OA12050A - Certain alkylene diamine-substituted heterocycles. - Google Patents
Certain alkylene diamine-substituted heterocycles. Download PDFInfo
- Publication number
- OA12050A OA12050A OA1200200089A OA1200200089A OA12050A OA 12050 A OA12050 A OA 12050A OA 1200200089 A OA1200200089 A OA 1200200089A OA 1200200089 A OA1200200089 A OA 1200200089A OA 12050 A OA12050 A OA 12050A
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- OA
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- Prior art keywords
- methylene
- compound
- formula
- hydrogen
- alkyl
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- 125000000623 heterocyclic group Chemical class 0.000 title claims description 28
- 125000002947 alkylene group Chemical group 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 565
- -1 eating disorders Chemical compound 0.000 claims abstract description 497
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 70
- 239000000203 mixture Substances 0.000 claims abstract description 68
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
- 125000001424 substituent group Chemical group 0.000 claims abstract description 34
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 30
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 27
- 101710151321 Melanostatin Proteins 0.000 claims abstract description 23
- 125000004429 atom Chemical group 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 6
- 208000008589 Obesity Diseases 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 235000020824 obesity Nutrition 0.000 claims abstract description 6
- 206010006550 Bulimia nervosa Diseases 0.000 claims abstract description 5
- 208000030814 Eating disease Diseases 0.000 claims abstract description 5
- 208000032841 Bulimia Diseases 0.000 claims abstract description 4
- 206010020772 Hypertension Diseases 0.000 claims abstract description 4
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
- 102400000064 Neuropeptide Y Human genes 0.000 claims abstract 10
- 125000006413 ring segment Chemical group 0.000 claims abstract 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 340
- 239000001257 hydrogen Substances 0.000 claims description 324
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 148
- 125000000217 alkyl group Chemical group 0.000 claims description 143
- 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 58
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 56
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 47
- 150000002367 halogens Chemical class 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 229910052721 tungsten Inorganic materials 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000001188 haloalkyl group Chemical group 0.000 claims description 29
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 230000027455 binding Effects 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 239000000651 prodrug Substances 0.000 claims description 21
- 229940002612 prodrug Drugs 0.000 claims description 21
- 208000035475 disorder Diseases 0.000 claims description 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 16
- 125000003386 piperidinyl group Chemical group 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 239000003981 vehicle Substances 0.000 claims description 14
- 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 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 9
- 238000000338 in vitro Methods 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 230000002159 abnormal effect Effects 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
- 235000012631 food intake Nutrition 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 229940088597 hormone Drugs 0.000 claims description 5
- 239000005556 hormone Substances 0.000 claims description 5
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 102000004877 Insulin Human genes 0.000 claims description 4
- 108090001061 Insulin Proteins 0.000 claims description 4
- 206010047163 Vasospasm Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 230000037406 food intake Effects 0.000 claims description 4
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 4
- 229940125396 insulin Drugs 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 230000000929 thyromimetic effect Effects 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 230000020595 eating behavior Effects 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 230000004899 motility Effects 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 210000002569 neuron Anatomy 0.000 claims description 3
- 239000002660 neuropeptide Y receptor antagonist Substances 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- 230000002889 sympathetic effect Effects 0.000 claims description 3
- 125000004306 triazinyl group Chemical group 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 2
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 108010051696 Growth Hormone Proteins 0.000 claims description 2
- 208000032843 Hemorrhage Diseases 0.000 claims description 2
- 206010061216 Infarction Diseases 0.000 claims description 2
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims description 2
- 206010049418 Sudden Cardiac Death Diseases 0.000 claims description 2
- 206010046543 Urinary incontinence Diseases 0.000 claims description 2
- 208000022531 anorexia Diseases 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 2
- 230000006399 behavior Effects 0.000 claims description 2
- 210000004204 blood vessel Anatomy 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 210000004351 coronary vessel Anatomy 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004427 diamine group Chemical group 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 239000000122 growth hormone Substances 0.000 claims description 2
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 2
- 230000001771 impaired effect Effects 0.000 claims description 2
- 230000007574 infarction Effects 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 208000030159 metabolic disease Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 208000023504 respiratory system disease Diseases 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 230000020341 sensory perception of pain Effects 0.000 claims description 2
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 645
- 150000002431 hydrogen Chemical group 0.000 claims 283
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 19
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 15
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 3
- 230000001850 reproductive effect Effects 0.000 claims 2
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 claims 1
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
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- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
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- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- C07D215/38—Nitrogen atoms
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- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D495/04—Ortho-condensed systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
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OA1200200089A OA12050A (en) | 1999-09-30 | 2000-09-29 | Certain alkylene diamine-substituted heterocycles. |
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EP (1) | EP1224187B1 (pl) |
JP (2) | JP2003510327A (pl) |
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CN (1) | CN1377356A (pl) |
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- 2000-09-29 CN CN00813704A patent/CN1377356A/zh active Pending
- 2000-09-29 KR KR1020027004150A patent/KR20020043223A/ko not_active Application Discontinuation
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- 2000-09-29 AU AU77380/00A patent/AU7738000A/en not_active Abandoned
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- 2000-09-29 WO PCT/US2000/026886 patent/WO2001023389A2/en active IP Right Grant
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NZ517575A (en) | 2004-04-30 |
JP2008007515A (ja) | 2008-01-17 |
HUP0202636A2 (hu) | 2002-12-28 |
KR20020043223A (ko) | 2002-06-08 |
DE60026155T2 (de) | 2006-08-10 |
CA2379640A1 (en) | 2001-04-05 |
IL148903A0 (en) | 2002-09-12 |
US6506762B1 (en) | 2003-01-14 |
ES2258476T3 (es) | 2006-09-01 |
WO2001023389A2 (en) | 2001-04-05 |
ATE318267T1 (de) | 2006-03-15 |
US7074929B2 (en) | 2006-07-11 |
US6696445B2 (en) | 2004-02-24 |
CA2379640C (en) | 2006-11-28 |
WO2001023389A3 (en) | 2002-05-10 |
JP2003510327A (ja) | 2003-03-18 |
EA200200424A1 (ru) | 2002-12-26 |
US20040229870A1 (en) | 2004-11-18 |
US20030158197A1 (en) | 2003-08-21 |
ZA200202518B (en) | 2003-08-27 |
NO20021358L (no) | 2002-05-27 |
PL354784A1 (pl) | 2004-02-23 |
BG106508A (en) | 2003-02-28 |
CN1377356A (zh) | 2002-10-30 |
AU7738000A (en) | 2001-04-30 |
HUP0202636A3 (en) | 2004-06-28 |
NO20021358D0 (no) | 2002-03-19 |
EP1224187A2 (en) | 2002-07-24 |
DE60026155D1 (de) | 2006-04-27 |
CZ20021086A3 (cs) | 2002-10-16 |
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