(2-metoksyetyl)amino-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-dJpyrazolo[ 1,5-ajpyrimidin,
(51) 8-(N-butyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(52) 8-(N-butyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(53) 8-(N-etyl-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(54) 8-(N-propyl-N-(2-butyryl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(55) 8-(N-propyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(56) 8-(N-propyl-N-(benz[d] 1, 3-dioksolan-5-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(57) 8-(N-benzyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfe 5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(58) 8-(N-cyklopropylmetyl-N-(4-trilfuormetylfenyl)me1ylamino)-2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(5 9) 8-(N-cyklopropylmetyl-N-(4-trifluorme1ylfenyl)metylamino)-2-metyl-3 -(2-metyl-4-metoksyfenyl)-5J-dihydro-mro[3,4-d]pyrazolo[l,5-a]pyrimidin,
(60) 8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihy(ko-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(61) 8-(N-cyklopropyl-N-(4-fluorfenyl)metylarnino)-2-metyl-3 -(2-klor-4-metoksyfenyl)-5J-dihydro-fliro[3,4-d]pyrazolo[l,5-a]pyrimidin,
(62) 8-(N-cyklopropyl-N-(4-fluorfenyl)metylamino)-2-me1yl-3-(2-metyl-metoksyfenyl)-5,7-dihydro-mro[3,4-d]pyrazolo[l55-a]pyrimidin,
(63) 8-(N-cyklopropylmetyl-N-(4-fluorfenyl)me1ylamino)-2-metyl-3-(2-mety inetoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(64) 8-(N-propyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(65) 8-(N-propyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(66) 8-(N-etyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(67) 8-(N-etyl-N-(4-metyltiofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[ 1,5-ajpyrimidin,
(68) 8-(N-butyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[ 1,5-ajpyrimidin,
(69) 8-(N-cyklopropylmetyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(70) 8-(N-propyl-N-(5-metylfuran-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-ajpyrimidin,
(71) 8-(N-propyl-N-(5-metylfuran-2-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(72) 8-(N-cyklopropylmetyl-N-(2-metoksyetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-ajpyrimidin,
(73) 8-(N-propyl-N-(4-trifluormetyloksyfenyl)metylamino)-2-metyl-3 -(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(74) 8-(N-propyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihy(ko-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(75) 8-(N-cyklopropylmetyl-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5J-dihydro^
(76) 8-(N-(2-metoksyetyl)-N-(2-butynyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(77) 8-(N-(2-metoksye1yl)-N-(2-butynyl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5J-dihydro-mro[3,4-d]pyrazolo[l,5-a]pyrimidin,
(78) 8-(N-benzyl-N-cyklopropylamino)-2-me1yl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ls5-a]pyrimidin,
(79) 8-(N-benzyl-N-cyklopropylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[354-d]pyrazolo[l55-a]pyrimidin,
(80) 8-(N-cyklopropylmelyl-N-(2-metoksye1yl)amino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5 J-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(81) 8-(3-pentylamino)-2-metyl-3-(2, 5-diklor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(82) 8-(N-cyklopropyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(83) 8-(N-cyklopropyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(84) 8-dibutylamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(85) 8-(N-etyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(86) 8-(N-etyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(87) 8-(N-cyklopropylmetyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(88) 8-(N-cyklopropylmetyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(89) 8-(N-propyl-N-(tiofen-3-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(90) 8-(N-propyl-N-(5-metyltiofen-2-yl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(91) 8-(N-butyl-N-cyklopropylmetylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[ 1,5-ajpyrimidin,
(92) 8-(N-butyl-N-cyklopropylmetylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(93) 8-(N-propyl-N-(tiofen-3-yl)m 5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(94) 8-(N-propyl-N-(5-metyltiofen-2-yl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(95) 8-(N-propyl-N-(2-fluorfenyl)me1ylamino)-2-me1yl-3-(2-klor-4-metoksyfe^ 5J-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(96) 8-(N-propyl-N-(2-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5 s7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(97) 8-(N-etyl-N-propylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro^ furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(98) 8-(N-e1yl-N-propylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5J-dihydr furo[3,4-d]pyrazolo[ 1,5 -ajpyrimidin,
(99) 8-(3-pentylamino)-2-metyl-3-(2, 6-dimetyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(100) 8-(N-etyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(101) 8-(N-etyl-N-(4-fluorfenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(102) 8-(3-pentylamino)-2-metyl-3-(2-klor-4, 6-dimetoksyfenyl)-5,7-dihydro-furo [3,4-d]pyrazolo [1,5 -ajpyrimidin,
(103) 8-(4-heptylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(104) 8-(N, N-dipropylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihy(ko-furo[3,4-d]pyrazolo[ 1,5-a]pyrimidin,
(105) 8-(N-cyklopropylmetyl-N-propylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(106) 8-(N-benzyl-N-cyklopropylmetylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(107) 8-(N-cyklopropylmetyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l ,5-a]pyrimidin,
(108) 8-(N-propyl-N-(2-butynyl)amino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(109) 8-(N-buty 1-N-cyklopropylmetylamino)-3 -(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-ajpyrimidin,
(110) 8-(3-pentylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(111) 8-(N-cyklopropylmetyl-N-(4-fluorfenyl)me1ylam metoksyfenyl)-5,7-dihydro-iuro[3,4-d]pyrazolo[l,5-a]pyrimidin,
(112) 8-(4-heptylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-to d]pyrazolo[ 1,5-a]pyrimidin,
(113) 8-(N-propyl-N-(4-melylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl) dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(114) 8-(N-propyl-N-(4-fluorfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(115) 8-dicyklopropylmetylamino-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-ajpyrimidin,
(116) 8-(N-cyklopropylmetyl-N-(4-trifluormetylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[ 1,5-ajpyrimidin,
(117) 8-(N-cyklopropyl-N-(4-metylfenyl)metylamino)-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-a]pyrimidin,
(118) 8-(N-propyl-N-(4-cyanofenyl)metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
(119) 8-(N-cyklopropylmetyl-N-metylamino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-ajpyrimidin,
(120) 8-(N-cyklopropylmetyl-N-metylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[l,5-ajpyrimidin,
(121) 8-(N-propyl-N-(2-metoksyiminoetyl)amino)-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[l,5-ajpyrimidin,
(122) 8-[(2S)-l-metoksyiminobutan-2-yljamino-2-metyl-3-(2-metyl-4-metoksyfenyl)-5,7-dihydro-furo[3,4-djpyrazolo[ 1,5-ajpyrimidin og
(123) 9-(3-pentylamino)-6-metyl-5-(2-metyl-4-metoksyfenyl)-furo[3,2-d]pyrazolo[ 1,5-ajpyrimidin,
et farmasøytisk aksepterbart salt derav eller et hydrat derav.
19. Forbindelse som angitt i krav 1, som er valgt fra
(1) 8-hydroksy-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(2) 2-metyl-3-(2-metyl-4-metoksyfenyl)-8-[(2S, 4R)-4-metoksy-2-metoksymetylpyrolidin-1 -ylj-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(3) 8-(l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(4) 8-(l, 2, 3,4-tetrahydroisokinolM dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(5) 8-((3S)-3-metoksymetyl-l, 2, 3,4-tetrahydroisokinolin-2-yl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(6) 8-(4-fenylpiperazin-1 -yl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6J7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(7) 8-(4-(2-klorfenyl)piperazin-1 -yl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-657-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(8) 8-(3-etoksykarbonyl-l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidinJ
(9) 8-(3-(3-metyl-l, 2, 4-oksadiazol-5-yl)-l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(10) 8-(4-(4-klorfenyl)-l, 2, 5, 6-tetrahydropyridyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6J-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(11) 8-(3-pentyloksy)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin,
(12) 8-(3-pentyloksy)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(13) 8-(4-heptyloksy)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(14) 8-isopropyloksy-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(15) 8-(l, 6-heptadien-4-yl)oksy-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(16) 8-(3-pentyltio)-2-metyl-3-(2-klor-5-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(17) 8-(4-metylfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[l,5-a]pyrimidin,
(18) 8-(2, 4-diklorfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(19) 8-(3-trifluormetylfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(20) 8-(4-metoksyfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[djpyrazolo[ 1,5-ajpyrimidin,
(21) 8-(3, 5-diklorfenyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-ajpyrimidin,
(22) 8-(2-metylfenyl)-2-metyl-3-(2-metyl-4-metoksyfeny cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(23) 8-bis(etoksykarbonyl)me1yl-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(24) 8-( 1 -dimetylamino-1,3-diokso-2-butyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(25) 8-(2,4-diokso-3-pentyl)-2-metyl-3-(2-m^ cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(26) 8-bis(etoksykarbonyl)me1yl-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(27) 8-(l,3-hydroksy-2-propyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(28) 8-( 1, 3-dimetoksy-2-propyl)-2-metyl-3-(2-metyl-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin,
(29) 8-(N,N-dimetylkarbamoylmetyty dihydro-5H-cyklopenta[d]pyrazolo[ 1,5-a]pyrimidin og
(30) l-cyano-2-metyl-8-hydroksy-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[ 1,2-a]pyrimidin,
et farmasøytisk aksepterbart salt derav eller et hydrat derav.
20. Forbindelse som angitt i krav 1, som er valgt fra
(1) 6-metyl-5-(2-metyl-4-metoksyfenyl)-9-[(2S, 4R)-4-metoksy-2-metoksymetylpyrolidin-l-yl]-2, S-dihydro-furofS^-dJpyrazolotljS-ajpyrimidin,
(2) 2-metyl-3-(2-metyl-4-metoksyfenyl)-8-[(2S, 4R)-4-metoksy-2-metoksymetylpyrolidin-l-yl]-5J-dihydro-furo[3,4-d]pyrazolo[l,5-a]pyrimidin,
(3) 6-metyl-5-(2-metyl-4-metoksyfenyl)-9-[(2S, 4R)-4-metoksy-2-metoksymetylpyrolidin-l-yl]-2, S-dihydro-pyrrolofS^-djpyrazolotljS-ajpyrimidin,
(4) 8-(3-pentyloksy)-2-me1yl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3J4-d]pyrazolo[l,5-a]pyrimidin og
(5) 8-bis(etoksykarbonyl)metyl-2-metyl-3-(2-klor-4-metoksyfenyl)-5,7-dihydro-furo[3,4-d]pyrazolo[ 1,5-ajpyrimidin,
et farmasøytisk aksepterbart salt derav eller et hydrat derav.
21. Forbindelse som angitt i krav 1, som er 8-(3-pentylamino)-2-metyl-3-(2-klor-4-metoksyfenyl)-6,7-dihydro-5H-cyklopenta[d]pyrazolo[l,5-a]pyrimidin, et farmasøytisk aksepterbar salt derav eller et hydrat derav.
22. Farmasøytisk preparat,
karakterisert ved at det omfatter en forbindelse med formel (I) som angitt i krav 1, et farmasøytisk aksepterbart salt derav eller et hydrat derav som en aktiv bestanddel.
23. Farmasøytisk preparat for behandling og/eller forebygging av sykdom indusert ved ekstraordinær sekresjon av kortikotropinfrigjørende faktor,
karakterisert ved at det omfatter en forbindelse med formel ( I)
hvor X og Y hver uavhengig er karbon eller nitrogen og hvor begge ikke er nitrogener samtidig;
W er karbon eller nitrogen;
U og Z er hver uavhengig CR2, NR<13>, nitrogen, oksygen, svovel, C=0 eller C=S; R<2> er (i) hydrogen, (ii) Cl-8 alkyl, (iii) C2-8 alkenyl, (iv) C2-8 alkynyl, (v) halogenatom, (vi) CF3, (vii) cyano, (viii) nitro, (ix) NR9R<10> hvor R<9> og R<10> hver uavhengig er (i) hydrogen, (ii) Cl-4 alkyl, (iii) C3-10 mono- eller bi-karbocyklisk ring, (iv) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (v) Cl-4 alkyl substituert med C3-10 mono- eller bi-karbocyklisk ring eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer, (x) OR<11> hvor R<1>'er (i) hydrogen, (ii) Cl-4 alkyl, (iii) C5-6 karbocyklisk ring, (iv) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (v) Cl-4 alkyl som er substituert med en C5-6 karbocyklisk ring eller en 5-eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom, (xi) SH, (xii) S(0)nR<12> hvor n er 0, 1 eller 2, R<12> er (i) Cl-4 alkyl, (ii) C5-6 karbocyklisk ring, (iii) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (iv) Cl-4 alkyl substituert med en C5-6 karbocyklisk ring eller en 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom, (xiii) COR11, (xiv) COOR11, (xv) CONR<9>R<10>, (xvi) C3-10 mono- eller bi-karbocyklisk ring, (xvii) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (xviii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<n>, SH, S(0)nR<12>, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi- karbocyklisk ring og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
R<13> er (i) hydrogen, (ii) Cl-4 alkyl, (iii) C2-4 alkenyl, (iv) C2-4 alkynyl, (v) C3-10 mono- eller bi-karbocyklisk ring, (vi) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer eller (vii) Cl-4 alkyl substituert med C3-10 mono- eller bi-karbocyklisk ring eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer,
'-^ er en enkeltbinding eller dobbeltbinding,
er C4-6 karbocyklisk ring eller 4-6-leddet heterocyklisk ring inneholdende minst ett nitrogenatom, oksygenatom og svovelatom og disse ringer er usubstituerte eller substituerte med 1-3 substituenter valgt fra Cl-4 alkyl, Cl-4 alkoksy, halogenatom og CF3,
med den betingelse at når X, Y, Z og U er karbon og W er nitrogen, da er ring A ikke benzen,
R<1> er (i) Cl-8 alkyl som er usubstituert eller substituert med 1-5 R<14>, (ii) C2-8 alkenyl som er usubstituert eller substituert med 1-5 R<14>, (iii) C2-8 alkynyl som er usubstituert eller substituert med 1-5 R<14>, (iv) NR<4>R<5> hvor R4 og R<5> hver uavhengig er, (i) hydrogen, (ii) Cl-15 alkyl som er usubstituert eller substituert med 1-5 R<17>, (iii) C2-15 alkenyl som er usubstituert eller substituert med 1-5 R<17>, (iv) C2-15 alkynyl som er usubstituert eller substituert med 1-5 R<17>, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-15 leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (v) OR<6> hvor R<6> er (i) hydrogen, (ii) C1-10 alkyl, (iii) C2-10 alkenyl, (iv) C2-10 alkynyl, (v) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (vii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<n>, SH, S(0)nR12, COR<11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R 1 R, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1 fl, (vi) SH, (vii) S(0)nR 7 hvor n er som definert i det foregående, R 7 er (i) Cl-8 alkyl, (ii) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (iii) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18>, (iv) Cl-4 alkyl substituert med C3-10 mono- eller bi- karbocyklisk ring, som er usubstituert eller substituert med 1-5 R 1 fl eller 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1 (2, (viii) COR<6>, (ix) COOR<6>, (x) CONR<4>R<5>, (xi) NR8COR6ahvorR6aer (i) hydrogen, (ii) Cl-10 alkyl, (iii) C2-10 alkenyl, (iv) C2-10 alkynyl eller (v) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R1<0>, OR<lla>, =N-OR<n>, SH, S(0)nR<12>, CO<R11>, COOR<11 >og CONR9R10, (xii) NR<8>COOR<6> hvor R<6> er som definert i det foregående, R<8> er (i) hydrogen, (ii) Cl-8 alkyl, (iii) C2-8 alkenyl, (iv) C2-8 alkynyl, (v) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, (vi) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18> eller (vii) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<u>, =N-OR<n>, SH, S(0)nR<12>, CO<R11>, COOR<11>, CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18>, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R 1R, (xiii) NR<8>CONR<4>R<5>, (xiv) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15> eller (xv) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>,
Rll<a> er (i) hydrogen, (ii) Cl-4 alkyl eller (iii) Cl-4 alkyl substituert med C5-6 karbocyklisk ring eller 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom,
R<14> er (a) halogenatom, (b) CF3, (c) OCF3, (d) cyano, (e) nitro, (f) NR<4>R<5>, (g) OR<6>, (h) =N-OR<6>,0) SH, (k) S(0)nR<7>, (1) COR<6>, (m) COOR<6>, (n) CONR<4>R<5>, (o) NR<8>COR6, (p) NR<8>COOR<6>, (q) NR<8>CONR<4>R<5>, (r) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<15> eller (s) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<15>, R<15> er (a) Cl-8 alkyl, (b) C2-8 alkenyl, (c) C2-8 alkynyl, (d) Cl-4 alkoksy(Cl-4)alkyl, (e) halogenatom, (f) CF3, (g) OCF3, (h) cyano, (j) nitro, (k) NR<4>R<5>, (1) OR<6>, (m) SH, (n) S(0)nR<7>, (o) COR<6>, (p) COOR<6>, (q) CONR<4>R<5>, (r) NR<8>COR<6>, (s) NR<8>COOR<6>, (t) NR<8>CONR<4>R<5>, (u) C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<19>, (v) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<19> eller (w) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro,
NR<4>R<5>, OR<6>, =N-OR<6>, SH, S(0)nR<7>, COR<6>, COOR<6>, CONR<4>R<5>, NR<8>COR<6>, NR<8>COOR<6>, NR<8>CONR<4>R<5>, C3-10 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<19>, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<19>,
R1<7> er (a) halogenatom, (b) CF3, (c) OCF3, (d) cyano, (e) nitro, (f) NR<9>R10, (g) OR<lla>, (h) =N-OR<n>, (j) SH, (k) S(0)nR<12>, (1) COR<11>, (m) COOR<11>, (n) CONR<9>R<10>, (o) NR<8>COR<n>, (p) NR<8>COOR<n>, (q) NR<8>CONR<9>R<10>, (r) C3-15 mono- eller bi-karbocyklisk ring som er usubstituert eller substituert med 1-5 R<18a> eller (s) 3-15-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer som er usubstituert eller substituert med 1-5 R<18a>,
R<18> er (a) Cl-4 alkyl, (b) C2-4 alkenyl, (c) C2-4 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) SH, (k) S(0)nR<12>, (1) NR<9>R10, (m) OR<11>, (n) COR<11>, (o) COOR<11>, (p) CONR<9>R<10>, (q) C5-6 karbocyklisk ring, (r) 5- eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom eller (s) Cl-4 alkyl substituert med C5-6 karbocyklisk ring eller 5 eller 6-leddet heterocyklisk ring inneholdende 1-2 nitrogenatomer, 1 oksygenatom og/eller 1 svovelatom,
R18<a> er (a) Cl-4 alkyl, (b) C2-4 alkenyl, (c) C2-4 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) SH, (k) S(0)nR<12>, (1) NR<9>R<10>, (m) OR<lla>, (n) COR<11>, (o) COOR<11> eller (p) CONR<9>R10,
R<19> er Cl-4 alkyl, Cl-4 alkoksy, halogenatom, CF3, OCF3, cyano, nitro, amino, NH(Cl-4 alkyl) eller N(Cl-4 alkyl)2,
RJ is (i) C5-10 mono- eller bi-karbocyklisk ring substituert med 1-5 R eller (ii) 5-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer substituert med 1-5 R<16>,
R<16> er (a) Cl-8 alkyl, (b) C2-8 alkenyl, (c) C2-8 alkynyl, (d) halogenatom, (e) CF3, (f) OCF3, (g) cyano, (h) nitro, (j) NR9R10,
(k)OR<11>,
(1) SH, (m) S(0)nR<12>, med unntak av fenyltio,
(n)COR<11>, (o) COOR11, (p) CONR<9>R<10>,
(q)NR<8>COR<n>,
(r)NR<8>COOR<n,>(s) NR<8>CONR<9>R<10>, (t) C3-10 mono- eller bi-karbocyklisk ring, (u) 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer, 1-2 oksygenatomer og/eller 1-2 svovelatomer, (v) Cl-4 alkyl substituert med 1-2 substituenter valgt fra halogenatom, CF3, OCF3, cyano, nitro, NR<9>R<10>, OR<11>, =N-OR<n>, SH, S(0)nR<12>, COR<11>, COO<R11>, CONR<9>R<10>,
NRtOR1 \ NR<8>COOR'', NR<8>CONR<9>R<10>, C3-10 mono- eller bi-karbocyklisk ring, og 3-10-leddet mono- eller bi-heterocyklisk ring inneholdende 1-4 nitrogenatomer,
1-2 oksygenatomer og/eller 1-2 svovelatomer,
med den betingelse at (1) når hver av X og W er karbonatomer, hver av Y og Z er nitrogenatomer, U er CR4 og R<1> er OR<6>, da er R<3> ikke fenyl substituert med 1 halogenatom, fenyl substituert med 1 trifluormetyl og fenyl substituert med trifluormetyl og nitro, (2) når hver av X, Y og Z er karbonatomer og hver av U og W er nitrogenatomer, da er R C5-10 mono- eller bi-karbocyklisk ring substituert med 1-5 R<16>,
et farmasøytisk aksepterbart salt derav eller et hydrat derav som aktiv bestanddel.
24. Farmasøytisk preparat som angitt i krav 23 for behandling og/eller forebygging av sykdommer indusert ved ekstraordinær sekresjon av kortikotropinfrigjørende faktor som depresjon, enkeltepisode depresjon, tilbakevendende depresjon, post partum depresjon, depresjon indusert ved barnemishandling, angst, angstrelaterte lidelser (panikklidelser, særlig fobier, frykt for å falle, sosiale fobier, obsessiv-kompulsiv lidelse), emosjonell lidelse, bipolar lidelse, posttraumatisk stresslidelse, peptisk ulcus, diaré, konstipasjon, irritabel tarm, inflammatorisk tarmsykdom (ulcerøs kolitt, Crohns sykdom), stress-indusert gastrointestinal forstyrrelse, nervøs emese, spiseforstyrrelse (anorexia nervosa, bulimia nervosa), fedme, stress-indusert søvnforstyrrelse, søvnforstyrrelse indusert ved muskelfibersmerte, stress-indusert immun-suppresjon, stress-indusert hodepine, stress-indusert feber, stress-indusert smerte, postoperativt stress, revmatoid artritt, osteoartritt, osteoporose, psoriasis, tyreoidea dysfunksjon, uveitt, astma, upassende antidiaréhormonindusert lidelse, smerte, inflammasjon, allergisk sykdom, hodeskade, ryggmargskade, iskemisk nevron-skade, toksisitets-nevronskade, Cushings sykdom, slag, spasme, muskulær spasme, epilepsi, iskemisk sykdom, Parkinsons sykdom, Huntington sykdom, urininkontinens, Alzheimers sykdom, senil demens av Alzheimer type, multi-infarkt demens, amyotrof lateralsklerose, hypoglykemi, kardiovaskulær eller hjerte-relatert sykdom (hypertensjon, takykardi, kongestiv hjertesvikt), narkotikaavhengighet eller alkoholavhengighet.
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- 2001-12-28 TW TW090132698A patent/TWI293630B/zh not_active IP Right Cessation
-
2003
- 2003-06-24 IL IL156609A patent/IL156609A/en not_active IP Right Cessation
- 2003-06-26 NO NO20032956A patent/NO326522B1/no not_active IP Right Cessation
- 2003-06-26 ZA ZA2003/05003A patent/ZA200305003B/en unknown
- 2003-12-05 JP JP2003406938A patent/JP4217968B2/ja not_active Expired - Fee Related
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2005
- 2005-09-07 US US11/219,736 patent/US7459459B2/en not_active Expired - Fee Related
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2008
- 2008-09-02 US US12/202,984 patent/US7807688B2/en not_active Expired - Fee Related
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