ZA200206077B - Adenosine receptor modulators. - Google Patents
Adenosine receptor modulators. Download PDFInfo
- Publication number
- ZA200206077B ZA200206077B ZA200206077A ZA200206077A ZA200206077B ZA 200206077 B ZA200206077 B ZA 200206077B ZA 200206077 A ZA200206077 A ZA 200206077A ZA 200206077 A ZA200206077 A ZA 200206077A ZA 200206077 B ZA200206077 B ZA 200206077B
- Authority
- ZA
- South Africa
- Prior art keywords
- amino
- furan
- pyrimidine
- carbonitrile
- pyridin
- Prior art date
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- 102000009346 Adenosine receptors Human genes 0.000 title claims description 10
- 108050000203 Adenosine receptors Proteins 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 166
- 125000000217 alkyl group Chemical group 0.000 claims description 139
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 95
- -1 CFs Chemical group 0.000 claims description 79
- 229910052736 halogen Inorganic materials 0.000 claims description 78
- 150000002367 halogens Chemical class 0.000 claims description 76
- 125000003545 alkoxy group Chemical group 0.000 claims description 57
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 57
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 30
- 125000005605 benzo group Chemical group 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 102000005962 receptors Human genes 0.000 claims description 26
- 108020003175 receptors Proteins 0.000 claims description 26
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 25
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 25
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 25
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 24
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 24
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- 239000001961 anticonvulsive agent Substances 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 206010021143 Hypoxia Diseases 0.000 claims description 9
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- 230000007954 hypoxia Effects 0.000 claims description 9
- 208000028867 ischemia Diseases 0.000 claims description 9
- 230000004112 neuroprotection Effects 0.000 claims description 9
- 206010010904 Convulsion Diseases 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 208000026935 allergic disease Diseases 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- LTGGOXVBFSHBCH-UHFFFAOYSA-N 6-amino-2-(furan-2-yl)-4-(pyridin-2-ylmethylamino)pyridine-3-carbonitrile Chemical compound N#CC=1C(C=2OC=CC=2)=NC(N)=CC=1NCC1=CC=CC=N1 LTGGOXVBFSHBCH-UHFFFAOYSA-N 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 229940125681 anticonvulsant agent Drugs 0.000 claims description 7
- 239000000164 antipsychotic agent Substances 0.000 claims description 7
- 229940005529 antipsychotics Drugs 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229940035363 muscle relaxants Drugs 0.000 claims description 7
- 239000003158 myorelaxant agent Substances 0.000 claims description 7
- 230000036407 pain Effects 0.000 claims description 7
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 7
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 201000009032 substance abuse Diseases 0.000 claims description 7
- 231100000736 substance abuse Toxicity 0.000 claims description 7
- 208000011117 substance-related disease Diseases 0.000 claims description 7
- 206010039897 Sedation Diseases 0.000 claims description 6
- 230000003556 anti-epileptic effect Effects 0.000 claims description 6
- 229960003965 antiepileptics Drugs 0.000 claims description 6
- 230000006735 deficit Effects 0.000 claims description 6
- 230000036280 sedation Effects 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000008062 neuronal firing Effects 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
- AHRQYOSAXZQCIG-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=C=NC=N[CH]1 AHRQYOSAXZQCIG-UHFFFAOYSA-N 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 239000003169 respiratory stimulant agent Substances 0.000 description 1
- 229940066293 respiratory stimulants Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
Classifications
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- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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