JP2009528282A - 修飾アミノ酸 - Google Patents
修飾アミノ酸 Download PDFInfo
- Publication number
- JP2009528282A JP2009528282A JP2008555632A JP2008555632A JP2009528282A JP 2009528282 A JP2009528282 A JP 2009528282A JP 2008555632 A JP2008555632 A JP 2008555632A JP 2008555632 A JP2008555632 A JP 2008555632A JP 2009528282 A JP2009528282 A JP 2009528282A
- Authority
- JP
- Japan
- Prior art keywords
- ester
- compound
- group
- acid
- mmol
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 150000001413 amino acids Chemical class 0.000 title claims description 74
- 150000001875 compounds Chemical class 0.000 claims abstract description 168
- 238000000034 method Methods 0.000 claims abstract description 70
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 63
- MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Substances OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 36
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 30
- 125000003277 amino group Chemical group 0.000 claims abstract description 11
- 125000004185 ester group Chemical group 0.000 claims abstract description 6
- -1 guanidinylbutyl Chemical group 0.000 claims description 148
- 239000007787 solid Substances 0.000 claims description 78
- 235000001014 amino acid Nutrition 0.000 claims description 76
- 229940024606 amino acid Drugs 0.000 claims description 75
- 108090000623 proteins and genes Proteins 0.000 claims description 54
- 102000004169 proteins and genes Human genes 0.000 claims description 53
- 235000018102 proteins Nutrition 0.000 claims description 49
- 125000006239 protecting group Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 150000002148 esters Chemical class 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 229920005989 resin Polymers 0.000 claims description 19
- 239000011347 resin Substances 0.000 claims description 19
- 150000001408 amides Chemical group 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 15
- 125000004429 atom Chemical group 0.000 claims description 14
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 230000003213 activating effect Effects 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 239000012634 fragment Substances 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical group NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 235000006408 oxalic acid Nutrition 0.000 claims description 6
- 150000003901 oxalic acid esters Chemical class 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 claims description 5
- VSOSXKMEQPYESP-UHFFFAOYSA-N 1,6-naphthyridine Chemical compound C1=CN=CC2=CC=CN=C21 VSOSXKMEQPYESP-UHFFFAOYSA-N 0.000 claims description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 5
- 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 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000006850 spacer group Chemical group 0.000 claims description 5
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 claims description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 4
- 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 4
- 239000002253 acid Substances 0.000 claims description 4
- 229960003767 alanine Drugs 0.000 claims description 4
- 235000004279 alanine Nutrition 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000003636 chemical group Chemical group 0.000 claims description 4
- FIRHQRGFVOSDDY-UHFFFAOYSA-N ethyl 1-hydroxytriazole-4-carboxylate Chemical compound CCOC(=O)C1=CN(O)N=N1 FIRHQRGFVOSDDY-UHFFFAOYSA-N 0.000 claims description 4
- 229960003136 leucine Drugs 0.000 claims description 4
- 229960005190 phenylalanine Drugs 0.000 claims description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 3
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 3
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 3
- 239000004473 Threonine Substances 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 229960003121 arginine Drugs 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 235000009697 arginine Nutrition 0.000 claims description 3
- 229960001230 asparagine Drugs 0.000 claims description 3
- 235000009582 asparagine Nutrition 0.000 claims description 3
- 229960005261 aspartic acid Drugs 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- 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 description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 229960002433 cysteine Drugs 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 3
- 235000004554 glutamine Nutrition 0.000 claims description 3
- 229960002885 histidine Drugs 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 229960000310 isoleucine Drugs 0.000 claims description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 239000004474 valine Substances 0.000 claims description 3
- ORLCYMQZIPSODD-UHFFFAOYSA-N 1-chloro-2-[chloro(2,2,2-trichloroethoxy)phosphoryl]oxybenzene Chemical compound ClC1=CC=CC=C1OP(Cl)(=O)OCC(Cl)(Cl)Cl ORLCYMQZIPSODD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 238000007792 addition Methods 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000004373 methylthiopropyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- IVWWFWFVSWOTLP-YVZVNANGSA-N (3'as,4r,7'as)-2,2,2',2'-tetramethylspiro[1,3-dioxolane-4,6'-4,7a-dihydro-3ah-[1,3]dioxolo[4,5-c]pyran]-7'-one Chemical compound C([C@@H]1OC(O[C@@H]1C1=O)(C)C)O[C@]21COC(C)(C)O2 IVWWFWFVSWOTLP-YVZVNANGSA-N 0.000 claims 1
- GZVGZNZUTVHRBN-LXNQBTANSA-N C1CC=CN1.OC1CN[C@H](C(O)=O)C1 Chemical compound C1CC=CN1.OC1CN[C@H](C(O)=O)C1 GZVGZNZUTVHRBN-LXNQBTANSA-N 0.000 claims 1
- 229960002989 glutamic acid Drugs 0.000 claims 1
- 229960002743 glutamine Drugs 0.000 claims 1
- 229960002449 glycine Drugs 0.000 claims 1
- 229960003646 lysine Drugs 0.000 claims 1
- 229960004452 methionine Drugs 0.000 claims 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 21
- 230000015572 biosynthetic process Effects 0.000 abstract description 19
- 150000003862 amino acid derivatives Chemical class 0.000 abstract description 7
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 150000001735 carboxylic acids Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 221
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 198
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 143
- 235000019439 ethyl acetate Nutrition 0.000 description 110
- 239000000243 solution Substances 0.000 description 76
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 72
- 239000011541 reaction mixture Substances 0.000 description 72
- 239000000047 product Substances 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 48
- 238000003756 stirring Methods 0.000 description 47
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 239000012267 brine Substances 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- 238000004440 column chromatography Methods 0.000 description 34
- 239000002904 solvent Substances 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
- 229910052786 argon Inorganic materials 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000010410 layer Substances 0.000 description 19
- 238000001914 filtration Methods 0.000 description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 16
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- WJYPVTGXUXXDBJ-LBPRGKRZSA-N methyl 2-[[(2s)-1-[2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoacetate Chemical compound CC(C)(C)OC(=O)NNC(=O)[C@@H](NC(=O)C(=O)OC)CC1=CC=CC=C1 WJYPVTGXUXXDBJ-LBPRGKRZSA-N 0.000 description 11
- 0 O=CNNC(*CC1c(cccc2)c2C2=C1CCC=C2)=O Chemical compound O=CNNC(*CC1c(cccc2)c2C2=C1CCC=C2)=O 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- ZYJPUMXJBDHSIF-NSHDSACASA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-NSHDSACASA-N 0.000 description 9
- JWLJETNHOHXCFW-NSHDSACASA-N 2-[[(2s)-1-[2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoacetic acid Chemical compound CC(C)(C)OC(=O)NNC(=O)[C@@H](NC(=O)C(O)=O)CC1=CC=CC=C1 JWLJETNHOHXCFW-NSHDSACASA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000001665 trituration Methods 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
- UBYXFTLJRVKYCK-HNNXBMFYSA-N benzyl n-[[(2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(C)C)C(=O)NNC(=O)OCC1=CC=CC=C1 UBYXFTLJRVKYCK-HNNXBMFYSA-N 0.000 description 7
- 238000010647 peptide synthesis reaction Methods 0.000 description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- WUTNXWKTRNEKJV-NSHDSACASA-N benzyl n-[[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)NNC(=O)OCC1=CC=CC=C1 WUTNXWKTRNEKJV-NSHDSACASA-N 0.000 description 6
- ZWNOZQLVOAUDBA-FQEVSTJZSA-N benzyl n-[[(2s)-3-(1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]carbamate Chemical compound O=C([C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)OC(C)(C)C)NNC(=O)OCC1=CC=CC=C1 ZWNOZQLVOAUDBA-FQEVSTJZSA-N 0.000 description 6
- RXUBZLMIGSAPEJ-UHFFFAOYSA-N benzyl n-aminocarbamate Chemical compound NNC(=O)OCC1=CC=CC=C1 RXUBZLMIGSAPEJ-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000003278 mimic effect Effects 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- YFKMJAJGYOZLOL-YTTGMZPUSA-N (2-bromophenyl)methyl [4-[(2s)-3-[2-(9h-fluoren-9-ylmethoxycarbonyl)hydrazinyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]phenyl] carbonate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)NNC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(C=C1)=CC=C1OC(=O)OCC1=CC=CC=C1Br YFKMJAJGYOZLOL-YTTGMZPUSA-N 0.000 description 5
- YGCGPEUVGHDMLO-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-aminocarbamate Chemical compound C1=CC=C2C(COC(=O)NN)C3=CC=CC=C3C2=C1 YGCGPEUVGHDMLO-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- LQVJCDOOWYETKN-SFHVURJKSA-N benzyl n-[[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)NNC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 LQVJCDOOWYETKN-SFHVURJKSA-N 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
- 125000005647 linker group Chemical group 0.000 description 5
- FLDSJXOSJUXULE-QHCPKHFHSA-N methyl 2-[[(2s)-1-[2-(9h-fluoren-9-ylmethoxycarbonyl)hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoacetate Chemical compound C([C@H](NC(=O)C(=O)OC)C(=O)NNC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C1=CC=CC=C1 FLDSJXOSJUXULE-QHCPKHFHSA-N 0.000 description 5
- CPHCMZGINLUPHJ-JSGCOSHPSA-N methyl 2-[[(2s)-1-[2-[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoacetate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)NNC(=O)[C@@H](NC(=O)C(=O)OC)CC1=CC=CC=C1 CPHCMZGINLUPHJ-JSGCOSHPSA-N 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 238000010532 solid phase synthesis reaction Methods 0.000 description 5
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 5
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 5
- SBFDMIXYISLNRP-AAEUAGOBSA-N 2-[[(2s)-1-[2-[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoacetic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)NNC(=O)[C@@H](NC(=O)C(O)=O)CC1=CC=CC=C1 SBFDMIXYISLNRP-AAEUAGOBSA-N 0.000 description 4
- KMJNYKLLEVXVGT-UHFFFAOYSA-N 2-anilinoethylcarbamic acid Chemical compound OC(=O)NCCNC1=CC=CC=C1 KMJNYKLLEVXVGT-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 125000003275 alpha amino acid group Chemical group 0.000 description 4
- LQVJCDOOWYETKN-UHFFFAOYSA-N benzyl n-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NNC(=O)C(NC(=O)OC(C)(C)C)CC1=CC=CC=C1 LQVJCDOOWYETKN-UHFFFAOYSA-N 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 125000002843 carboxylic acid group Chemical group 0.000 description 4
- 125000000524 functional group Chemical class 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229960002429 proline Drugs 0.000 description 4
- 229960004799 tryptophan Drugs 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- ZLOKKBDTYOLTOR-PXNSSMCTSA-N benzyl n-[(2s)-1-[2-[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)NNC(=O)[C@@H](NC(=O)OC(C)(C)C)C)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 ZLOKKBDTYOLTOR-PXNSSMCTSA-N 0.000 description 3
- 230000031018 biological processes and functions Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 108091005601 modified peptides Proteins 0.000 description 3
- OCIDXARMXNJACB-UHFFFAOYSA-N n'-phenylethane-1,2-diamine Chemical group NCCNC1=CC=CC=C1 OCIDXARMXNJACB-UHFFFAOYSA-N 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 2
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 2
- UYWMYJQSTUVRHR-SFHVURJKSA-N (2s)-3-[4-[(2-bromophenyl)methoxycarbonyloxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC=C1OC(=O)OCC1=CC=CC=C1Br UYWMYJQSTUVRHR-SFHVURJKSA-N 0.000 description 2
- RRONHWAVOYADJL-HNNXBMFYSA-N (2s)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-HNNXBMFYSA-N 0.000 description 2
- JTTZSFVEQXVADL-QMMMGPOBSA-N (6s)-6-benzyl-1,2,5-triazepane-3,4,7-trione Chemical compound O=C1NNC(=O)C(=O)N[C@H]1CC1=CC=CC=C1 JTTZSFVEQXVADL-QMMMGPOBSA-N 0.000 description 2
- STEHILAYWZFAOU-UHFFFAOYSA-N 1h-1,2,5-triazepine Chemical group N1C=CN=CC=N1 STEHILAYWZFAOU-UHFFFAOYSA-N 0.000 description 2
- ZYJPUMXJBDHSIF-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-UHFFFAOYSA-N 0.000 description 2
- YKESXUSSXPNJNL-UHFFFAOYSA-N 2-[2-(9h-fluoren-9-ylmethoxycarbonyl)hydrazinyl]-2-oxoacetic acid Chemical compound C1=CC=C2C(COC(=O)NNC(=O)C(=O)O)C3=CC=CC=C3C2=C1 YKESXUSSXPNJNL-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 2
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- NFVNYBJCJGKVQK-ZDUSSCGKSA-N N-[(Tert-butoxy)carbonyl]-L-tryptophan Chemical compound C1=CC=C2C(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CNC2=C1 NFVNYBJCJGKVQK-ZDUSSCGKSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012455 biphasic mixture Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- QVDYYQXUNAQSNI-UHFFFAOYSA-N ethyl acetate;pentane Chemical compound CCCCC.CCOC(C)=O QVDYYQXUNAQSNI-UHFFFAOYSA-N 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002391 heterocyclic compounds Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 2
- JRMBAKAOMNINKA-PMERELPUSA-N methyl 2-[[(2s)-3-[4-[(2-bromophenyl)methoxycarbonyloxy]phenyl]-1-[2-(9h-fluoren-9-ylmethoxycarbonyl)hydrazinyl]-1-oxopropan-2-yl]amino]-2-oxoacetate Chemical compound C([C@H](NC(=O)C(=O)OC)C(=O)NNC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21)C(C=C1)=CC=C1OC(=O)OCC1=CC=CC=C1Br JRMBAKAOMNINKA-PMERELPUSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- UWBHMRBRLOJJAA-UHFFFAOYSA-N oxaluric acid Chemical compound NC(=O)NC(=O)C(O)=O UWBHMRBRLOJJAA-UHFFFAOYSA-N 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 230000005522 programmed cell death Effects 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- WCFHROBSKKMMJN-VWLOTQADSA-N (2-bromophenyl)methyl [4-[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxo-3-(2-phenylmethoxycarbonylhydrazinyl)propyl]phenyl] carbonate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)NNC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1OC(=O)OCC1=CC=CC=C1Br WCFHROBSKKMMJN-VWLOTQADSA-N 0.000 description 1
- QFKHMZOHRSWAQB-UHFFFAOYSA-N (2-bromophenyl)methyl hydrogen carbonate Chemical compound OC(=O)OCC1=CC=CC=C1Br QFKHMZOHRSWAQB-UHFFFAOYSA-N 0.000 description 1
- ZYJPUMXJBDHSIF-LLVKDONJSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-LLVKDONJSA-N 0.000 description 1
- WSFGOLVWRKEQOW-BYPYZUCNSA-N (2s)-2-amino-n,n-dimethylpropanamide Chemical compound C[C@H](N)C(=O)N(C)C WSFGOLVWRKEQOW-BYPYZUCNSA-N 0.000 description 1
- URQQEIOTRWJXBA-QRPNPIFTSA-N (2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid;hydrate Chemical compound O.CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C URQQEIOTRWJXBA-QRPNPIFTSA-N 0.000 description 1
- QJCNLJWUIOIMMF-YUMQZZPRSA-N (2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C QJCNLJWUIOIMMF-YUMQZZPRSA-N 0.000 description 1
- FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000000980 1H-indol-3-ylmethyl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[*])C2=C1[H] 0.000 description 1
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
- NHZLLKNRTDIFAD-UHFFFAOYSA-N 2,5-dihydro-1,3-oxazole Chemical compound C1OCN=C1 NHZLLKNRTDIFAD-UHFFFAOYSA-N 0.000 description 1
- FUTNAVWVHCUJLT-NSHDSACASA-N 2-[[(2s)-1-[2-(9h-fluoren-9-ylmethoxycarbonyl)hydrazinyl]-1-oxopropan-2-yl]amino]-2-oxoacetic acid Chemical compound C1=CC=C2C(COC(=O)NNC(=O)[C@@H](NC(=O)C(O)=O)C)C3=CC=CC=C3C2=C1 FUTNAVWVHCUJLT-NSHDSACASA-N 0.000 description 1
- UAMZVBOUIXSJJB-YYWHXJBOSA-N 2-[[(2s)-1-[2-[(2s)-2-[[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoacetic acid Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)NNC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)C(O)=O)NC(=O)OC(C)(C)C)C1=CC=CC=C1 UAMZVBOUIXSJJB-YYWHXJBOSA-N 0.000 description 1
- WSFGOLVWRKEQOW-UHFFFAOYSA-N 2-amino-n,n-dimethylpropanamide Chemical compound CC(N)C(=O)N(C)C WSFGOLVWRKEQOW-UHFFFAOYSA-N 0.000 description 1
- HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- URUSTUSXVJKDQW-QMMMGPOBSA-N 2-oxo-2-[[(2s)-1-oxo-1-(2-phenylmethoxycarbonylhydrazinyl)propan-2-yl]amino]acetic acid Chemical compound OC(=O)C(=O)N[C@@H](C)C(=O)NNC(=O)OCC1=CC=CC=C1 URUSTUSXVJKDQW-QMMMGPOBSA-N 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- IWTYTFSSTWXZFU-UHFFFAOYSA-N 3-chloroprop-1-enylbenzene Chemical compound ClCC=CC1=CC=CC=C1 IWTYTFSSTWXZFU-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000001845 4 membered carbocyclic group Chemical group 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- LWWPSEIFAKNPKQ-UHFFFAOYSA-N 5-amino-2-methoxybenzoic acid Chemical compound COC1=CC=C(N)C=C1C(O)=O LWWPSEIFAKNPKQ-UHFFFAOYSA-N 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- ZZOKVYOCRSMTSS-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl carbamate Chemical compound C1=CC=C2C(COC(=O)N)C3=CC=CC=C3C2=C1 ZZOKVYOCRSMTSS-UHFFFAOYSA-N 0.000 description 1
- WTNNKSSOVUZBKC-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(methylamino)carbamate Chemical compound C1=CC=C2C(COC(=O)NNC)C3=CC=CC=C3C2=C1 WTNNKSSOVUZBKC-UHFFFAOYSA-N 0.000 description 1
- XMDBCHVNHJBYMO-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-amino-n-methylcarbamate Chemical compound C1=CC=C2C(COC(=O)N(N)C)C3=CC=CC=C3C2=C1 XMDBCHVNHJBYMO-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 1
- LPQZERIRKRYGGM-UHFFFAOYSA-N CC(C)(C)OC(N1CCCC1)=O Chemical compound CC(C)(C)OC(N1CCCC1)=O LPQZERIRKRYGGM-UHFFFAOYSA-N 0.000 description 1
- XKDQTOQVGGBFCX-QMMMGPOBSA-N CC(C)NC(C(N(CCC1)[C@@H]1C(OC)=O)=O)=O Chemical compound CC(C)NC(C(N(CCC1)[C@@H]1C(OC)=O)=O)=O XKDQTOQVGGBFCX-QMMMGPOBSA-N 0.000 description 1
- PLRXWMCCEJDLIH-UHFFFAOYSA-N CCNC(C(NC(C)C(NNC(N(CCNC(OCC1C(C=CCC2)=C2c2ccccc12)=O)c1ccccc1)=O)O)=O)=O Chemical compound CCNC(C(NC(C)C(NNC(N(CCNC(OCC1C(C=CCC2)=C2c2ccccc12)=O)c1ccccc1)=O)O)=O)=O PLRXWMCCEJDLIH-UHFFFAOYSA-N 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- FIOTXFHDYJPVQV-YFKPBYRVSA-N COC([C@H](CCC1)N1C(C(O)=O)=O)=O Chemical compound COC([C@H](CCC1)N1C(C(O)=O)=O)=O FIOTXFHDYJPVQV-YFKPBYRVSA-N 0.000 description 1
- HRDYWACIVOHHPD-HNNXBMFYSA-N C[C@@H](C(NNC(N(CCNCCC#N)c1ccccc1)=O)=O)NC(C(NC(C)(C)C)=O)=O Chemical compound C[C@@H](C(NNC(N(CCNCCC#N)c1ccccc1)=O)=O)NC(C(NC(C)(C)C)=O)=O HRDYWACIVOHHPD-HNNXBMFYSA-N 0.000 description 1
- PPUYUEPZGGATCN-QMMMGPOBSA-N C[C@@H](CCC1)N1C(OC(C)(C)C)=O Chemical compound C[C@@H](CCC1)N1C(OC(C)(C)C)=O PPUYUEPZGGATCN-QMMMGPOBSA-N 0.000 description 1
- PIYBYJYFNJMCHX-WDHXSWFYSA-N C[C@@H]([C@H](NC)O)C(C(C(C(C(C)(C)C)=N)[O]=C)O)=N Chemical compound C[C@@H]([C@H](NC)O)C(C(C(C(C(C)(C)C)=N)[O]=C)O)=N PIYBYJYFNJMCHX-WDHXSWFYSA-N 0.000 description 1
- 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 102100022339 Integrin alpha-L Human genes 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 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
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 229920001367 Merrifield resin Polymers 0.000 description 1
- 101710180087 Met repressor Proteins 0.000 description 1
- 241000640827 Mimetica Species 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- DCQBQMBNQZVDLP-MWFHZGJYSA-N OC(CCCCNC1=CCCCC1)C1C(CC2C(CCCC3)=C3C3[C@@H]2C=CCC3)C1 Chemical compound OC(CCCCNC1=CCCCC1)C1C(CC2C(CCCC3)=C3C3[C@@H]2C=CCC3)C1 DCQBQMBNQZVDLP-MWFHZGJYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 description 1
- 108050008994 PDZ domains Proteins 0.000 description 1
- 102000000470 PDZ domains Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- SRXGZRZZFQUPMB-UHFFFAOYSA-N [(2-ethoxy-2-oxoethyl)carbamoylamino]carbamic acid Chemical compound CCOC(=O)CNC(=O)NNC(O)=O SRXGZRZZFQUPMB-UHFFFAOYSA-N 0.000 description 1
- NEHJQDYHECYLJD-UHFFFAOYSA-N [[3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]carbamic acid Chemical compound C=1C=CC=CC=1COC(=O)NC(C(=O)NNC(=O)O)CC1=CC=CC=C1 NEHJQDYHECYLJD-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000000033 alkoxyamino group Chemical group 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000002852 cysteine proteinase inhibitor Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 108700023159 delta Opioid Receptors Proteins 0.000 description 1
- 102000048124 delta Opioid Receptors Human genes 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 description 1
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 description 1
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- WBHICAWASPYOHL-UHFFFAOYSA-N dioxane tetraketone Chemical compound O=C1OC(=O)C(=O)OC1=O WBHICAWASPYOHL-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000011982 enantioselective catalyst Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 1
- 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000005368 heteroarylthio group Chemical group 0.000 description 1
- 125000004470 heterocyclooxy group Chemical group 0.000 description 1
- 125000004468 heterocyclylthio 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
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000005184 irreversible process Methods 0.000 description 1
- 125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 description 1
- 125000005990 isobenzothienyl group Chemical group 0.000 description 1
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 1
- UYJWNPWEPDIPNU-FQEVSTJZSA-N methyl 2-[[(2s)-1-[2-(9h-fluoren-9-ylmethoxycarbonyl)hydrazinyl]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoacetate Chemical compound C1=CC=C2C(COC(=O)NNC(=O)[C@H](CC(C)C)NC(=O)C(=O)OC)C3=CC=CC=C3C2=C1 UYJWNPWEPDIPNU-FQEVSTJZSA-N 0.000 description 1
- WTYVPGUGJQIVIC-NYVOZVTQSA-N methyl 2-[[(2s)-1-[2-[(2s)-2-[[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoacetate Chemical compound C([C@H](NC(=O)C(=O)OC)C(=O)NNC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 WTYVPGUGJQIVIC-NYVOZVTQSA-N 0.000 description 1
- CIHQMYJTRBWILK-SFHVURJKSA-N methyl 2-[[(2s)-3-(1h-indol-3-yl)-1-oxo-1-(2-phenylmethoxycarbonylhydrazinyl)propan-2-yl]amino]-2-oxoacetate Chemical compound O=C([C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)C(=O)OC)NNC(=O)OCC1=CC=CC=C1 CIHQMYJTRBWILK-SFHVURJKSA-N 0.000 description 1
- CMAXLPQBQKPVAD-QHCPKHFHSA-N methyl 2-[[(2s)-3-[4-[(2-bromophenyl)methoxycarbonyloxy]phenyl]-1-oxo-1-(2-phenylmethoxycarbonylhydrazinyl)propan-2-yl]amino]-2-oxoacetate Chemical compound C([C@H](NC(=O)C(=O)OC)C(=O)NNC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1OC(=O)OCC1=CC=CC=C1Br CMAXLPQBQKPVAD-QHCPKHFHSA-N 0.000 description 1
- GRAAGFGAULJADL-VIFPVBQESA-N methyl 2-[[(2s)-4-methyl-1-[2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]-1-oxopentan-2-yl]amino]-2-oxoacetate Chemical compound COC(=O)C(=O)N[C@@H](CC(C)C)C(=O)NNC(=O)OC(C)(C)C GRAAGFGAULJADL-VIFPVBQESA-N 0.000 description 1
- HRBVUKJMCNLVJT-ZDUSSCGKSA-N methyl 2-[[(2s)-4-methyl-1-oxo-1-(2-phenylmethoxycarbonylhydrazinyl)pentan-2-yl]amino]-2-oxoacetate Chemical compound COC(=O)C(=O)N[C@@H](CC(C)C)C(=O)NNC(=O)OCC1=CC=CC=C1 HRBVUKJMCNLVJT-ZDUSSCGKSA-N 0.000 description 1
- VWQMJILEJVSVBN-LBPRGKRZSA-N methyl 2-oxo-2-[(2s)-2-(phenylmethoxycarbonylaminocarbamoyl)pyrrolidin-1-yl]acetate Chemical compound COC(=O)C(=O)N1CCC[C@H]1C(=O)NNC(=O)OCC1=CC=CC=C1 VWQMJILEJVSVBN-LBPRGKRZSA-N 0.000 description 1
- YLZXXMSBPOUGRB-VIFPVBQESA-N methyl 2-oxo-2-[[(2s)-1-oxo-1-(2-phenylmethoxycarbonylhydrazinyl)propan-2-yl]amino]acetate Chemical compound COC(=O)C(=O)N[C@@H](C)C(=O)NNC(=O)OCC1=CC=CC=C1 YLZXXMSBPOUGRB-VIFPVBQESA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000013048 microbiological method Methods 0.000 description 1
- 238000000324 molecular mechanic Methods 0.000 description 1
- 239000002062 molecular scaffold Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 102000051367 mu Opioid Receptors Human genes 0.000 description 1
- UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- PFPYHYZFFJJQFD-UHFFFAOYSA-N oxalic anhydride Chemical compound O=C1OC1=O PFPYHYZFFJJQFD-UHFFFAOYSA-N 0.000 description 1
- 229960003625 oxolamine Drugs 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- AFDMODCXODAXLC-UHFFFAOYSA-N phenylmethanimine Chemical compound N=CC1=CC=CC=C1 AFDMODCXODAXLC-UHFFFAOYSA-N 0.000 description 1
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
- 125000005499 phosphonyl group Chemical group 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 150000003147 proline derivatives Chemical class 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- DBGRZURIIFFWFO-UHFFFAOYSA-N tert-butyl hydrazinecarbonyl carbonate Chemical compound CC(C)(C)OC(=O)OC(=O)NN DBGRZURIIFFWFO-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229940105642 tridione Drugs 0.000 description 1
- IRYJRGCIQBGHIV-UHFFFAOYSA-N trimethadione Chemical compound CN1C(=O)OC(C)(C)C1=O IRYJRGCIQBGHIV-UHFFFAOYSA-N 0.000 description 1
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical group C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 108020001612 μ-opioid receptors Proteins 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/06—Compounds containing any of the groups, e.g. semicarbazides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D255/00—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00
- C07D255/02—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00 not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06450025A EP1826199A1 (en) | 2006-02-27 | 2006-02-27 | Modified amino acids |
| PCT/EP2006/011264 WO2007095980A1 (en) | 2006-02-27 | 2006-11-24 | Modified amino acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009528282A true JP2009528282A (ja) | 2009-08-06 |
| JP2009528282A5 JP2009528282A5 (enExample) | 2009-11-26 |
Family
ID=36645811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008555632A Pending JP2009528282A (ja) | 2006-02-27 | 2006-11-24 | 修飾アミノ酸 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20090105091A1 (enExample) |
| EP (2) | EP1826199A1 (enExample) |
| JP (1) | JP2009528282A (enExample) |
| CN (1) | CN101389599A (enExample) |
| WO (1) | WO2007095980A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106924753B (zh) * | 2015-12-30 | 2021-11-09 | 北京大学 | 制备蛋白质-聚氨基酸环状偶联物的方法 |
| EP4355758A4 (en) * | 2021-06-17 | 2025-05-28 | The Regents Of The University Of California | Rippled antiparallel cross-beta dimers and related materials, compositions and methods |
| US20250262315A1 (en) * | 2021-12-20 | 2025-08-21 | The Board Of Regents Of The University Of Texas System | Tripeptide linkers and methods of use thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4863947A (en) * | 1985-01-11 | 1989-09-05 | Rohm And Haas | N-aryl-3-aryl-4,5-dihydro-1H-pyrazole-1-carboxamides and methods of their production |
| WO1995000534A1 (en) * | 1993-06-18 | 1995-01-05 | The Board Of Trustees Of The University Of Illinois | Alpha-helix mimetics and methods relating thereto |
| JP2000141893A (ja) * | 1998-11-06 | 2000-05-23 | Mitsubishi Paper Mills Ltd | 可逆性感熱記録材料 |
| WO2001014412A1 (en) * | 1999-08-23 | 2001-03-01 | The Regents Of The University Of California | Compounds useful to mimic peptide beta-strands |
| JP2002507961A (ja) * | 1995-12-20 | 2002-03-12 | バーテックス ファーマシューティカルズ インコーポレイテッド | インターロイキン―１β変換酵素のインヒビター |
| WO2005075475A1 (ja) * | 2004-02-04 | 2005-08-18 | Shionogi & Co., Ltd. | Ｈｉｖインテグラーゼ阻害活性を有するナフチリジン誘導体 |
| WO2005103012A1 (ja) * | 2004-04-21 | 2005-11-03 | Ono Pharmaceutical Co., Ltd. | ヒドラジノ複素環ニトリル化合物およびその用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1150391B (de) | 1962-04-19 | 1963-06-20 | Bayer Ag | Verfahren zur Herstellung von N-Alkoxycarbonyl-carbonylaminoaryl-o-carbonsaeure-acylhydraziden |
| EP0573608A1 (en) | 1991-02-07 | 1993-12-15 | Molecumetics, Ltd. | Conformationally restricted mimetics of beta turns and beta bulges and peptides containing the same |
| AU667578B2 (en) | 1992-08-27 | 1996-03-28 | Deakin Research Limited | Retro-, inverso-, and retro-inverso synthetic peptide analogues |
-
2006
- 2006-02-27 EP EP06450025A patent/EP1826199A1/en not_active Withdrawn
- 2006-11-24 WO PCT/EP2006/011264 patent/WO2007095980A1/en not_active Ceased
- 2006-11-24 CN CNA2006800534712A patent/CN101389599A/zh active Pending
- 2006-11-24 EP EP06818783A patent/EP1989180A1/en not_active Withdrawn
- 2006-11-24 US US12/280,919 patent/US20090105091A1/en not_active Abandoned
- 2006-11-24 JP JP2008555632A patent/JP2009528282A/ja active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4863947A (en) * | 1985-01-11 | 1989-09-05 | Rohm And Haas | N-aryl-3-aryl-4,5-dihydro-1H-pyrazole-1-carboxamides and methods of their production |
| WO1995000534A1 (en) * | 1993-06-18 | 1995-01-05 | The Board Of Trustees Of The University Of Illinois | Alpha-helix mimetics and methods relating thereto |
| JP2002507961A (ja) * | 1995-12-20 | 2002-03-12 | バーテックス ファーマシューティカルズ インコーポレイテッド | インターロイキン―１β変換酵素のインヒビター |
| JP2000141893A (ja) * | 1998-11-06 | 2000-05-23 | Mitsubishi Paper Mills Ltd | 可逆性感熱記録材料 |
| WO2001014412A1 (en) * | 1999-08-23 | 2001-03-01 | The Regents Of The University Of California | Compounds useful to mimic peptide beta-strands |
| WO2005075475A1 (ja) * | 2004-02-04 | 2005-08-18 | Shionogi & Co., Ltd. | Ｈｉｖインテグラーゼ阻害活性を有するナフチリジン誘導体 |
| WO2005103012A1 (ja) * | 2004-04-21 | 2005-11-03 | Ono Pharmaceutical Co., Ltd. | ヒドラジノ複素環ニトリル化合物およびその用途 |
Non-Patent Citations (2)
| Title |
|---|
| JPN6012031934; Ｊｏｕｒｎａｌ ｏｆ ｔｈｅ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ， Ｃｈｅｍｉｃａｌ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ （１）, 1993, ９２-４ * |
| JPN6012031935; Ｅｕｒｏｐｅａｎ Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ ２５（１）, 1990, ７５-９ * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1989180A1 (en) | 2008-11-12 |
| WO2007095980A8 (en) | 2007-10-18 |
| US20090105091A1 (en) | 2009-04-23 |
| EP1826199A1 (en) | 2007-08-29 |
| WO2007095980A1 (en) | 2007-08-30 |
| CN101389599A (zh) | 2009-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108727468B (zh) | 环肽、包含其的医药或化妆品组成物及其制备方法 | |
| JP2023052381A (ja) | 液相ペプチド合成のための方法およびその保護戦略 | |
| Manne et al. | OxymaPure coupling reagents: beyond solid-phase peptide synthesis | |
| CN107810189B (zh) | 用于制备氮芥衍生物的方法 | |
| JP2003073396A (ja) | ペプチドの製造方法 | |
| KR20220059479A (ko) | 트로피네타이드의 조성물 | |
| JP2009528282A (ja) | 修飾アミノ酸 | |
| TW201938576A (zh) | 環胜肽、包含其之醫藥或化妝品組成物及其製備方法 | |
| WO2021177336A1 (ja) | ペプチド及び細胞膜透過剤 | |
| JPH069628A (ja) | ヒドロキシエチレン等量型のジチオラニルグリシン−含有ｈｉｖプロテアーゼインヒビター | |
| Neo et al. | A multicomponent approach to the synthesis of 1, 3-dicarbonylic compounds | |
| Chen et al. | Metal-free direct amidation of peptidyl thiol esters with α-amino acid esters | |
| CN120476131A (zh) | 涉及位阻三叔丁基色氨酸（Tbt）残基的肽合成方法 | |
| Nie et al. | A diastereoselective approach to amino alcohols and application for divergent synthesis of dolastatin 10 | |
| CN117916250A (zh) | 空间位阻混合酸酐中间体参与的肽合成方法 | |
| KR101890979B1 (ko) | 알카인을 이용한 아마이드 화합물의 제조방법 및 이를 이용한 펩타이드 제조 방법 | |
| Olma et al. | A convenient route to optically pure α-alkyl-β-(sec-amino) alanines | |
| Tanaka et al. | A novel oxazolidine linker for the synthesis of peptide aldehydes | |
| KR20160120345A (ko) | H-inp-(d)bal-(d)trp-phe-apc-nh2의 액체상 합성을 위한 공정, 및 이들의 약학적으로 허용 가능한 염들 | |
| CN118909030A (zh) | 一种谷胱甘肽及其衍生物的制备方法及其应用 | |
| KR20060013676A (ko) | 헤테로사이클릭 화합물의 합성방법 | |
| AU651557B2 (en) | Thioacylating reagents and intermediates, thiopeptides, and methods for preparing and using same | |
| Sureshbabu et al. | Synthesis of ureidopeptides using pentafluorophenyl carbamates from Nα-Fmoc-peptide acids | |
| Walsh | Synthetic organic approaches towards heterocyclic and acyclic peptidomimetics | |
| Suhs | New guanidinium compounds for the molecular recognition of carboxylates and contributions to the synthesis of bivalent NPY Y1 receptor antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091008 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20091008 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20120522 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120626 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20121204 |