SK1892001A3 - Muscarinic agonists and antagonists, pharmaceutical composition them comprising and use thereof - Google Patents

Muscarinic agonists and antagonists, pharmaceutical composition them comprising and use thereof Download PDF

Info

Publication number: SK1892001A3
Authority: SK; Slovakia
Prior art keywords: alkyl; azatricyclo; independently; compound; halogen
Prior art date: 1998-08-18

Application number

SK189-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Gurmit Grewal

Anna Toy-Palmer

Xiong Cai

George Mark Latham

Original Assignee

Ucb Sa

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-08-18

Filing date

1999-08-16

Publication date

2001-11-06

1999-08-16 Application filed by Ucb Sa filed Critical Ucb Sa

2001-11-06 Publication of SK1892001A3 publication Critical patent/SK1892001A3/sk

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
239000000472 muscarinic agonist Substances 0.000 title description 9
239000003149 muscarinic antagonist Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 89
208000002193 Pain Diseases 0.000 claims abstract description 18
230000036407 pain Effects 0.000 claims abstract description 15
-1 -OH Inorganic materials 0.000 claims description 65
238000000034 method Methods 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 22
229920006395 saturated elastomer Polymers 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 20
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 16
125000003118 aryl group Chemical group 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 12
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 12
125000005842 heteroatom Chemical group 0.000 claims description 12
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 10
DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
MZAGXDHQGXUDDX-JSRXJHBZSA-N (e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/C(N)=O MZAGXDHQGXUDDX-JSRXJHBZSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000004122 cyclic group Chemical group 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
239000000651 prodrug Substances 0.000 claims description 6
229940002612 prodrug Drugs 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
208000024827 Alzheimer disease Diseases 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
150000002431 hydrogen Chemical group 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000000304 alkynyl group Chemical group 0.000 claims description 3
230000006949 cholinergic function Effects 0.000 claims description 3
201000000980 schizophrenia Diseases 0.000 claims description 3
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
208000015114 central nervous system disease Diseases 0.000 claims description 2
208000010877 cognitive disease Diseases 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 4
125000003342 alkenyl group Chemical group 0.000 claims 4
238000004519 manufacturing process Methods 0.000 claims 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 3
208000035475 disorder Diseases 0.000 claims 3
BVLWZZNUQSYJOG-UHFFFAOYSA-N BrC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 Chemical compound BrC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 BVLWZZNUQSYJOG-UHFFFAOYSA-N 0.000 claims 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
230000000202 analgesic effect Effects 0.000 claims 2
INDYXBQOPZTSTJ-UHFFFAOYSA-N 2-pyridin-3-yl-1-azatricyclo[3.3.1.13,7]decane Chemical compound C1C(C2)CC3CC1CN2C3C1=CC=CN=C1 INDYXBQOPZTSTJ-UHFFFAOYSA-N 0.000 claims 1
ADMGCHXOTILZAP-UHFFFAOYSA-N CC(C)OC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 Chemical compound CC(C)OC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 ADMGCHXOTILZAP-UHFFFAOYSA-N 0.000 claims 1
WTTLLKAMZRPQQS-UHFFFAOYSA-N CCOC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 Chemical compound CCOC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 WTTLLKAMZRPQQS-UHFFFAOYSA-N 0.000 claims 1
NRJLFPGRQMOVIQ-UHFFFAOYSA-N NC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 Chemical compound NC1=CN=CC(C2N3CC4CC(C3)CC2C4)=C1 NRJLFPGRQMOVIQ-UHFFFAOYSA-N 0.000 claims 1
VODCVOLSDCFBLD-UHFFFAOYSA-N OC1C(C2)CC3CC1CN2C3C1=CC=CN=C1 Chemical compound OC1C(C2)CC3CC1CN2C3C1=CC=CN=C1 VODCVOLSDCFBLD-UHFFFAOYSA-N 0.000 claims 1
125000004432 carbon atom Chemical group C* 0.000 claims 1
230000001684 chronic effect Effects 0.000 claims 1
ACUZDYFTRHEKOS-UHFFFAOYSA-N decan-2-ol Chemical compound CCCCCCCCC(C)O ACUZDYFTRHEKOS-UHFFFAOYSA-N 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
125000005936 piperidyl group Chemical group 0.000 claims 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
230000001624 sedative effect Effects 0.000 description 12
239000000243 solution Substances 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 10
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
230000000694 effects Effects 0.000 description 8
238000012360 testing method Methods 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
230000003502 anti-nociceptive effect Effects 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
238000003756 stirring Methods 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 5
108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
238000003556 assay Methods 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
230000001713 cholinergic effect Effects 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
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239000000126 substance Substances 0.000 description 5
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HDJRNMVQLGESEX-UHFFFAOYSA-N 4-chlorothiadiazole Chemical compound ClC1=CSN=N1 HDJRNMVQLGESEX-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
150000001347 alkyl bromides Chemical class 0.000 description 4
230000036592 analgesia Effects 0.000 description 4
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238000006243 chemical reaction Methods 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000000064 cholinergic agonist Substances 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
230000000926 neurological effect Effects 0.000 description 4
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238000002360 preparation method Methods 0.000 description 4
210000003296 saliva Anatomy 0.000 description 4
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229910000104 sodium hydride Inorganic materials 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 3
FWWBBQGYQSXIPP-UHFFFAOYSA-N 1-azabicyclo[3.3.1]non-2-ene Chemical class C1C=CN2CCCC1C2 FWWBBQGYQSXIPP-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
102000009660 Cholinergic Receptors Human genes 0.000 description 3
108010009685 Cholinergic Receptors Proteins 0.000 description 3
208000000094 Chronic Pain Diseases 0.000 description 3
241000283086 Equidae Species 0.000 description 3
102000007216 Muscarinic M4 Receptor Human genes 0.000 description 3
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208000025966 Neurological disease Diseases 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
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FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
235000010323 ascorbic acid Nutrition 0.000 description 3
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239000012267 brine Substances 0.000 description 3
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125000001072 heteroaryl group Chemical group 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
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SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 3
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 3
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239000000018 receptor agonist Substances 0.000 description 3
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125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
WZZPXVURFDJHGI-LLVKDONJSA-N 3-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-4-butylsulfanyl-1,2,5-thiadiazole Chemical compound CCCCSC1=NSN=C1[C@H]1C(CC2)CCN2C1 WZZPXVURFDJHGI-LLVKDONJSA-N 0.000 description 2
125000005917 3-methylpentyl group Chemical group 0.000 description 2
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101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 2
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QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
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239000007788 liquid Substances 0.000 description 2
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
230000003551 muscarinic effect Effects 0.000 description 2
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150000007524 organic acids Chemical class 0.000 description 1
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102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
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125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
239000000523 sample Substances 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
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239000012312 sodium hydride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
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239000007858 starting material Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
235000015523 tannic acid Nutrition 0.000 description 1
229920002258 tannic acid Polymers 0.000 description 1
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239000011975 tartaric acid Substances 0.000 description 1
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150000004867 thiadiazoles Chemical class 0.000 description 1
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230000002588 toxic effect Effects 0.000 description 1
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229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
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238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Landscapes

Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)

SK189-2001A 1998-08-18 1999-08-16 Muscarinic agonists and antagonists, pharmaceutical composition them comprising and use thereof SK1892001A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US9697798P	1998-08-18	1998-08-18
PCT/US1999/018570 WO2000011001A1 (en)	1998-08-18	1999-08-16	Muscarinic agonists and antagonists

Publications (1)

Publication Number	Publication Date
SK1892001A3 true SK1892001A3 (en)	2001-11-06

Family

ID=22260061

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK189-2001A SK1892001A3 (en)	1998-08-18	1999-08-16	Muscarinic agonists and antagonists, pharmaceutical composition them comprising and use thereof

Country Status (30)

Country	Link
US (5)	US6093724A (de)
EP (1)	EP1112272B1 (de)
JP (1)	JP2002523416A (de)
KR (1)	KR20010072784A (de)
CN (1)	CN1312812A (de)
AR (1)	AR020199A1 (de)
AT (1)	ATE227724T1 (de)
AU (1)	AU750566B2 (de)
BG (1)	BG105256A (de)
BR (1)	BR9913072A (de)
CA (1)	CA2340946A1 (de)
CO (1)	CO5130018A1 (de)
DE (1)	DE69903961T2 (de)
EE (1)	EE200100096A (de)
ES (1)	ES2191455T3 (de)
HK (1)	HK1038918A1 (de)
HU (1)	HUP0103203A3 (de)
ID (1)	ID27544A (de)
IL (1)	IL141050A0 (de)
IS (1)	IS5827A (de)
NO (1)	NO20010804L (de)
NZ (1)	NZ509762A (de)
PE (1)	PE20000988A1 (de)
PL (1)	PL346247A1 (de)
RU (1)	RU2219179C2 (de)
SK (1)	SK1892001A3 (de)
TR (1)	TR200100462T2 (de)
WO (1)	WO2000011001A1 (de)
YU (1)	YU13301A (de)
ZA (1)	ZA200100978B (de)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HUP0301442A3 (en) *	2000-10-19	2007-03-28	Pfizer Prod Inc	Bridged piperazine derivatives and pharmaceutical compositions containing them
GB0117950D0 (en) *	2001-02-16	2001-09-19	Aventis Pharma Inc	Novel heterocyclic urea derivatives andd their use as dopamine D3 receptor ligands
WO2002094827A1 (en) *	2001-05-23	2002-11-28	Neurosearch A/S	Fused tropane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
US20030064979A1 (en) *	2001-06-29	2003-04-03	Hansen Thomas Kruse	Method of inhibiting PTP 1B and /or T-cell PTP and/or other PTPases with an Asp residue at position 48
US6828328B1 (en) *	2002-03-01	2004-12-07	Ucb S.A.	Analgesic combination of muscarinic agonists
US7897766B2 (en) *	2005-09-23	2011-03-01	Abbott Laboratories	Amino-aza-adamantane derivatives and methods of use
US8314119B2 (en) *	2006-11-06	2012-11-20	Abbvie Inc.	Azaadamantane derivatives and methods of use
US8076350B2 (en) *	2006-12-22	2011-12-13	Abbott Laboratories	Spirocyclic azaadamantane derivatives and methods of use
MX2009010176A (es) *	2007-03-23	2009-10-12	Abbott Lab	Derivados de aza-adamantano 4-substituidos y metodos de uso de los mismos.
MX2009010175A (es)	2007-03-23	2009-10-12	Abbott Lab	Derivados de acetamida y carboxamida de aza-adamantano y metodos de uso de los mismos.
KR20120044978A (ko) *	2009-06-19	2012-05-08	아보트 러보러터리즈	디아자호모아다만탄 유도체 및 이들의 사용 방법
US10265311B2 (en)	2009-07-22	2019-04-23	PureTech Health LLC	Methods and compositions for treatment of disorders ameliorated by muscarinic receptor activation
EP3061821B1 (de)	2009-07-22	2019-07-10	Puretech Health LLC	Zusammensetzungen zur behandlung von durch muscarinrezeptoraktivierung gelinderten leiden
AR081626A1 (es)	2010-04-23	2012-10-10	Cytokinetics Inc	Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos
EP2560488B1 (de)	2010-04-23	2015-10-28	Cytokinetics, Inc.	Bestimmte aminopyrimidine und aminotriazine, zusammensetzungen daraus und verfahren zu ihrer verwendung
AR081331A1 (es)	2010-04-23	2012-08-08	Cytokinetics Inc	Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos
US9464078B2 (en)	2010-09-23	2016-10-11	Abbvie Inc.	Monohydrate of azaadamantane derivatives
US8759380B2 (en)	2011-04-22	2014-06-24	Cytokinetics, Inc.	Certain heterocycles, compositions thereof, and methods for their use
AU2018300980A1 (en)	2017-07-12	2020-01-02	Vanderbilt University	Antagonists of the muscarinic acetylcholine receptor M4
ES3064093T3 (en)	2017-10-20	2026-04-22	Univ Vanderbilt	Antagonists of the muscarinic acetylcholine receptor m4
WO2019126559A1 (en)	2017-12-20	2019-06-27	Vanderbilt University	Antagonists of the muscarinic acetylcholine receptor m4
IL281809B (en)	2018-09-28	2022-09-01	Karuna Therapeutics Inc	Compositions and methods for the treatment of diseases improved by the activation of muscarinic receptors

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4739074A (en) *	1986-01-22	1988-04-19	Pennwalt Corporation	Adamantane spiro-pyrrolidine derivatives
IE63906B1 (en) *	1987-11-13	1995-06-14	Novo Nordisk As	Azabicyclic compounds and their preparation and use
US5527813A (en) *	1990-08-21	1996-06-18	Novo Nordisk A/S	Heterocyclic compounds and their preparation and use
WO1992011261A1 (en) *	1990-12-21	1992-07-09	Merck Sharp & Dohme Limited	4-azatricyclo[2.2.1.02,6]heptanes and pharmaceutical compositions
US5955470A (en) *	1991-06-11	1999-09-21	Merrell Pharmaceuticals, Inc.	Derivatives of amide analogs of certain methano bridged quinolizines
US5641791A (en) *	1991-08-13	1997-06-24	Novo Nordisk A.S	Heterocyclic compounds and their preparation and use
AU702720B2 (en) *	1995-11-02	1999-03-04	Neurosearch A/S	Fused tropane-derivatives as neurotransmitter reuptake inhibitors
US5914338A (en) *	1996-04-02	1999-06-22	Novo Nordisk	Heterocyclic compounds and their preparation and use
US5952339A (en) *	1998-04-02	1999-09-14	Bencherif; Merouane	Pharmaceutical compositions and methods of using nicotinic antagonists for treating a condition or disorder characterized by alteration in normal neurotransmitter release
US5986100A (en) *	1998-04-02	1999-11-16	Crooks; Peter Anthony	Pharmaceutical compositions and methods for use
US6057446A (en) *	1998-04-02	2000-05-02	Crooks; Peter Anthony	Certain 1-aza-tricyclo [3.3.1-13,7 ] decane compounds

1999
- 1999-08-16 ID IDW20010377A patent/ID27544A/id unknown
- 1999-08-16 PL PL99346247A patent/PL346247A1/xx not_active Application Discontinuation
- 1999-08-16 ES ES99945064T patent/ES2191455T3/es not_active Expired - Lifetime
- 1999-08-16 TR TR2001/00462T patent/TR200100462T2/xx unknown
- 1999-08-16 CA CA002340946A patent/CA2340946A1/en not_active Abandoned
- 1999-08-16 IL IL14105099A patent/IL141050A0/xx unknown
- 1999-08-16 US US09/375,149 patent/US6093724A/en not_active Expired - Fee Related
- 1999-08-16 AU AU57758/99A patent/AU750566B2/en not_active Ceased
- 1999-08-16 AT AT99945064T patent/ATE227724T1/de not_active IP Right Cessation
- 1999-08-16 HK HK02100409.3A patent/HK1038918A1/zh unknown
- 1999-08-16 BR BR9913072-6A patent/BR9913072A/pt not_active IP Right Cessation
- 1999-08-16 NZ NZ509762A patent/NZ509762A/xx unknown
- 1999-08-16 CN CN99809775A patent/CN1312812A/zh active Pending
- 1999-08-16 YU YU13301A patent/YU13301A/sh unknown
- 1999-08-16 KR KR1020017002128A patent/KR20010072784A/ko not_active Withdrawn
- 1999-08-16 EE EEP200100096A patent/EE200100096A/xx unknown
- 1999-08-16 JP JP2000566274A patent/JP2002523416A/ja active Pending
- 1999-08-16 SK SK189-2001A patent/SK1892001A3/sk unknown
- 1999-08-16 HU HU0103203A patent/HUP0103203A3/hu unknown
- 1999-08-16 WO PCT/US1999/018570 patent/WO2000011001A1/en not_active Ceased
- 1999-08-16 RU RU2001107139/04A patent/RU2219179C2/ru not_active IP Right Cessation
- 1999-08-16 DE DE69903961T patent/DE69903961T2/de not_active Expired - Fee Related
- 1999-08-16 EP EP99945064A patent/EP1112272B1/de not_active Expired - Lifetime
- 1999-08-17 AR ARP990104100A patent/AR020199A1/es unknown
- 1999-08-18 PE PE1999000838A patent/PE20000988A1/es not_active Application Discontinuation
- 1999-08-18 CO CO99052330A patent/CO5130018A1/es unknown
2000
- 2000-05-09 US US09/567,785 patent/US6251916B1/en not_active Expired - Fee Related
- 2000-10-17 US US09/690,494 patent/US6323194B1/en not_active Expired - Fee Related
2001
- 2001-01-26 IS IS5827A patent/IS5827A/is unknown
- 2001-02-05 ZA ZA200100978A patent/ZA200100978B/xx unknown
- 2001-02-14 BG BG105256A patent/BG105256A/xx unknown
- 2001-02-16 NO NO20010804A patent/NO20010804L/no not_active Application Discontinuation
- 2001-10-05 US US09/972,415 patent/US6423842B1/en not_active Expired - Fee Related
2002
- 2002-03-27 US US10/108,046 patent/US6555550B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
AU750566B2 (en)	2002-07-25
HK1038918A1 (zh)	2002-04-04
PL346247A1 (en)	2002-01-28
DE69903961T2 (de)	2003-07-03
US6423842B1 (en)	2002-07-23
HUP0103203A3 (en)	2002-10-28
NZ509762A (en)	2002-12-20
ES2191455T3 (es)	2003-09-01
NO20010804L (no)	2001-04-11
CO5130018A1 (es)	2002-02-27
BR9913072A (pt)	2001-05-15
US6251916B1 (en)	2001-06-26
NO20010804D0 (no)	2001-02-16
DE69903961D1 (de)	2002-12-19
BG105256A (en)	2001-11-30
EE200100096A (et)	2002-06-17
IS5827A (is)	2001-01-26
ID27544A (id)	2001-04-12
JP2002523416A (ja)	2002-07-30
WO2000011001A1 (en)	2000-03-02
YU13301A (sh)	2005-06-10
IL141050A0 (en)	2002-02-10
US20020045617A1 (en)	2002-04-18
CN1312812A (zh)	2001-09-12
AR020199A1 (es)	2002-05-02
AU5775899A (en)	2000-03-14
PE20000988A1 (es)	2000-09-30
US6555550B1 (en)	2003-04-29
ZA200100978B (en)	2002-02-05
EP1112272A1 (de)	2001-07-04
HUP0103203A2 (hu)	2002-01-28
US6093724A (en)	2000-07-25
EP1112272B1 (de)	2002-11-13
TR200100462T2 (tr)	2001-09-21
ATE227724T1 (de)	2002-11-15
CA2340946A1 (en)	2000-03-02
US6323194B1 (en)	2001-11-27
KR20010072784A (ko)	2001-07-31
RU2219179C2 (ru)	2003-12-20

Publication	Publication Date	Title
US6093724A (en)	2000-07-25	Muscarinic agonists and antagonists
AU775426B2 (en)	2004-07-29	New compounds
DE3878833T2 (de)	1993-06-09	Thieno(triazolo)diazepinverbindungen, und medizinische verwendung derselben.
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US6890936B2 (en)	2005-05-10	Muscarinic antagonists
HUT77938A (hu)	1998-11-30	7-Azabiciklo[2,2,1]-heptán- és -heptén-származékok és kolinerg receptor ligandumként történő alkalmazásuk
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CA1321996C (en)	1993-09-07	Condensed diazepinones, processes for preparing them and pharmaceutical compositions containing these compounds
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