SK17172002A3 - Deriváty 3-azabicyklo[3,1,0]hexánu vykazujúce afinitu k opiátovým receptorom - Google Patents

Deriváty 3-azabicyklo[3,1,0]hexánu vykazujúce afinitu k opiátovým receptorom Download PDF

Info

Publication number: SK17172002A3
Authority: SK; Slovakia
Prior art keywords: alkyl; aryl; heteroaryl; optionally substituted; cycloalkyl
Prior art date: 2000-06-23

Application number

SK1717-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Bernard Joseph Banks

Douglas James Critcher

Ashley Edward Fenwick

David Morris Gethin

Stephen Paul Gibson

Graham Lunn

Original Assignee

Pfizer Inc.

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.)

2000-06-23

Filing date

2001-06-07

Publication date

2004-09-08

2001-06-07 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

2004-09-08 Publication of SK17172002A3 publication Critical patent/SK17172002A3/sk

Links

108090000137 Opioid Receptors Proteins 0.000 title claims abstract description 16
102000003840 Opioid Receptors Human genes 0.000 title claims abstract description 15
239000003446 ligand Substances 0.000 title description 5
HGWUUOXXAIISDB-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane Chemical class C1NCC2CC21 HGWUUOXXAIISDB-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 220
238000011282 treatment Methods 0.000 claims abstract description 21
201000010099 disease Diseases 0.000 claims abstract description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
239000000651 prodrug Substances 0.000 claims abstract description 10
229940002612 prodrug Drugs 0.000 claims abstract description 10
125000000217 alkyl group Chemical group 0.000 claims description 270
125000003118 aryl group Chemical group 0.000 claims description 236
125000001072 heteroaryl group Chemical group 0.000 claims description 143
238000000034 method Methods 0.000 claims description 124
229910052736 halogen Inorganic materials 0.000 claims description 84
150000002367 halogens Chemical class 0.000 claims description 80
125000003545 alkoxy group Chemical group 0.000 claims description 79
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 77
-1 C4-9 cycloalkanoyl Chemical group 0.000 claims description 66
229910052799 carbon Inorganic materials 0.000 claims description 63
125000001424 substituent group Chemical group 0.000 claims description 59
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
238000006243 chemical reaction Methods 0.000 claims description 53
125000000753 cycloalkyl group Chemical group 0.000 claims description 51
239000000203 mixture Substances 0.000 claims description 39
125000000623 heterocyclic group Chemical group 0.000 claims description 37
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 28
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 27
125000004104 aryloxy group Chemical group 0.000 claims description 27
125000003342 alkenyl group Chemical group 0.000 claims description 22
239000003638 chemical reducing agent Substances 0.000 claims description 22
125000005842 heteroatom Chemical group 0.000 claims description 22
229910052760 oxygen Inorganic materials 0.000 claims description 22
125000000304 alkynyl group Chemical group 0.000 claims description 20
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 20
125000005843 halogen group Chemical group 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 19
229910052717 sulfur Inorganic materials 0.000 claims description 17
239000002253 acid Substances 0.000 claims description 16
125000004423 acyloxy group Chemical group 0.000 claims description 15
125000005037 alkyl phenyl group Chemical group 0.000 claims description 15
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 14
125000004429 atom Chemical class 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
229910052757 nitrogen Inorganic materials 0.000 claims description 13
230000009467 reduction Effects 0.000 claims description 13
238000006722 reduction reaction Methods 0.000 claims description 13
125000002837 carbocyclic group Chemical group 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 10
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
125000001589 carboacyl group Chemical group 0.000 claims description 8
239000007800 oxidant agent Substances 0.000 claims description 8
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 7
229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
125000005741 alkyl alkenyl group Chemical group 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
125000001188 haloalkyl group Chemical group 0.000 claims description 6
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 description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
230000001404 mediated effect Effects 0.000 claims description 5
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 4
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 4
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
229910052740 iodine Inorganic materials 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
238000006268 reductive amination reaction Methods 0.000 claims description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 4
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 3
235000001014 amino acid Nutrition 0.000 claims description 3
229940024606 amino acid Drugs 0.000 claims description 3
125000000539 amino acid group Chemical group 0.000 claims description 3
150000001413 amino acids Chemical class 0.000 claims description 3
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
150000001721 carbon Chemical group 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
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 3
102000005962 receptors Human genes 0.000 claims description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 2
125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 2
125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 2
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 2
RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 claims description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=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
125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 2
239000004475 Arginine Substances 0.000 claims description 2
229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
239000004471 Glycine Substances 0.000 claims description 2
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 2
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 2
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 2
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 2
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 2
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 2
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 2
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 2
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
239000004472 Lysine Substances 0.000 claims description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 2
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 2
239000004473 Threonine Substances 0.000 claims description 2
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 2
235000004279 alanine Nutrition 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 2
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
235000018417 cysteine Nutrition 0.000 claims description 2
125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 2
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
229960000310 isoleucine Drugs 0.000 claims description 2
229930182817 methionine Natural products 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
125000005544 phthalimido group Chemical group 0.000 claims description 2
125000005545 phthalimidyl group Chemical group 0.000 claims description 2
125000003367 polycyclic group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
235000010288 sodium nitrite Nutrition 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 2
239000004474 valine Substances 0.000 claims description 2
229930195712 glutamate Natural products 0.000 claims 2
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 1
235000003704 aspartic acid Nutrition 0.000 claims 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims 1
206010010774 Constipation Diseases 0.000 abstract description 5
208000030814 Eating disease Diseases 0.000 abstract description 5
208000019454 Feeding and Eating disease Diseases 0.000 abstract description 5
206010019196 Head injury Diseases 0.000 abstract description 5
206010028813 Nausea Diseases 0.000 abstract description 5
208000012488 Opiate Overdose Diseases 0.000 abstract description 5
201000001880 Sexual dysfunction Diseases 0.000 abstract description 5
206010047700 Vomiting Diseases 0.000 abstract description 5
208000010668 atopic eczema Diseases 0.000 abstract description 5
235000014632 disordered eating Nutrition 0.000 abstract description 5
230000008693 nausea Effects 0.000 abstract description 5
231100000872 sexual dysfunction Toxicity 0.000 abstract description 5
230000035939 shock Effects 0.000 abstract description 5
230000000391 smoking effect Effects 0.000 abstract description 5
230000008673 vomiting Effects 0.000 abstract description 5
206010012434 Dermatitis allergic Diseases 0.000 abstract description 4
201000008937 atopic dermatitis Diseases 0.000 abstract description 4
208000002551 irritable bowel syndrome Diseases 0.000 abstract description 4
206010003645 Atopy Diseases 0.000 abstract description 3
101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 abstract description 3
108700023159 delta Opioid Receptors Proteins 0.000 abstract description 3
102000048124 delta Opioid Receptors Human genes 0.000 abstract description 3
102000048260 kappa Opioid Receptors Human genes 0.000 abstract description 3
208000017520 skin disease Diseases 0.000 abstract description 3
108020001588 κ-opioid receptors Proteins 0.000 abstract description 3
208000007848 Alcoholism Diseases 0.000 abstract description 2
102000051367 mu Opioid Receptors Human genes 0.000 abstract description 2
108020001612 μ-opioid receptors Proteins 0.000 abstract description 2
230000001823 pruritic effect Effects 0.000 abstract 1
238000002360 preparation method Methods 0.000 description 56
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
239000000243 solution Substances 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 29
239000002904 solvent Substances 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
238000010992 reflux Methods 0.000 description 24
125000000524 functional group Chemical group 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
239000000047 product Substances 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 20
238000005160 1H NMR spectroscopy Methods 0.000 description 18
239000002585 base Substances 0.000 description 18
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
241001465754 Metazoa Species 0.000 description 17
235000019439 ethyl acetate Nutrition 0.000 description 17
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 14
230000008569 process Effects 0.000 description 14
208000003251 Pruritus Diseases 0.000 description 13
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
239000003054 catalyst Substances 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 11
238000010828 elution Methods 0.000 description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
239000000543 intermediate Substances 0.000 description 11
239000012280 lithium aluminium hydride Substances 0.000 description 10
238000005481 NMR spectroscopy Methods 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
150000001299 aldehydes Chemical class 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
238000000825 ultraviolet detection Methods 0.000 description 8
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 7
239000005695 Ammonium acetate Substances 0.000 description 7
229910010082 LiAlH Inorganic materials 0.000 description 7
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
150000001408 amides Chemical class 0.000 description 7
235000019257 ammonium acetate Nutrition 0.000 description 7
229940043376 ammonium acetate Drugs 0.000 description 7
238000006757 chemical reactions by type Methods 0.000 description 7
239000010410 layer Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000007983 Tris buffer Substances 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
235000009518 sodium iodide Nutrition 0.000 description 6
239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
230000002411 adverse Effects 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000004220 glutamic acid Substances 0.000 description 5
235000013922 glutamic acid Nutrition 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
239000002002 slurry Substances 0.000 description 5
239000011734 sodium Substances 0.000 description 5
208000024891 symptom Diseases 0.000 description 5
238000012360 testing method Methods 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
229910000085 borane Inorganic materials 0.000 description 4
239000012267 brine Substances 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
125000004093 cyano group Chemical group *C#N 0.000 description 4
NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 4
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
239000000463 material Substances 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
NUDGACANKYSDOG-UHFFFAOYSA-N n-[3-(6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl)phenyl]methanesulfonamide Chemical compound C12CNCC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 NUDGACANKYSDOG-UHFFFAOYSA-N 0.000 description 4
150000007530 organic bases Chemical class 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
229910052697 platinum Inorganic materials 0.000 description 4
239000002798 polar solvent Substances 0.000 description 4
238000002953 preparative HPLC Methods 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
208000020431 spinal cord injury Diseases 0.000 description 4
150000003512 tertiary amines Chemical class 0.000 description 4
ZUMMSMIGLBISIB-UHFFFAOYSA-N 3-(6-ethyl-3-prop-2-enyl-3-azabicyclo[3.1.0]hexan-6-yl)aniline Chemical compound C12CN(CC=C)CC2C1(CC)C1=CC=CC(N)=C1 ZUMMSMIGLBISIB-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
150000001241 acetals Chemical class 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
235000019445 benzyl alcohol Nutrition 0.000 description 3
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 3
229940073608 benzyl chloride Drugs 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 3
238000001514 detection method Methods 0.000 description 3
235000015872 dietary supplement Nutrition 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
238000011321 prophylaxis Methods 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
210000000278 spinal cord Anatomy 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
239000007858 starting material Substances 0.000 description 3
230000009466 transformation Effects 0.000 description 3
238000000844 transformation Methods 0.000 description 3
239000011701 zinc Substances 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
LJFSBVOGLOOTKX-UHFFFAOYSA-N 1-(2-chloroethoxy)-4-cyclopropylbenzene Chemical compound C1=CC(OCCCl)=CC=C1C1CC1 LJFSBVOGLOOTKX-UHFFFAOYSA-N 0.000 description 2
PRSIVKNGHKMCKO-UHFFFAOYSA-N 1-(3-nitrophenyl)propylidenehydrazine Chemical compound CCC(=NN)C1=CC=CC([N+]([O-])=O)=C1 PRSIVKNGHKMCKO-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
PSFDAYXWBWRTSM-UHFFFAOYSA-N 1-prop-2-enylpyrrole-2,5-dione Chemical compound C=CCN1C(=O)C=CC1=O PSFDAYXWBWRTSM-UHFFFAOYSA-N 0.000 description 2
JUNYVHHAHPUADU-UHFFFAOYSA-N 3-benzyl-6-ethyl-6-(3-nitrophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C1(CC)C(C2=O)C1C(=O)N2CC1=CC=CC=C1 JUNYVHHAHPUADU-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
QJWXRTLKPRVYLP-UHFFFAOYSA-N 6-(3-aminophenyl)-3-benzyl-6-ethyl-3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound C=1C=CC(N)=CC=1C1(CC)C(C2=O)C1C(=O)N2CC1=CC=CC=C1 QJWXRTLKPRVYLP-UHFFFAOYSA-N 0.000 description 2
GDYHRBRBERUVFN-UHFFFAOYSA-N 6-(3-aminophenyl)-3-benzyl-6-methyl-3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound C=1C=CC(N)=CC=1C1(C)C(C2=O)C1C(=O)N2CC1=CC=CC=C1 GDYHRBRBERUVFN-UHFFFAOYSA-N 0.000 description 2
MSVXGXPQMMLPPJ-UHFFFAOYSA-N 6-(3-aminophenyl)-6-ethyl-3-prop-2-enyl-3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound O=C1N(CC=C)C(=O)C2C1C2(CC)C1=CC=CC(N)=C1 MSVXGXPQMMLPPJ-UHFFFAOYSA-N 0.000 description 2
239000005660 Abamectin Substances 0.000 description 2
VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
208000006877 Insect Bites and Stings Diseases 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
238000006859 Swern oxidation reaction Methods 0.000 description 2
229910007926 ZrCl Inorganic materials 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 2
150000008052 alkyl sulfonates Chemical class 0.000 description 2
125000005233 alkylalcohol group Chemical group 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
229940125715 antihistaminic agent Drugs 0.000 description 2
239000000739 antihistaminic agent Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
150000003938 benzyl alcohols Chemical class 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical group [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 2
210000005013 brain tissue Anatomy 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
230000007803 itching Effects 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
239000012528 membrane Substances 0.000 description 2
OMMRVDHWMIFTOS-UHFFFAOYSA-N n-[3-(3-benzyl-6-ethyl-2,4-dioxo-3-azabicyclo[3.1.0]hexan-6-yl)phenyl]methanesulfonamide Chemical compound C=1C=CC(NS(C)(=O)=O)=CC=1C1(CC)C(C2=O)C1C(=O)N2CC1=CC=CC=C1 OMMRVDHWMIFTOS-UHFFFAOYSA-N 0.000 description 2
229910052759 nickel Inorganic materials 0.000 description 2
239000002674 ointment Substances 0.000 description 2
238000006053 organic reaction Methods 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
239000008188 pellet Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 2
239000002243 precursor Substances 0.000 description 2
150000003138 primary alcohols Chemical class 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000001525 receptor binding assay Methods 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
239000011347 resin Substances 0.000 description 2
229920005989 resin Polymers 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
230000003595 spectral effect Effects 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000001308 synthesis method Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
125000004665 trialkylsilyl group Chemical group 0.000 description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
125000001506 1,2,3-triazol-5-yl group Chemical group [H]N1N=NC([H])=C1[*] 0.000 description 1
125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 description 1
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
CUEIIDSEGRHPOU-UHFFFAOYSA-N 1-(3-nitrophenyl)ethylidenehydrazine Chemical compound NN=C(C)C1=CC=CC([N+]([O-])=O)=C1 CUEIIDSEGRHPOU-UHFFFAOYSA-N 0.000 description 1
VSPOTMOYDHRALZ-UHFFFAOYSA-N 1-(3-nitrophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC([N+]([O-])=O)=C1 VSPOTMOYDHRALZ-UHFFFAOYSA-N 0.000 description 1
MKRBAPNEJMFMHU-UHFFFAOYSA-N 1-benzylpyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CC1=CC=CC=C1 MKRBAPNEJMFMHU-UHFFFAOYSA-N 0.000 description 1
NIOHSOXYJMSVOA-UHFFFAOYSA-N 1-chloro-3-phenylpropan-2-one Chemical compound ClCC(=O)CC1=CC=CC=C1 NIOHSOXYJMSVOA-UHFFFAOYSA-N 0.000 description 1
VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 1
ZXNMIUJDTOMBPV-UHFFFAOYSA-N 2-chloroethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCl)C=C1 ZXNMIUJDTOMBPV-UHFFFAOYSA-N 0.000 description 1
125000001847 2-phenylcyclopropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1([H])C([H])([H])C1([H])* 0.000 description 1
PBEJTRAJWCNHRS-UHFFFAOYSA-N 2-phenylmethoxybenzaldehyde Chemical compound O=CC1=CC=CC=C1OCC1=CC=CC=C1 PBEJTRAJWCNHRS-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 description 1
DOIMKQQHDSWKGQ-UHFFFAOYSA-N 3-benzyl-6-methyl-6-(3-nitrophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C1(C)C(C2=O)C1C(=O)N2CC1=CC=CC=C1 DOIMKQQHDSWKGQ-UHFFFAOYSA-N 0.000 description 1
WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
IGIWPHRUBXKMAR-UHFFFAOYSA-N 4-cyclopropylphenol Chemical compound C1=CC(O)=CC=C1C1CC1 IGIWPHRUBXKMAR-UHFFFAOYSA-N 0.000 description 1
ZOCSXAVNDGMNBV-UHFFFAOYSA-N 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile Chemical compound NC1=C(S(=O)C(F)(F)F)C(C#N)=NN1C1=C(Cl)C=C(C(F)(F)F)C=C1Cl ZOCSXAVNDGMNBV-UHFFFAOYSA-N 0.000 description 1
IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
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 description 1
SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 description 1
241000238876 Acari Species 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 description 1
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
101150098958 CMD1 gene Proteins 0.000 description 1
101100382321 Caenorhabditis elegans cal-1 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000282465 Canis Species 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 description 1
241000283086 Equidae Species 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
239000005899 Fipronil Substances 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
239000005906 Imidacloprid Substances 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
239000004166 Lanolin Substances 0.000 description 1
URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
239000005912 Lufenuron Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical compound C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
229920002873 Polyethylenimine Polymers 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
239000004902 Softening Agent Substances 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
238000007239 Wittig reaction Methods 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
CJTQFXWMASVOIT-UHFFFAOYSA-N [4-[2-[6-ethyl-6-[3-(methanesulfonamido)phenyl]-3-azabicyclo[3.1.0]hexan-3-yl]ethoxy]phenyl]urea Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCOC1=CC=C(NC(N)=O)C=C1 CJTQFXWMASVOIT-UHFFFAOYSA-N 0.000 description 1
229950008167 abamectin Drugs 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000003732 agents acting on the eye Substances 0.000 description 1
201000007930 alcohol dependence Diseases 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
239000013566 allergen Substances 0.000 description 1
125000005336 allyloxy group Chemical group 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
229960003022 amoxicillin Drugs 0.000 description 1
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
229960003942 amphotericin b Drugs 0.000 description 1
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
229960000723 ampicillin Drugs 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000003096 antiparasitic agent Substances 0.000 description 1
229940125687 antiparasitic agent Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
229960002537 betamethasone Drugs 0.000 description 1
VEMKTZHHVJILDY-UXHICEINSA-N bioresmethrin Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-UXHICEINSA-N 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
229960003184 carprofen Drugs 0.000 description 1
IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
239000013058 crude material Substances 0.000 description 1
229940045803 cuprous chloride Drugs 0.000 description 1
238000009109 curative therapy Methods 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
238000013461 design Methods 0.000 description 1
239000000645 desinfectant Substances 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
150000004887 dithianes Chemical class 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
QLFZZSKTJWDQOS-YDBLARSUSA-N doramectin Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C3CCCCC3)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C QLFZZSKTJWDQOS-YDBLARSUSA-N 0.000 description 1
229960003997 doramectin Drugs 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000000132 electrospray ionisation Methods 0.000 description 1
229960000740 enrofloxacin Drugs 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
235000004626 essential fatty acids Nutrition 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
ZLQJCGFFUHWXES-UHFFFAOYSA-N ethyl 2-[2-[2-[6-ethyl-6-[3-(methanesulfonamido)phenyl]-3-azabicyclo[3.1.0]hexan-3-yl]ethoxy]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC=C1OCCN1CC(C2(CC)C=3C=C(NS(C)(=O)=O)C=CC=3)C2C1 ZLQJCGFFUHWXES-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
229940013764 fipronil Drugs 0.000 description 1
RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
229960004884 fluconazole Drugs 0.000 description 1
239000006260 foam Substances 0.000 description 1
XVVLAOSRANDVDB-UHFFFAOYSA-N formic acid Chemical compound OC=O.OC=O XVVLAOSRANDVDB-UHFFFAOYSA-N 0.000 description 1
XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 1
239000012458 free base Substances 0.000 description 1
229940098330 gamma linoleic acid Drugs 0.000 description 1
VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 description 1
VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 description 1
229960002867 griseofulvin Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000004438 haloalkoxy group Chemical group 0.000 description 1
AKRQHOWXVSDJEF-UHFFFAOYSA-N heptane-1-sulfonic acid Chemical compound CCCCCCCS(O)(=O)=O AKRQHOWXVSDJEF-UHFFFAOYSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
229940056881 imidacloprid Drugs 0.000 description 1
YWTYJOPNNQFBPC-UHFFFAOYSA-N imidacloprid Chemical compound [O-][N+](=O)\N=C1/NCCN1CC1=CC=C(Cl)N=C1 YWTYJOPNNQFBPC-UHFFFAOYSA-N 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
239000002085 irritant Substances 0.000 description 1
231100000021 irritant Toxicity 0.000 description 1
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
230000000155 isotopic effect Effects 0.000 description 1
229960004130 itraconazole Drugs 0.000 description 1
229960002418 ivermectin Drugs 0.000 description 1
229960004125 ketoconazole Drugs 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
229960000991 ketoprofen Drugs 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
235000019388 lanolin Nutrition 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
239000012035 limiting reagent Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
229960000521 lufenuron Drugs 0.000 description 1
PWPJGUXAGUPAHP-UHFFFAOYSA-N lufenuron Chemical compound C1=C(Cl)C(OC(F)(F)C(C(F)(F)F)F)=CC(Cl)=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F PWPJGUXAGUPAHP-UHFFFAOYSA-N 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 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
FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
FXWHFKOXMBTCMP-WMEDONTMSA-N milbemycin Natural products COC1C2OCC3=C/C=C/C(C)CC(=CCC4CC(CC5(O4)OC(C)C(C)C(OC(=O)C(C)CC(C)C)C5O)OC(=O)C(C=C1C)C23O)C FXWHFKOXMBTCMP-WMEDONTMSA-N 0.000 description 1
ZLBGSRMUSVULIE-GSMJGMFJSA-N milbemycin A3 Chemical class O1[C@H](C)[C@@H](C)CC[C@@]11O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 ZLBGSRMUSVULIE-GSMJGMFJSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
MTFXNFSIUFGXSX-UHFFFAOYSA-N n-[2-[6-ethyl-6-[3-(methanesulfonamido)phenyl]-3-azabicyclo[3.1.0]hexan-3-yl]ethyl]benzenesulfonamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCNS(=O)(=O)C1=CC=CC=C1 MTFXNFSIUFGXSX-UHFFFAOYSA-N 0.000 description 1
BJXJURGMHBDQQI-UHFFFAOYSA-N n-[2-[6-ethyl-6-[3-(methanesulfonamido)phenyl]-3-azabicyclo[3.1.0]hexan-3-yl]ethyl]pyridine-4-carboxamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCNC(=O)C1=CC=NC=C1 BJXJURGMHBDQQI-UHFFFAOYSA-N 0.000 description 1
HXNFBHSHHRXNAR-UHFFFAOYSA-N n-[3-(6-methyl-3-azabicyclo[3.1.0]hexan-6-yl)phenyl]methanesulfonamide Chemical compound C12CNCC2C1(C)C1=CC=CC(NS(C)(=O)=O)=C1 HXNFBHSHHRXNAR-UHFFFAOYSA-N 0.000 description 1
IZSDHLRRUWZYOX-UHFFFAOYSA-N n-[3-[3-[2-(4-benzylphenoxy)ethyl]-6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCOC(C=C1)=CC=C1CC1=CC=CC=C1 IZSDHLRRUWZYOX-UHFFFAOYSA-N 0.000 description 1
XEJMRIOMBDNIAW-UHFFFAOYSA-N n-[3-[3-[2-(benzenesulfonyl)ethyl]-6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCS(=O)(=O)C1=CC=CC=C1 XEJMRIOMBDNIAW-UHFFFAOYSA-N 0.000 description 1
IDDOMXLQOKPRCB-UHFFFAOYSA-N n-[3-[3-[2-(cyclohexylmethoxy)ethyl]-6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCOCC1CCCCC1 IDDOMXLQOKPRCB-UHFFFAOYSA-N 0.000 description 1
RXALNJCOTDTONG-UHFFFAOYSA-N n-[3-[3-[2-[2-(dimethylamino)ethoxy]ethyl]-6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CCOCCN(C)C)CC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 RXALNJCOTDTONG-UHFFFAOYSA-N 0.000 description 1
VUVQLYRSBQTECY-UHFFFAOYSA-N n-[3-[3-[2-[4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]ethyl]-6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCOC(C=C1)=CC=C1C1=NCCO1 VUVQLYRSBQTECY-UHFFFAOYSA-N 0.000 description 1
ZIUQQYGFIYVZDV-UHFFFAOYSA-N n-[3-[6-ethyl-3-(2-ethylsulfonylethyl)-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CCS(=O)(=O)CC)CC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 ZIUQQYGFIYVZDV-UHFFFAOYSA-N 0.000 description 1
YNIOOPISFSJPDG-UHFFFAOYSA-N n-[3-[6-ethyl-3-(2-prop-2-ynoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CCOCC#C)CC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 YNIOOPISFSJPDG-UHFFFAOYSA-N 0.000 description 1
OWZRYRQEPOVYPD-UHFFFAOYSA-N n-[3-[6-ethyl-3-[(2-phenylcyclopropyl)methyl]-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CC1CC1C1=CC=CC=C1 OWZRYRQEPOVYPD-UHFFFAOYSA-N 0.000 description 1
HIVOJIFHQKFNHD-UHFFFAOYSA-N n-[3-[6-ethyl-3-[2-(2,2,2-trifluoroethoxy)ethyl]-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CCOCC(F)(F)F)CC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 HIVOJIFHQKFNHD-UHFFFAOYSA-N 0.000 description 1
SODRSNDBDBKZHM-UHFFFAOYSA-N n-[3-[6-ethyl-3-[2-(2-hydroxyethoxy)ethyl]-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CCOCCO)CC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 SODRSNDBDBKZHM-UHFFFAOYSA-N 0.000 description 1
QQUNCNJAFMIGCP-UHFFFAOYSA-N n-[3-[6-ethyl-3-[2-(2-methoxyethoxy)ethyl]-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CCOCCOC)CC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 QQUNCNJAFMIGCP-UHFFFAOYSA-N 0.000 description 1
OGYMITMDEJTOBK-UHFFFAOYSA-N n-[3-[6-ethyl-3-[2-[(4-methoxyphenyl)methoxy]ethyl]-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C1C2C(CC)(C=3C=C(NS(C)(=O)=O)C=CC=3)C2CN1CCOCC1=CC=C(OC)C=C1 OGYMITMDEJTOBK-UHFFFAOYSA-N 0.000 description 1
239000003887 narcotic antagonist Substances 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
229940125702 ophthalmic agent Drugs 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
ABOYDMHGKWRPFD-UHFFFAOYSA-N phenylmethanesulfonamide Chemical compound NS(=O)(=O)CC1=CC=CC=C1 ABOYDMHGKWRPFD-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229920006324 polyoxymethylene Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
229920001343 polytetrafluoroethylene Polymers 0.000 description 1
239000004810 polytetrafluoroethylene Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
239000012264 purified product Substances 0.000 description 1
239000004248 saffron Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
239000002453 shampoo Substances 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
238000003307 slaughter Methods 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction 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
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
125000001174 sulfone group Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- 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
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/24—Antidepressants
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—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
- C07D413/12—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 linked by a chain containing hetero atoms as chain links

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Addiction (AREA)
Psychiatry (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Pain & Pain Management (AREA)
Dermatology (AREA)
Nutrition Science (AREA)
Gynecology & Obstetrics (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

SK1717-2002A 2000-06-23 2001-06-07 Deriváty 3-azabicyklo[3,1,0]hexánu vykazujúce afinitu k opiátovým receptorom SK17172002A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0015562.2A GB0015562D0 (en)	2000-06-23	2000-06-23	Heterocycles
PCT/IB2001/001035 WO2001098267A1 (fr)	2000-06-23	2001-06-07	Derives 3-azabicyclo[3.1.0] hexane ayant une affinite pour le recepteur opioide

Publications (1)

Publication Number	Publication Date
SK17172002A3 true SK17172002A3 (sk)	2004-09-08

Family

ID=9894368

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1717-2002A SK17172002A3 (sk)	2000-06-23	2001-06-07	Deriváty 3-azabicyklo[3,1,0]hexánu vykazujúce afinitu k opiátovým receptorom

Country Status (34)

Country	Link
EP (1)	EP1292574A1 (fr)
JP (1)	JP2004512263A (fr)
KR (1)	KR20040002386A (fr)
CN (1)	CN1639121A (fr)
AP (1)	AP2002002698A0 (fr)
AR (1)	AR028969A1 (fr)
AU (1)	AU781837B2 (fr)
BG (1)	BG107329A (fr)
BR (1)	BR0111867A (fr)
CA (1)	CA2412188A1 (fr)
CZ (1)	CZ20023967A3 (fr)
DO (1)	DOP2001000187A (fr)
DZ (1)	DZ3368A1 (fr)
EA (1)	EA005117B1 (fr)
GB (1)	GB0015562D0 (fr)
HR (1)	HRP20020998A2 (fr)
HU (1)	HUP0301228A3 (fr)
IL (1)	IL153427A0 (fr)
IS (1)	IS6637A (fr)
MA (1)	MA26915A1 (fr)
MX (1)	MXPA02012878A (fr)
NO (1)	NO20026168L (fr)
NZ (1)	NZ523141A (fr)
OA (1)	OA12293A (fr)
PA (1)	PA8519401A1 (fr)
PE (1)	PE20020253A1 (fr)
PL (1)	PL365956A1 (fr)
SK (1)	SK17172002A3 (fr)
TN (1)	TNSN01094A1 (fr)
UA (1)	UA73176C2 (fr)
UY (1)	UY26787A1 (fr)
WO (1)	WO2001098267A1 (fr)
YU (1)	YU91802A (fr)
ZA (1)	ZA200210278B (fr)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE60226161T2 (de) *	2001-10-22	2009-07-02	Pfizer Products Inc., Groton	3-azabicyclo[3.1.0]hexan derivative als antagonisten der opioid rezeptoren
CN100411618C (zh) *	2002-05-17	2008-08-20	迪欧加药品公司	有效的选择性阿片受体调制剂化合物的用途
DE10259245A1 (de)	2002-12-17	2004-07-01	Merck Patent Gmbh	Derivate des Asimadolins mit kovalent gebundenen Säuren
ATE451364T1 (de)	2004-02-23	2009-12-15	Glaxo Group Ltd	Als modulatoren des dopamin-d3-rezeptors geeignete azabicycloä3.1.0ühexanderivate
GB0507680D0 (en) *	2005-04-15	2005-05-25	Glaxo Group Ltd	Compounds
ATE484502T1 (de) *	2005-06-14	2010-10-15	Glaxo Group Ltd	Neue verbindungen
WO2007113258A1 (fr) *	2006-04-03	2007-10-11	Glaxo Group Limited	Dérivés d'azabicyclo [3. 1. o] hexane utilisés comme modulateurs des récepteurs de la dopamine d3
EP2636407A3 (fr)	2007-03-30	2013-11-06	Tioga Pharmaceuticals, Inc.	Agonistes du récepteur opiacé kappa pour le traitement du syndrome du côlon irritable avec alternance ou à diarrhée prédominante
TWI423801B (zh) *	2007-08-27	2014-01-21	Theravance Inc	作為μ類鴉片受體拮抗劑之８－氮雜雙環〔３．２．１〕辛基－２－羥基苯甲醯胺化合物
ES2645725T3 (es)	2010-06-11	2017-12-07	Rhodes Technologies	Procesos catalizados por metales de transición para la preparación de compuestos de N-alilo y uso de los mismos
BR112013007566A2 (pt)	2010-09-28	2016-08-02	Panacea Biotec Ltd	novos compostos bicíclicos
CA2927527C (fr) *	2013-11-20	2021-06-01	Sanwa Kagaku Kenkyusho Co., Ltd.	Derive 3-azabicyclo[3.1.0]hexane et son utilisation a des fins d'antagoniste de recepteur u-opioide
HK1246778A1 (zh)	2015-05-20	2018-09-14	株式会社三和化学研究所	一种新型的3-氮杂双环[3.1.0]己烷衍生物的盐的晶体以及其医药应用
JP7185633B2 (ja)	2017-02-17	2022-12-07	トレベナ・インコーポレイテッド	７員アザ複素環を含有するデルタ－オピオイド受容体調節化合物、その使用方法及び製造方法
BR112019016827A2 (pt)	2017-02-17	2020-04-07	Trevena Inc	compostos moduladores de receptor delta-opioide contendo aza-heterocíclico com 5 membros, métodos de uso e produção dos mesmos
EP3590511A4 (fr)	2017-03-02	2020-09-02	Sanwa Kagaku Kenkyusho Co., Ltd	Agent thérapeutique pour troubles liés à la consommation d'alcool
CN108250088B (zh) *	2018-01-04	2020-10-30	四川之江高新材料股份有限公司	N，n，n′-三甲基-n′-羟乙基双氨基乙基醚的制备方法
CN115825305B (zh) *	2022-10-21	2024-09-20	昆明理工大学	一种分子印迹固相微萃取纤维及其制备方法与应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3065230A (en) *	1959-03-16	1962-11-20	Burroughs Wellcome Co	Azabicyclohexanes and method of preparing them
ATE110057T1 (de) *	1987-04-16	1994-09-15	Lilly Co Eli	Piperidine als opioid-antagoniste.
US5159081A (en) *	1991-03-29	1992-10-27	Eli Lilly And Company	Intermediates of peripherally selective n-carbonyl-3,4,4-trisubstituted piperidine opioid antagonists
DE4341403A1 (de) *	1993-12-04	1995-06-08	Basf Ag	N-substituierte 3-Azabicycloalkan-Derivate, ihre Herstellung und Verwendung
PE20001420A1 (es) *	1998-12-23	2000-12-18	Pfizer	Moduladores de ccr5
TWI244481B (en) *	1998-12-23	2005-12-01	Pfizer	3-azabicyclo[3.1.0]hexane derivatives useful in therapy

2000
- 2000-06-23 GB GBGB0015562.2A patent/GB0015562D0/en not_active Ceased
2001
- 2001-06-06 DO DO2001000187A patent/DOP2001000187A/es unknown
- 2001-06-07 WO PCT/IB2001/001035 patent/WO2001098267A1/fr not_active Ceased
- 2001-06-07 YU YU91802A patent/YU91802A/sh unknown
- 2001-06-07 JP JP2002504223A patent/JP2004512263A/ja not_active Withdrawn
- 2001-06-07 AU AU62591/01A patent/AU781837B2/en not_active Ceased
- 2001-06-07 DZ DZ013368A patent/DZ3368A1/fr active
- 2001-06-07 HU HU0301228A patent/HUP0301228A3/hu unknown
- 2001-06-07 EA EA200201269A patent/EA005117B1/ru not_active IP Right Cessation
- 2001-06-07 BR BR0111867-6A patent/BR0111867A/pt not_active IP Right Cessation
- 2001-06-07 IL IL15342701A patent/IL153427A0/xx unknown
- 2001-06-07 SK SK1717-2002A patent/SK17172002A3/sk unknown
- 2001-06-07 AP APAP/P/2002/002698A patent/AP2002002698A0/en unknown
- 2001-06-07 MX MXPA02012878A patent/MXPA02012878A/es unknown
- 2001-06-07 PL PL01365956A patent/PL365956A1/xx not_active Application Discontinuation
- 2001-06-07 CA CA002412188A patent/CA2412188A1/fr not_active Abandoned
- 2001-06-07 NZ NZ523141A patent/NZ523141A/en unknown
- 2001-06-07 OA OA1200200386A patent/OA12293A/en unknown
- 2001-06-07 CN CNA018116086A patent/CN1639121A/zh active Pending
- 2001-06-07 EP EP01936728A patent/EP1292574A1/fr not_active Withdrawn
- 2001-06-07 KR KR1020027017503A patent/KR20040002386A/ko not_active Ceased
- 2001-06-07 HR HR20020998A patent/HRP20020998A2/hr not_active Application Discontinuation
- 2001-06-07 CZ CZ20023967A patent/CZ20023967A3/cs unknown
- 2001-06-12 PA PA20018519401A patent/PA8519401A1/es unknown
- 2001-06-21 PE PE2001000604A patent/PE20020253A1/es not_active Application Discontinuation
- 2001-06-21 UY UY26787A patent/UY26787A1/es not_active Application Discontinuation
- 2001-06-21 AR ARP010102957A patent/AR028969A1/es unknown
- 2001-06-22 TN TNTNSN01094A patent/TNSN01094A1/fr unknown
- 2001-07-06 UA UA20021210406A patent/UA73176C2/uk unknown
2002
- 2002-11-28 IS IS6637A patent/IS6637A/is unknown
- 2002-11-28 BG BG107329A patent/BG107329A/xx unknown
- 2002-12-16 MA MA26955A patent/MA26915A1/fr unknown
- 2002-12-19 ZA ZA200210278A patent/ZA200210278B/xx unknown
- 2002-12-20 NO NO20026168A patent/NO20026168L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
EA200201269A1 (ru)	2003-06-26
MXPA02012878A (es)	2003-05-14
WO2001098267A1 (fr)	2001-12-27
HUP0301228A3 (en)	2005-08-29
WO2001098267A8 (fr)	2003-02-27
CZ20023967A3 (cs)	2004-02-18
IL153427A0 (en)	2003-07-06
AP2002002698A0 (en)	2002-12-31
HUP0301228A2 (hu)	2003-08-28
BR0111867A (pt)	2003-07-01
UA73176C2 (en)	2005-06-15
JP2004512263A (ja)	2004-04-22
AU781837B2 (en)	2005-06-16
YU91802A (sh)	2006-05-25
UY26787A1 (es)	2002-01-31
ZA200210278B (en)	2003-12-19
AR028969A1 (es)	2003-05-28
IS6637A (is)	2002-11-28
AU6259101A (en)	2002-01-02
DOP2001000187A (es)	2002-03-30
GB0015562D0 (en)	2000-08-16
NO20026168D0 (no)	2002-12-20
TNSN01094A1 (fr)	2005-11-10
HRP20020998A2 (en)	2004-02-29
MA26915A1 (fr)	2004-12-20
BG107329A (en)	2003-07-31
EP1292574A1 (fr)	2003-03-19
CA2412188A1 (fr)	2001-12-27
PE20020253A1 (es)	2002-04-08
EA005117B1 (ru)	2004-10-28
PA8519401A1 (es)	2002-12-30
NZ523141A (en)	2005-06-24
NO20026168L (no)	2003-02-18
KR20040002386A (ko)	2004-01-07
DZ3368A1 (fr)	2001-12-27
OA12293A (en)	2004-03-18
CN1639121A (zh)	2005-07-13
PL365956A1 (en)	2005-01-24

Publication	Publication Date	Title
US7723321B2 (en)	2010-05-25	Chromane substituted benzimidazole derivatives
EP1499589B1 (fr)	2007-05-02	Derives de n-¬phenyl(piperidin-2-yl)methyl\|benzamide, leur preparation et leur application en therapeutique
AU662960B2 (en)	1995-09-21	N-sulphonyl-2-oxoindole derivatives having affinity for vasopressin and/or ocytocin receptors
EP1791821B1 (fr)	2013-06-05	Derives d'imidazolidine-2-one en tant que modulateurs selectifs du recepteur androgenique
AU781837B2 (en)	2005-06-16	3-azabicyclo (3.1.0) hexane derivatives having opioid receptor affinity
US20030013875A1 (en)	2003-01-16	3-azabicyclo[3.1.0]hexane derivatives useful in therapy
AU1382500A (en)	2000-06-13	Pyrrolidine derivatives-ccr-3 receptor antagonists
AU2008244576A1 (en)	2008-11-06	2-substituted indole derivatives as calcium channel blockers
FR2842805A1 (fr)	2004-01-30	Derives de n-[phenyl(piperidin-2-yl)methyl]benzamide,leur preparation et leur application et therapeutique
JP2001500850A (ja)	2001-01-23	非―ペプチドボンベシン受容体アンタゴニスト
US20020025948A1 (en)	2002-02-28	3-azabicyclo[3.1.0]hexane derivatives useful in therapy
KR101800594B1 (ko)	2017-11-22	미량 아민 결합 수용체(taar) 조절제로서 6-아미노-5,6,7,8-테트라하이드로나프탈렌-2-일 또는 3-아미노크로만-7-일 유도체
US20060247225A1 (en)	2006-11-02	3,6-Disubstituted azabicyclo hexane derivatives as muscarinic receptor antagonists
JP2009511592A (ja)	2009-03-19	新規ヘテロ環化合物
EP2097374B1 (fr)	2010-06-09	Derives de 5-alkyloxy-indolin-2-one, leur preparation et leurs applications en therapeutique comme ligands selectives des recepteurs v2 de la vasopressine
US20030207876A1 (en)	2003-11-06	3-Azabicyclo[3.1.0]hexane derivatives useful in therapy
US20070135508A1 (en)	2007-06-14	3,6-Disubstituted azabicyclo hexane derivatives as muscarinic receptor antagonists
CN101415711A (zh)	2009-04-22	用于治疗香草素受体1相关病症的新的螺[咪唑烷-4，3’-吲哚]2,2’’,5’(1h)-三酮
HK1040247A1 (zh)	2002-05-31	新穎的環丁烷並吲羧酰胺化合物、其製備方法和含有它們的藥物組合物
RS50051B (sr)	2008-11-28	Derivati 3-azabiciklo(3.1.0) heksana kao ligandi opijatskih receptora
MXPA01005034A (en)	2001-12-04	Pyrrolidine derivatives-ccr-3 receptor antagonists
HK1058671A (en)	2004-05-28	Novel aminotriazolone compounds, method for preparing same and pharmaceutical compositions containing same