DK2649075T3 - Substituerede pyrazolopyrimidiner som glucocerebrosidase-aktivatorer - Google Patents
Substituerede pyrazolopyrimidiner som glucocerebrosidase-aktivatorer Download PDFInfo
- Publication number
- DK2649075T3 DK2649075T3 DK11810714.3T DK11810714T DK2649075T3 DK 2649075 T3 DK2649075 T3 DK 2649075T3 DK 11810714 T DK11810714 T DK 11810714T DK 2649075 T3 DK2649075 T3 DK 2649075T3
- Authority
- DK
- Denmark
- Prior art keywords
- carboxamide
- pyrimidine
- phenyl
- alkyl
- pyrazolo
- Prior art date
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- 108010017544 Glucosylceramidase Proteins 0.000 title description 13
- 102000004547 Glucosylceramidase Human genes 0.000 title description 13
- 239000012190 activator Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 106
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 208000015872 Gaucher disease Diseases 0.000 claims abstract description 18
- -1 cyano, nitro, amino Chemical group 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 208000024891 symptom Diseases 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- HVZPJBKUFRREQC-UHFFFAOYSA-N n-(4-ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=C(C#C)C=C1 HVZPJBKUFRREQC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 101150028412 GBA gene Proteins 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
- 206010064571 Gene mutation Diseases 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 2
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- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
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- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 2
- MXUJAPVDZMJYBX-UHFFFAOYSA-N n-(4-bromophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=C(Br)C=C1 MXUJAPVDZMJYBX-UHFFFAOYSA-N 0.000 claims 2
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims 1
- YDKKMPMIQSIIKC-UHFFFAOYSA-N 7-(difluoromethyl)-5-methyl-n-(4-methylphenyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(C)=CC=C1NC(=O)C1=C2N=C(C)C=C(C(F)F)N2N=C1 YDKKMPMIQSIIKC-UHFFFAOYSA-N 0.000 claims 1
- VCRFPNNYMJNLSQ-UHFFFAOYSA-N 7-(difluoromethyl)-5-methyl-n-[4-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C(F)F)N2N=CC=1C(=O)NC1=CC=C(C(F)(F)F)C=C1 VCRFPNNYMJNLSQ-UHFFFAOYSA-N 0.000 claims 1
- KMOYDBZAUGGJNC-UHFFFAOYSA-N 7-(difluoromethyl)-n-(4-ethylphenyl)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(CC)=CC=C1NC(=O)C1=C2N=C(C)C=C(C(F)F)N2N=C1 KMOYDBZAUGGJNC-UHFFFAOYSA-N 0.000 claims 1
- WICPNVMYTPNMIV-UHFFFAOYSA-N 7-(difluoromethyl)-n-(4-ethynylphenyl)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C(F)F)N2N=CC=1C(=O)NC1=CC=C(C#C)C=C1 WICPNVMYTPNMIV-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
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- QSACGBUNBSFHBK-UHFFFAOYSA-N n-(2-acetamidophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound CC(=O)NC1=CC=CC=C1NC(=O)C1=C2N=C(C)C=C(C)N2N=C1 QSACGBUNBSFHBK-UHFFFAOYSA-N 0.000 claims 1
- POUWXDPADZXHFI-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-7-(difluoromethyl)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C(F)F)N2N=CC=1C(=O)NC1=CC=C(Cl)C(Cl)=C1 POUWXDPADZXHFI-UHFFFAOYSA-N 0.000 claims 1
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- GUBFWHDFZJSMKW-UHFFFAOYSA-N n-(4-acetamidophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC(=O)C1=C2N=C(C)C=C(C)N2N=C1 GUBFWHDFZJSMKW-UHFFFAOYSA-N 0.000 claims 1
- BLOQLAGLYRHRFK-UHFFFAOYSA-N n-(4-cyanophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=C(C#N)C=C1 BLOQLAGLYRHRFK-UHFFFAOYSA-N 0.000 claims 1
- NVEKWWBEUSXOPO-UHFFFAOYSA-N n-(4-iodophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1=CC=C(I)C=C1 NVEKWWBEUSXOPO-UHFFFAOYSA-N 0.000 claims 1
- MCQYBGOYJAACFA-UHFFFAOYSA-N n-(4-tert-butylcyclohexyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=12N=C(C)C=C(C)N2N=CC=1C(=O)NC1CCC(C(C)(C)C)CC1 MCQYBGOYJAACFA-UHFFFAOYSA-N 0.000 claims 1
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Claims (7)
- 1. Farmaceutisk sammensætning, der omfatter en forbindelse med formleneller et farmaceutisk acceptabelt salt deraf sammen med et farmaceutisk acceptabelt bæremiddel, hvor den ene af betingelserne (a) og (b) nedenfor er opfyldt: (a) Ri er phenyl, naphthyl, tetrahydronaphthyl eller dihydroindenyl, som hver er usubstitueret eller substitueret med en eller flere substituenter valgt uafhængigt blandt halogen, hydroxyl, cyano, nitro, amino, -CHO, -COOH, Cr C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkanoyl, mono- eller di-Ci-C6alkylamino, mono- eller di-Ci-C6alkylcarboxamid, Ci-C6alkylthio, Cr C6alkylsulfonyl, Ci-C2halogenalkyl og Ci-C2halogenalkoxy og med 0 eller 1 substituent valgt blandt Y-Z-, hvor Z er en kovalent binding, Ci-C4alkylen, -S-, -O-, -NR-, -C(O)-, -NHC(O)- eller -C(O)NH-, hvor R er hydrogen eller Cr C4alkyl, og Y er phenyl eller pyridyl, som hver er usubstitueret eller substitueret med 1 til 3 substituenter valgt uafhængigt blandt halogen, hydroxyl, cyano, nitro, amino, Ci-C4alkyl og Ci-C4alkoxy; eller (b) Ri er cyclohexyl substitueret med mindst én trifluormethyl eller C3-C6alkyl; R2 er hydrogen eller methyl; R3 er hydrogen; R5 og R7 begge er methyl; eller den ene af R5 og Ry er methyl, og den anden er phenyl; eller den ene af R5 og Ry er methyl, og den anden er difluormethyl; R6 er hydrogen, halogen, hydroxyl, Ci-C4alkyl eller Ci-C4alkoxy; og hvor Ri ikke er usubstitueret phenyl, dihydroindenyl eller phenyl substitueret med 1 eller 2 substituenter valgt uafhængigt blandt chlor, fluor, Ci-C4alkyl, acetyl og trifluormethyl, (1) når R6 er hydrogen, og R5 og Ry begge er methyl, eller (2) når R6 er hydrogen, og den ene af R5 og Ry er methyl, og den anden er phenyl.
- 2. Farmaceutisk sammensætning ifølge krav 1, hvor R3 og R6 begge er hydrogen.
- 3. Farmaceutisk sammensætning ifølge et hvilket som helst af kravene 1 til 2, hvor: Ri er phenyl, naphthyl, tetrahydronaphthyl eller dihydroindenyl, som er usubstitueret eller substitueret med en eller flere substituenter valgt uafhængigt blandt halogen, hydroxyl, cyano, nitro, amino, -CHO, -COOH, Cr C6alkyl, C2-C6alkanoyl, mono- eller di-Ci-C6alkylamino, mono- eller di-Ci-C6alkylcarboxamid, Ci-C6alkylthio, Ci-C6alkylsulfonyl, Ci-C2halogenalkyl og Ci-C2halogenalkoxy og med 0 eller 1 substituent valgt blandt Y-Z-, hvor Z er en kovalent binding, Ci-C4alkylen, -S-, -O-, -NR-, -C(O)-, - NHC(O)- eller -C(O)NH-, hvor R er hydrogen eller Ci-C4alkyl, og Y er phenyl eller pyridyl, som hver er usubstitueret eller substitueret med 1 til 3 substituenter valgt uafhængigt blandt halogen, hydroxyl, cyano, nitro, amino, Ci-C4alkyl og Cr C4alkoxy.
- 4. Forbindelse eller farmaceutisk acceptabelt salt deraf, hvor forbindelsen er: N-(4-ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-bromphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; 5.7- dimethyl-N-(2-(phenylthio)phenyl)pyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-cyanophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-tert-butylcyclohexyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-tert-butylcyclohexyl)-5-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-3- carboxamid; N-(3-cyanophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; 5.7- dimethyl-N-(4-(methylsulfonyl)phenyl)pyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(2-acetamidophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-acetamidophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; 5-methyl-7-phenyl-N-(2-(phenylthio)phenyl)pyrazolo[1,5-a]pyrimidin-3-carboxamid; 7-(difluormethyl)-5-methyl-N-p-tolylpyrazolo[1,5-a]pyrimidin-3-carboxamid; 7-(difluormethyl)-N-(4-ethylphenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-carboxamid; 7-(difluormethyl)-5-methyl-N-(4-(trifluormethyl)phenyl) pyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(3,4-dichlorphenyl)-7-(difluormethyl)-5-methylpyrazolo[1,5-a]pyrimidin-3- carboxamid; 7-(difluormethyl)-N-(4-ethynylphenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-tert-butylcyclohexyl)-5-(difluormethyl)-7-methylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(3-(dimethylamino)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-(dimethylamino)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4-bromphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4'-cyanobiphenyl-4-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(3'-methoxybiphenyl-4-yl)-5,7 -dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(3'-cyanobiphenyl-4-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4'-(dimethylamino)biphenyl-4-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3- carboxamid; N-(4'-methoxybiphenyl-4-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(3'-(dimethylamino)biphenyl-4-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3- carboxamid; N-(4-iodphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(3-bromphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4'-methoxybiphenyl-3 -yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4'-cyanobiphenyl-3-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(3'-methoxybiphenyl-3-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid; N-(4'-(dimethylamino)biphenyl-3-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3- carboxamid; N-(3'-(dimethylamino)biphenyl-3-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3- carboxamid; 5,7-dimethyl-N-(3-(pyrimidin-5-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-carboxamid;N-(3'-cyanobiphenyl-3-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid;
- 5. Forbindelse ifølge krav 4, hvor forbindelsen er N-(4-ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-carboxamid.
- 6. Farmaceutisk sammensætning ifølge et hvilket som helst af kravene 1-3 eller en farmaceutisk sammensætning, der omfatter forbindelsen ifølge krav 4 eller 5 eller et salt deraf sammen med et farmaceutisk acceptabelt bæremiddel; hvor sammensætningen eventuelt er i form af en oral doseringsform.
- 7. Forbindelse med formel (I) eller et farmaceutisk acceptabelt salt deraf til anvendelse til behandling af Gauchers sygdom hos en patient eller forebyggelse af symptomerne på Gauchers sygdom hos en patient, der har en GBA-genmutation, hvor formel (I) er:Formula (I) hvor ringener et ringsystem med formlen (i)hvori R5 er en eventuelt substitueret alkylidengruppe, og R6 og R7 bærer definitionerne, der er anført nedenfor, eller(ϋ)hvori R5, R6 og R7 bærer definitionerne, der er anført nedenfor; Ri er Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, (mono- eller bicyklisk carbocyclyl)C0-C4alkyl eller (mono- eller bicyklisk heterocyclyl)C0-C4alkyl, hvor hver Ri er usubstitueret eller substitueret med en eller flere substituenter valgt uafhængigt blandt halogen, hydroxyl, cyano, nitro, amino, -CHO, -COOH, Ci-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, Ci-C6alkoxy, C2-C6alkanoyl, (mono- eller di-Ci-C6alkylamino)C0-C4alkyl, mono- eller di-Ci-C6alkylcarboxamid, Ci-C6alkylester, Ci-C6alkylthio, Ci-C6alkylsulfonyl, Cr C2halogenalkyl og Ci-C2halogenalkoxy og med 0 eller 1 substituent valgt blandt Y-Z-, hvor Z er en kovalent binding, Ci-C4alkylen, C2-C4alkenylen, C2-C4alkynylen, -S-, -O-, -NR-, -C(O)-, -NHC(O)- eller -C(O)NH-, hvor R er hydrogen eller Ci-C4alkyl, og Y er phenyl, pyrimidinyl, en 5- eller 6-leddet heterocycloalkyl eller pyridyl, som hver er substitueret med 0 til 3 substituenter valgt uafhængigt blandt halogen, hydroxyl, cyano, nitro, amino, Ci-C4alkyl, Ci-C4alkoxy, mono- og di-Ci-C4alkylamino, trifluormethyl, difluormethyl, trifluormethoxy og phenyl; R2 er hydrogen, Ci-C6alkyl, C3-C7cycloalkyl eller (phenyl)C0-C2alkyl; eller Ri og R2 sammen danner en 5- til 7-leddet heterocycloalkylring med 0 eller 1 yderligere heteroatom valgt blandt N, O og S, hvilken 5- til 7-leddede heterocycloalkylring eventuelt er fusioneret til en phenyl eller pyridyl; hvilken 5- til 7-leddede heterocycloalkylring er usubstitueret eller substitueret med en eller flere substituenter valgt uafhængigt blandt halogen, hydroxyl, Ci-C2alkyl og Ci-C2alkoxy; R3 er hydrogen eller Ci-C2alkyl; R5 er halogen, hydroxyl, amino, cyano, vinyl, cyclopropyl, cyclopropylidenyl, Ci-C4alkyl, Ci-C4alkoxy, difluormethyl, trifluormethyl eller phenyl; Re er hydrogen, halogen, hydroxyl, Ci-C4alkyl eller Ci-C4alkoxy; og R7 er halogen, hydroxyl, amino, cyano, Ci-C4alkyl, Ci-C4alkoxy, difluormethyl eller trifluormethyl, eller R7 er phenyl eller en 5- til 7-leddet heterocycloalkylring med 1 eller 2 heteroatomer valgt blandt N, O og S, hvor hver R7 er direkte bundet via en kovalent binding eller bundet via en Ci-C4alkyl, Ci-C4alkoxy eller Cr C4alkylaminogruppe, og hvor hver R7 er usubstitueret eller substitueret med 1 til 3 substituenter valgt uafhængigt blandt halogen, hydroxyl, Ci-C4alkyl, Cr C4alkoxy, (mono- og di-Ci-C2alkylamino)C0-C4alkyl, Ci-C2halogenalkyl og Ci-C2halogenalkoxy; eller R6 og R7 sammen danner en 5- eller 6-leddet carbobicyklisk ring med ingen yderligere punkter med umættethed, hvilken ring er usubstitueret eller substitueret med 1 til 3 substituenter valgt uafhængigt blandt Ci-C2alkyl og Ci-C2alkoxy, hvor Ri ikke er usubstitueret phenyl, dihydroindenyl, benzo[b] [1,4]dioxolyl, benzo[d] [1,3]dioxol-5-yl, cyclohexyl, pyridyl eller phenyl substitueret med 1 eller 2 substituenter valgt uafhængigt blandt chlor, fluor, Ci-C4alkyl, Cr C2alkoxy, acetyl, trifluormethyl, når R6 er hydrogen, R5 og R7 begge er methyl, eller når R6 er hydrogen, og den ene af R5 og R7 er methyl, og den anden er phenyl; og Ri ikke er 1-(4-fluorbenzyl)-1 H-pyrazolo-4-yl, når R6 er hydrogen, og den ene af R5 og R7 er methyl, og den anden er phenyl.
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