EA005117B1 - Производные 3-азабицикло(3.1.0)гексана, обладающие сродством к опиодному рецептору - Google Patents

Производные 3-азабицикло(3.1.0)гексана, обладающие сродством к опиодному рецептору Download PDF

Info

Publication number: EA005117B1
Authority: EA; Eurasian Patent Office
Prior art keywords: formula; compound; phenyl; ethyl; alkyl
Prior art date: 2000-06-23

Application number

EA200201269A

Other languages

English (en)

Russian (ru)

Other versions

EA200201269A1 (ru

Inventor

Стефен Пол Гибсон

Грэхем Ланн

Эшли Эдвард Фенвик

Дэвид Моррис Гетин

Original Assignee

Пфайзер Инк

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

2004-10-28

2001-06-07 Application filed by Пфайзер Инк filed Critical Пфайзер Инк

2003-06-26 Publication of EA200201269A1 publication Critical patent/EA200201269A1/ru

2004-10-28 Publication of EA005117B1 publication Critical patent/EA005117B1/ru

Links

150000005228 3‐azabicyclo[3.1.0]hexanes Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 248
125000003118 aryl group Chemical group 0.000 claims abstract description 125
125000000217 alkyl group Chemical group 0.000 claims abstract description 124
238000000034 method Methods 0.000 claims abstract description 116
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 67
229910052736 halogen Inorganic materials 0.000 claims abstract description 52
150000002367 halogens Chemical class 0.000 claims abstract description 51
150000003839 salts Chemical class 0.000 claims abstract description 44
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 36
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 33
238000004519 manufacturing process Methods 0.000 claims abstract description 28
239000003638 chemical reducing agent Substances 0.000 claims abstract description 25
125000001424 substituent group Chemical group 0.000 claims abstract description 24
229910052799 carbon Inorganic materials 0.000 claims abstract description 23
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 22
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
125000005842 heteroatom Chemical group 0.000 claims abstract description 17
238000011282 treatment Methods 0.000 claims abstract description 17
125000004104 aryloxy group Chemical group 0.000 claims abstract description 16
125000004429 atom Chemical group 0.000 claims abstract description 16
239000003814 drug Substances 0.000 claims abstract description 15
108090000137 Opioid Receptors Proteins 0.000 claims abstract description 14
201000010099 disease Diseases 0.000 claims abstract description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
102000003840 Opioid Receptors Human genes 0.000 claims abstract description 12
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 9
125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
125000000304 alkynyl group Chemical group 0.000 claims abstract description 9
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 8
150000001412 amines Chemical class 0.000 claims abstract description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract 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 abstract description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 5
102000005962 receptors Human genes 0.000 claims abstract description 5
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims abstract description 4
238000006268 reductive amination reaction Methods 0.000 claims abstract description 4
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 3
125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
229940127240 opiate Drugs 0.000 claims abstract description 3
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
125000003367 polycyclic group Chemical group 0.000 claims abstract description 3
230000001404 mediated effect Effects 0.000 claims abstract 6
239000003937 drug carrier Substances 0.000 claims abstract 2
GOKSBRBRCBERJS-UHFFFAOYSA-N n-[3-[3-[(4-cyanophenyl)methyl]-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)C2CN1CC1=CC=C(C#N)C=C1 GOKSBRBRCBERJS-UHFFFAOYSA-N 0.000 claims abstract 2
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 claims description 3
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 claims description 2
RZKIOIXPEJMUTF-UHFFFAOYSA-N n-[3-[6-ethyl-3-[(2-phenylmethoxyphenyl)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)C2CN1CC1=CC=CC=C1OCC1=CC=CC=C1 RZKIOIXPEJMUTF-UHFFFAOYSA-N 0.000 claims description 2
JPCCBFONOGLRDA-UHFFFAOYSA-N n-[3-[3-(2,3,3a,4,5,6,7,7a-octahydro-1h-inden-2-ylmethyl)-6-ethyl-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CC3CC4CCCCC4C3)CC2C1(CC)C1=CC=CC(NS(C)(=O)=O)=C1 JPCCBFONOGLRDA-UHFFFAOYSA-N 0.000 claims 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 claims 1
SBEFXMQCOVVVCL-UHFFFAOYSA-N n-[3-[6-ethyl-3-[2-(4-phenoxyphenoxy)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=C1OC1=CC=CC=C1 SBEFXMQCOVVVCL-UHFFFAOYSA-N 0.000 claims 1
125000003107 substituted aryl group Chemical group 0.000 claims 1
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 abstract description 32
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 22
238000002360 preparation method Methods 0.000 abstract description 22
230000009467 reduction Effects 0.000 abstract description 11
238000006722 reduction reaction Methods 0.000 abstract description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 9
230000008569 process Effects 0.000 abstract description 7
229910052760 oxygen Inorganic materials 0.000 abstract description 4
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract description 3
RJVXDFVGLNHOOW-UHFFFAOYSA-N n-[3-[3-[2-(4-cyclopropylphenoxy)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=C1C1CC1 RJVXDFVGLNHOOW-UHFFFAOYSA-N 0.000 abstract description 3
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 abstract description 2
HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 abstract 2
OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 abstract 1
229910052717 sulfur Inorganic materials 0.000 abstract 1
-1 ΝΗ2 Chemical group 0.000 description 84
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
238000006243 chemical reaction Methods 0.000 description 46
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
125000001072 heteroaryl group Chemical group 0.000 description 43
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
239000011541 reaction mixture Substances 0.000 description 32
239000000243 solution Substances 0.000 description 32
239000002904 solvent Substances 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
238000005481 NMR spectroscopy Methods 0.000 description 27
239000000047 product Substances 0.000 description 26
125000003545 alkoxy group Chemical group 0.000 description 24
238000004949 mass spectrometry Methods 0.000 description 24
239000002585 base Chemical class 0.000 description 23
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 18
241001465754 Metazoa Species 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
229910052739 hydrogen Inorganic materials 0.000 description 17
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 14
239000002253 acid Substances 0.000 description 14
238000010828 elution Methods 0.000 description 14
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
239000003054 catalyst Substances 0.000 description 13
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 12
208000003251 Pruritus Diseases 0.000 description 12
125000005037 alkyl phenyl group Chemical group 0.000 description 12
239000000543 intermediate Substances 0.000 description 12
238000000825 ultraviolet detection Methods 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
239000000872 buffer Substances 0.000 description 10
239000012280 lithium aluminium hydride Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
125000004423 acyloxy group Chemical group 0.000 description 9
239000010410 layer Substances 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
101000587820 Homo sapiens Selenide, water dikinase 1 Proteins 0.000 description 8
101000701815 Homo sapiens Spermidine synthase Proteins 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
102100030413 Spermidine synthase Human genes 0.000 description 8
150000001299 aldehydes Chemical class 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
238000009835 boiling Methods 0.000 description 8
125000000524 functional group Chemical group 0.000 description 8
239000007800 oxidant agent Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 7
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
102000052567 Anaphase-Promoting Complex-Cyclosome Apc1 Subunit Human genes 0.000 description 7
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 7
108091006463 SLC25A24 Proteins 0.000 description 7
235000019257 ammonium acetate Nutrition 0.000 description 7
229940043376 ammonium acetate Drugs 0.000 description 7
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
238000001914 filtration Methods 0.000 description 7
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 6
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
239000000651 prodrug Substances 0.000 description 6
229940002612 prodrug Drugs 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
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
125000001589 carboacyl group Chemical group 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
230000003993 interaction Effects 0.000 description 5
230000007803 itching Effects 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
239000000126 substance Substances 0.000 description 5
208000024891 symptom Diseases 0.000 description 5
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 4
208000007848 Alcoholism Diseases 0.000 description 4
208000027559 Appetite disease Diseases 0.000 description 4
206010010774 Constipation Diseases 0.000 description 4
208000019454 Feeding and Eating disease Diseases 0.000 description 4
206010019196 Head injury Diseases 0.000 description 4
206010028813 Nausea Diseases 0.000 description 4
208000012488 Opiate Overdose Diseases 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
102100037580 Sesquipedalian-1 Human genes 0.000 description 4
101710169844 Sesquipedalian-1 Proteins 0.000 description 4
201000001880 Sexual dysfunction Diseases 0.000 description 4
208000006011 Stroke Diseases 0.000 description 4
208000025569 Tobacco Use disease Diseases 0.000 description 4
206010047700 Vomiting Diseases 0.000 description 4
150000001241 acetals Chemical class 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000002411 adverse Effects 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
208000010668 atopic eczema Diseases 0.000 description 4
229910000085 borane Inorganic materials 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
150000002148 esters Chemical class 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
125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
239000003446 ligand Substances 0.000 description 4
102000051367 mu Opioid Receptors Human genes 0.000 description 4
230000008693 nausea Effects 0.000 description 4
150000007530 organic bases Chemical class 0.000 description 4
239000002798 polar solvent Substances 0.000 description 4
238000002953 preparative HPLC Methods 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
231100000872 sexual dysfunction Toxicity 0.000 description 4
235000012239 silicon dioxide Nutrition 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 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
208000011580 syndromic disease Diseases 0.000 description 4
150000003512 tertiary amines Chemical class 0.000 description 4
230000008673 vomiting Effects 0.000 description 4
108020001612 μ-opioid receptors Proteins 0.000 description 4
PRSIVKNGHKMCKO-UHFFFAOYSA-N 1-(3-nitrophenyl)propylidenehydrazine Chemical compound CCC(=NN)C1=CC=CC([N+]([O-])=O)=C1 PRSIVKNGHKMCKO-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-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
206010012434 Dermatitis allergic Diseases 0.000 description 3
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 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 description 3
125000005741 alkyl alkenyl group Chemical group 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
201000008937 atopic dermatitis Diseases 0.000 description 3
239000012267 brine Substances 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
108700023159 delta Opioid Receptors Proteins 0.000 description 3
102000048124 delta Opioid Receptors Human genes 0.000 description 3
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 3
235000015872 dietary supplement Nutrition 0.000 description 3
229940079593 drug Drugs 0.000 description 3
230000000694 effects Effects 0.000 description 3
125000004438 haloalkoxy group Chemical group 0.000 description 3
230000002757 inflammatory effect Effects 0.000 description 3
102000048260 kappa Opioid Receptors Human genes 0.000 description 3
229910052745 lead Inorganic materials 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 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
230000000144 pharmacologic effect Effects 0.000 description 3
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
239000011734 sodium Substances 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
108020001588 κ-opioid receptors Proteins 0.000 description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 2
125000003161 (C1-C6) alkylene group Chemical group 0.000 description 2
125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 2
125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 description 2
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 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
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
QELFPXSQFIOJDM-UHFFFAOYSA-N 1-[4-(3-chloropropyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=C(CCCCl)C=C1 QELFPXSQFIOJDM-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
125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 2
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 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
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 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
239000005660 Abamectin Substances 0.000 description 2
VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
206010003645 Atopy Diseases 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-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
SPAGIJMPHSUYSE-UHFFFAOYSA-N Magnesium peroxide Chemical compound [Mg+2].[O-][O-] SPAGIJMPHSUYSE-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
ZZHLYYDVIOPZBE-UHFFFAOYSA-N Trimeprazine Chemical compound C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 ZZHLYYDVIOPZBE-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000009471 action 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
238000005576 amination reaction Methods 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
150000001413 amino acids Chemical group 0.000 description 2
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
150000001448 anilines Chemical class 0.000 description 2
229940125715 antihistaminic agent Drugs 0.000 description 2
239000000739 antihistaminic agent Substances 0.000 description 2
239000011260 aqueous acid Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000007864 aqueous solution Substances 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
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
210000004556 brain Anatomy 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
229910052794 bromium Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
125000002843 carboxylic acid group Chemical group 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000000000 cycloalkoxy group Chemical group 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
239000003974 emollient agent Substances 0.000 description 2
MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
238000009472 formulation Methods 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
229910052602 gypsum Inorganic materials 0.000 description 2
239000010440 gypsum Substances 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
125000005843 halogen group Chemical group 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
125000002883 imidazolyl group Chemical group 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
150000002500 ions Chemical class 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
239000000463 material Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
LBTPIFQNEKOAIM-UHFFFAOYSA-N n-phenylmethanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1 LBTPIFQNEKOAIM-UHFFFAOYSA-N 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
125000004043 oxo group Chemical group O=* 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
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
229910052698 phosphorus Inorganic materials 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
239000012256 powdered iron Substances 0.000 description 2
230000001823 pruritic effect Effects 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
208000017520 skin disease Diseases 0.000 description 2
239000010802 sludge Substances 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
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000007751 thermal spraying Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-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
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
125000001506 1,2,3-triazol-5-yl group Chemical group [H]N1N=NC([H])=C1[*] 0.000 description 1
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=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
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
APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
BIRKTWKDHSMSLN-UHFFFAOYSA-N 1-(3-aminophenyl)-6-ethyl-3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound NC=1C=C(C=CC=1)C12C(NC(C2C1CC)=O)=O BIRKTWKDHSMSLN-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
PSFDAYXWBWRTSM-UHFFFAOYSA-N 1-prop-2-enylpyrrole-2,5-dione Chemical compound C=CCN1C(=O)C=CC1=O PSFDAYXWBWRTSM-UHFFFAOYSA-N 0.000 description 1
JRQRCGAQNZQEJS-WPPIEQSHSA-N 2-[(2e,6e,10e,14e,18e,22e,26e,30e,34e,38e,42e)-3,7,11,15,19,23,27,31,35,39,43,47-dodecamethyloctatetraconta-2,6,10,14,18,22,26,30,34,38,42,46-dodecaenyl]-3-methylnaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 JRQRCGAQNZQEJS-WPPIEQSHSA-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
RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 1
LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 1
SPCKHVPPRJWQRZ-UHFFFAOYSA-N 2-benzhydryloxy-n,n-dimethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 SPCKHVPPRJWQRZ-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
QVTPWONEVZJCCS-UHFFFAOYSA-N 2-formylbenzonitrile Chemical compound O=CC1=CC=CC=C1C#N QVTPWONEVZJCCS-UHFFFAOYSA-N 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
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
XZBXAYCCBFTQHH-UHFFFAOYSA-N 3-chloropropylbenzene Chemical compound ClCCCC1=CC=CC=C1 XZBXAYCCBFTQHH-UHFFFAOYSA-N 0.000 description 1
VLMTVJTVYPCOOM-UHFFFAOYSA-N 4-(3-chloropropyl)phenol Chemical compound OC1=CC=C(CCCCl)C=C1 VLMTVJTVYPCOOM-UHFFFAOYSA-N 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-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
125000006163 5-membered heteroaryl group Chemical group 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
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 1
101150106709 ARC1 gene Proteins 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
101100013575 Arabidopsis thaliana FTSHI1 gene Proteins 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
206010003399 Arthropod bite Diseases 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
125000006374 C2-C10 alkenyl group Chemical group 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
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
206010012442 Dermatitis contact Diseases 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
241001331845 Equus asinus x caballus 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
241000400611 Eucalyptus deanei Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
239000005899 Fipronil Substances 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
244000068988 Glycine max Species 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 class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
239000005906 Imidacloprid Substances 0.000 description 1
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
BPFYOAJNDMUVBL-UHFFFAOYSA-N LSM-5799 Chemical compound C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3N(C)COC1=C32 BPFYOAJNDMUVBL-UHFFFAOYSA-N 0.000 description 1
239000004166 Lanolin Substances 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-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
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000948268 Meda Species 0.000 description 1
208000031888 Mycoses Diseases 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
206010028980 Neoplasm Diseases 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
101100352425 Pithecopus hypochondrialis psn2 gene Proteins 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
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
241000238711 Pyroglyphidae Species 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
238000006859 Swern oxidation reaction Methods 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 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
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
159000000021 acetate salts Chemical class 0.000 description 1
150000001242 acetic acid derivatives Chemical class 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
239000002671 adjuvant Substances 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
229960003790 alimemazine Drugs 0.000 description 1
125000004450 alkenylene group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000004419 alkynylene group Chemical group 0.000 description 1
239000013566 allergen Substances 0.000 description 1
229960004784 allergens Drugs 0.000 description 1
125000005336 allyloxy group Chemical group 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 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
238000004458 analytical method Methods 0.000 description 1
125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940124599 anti-inflammatory drug Drugs 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000003096 antiparasitic agent Substances 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
230000008901 benefit Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 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 description 1
229960002537 betamethasone Drugs 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
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
235000010290 biphenyl Nutrition 0.000 description 1
UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical group [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
238000009395 breeding Methods 0.000 description 1
230000001488 breeding effect Effects 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
201000011510 cancer Diseases 0.000 description 1
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
238000000451 chemical ionisation Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
229960003291 chlorphenamine Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000004440 column chromatography Methods 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
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
229960000520 diphenhydramine Drugs 0.000 description 1
238000007598 dipping method Methods 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 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
244000078703 ectoparasite Species 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
235000004626 essential fatty acids Nutrition 0.000 description 1
ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 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
ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
125000006125 ethylsulfonyl group Chemical group 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
229940013764 fipronil Drugs 0.000 description 1
229960004884 fluconazole 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
239000006260 foam Substances 0.000 description 1
TWVBEFREQNKFGN-UHFFFAOYSA-N formic acid;hydrazine Chemical compound NN.OC=O TWVBEFREQNKFGN-UHFFFAOYSA-N 0.000 description 1
239000012634 fragment Substances 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 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
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 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
125000001188 haloalkyl group Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
AKRQHOWXVSDJEF-UHFFFAOYSA-N heptane-1-sulfonic acid Chemical compound CCCCCCCS(O)(=O)=O AKRQHOWXVSDJEF-UHFFFAOYSA-N 0.000 description 1
125000005844 heterocyclyloxy group Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
235000014304 histidine Nutrition 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
235000012907 honey Nutrition 0.000 description 1
229940046533 house dust mites Drugs 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000002209 hydrophobic effect Effects 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
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 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
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
229960000310 isoleucine Drugs 0.000 description 1
230000000155 isotopic effect Effects 0.000 description 1
229960004130 itraconazole 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
150000003893 lactate salts Chemical class 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
235000019388 lanolin Nutrition 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
229910052744 lithium Inorganic materials 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
229960000521 lufenuron Drugs 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
229960002531 marbofloxacin Drugs 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000002483 medication Methods 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
235000006109 methionine Nutrition 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])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
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 1
LUBYGJKFYBSEMW-UHFFFAOYSA-N n-[3-[3-[3-(4-acetylphenyl)propyl]-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)C2CN1CCCC1=CC=C(C(C)=O)C=C1 LUBYGJKFYBSEMW-UHFFFAOYSA-N 0.000 description 1
239000003887 narcotic antagonist Substances 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000010502 orange oil Substances 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
230000001575 pathological effect Effects 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 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
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
125000005545 phthalimidyl group Chemical group 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
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
229960005205 prednisolone Drugs 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
150000003138 primary alcohols Chemical class 0.000 description 1
TURAMGVWNUTQKH-UHFFFAOYSA-N propa-1,2-dien-1-one Chemical group C=C=C=O TURAMGVWNUTQKH-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
239000012264 purified product Substances 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000000523 sample Substances 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
235000004400 serine Nutrition 0.000 description 1
239000002453 shampoo Substances 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000002689 soil Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000005507 spraying Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
150000003892 tartrate salts Chemical class 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
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
235000008521 threonine Nutrition 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000012549 training Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
238000011426 transformation method Methods 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
235000002374 tyrosine Nutrition 0.000 description 1
239000004474 valine Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1
ZFNVDHOSLNRHNN-UHFFFAOYSA-N xi-3-(4-Isopropylphenyl)-2-methylpropanal Chemical compound O=CC(C)CC1=CC=C(C(C)C)C=C1 ZFNVDHOSLNRHNN-UHFFFAOYSA-N 0.000 description 1
239000008096 xylene Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 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)
Neurosurgery (AREA)
Neurology (AREA)
Addiction (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Dermatology (AREA)
Pain & Pain Management (AREA)
Reproductive Health (AREA)
Endocrinology (AREA)
Gynecology & Obstetrics (AREA)
Hospice & Palliative Care (AREA)
Otolaryngology (AREA)
Cardiology (AREA)
Nutrition Science (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

EA200201269A 2000-06-23 2001-06-07 Производные 3-азабицикло(3.1.0)гексана, обладающие сродством к опиодному рецептору EA005117B1 (ru)

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 (en)	2000-06-23	2001-06-07	3-azabicyclo (3.1.0) hexane derivatives having opioid receptor affinity

Publications (2)

Publication Number	Publication Date
EA200201269A1 EA200201269A1 (ru)	2003-06-26
EA005117B1 true EA005117B1 (ru)	2004-10-28

Family

ID=9894368

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EA200201269A EA005117B1 (ru)	2000-06-23	2001-06-07	Производные 3-азабицикло(3.1.0)гексана, обладающие сродством к опиодному рецептору

Country Status (34)

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

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EA006708B1 (ru) *	2001-10-22	2006-02-24	Пфайзер Продактс Инк.	Производные 3-азабицикло (3.1.0) гексана в качестве антагонистов опиоидного рецептора
WO2003097051A2 (en) *	2002-05-17	2003-11-27	Merck Patent Gmbh	Use of compounds that are effective as selective opiate receptor modulators
DE10259245A1 (de)	2002-12-17	2004-07-01	Merck Patent Gmbh	Derivate des Asimadolins mit kovalent gebundenen Säuren
PT1745040E (pt)	2004-02-23	2010-03-08	Glaxo Group Ltd	Derivados do azabiciclo3.1.0-hexano úteis como moduladores dos receptores d3 da dopamina
GB0507680D0 (en) *	2005-04-15	2005-05-25	Glaxo Group Ltd	Compounds
EP1891056B1 (en) *	2005-06-14	2010-10-13	Glaxo Group Limited	Novel compounds
WO2007113258A1 (en) *	2006-04-03	2007-10-11	Glaxo Group Limited	Azabicyclo [3. 1. o] hexane derivatives as modulators of dopamine d3 receptors
CA2682608A1 (en)	2007-03-30	2008-10-09	Tioga Pharmaceuticals, Inc.	Kappa-opiate agonists for the treatment of diarrhea-predominant and alternating irritable bowel syndrome
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
EP2580201B1 (en)	2010-06-11	2017-08-02	Rhodes Technologies	Transition metal-catalyzed processes for the preparation of n-allyl compounds and use thereof
BR112013007566A2 (pt)	2010-09-28	2016-08-02	Panacea Biotec Ltd	novos compostos bicíclicos
CN105764888B (zh) *	2013-11-20	2018-04-06	株式会社三和化学研究所	一种新的3‑氮杂双环[3.1.0]己烷衍生物以及其医药用途
CN107428687B (zh)	2015-05-20	2021-06-11	宇部兴产株式会社	一种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
CN110446495B (zh)	2017-02-17	2023-09-05	特维娜有限公司	含有7元氮杂杂环的δ阿片受体调节化合物及其使用和制备方法
AU2018221148B2 (en)	2017-02-17	2022-05-05	Trevena, Inc.	5-membered aza-heterocyclic containing delta-opioid receptor modulating compounds, methods of using and making the same
JPWO2018159716A1 (ja)	2017-03-02	2019-12-26	株式会社三和化学研究所	アルコール使用障害の治療薬
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
DE3851081T2 (de) *	1987-04-16	1995-02-16	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
TWI244481B (en) *	1998-12-23	2005-12-01	Pfizer	3-azabicyclo[3.1.0]hexane derivatives useful in therapy
PE20001420A1 (es) *	1998-12-23	2000-12-18	Pfizer	Moduladores de ccr5

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 HU HU0301228A patent/HUP0301228A3/hu unknown
- 2001-06-07 JP JP2002504223A patent/JP2004512263A/ja not_active Withdrawn
- 2001-06-07 EP EP01936728A patent/EP1292574A1/en not_active Withdrawn
- 2001-06-07 OA OA1200200386A patent/OA12293A/en unknown
- 2001-06-07 DZ DZ013368A patent/DZ3368A1/xx active
- 2001-06-07 KR KR1020027017503A patent/KR20040002386A/ko not_active Ceased
- 2001-06-07 CA CA002412188A patent/CA2412188A1/en not_active Abandoned
- 2001-06-07 NZ NZ523141A patent/NZ523141A/en unknown
- 2001-06-07 PL PL01365956A patent/PL365956A1/xx not_active Application Discontinuation
- 2001-06-07 HR HR20020998A patent/HRP20020998A2/hr not_active Application Discontinuation
- 2001-06-07 MX MXPA02012878A patent/MXPA02012878A/es unknown
- 2001-06-07 SK SK1717-2002A patent/SK17172002A3/sk unknown
- 2001-06-07 IL IL15342701A patent/IL153427A0/xx unknown
- 2001-06-07 YU YU91802A patent/YU91802A/sh unknown
- 2001-06-07 AU AU62591/01A patent/AU781837B2/en not_active Ceased
- 2001-06-07 CN CNA018116086A patent/CN1639121A/zh active Pending
- 2001-06-07 AP APAP/P/2002/002698A patent/AP2002002698A0/en unknown
- 2001-06-07 EA EA200201269A patent/EA005117B1/ru not_active IP Right Cessation
- 2001-06-07 WO PCT/IB2001/001035 patent/WO2001098267A1/en not_active Ceased
- 2001-06-07 CZ CZ20023967A patent/CZ20023967A3/cs unknown
- 2001-06-07 BR BR0111867-6A patent/BR0111867A/pt not_active IP Right Cessation
- 2001-06-12 PA PA20018519401A patent/PA8519401A1/es unknown
- 2001-06-21 AR ARP010102957A patent/AR028969A1/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
- 2001-06-22 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
OA12293A (en)	2004-03-18
MXPA02012878A (es)	2003-05-14
TNSN01094A1 (fr)	2005-11-10
SK17172002A3 (sk)	2004-09-08
UA73176C2 (en)	2005-06-15
HUP0301228A2 (hu)	2003-08-28
NO20026168D0 (no)	2002-12-20
HRP20020998A2 (en)	2004-02-29
DOP2001000187A (es)	2002-03-30
HUP0301228A3 (en)	2005-08-29
KR20040002386A (ko)	2004-01-07
AU6259101A (en)	2002-01-02
MA26915A1 (fr)	2004-12-20
BR0111867A (pt)	2003-07-01
ZA200210278B (en)	2003-12-19
AU781837B2 (en)	2005-06-16
AP2002002698A0 (en)	2002-12-31
NO20026168L (no)	2003-02-18
CA2412188A1 (en)	2001-12-27
AR028969A1 (es)	2003-05-28
PL365956A1 (en)	2005-01-24
GB0015562D0 (en)	2000-08-16
EP1292574A1 (en)	2003-03-19
IS6637A (is)	2002-11-28
PE20020253A1 (es)	2002-04-08
UY26787A1 (es)	2002-01-31
DZ3368A1 (fr)	2001-12-27
NZ523141A (en)	2005-06-24
WO2001098267A1 (en)	2001-12-27
BG107329A (en)	2003-07-31
PA8519401A1 (es)	2002-12-30
IL153427A0 (en)	2003-07-06
WO2001098267A8 (en)	2003-02-27
CZ20023967A3 (cs)	2004-02-18
YU91802A (sh)	2006-05-25
CN1639121A (zh)	2005-07-13
JP2004512263A (ja)	2004-04-22
EA200201269A1 (ru)	2003-06-26

Legal Events

Date	Code	Title	Description
2007-04-27	MM4A	Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)	Designated state(s): AM AZ BY KZ KG MD TJ TM RU

Publication	Publication Date	Title
US7049444B2 (en)	2006-05-23	3-azabicyclo[3.1.0]hexane derivatives useful in therapy
AU722883B2 (en)	2000-08-10	Cyclopentyl tachykinin receptor antagonists
JP3925662B2 (ja)	2007-06-06	タキキニンアンタゴニスト活性を有するピペリジン誘導体
US5750549A (en)	1998-05-12	Cycloalkyl tachykinin receptor antagonists
EA005117B1 (ru)	2004-10-28	Производные 3-азабицикло(3.1.0)гексана, обладающие сродством к опиодному рецептору
US5830892A (en)	1998-11-03	Piperidine and morphonline derivatives and their use as therapeutic agents
US5607936A (en)	1997-03-04	Substituted aryl piperazines as neurokinin antagonists
CN110997661B (zh)	2023-03-31	环丙基脲甲酰肽2受体和甲酰肽1受体激动剂
RS51888B (sr)	2012-02-29	N-(fenil(piperidin-2-il)metil)benzamidni derivati, njihovo dobijanje i njihova primena u terapiji
HRP940575A2 (en)	1997-02-28	Piperidine derivatives
JP2000500760A (ja)	2000-01-25	スピロピペリジン誘導体およびタキキニン拮抗薬としてのその使用
US20080103178A1 (en)	2008-05-01	N-dihydroxyalkyl-substituted 2-oxo-imidazole derivatives
US20020025948A1 (en)	2002-02-28	3-azabicyclo[3.1.0]hexane derivatives useful in therapy
US7906510B2 (en)	2011-03-15	Amide derivative and pharmaceutical composition containing the same
US20030207876A1 (en)	2003-11-06	3-Azabicyclo[3.1.0]hexane derivatives useful in therapy
ES2355580T3 (es)	2011-03-29	Derivados de 2-oxoimidazol sustituidos con n-dihidroxialquilo.
JP4943826B2 (ja)	2012-05-30	医薬組成物
CN105899506A (zh)	2016-08-24	作为RORc调节剂的杂芳基磺内酰胺衍生物
TWI917479B (zh)	2026-03-11	用於治療ｔｒｐｍ３介導病症之芳基衍生物
KR20010086462A (ko)	2001-09-12	오피에이트 수용체 리간드로서의 3-아자비시클로[3.1.0.]헥산 유도체