NZ198702A - Antihypertensive compounds containing amide linkage and pharmaceutical compositions - Google Patents

Info

Publication number

NZ198702A

NZ198702A NZ198702A NZ19870281A NZ198702A NZ 198702 A NZ198702 A NZ 198702A NZ 198702 A NZ198702 A NZ 198702A NZ 19870281 A NZ19870281 A NZ 19870281A NZ 198702 A NZ198702 A NZ 198702A

Authority

NZ

New Zealand

Prior art keywords

alanyl

carboxylic acid

phenylpropyl

carboethoxy

azaspiro

Prior art date

1980-10-23

Links

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• 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
• 239000002220 antihypertensive agent Substances 0.000 title abstract description 3
• 150000001408 amides Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 293
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 116
• 238000000034 method Methods 0.000 claims abstract description 76
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 63
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
• 239000001257 hydrogen Substances 0.000 claims abstract description 37
• 150000003839 salts Chemical class 0.000 claims abstract description 27
• 125000004104 aryloxy group Chemical group 0.000 claims abstract description 26
• 150000001413 amino acids Chemical class 0.000 claims abstract description 23
• 235000001014 amino acid Nutrition 0.000 claims abstract description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 20
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 17
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
• 108010016626 Dipeptides Proteins 0.000 claims abstract description 16
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
• 238000009833 condensation Methods 0.000 claims abstract description 12
• 230000005494 condensation Effects 0.000 claims abstract description 12
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 6
• 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
• 125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
• 229910052720 vanadium Inorganic materials 0.000 claims abstract description 4
• 229910052727 yttrium Inorganic materials 0.000 claims abstract description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 20
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 300
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 138
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 124
• 239000002253 acid Substances 0.000 claims description 117
• 239000000203 mixture Substances 0.000 claims description 107
• -1 aryllower elkoxy Chemical group 0.000 claims description 105
• 239000012141 concentrate Substances 0.000 claims description 97
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 81
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 75
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 59
• 238000003756 stirring Methods 0.000 claims description 56
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 54
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 46
• 239000000243 solution Substances 0.000 claims description 45
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 41
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 38
• 125000004494 ethyl ester group Chemical group 0.000 claims description 38
• 239000011347 resin Substances 0.000 claims description 37
• 229920005989 resin Polymers 0.000 claims description 37
• 229960003767 alanine Drugs 0.000 claims description 36
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
• 239000000741 silica gel Substances 0.000 claims description 34
• 229910002027 silica gel Inorganic materials 0.000 claims description 34
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
• KUSYIGBGHPOWEL-VIFPVBQESA-N (2s)-2-methylnonanoic acid Chemical compound CCCCCCC[C@H](C)C(O)=O KUSYIGBGHPOWEL-VIFPVBQESA-N 0.000 claims description 27
• 150000004702 methyl esters Chemical class 0.000 claims description 25
• 239000011541 reaction mixture Substances 0.000 claims description 25
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 24
• 239000003921 oil Substances 0.000 claims description 23
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 21
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
• 229960000583 acetic acid Drugs 0.000 claims description 20
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 20
• 150000002148 esters Chemical class 0.000 claims description 19
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
• 125000003282 alkyl amino group Chemical group 0.000 claims description 18
• 229940024606 amino acid Drugs 0.000 claims description 18
• 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 18
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 17
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 17
• 125000001980 alanyl group Chemical group 0.000 claims description 17
• 239000000908 ammonium hydroxide Substances 0.000 claims description 17
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 17
• NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 17
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 16
• 238000006243 chemical reaction Methods 0.000 claims description 16
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
• 239000007787 solid Substances 0.000 claims description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 15
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
• 229930182821 L-proline Natural products 0.000 claims description 15
• 125000004442 acylamino group Chemical group 0.000 claims description 15
• 239000007864 aqueous solution Substances 0.000 claims description 15
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 15
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
• 239000012362 glacial acetic acid Substances 0.000 claims description 14
• 239000012044 organic layer Substances 0.000 claims description 14
• WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 claims description 14
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 13
• 125000004414 alkyl thio group Chemical group 0.000 claims description 13
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
• 239000012074 organic phase Substances 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 13
• 239000000047 product Substances 0.000 claims description 13
• 229910052708 sodium Inorganic materials 0.000 claims description 13
• 239000011734 sodium Substances 0.000 claims description 13
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 12
• 235000019341 magnesium sulphate Nutrition 0.000 claims description 12
• 239000002808 molecular sieve Substances 0.000 claims description 12
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 12
• 239000002904 solvent Substances 0.000 claims description 12
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 12
• 125000001769 aryl amino group Chemical group 0.000 claims description 11
• 125000005110 aryl thio group Chemical group 0.000 claims description 11
• 239000000706 filtrate Substances 0.000 claims description 11
• 230000007062 hydrolysis Effects 0.000 claims description 11
• 238000006460 hydrolysis reaction Methods 0.000 claims description 11
• 229910052721 tungsten Inorganic materials 0.000 claims description 11
• 229920002261 Corn starch Polymers 0.000 claims description 10
• 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 claims description 10
• 239000012230 colorless oil Substances 0.000 claims description 10
• 239000008120 corn starch Substances 0.000 claims description 10
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 10
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 10
• TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 claims description 10
• 239000008188 pellet Substances 0.000 claims description 10
• 238000010992 reflux Methods 0.000 claims description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 9
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• 239000005977 Ethylene Substances 0.000 claims description 8
• 206010020772 Hypertension Diseases 0.000 claims description 8
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 8
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
• 230000002378 acidificating effect Effects 0.000 claims description 8
• 230000029936 alkylation Effects 0.000 claims description 8
• 238000005804 alkylation reaction Methods 0.000 claims description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
• 230000032050 esterification Effects 0.000 claims description 8
• 238000005886 esterification reaction Methods 0.000 claims description 8
• 125000001041 indolyl group Chemical group 0.000 claims description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
• 239000001301 oxygen Substances 0.000 claims description 8
• 239000011593 sulfur Substances 0.000 claims description 8
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
• STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 claims description 7
• 238000009472 formulation Methods 0.000 claims description 7
• 125000002541 furyl group Chemical group 0.000 claims description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
• 239000008101 lactose Substances 0.000 claims description 7
• PRRCQQGBVXMEKW-YFKPBYRVSA-N (8s)-1,4-dithia-7-azoniaspiro[4.4]nonane-8-carboxylate Chemical compound C1N[C@H](C(=O)O)CC21SCCS2 PRRCQQGBVXMEKW-YFKPBYRVSA-N 0.000 claims description 6
• FQISISIMLFMVEY-DJNXLDHESA-N (8s)-7-[2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound N1([C@@H](CC2(C1)SCCS2)C(O)=O)C(=O)CNC(C(=O)OCC)CCC1=CC=CC=C1 FQISISIMLFMVEY-DJNXLDHESA-N 0.000 claims description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
• 239000002775 capsule Substances 0.000 claims description 6
• UOQACRNTVQWTFF-UHFFFAOYSA-N decane-1,10-dithiol Chemical compound SCCCCCCCCCCS UOQACRNTVQWTFF-UHFFFAOYSA-N 0.000 claims description 6
• 125000002883 imidazolyl group Chemical group 0.000 claims description 6
• 229940107700 pyruvic acid Drugs 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 5
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 5
• 229920002472 Starch Polymers 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 238000004587 chromatography analysis Methods 0.000 claims description 5
• ULGUQTOELKSOAJ-UHFFFAOYSA-N ethyl 2,3,3a,4,5,6,7,7a-octahydro-1h-indole-2-carboxylate Chemical compound C1CCCC2NC(C(=O)OCC)CC21 ULGUQTOELKSOAJ-UHFFFAOYSA-N 0.000 claims description 5
• 125000001072 heteroaryl group Chemical group 0.000 claims description 5
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 5
• 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 5
• 239000005457 ice water Substances 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 229960002429 proline Drugs 0.000 claims description 5
• 235000019698 starch Nutrition 0.000 claims description 5
• ZITOPJKFJBLAMM-LURJTMIESA-N (2s)-1-(2-oxopropanoyl)pyrrolidine-2-carboxylic acid Chemical compound CC(=O)C(=O)N1CCC[C@H]1C(O)=O ZITOPJKFJBLAMM-LURJTMIESA-N 0.000 claims description 4
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 claims description 4
• WPWUFUBLGADILS-WDSKDSINSA-N Ala-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WPWUFUBLGADILS-WDSKDSINSA-N 0.000 claims description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 4
• 229930195722 L-methionine Natural products 0.000 claims description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
• MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 4
• 125000004423 acyloxy group Chemical group 0.000 claims description 4
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 4
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 238000005984 hydrogenation reaction Methods 0.000 claims description 4
• 238000002955 isolation Methods 0.000 claims description 4
• 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
• 235000019359 magnesium stearate Nutrition 0.000 claims description 4
• ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 239000008107 starch Substances 0.000 claims description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
• JKIMNUINHCZQLM-IUCAKERBSA-N (2s)-1-[(2s)-2-aminopropanoyl]azocane-2-carboxylic acid Chemical compound C[C@H](N)C(=O)N1CCCCCC[C@H]1C(O)=O JKIMNUINHCZQLM-IUCAKERBSA-N 0.000 claims description 3
• MWOPNYRIFCCIKC-UUEFVBAFSA-N (8s)-2-thia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound C1N[C@H](C(=O)O)CC11CSCC1 MWOPNYRIFCCIKC-UUEFVBAFSA-N 0.000 claims description 3
• VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 claims description 3
• GSXWVOZWKACRTO-UHFFFAOYSA-N 1-ethyl-2,3,3a,4,5,6,7,7a-octahydroindole Chemical compound C1CCCC2N(CC)CCC21 GSXWVOZWKACRTO-UHFFFAOYSA-N 0.000 claims description 3
• SRXRBNCPSVMKIE-UHFFFAOYSA-N 2-azaspiro[4.4]nonane-3-carboxylic acid Chemical compound C1NC(C(=O)O)CC11CCCC1 SRXRBNCPSVMKIE-UHFFFAOYSA-N 0.000 claims description 3
• TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 claims description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 3
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 3
• 239000007868 Raney catalyst Substances 0.000 claims description 3
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
• 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims description 3
• 239000003054 catalyst Substances 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 3
• YULCQASHDYTPMM-UHFFFAOYSA-N ethyl 2,3,3a,4,6,6a-hexahydro-1h-furo[3,4-b]pyrrole-2-carboxylate Chemical compound C1OCC2NC(C(=O)OCC)CC21 YULCQASHDYTPMM-UHFFFAOYSA-N 0.000 claims description 3
• 239000000499 gel Substances 0.000 claims description 3
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
• 239000000463 material Substances 0.000 claims description 3
• 238000002844 melting Methods 0.000 claims description 3
• 230000008018 melting Effects 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 238000003801 milling Methods 0.000 claims description 3
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• TUYBOIMEBPVOHZ-ACAXCVFMSA-N (2S)-4-(1,3-dioxan-2-yl)-1-[(2S)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]pyrrolidine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC(C1)C1OCCCO1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 TUYBOIMEBPVOHZ-ACAXCVFMSA-N 0.000 claims 1
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• YTSYVKPZVVBZQW-HRNJWANLSA-N (2r)-1-[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]-2,3,3a,4,6,6a-hexahydrofuro[3,4-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@H](CC2COCC21)C(O)=O)C(=O)OCC1=CC=CC=C1 YTSYVKPZVVBZQW-HRNJWANLSA-N 0.000 claims 1
• YTSYVKPZVVBZQW-HQSMGLLHSA-N (2s)-1-[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]-2,3,3a,4,6,6a-hexahydrofuro[3,4-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2COCC21)C(O)=O)C(=O)OCC1=CC=CC=C1 YTSYVKPZVVBZQW-HQSMGLLHSA-N 0.000 claims 1
• PACMRGBNUMAUGT-NWJMBBFGSA-N (2s)-1-[(2s)-2-[(1-carboxy-2-phenylethyl)amino]propanoyl]-2,3,3a,4,6,6a-hexahydrofuro[3,4-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2COCC21)C(O)=O)C(C(O)=O)CC1=CC=CC=C1 PACMRGBNUMAUGT-NWJMBBFGSA-N 0.000 claims 1
• HBDXAKVDTKRNCN-JDLVMGNASA-N (2s)-1-[(2s)-2-[(1-carboxy-2-phenylmethoxyethyl)amino]propanoyl]pyrrolidine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(C(O)=O)COCC1=CC=CC=C1 HBDXAKVDTKRNCN-JDLVMGNASA-N 0.000 claims 1
• KUYZPVSKVPZRSB-ZBBQRLJZSA-N (2s)-1-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2CCCCC21)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 KUYZPVSKVPZRSB-ZBBQRLJZSA-N 0.000 claims 1
• RMHMFHUUHHBAFR-GSCOYNGXSA-N (2s)-1-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-3,4,4a,5,7,7a-hexahydro-2h-thieno[3,4-b]pyridine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2CSCC21)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 RMHMFHUUHHBAFR-GSCOYNGXSA-N 0.000 claims 1
• WPVBIYSYVRRCBO-SPFPWHRZSA-N (2s)-1-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]azecane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCCCCCCC1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 WPVBIYSYVRRCBO-SPFPWHRZSA-N 0.000 claims 1
• PGHXCKQBZHVDNP-NMBLWERJSA-N (2s)-1-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]azonane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCCCCCC1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 PGHXCKQBZHVDNP-NMBLWERJSA-N 0.000 claims 1
• IXTKBHQGHSKATI-WNHJAPTLSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-3-phenylmethoxypropan-2-yl)amino]propanoyl]-3,3a,4,5,6,7,8,8a-octahydro-2h-cyclohepta[b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2CCCCCC21)C(O)=O)C(C(=O)OCC)COCC1=CC=CC=C1 IXTKBHQGHSKATI-WNHJAPTLSA-N 0.000 claims 1
• PNQLPBNDLYSMGA-GSCOYNGXSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-3-phenylpropan-2-yl)amino]propanoyl]-2,3,3a,4,6,6a-hexahydrofuro[3,4-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2COCC21)C(O)=O)C(C(=O)OCC)CC1=CC=CC=C1 PNQLPBNDLYSMGA-GSCOYNGXSA-N 0.000 claims 1
• DHFHQURKYJFDGJ-OTTZHXMRSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2,3,3a,4,6,6a-hexahydrofuro[3,4-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2COCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 DHFHQURKYJFDGJ-OTTZHXMRSA-N 0.000 claims 1
• HDACQVRGBOVJII-ZBBQRLJZSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2CCCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 HDACQVRGBOVJII-ZBBQRLJZSA-N 0.000 claims 1
• CNUOSHSHDCWHCW-FJSDZJTPSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,3a,4,5,7,7a-hexahydro-2h-pyrano[3,4-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2CCOCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 CNUOSHSHDCWHCW-FJSDZJTPSA-N 0.000 claims 1
• ZWLYEPALGWWWHN-ZBBQRLJZSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,3a,4,6,7,7a-hexahydro-2h-pyrano[4,3-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2COCCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZWLYEPALGWWWHN-ZBBQRLJZSA-N 0.000 claims 1
• MCVKCKYRBUPDMU-WNHJAPTLSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,4,4a,5,6,7,8,8a-octahydro-2h-quinoline-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2CCCCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 MCVKCKYRBUPDMU-WNHJAPTLSA-N 0.000 claims 1
• LOSAGHGGOQMUDV-FJSDZJTPSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,4,4a,5,7,7a-hexahydro-2h-thieno[3,4-b]pyridine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2CSCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 LOSAGHGGOQMUDV-FJSDZJTPSA-N 0.000 claims 1
• NZXYCGPMZQYNIV-QJQMAANRSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-4,4-bis(ethylsulfanyl)piperidine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC(CC1)(SCC)SCC)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 NZXYCGPMZQYNIV-QJQMAANRSA-N 0.000 claims 1
• VIDIAEZCTIMBRM-FHNOQDHRSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-7-thia-1-azaspiro[4.4]nonane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1C2(CSCC2)CC[C@H]1C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 VIDIAEZCTIMBRM-FHNOQDHRSA-N 0.000 claims 1
• ZNPFWTMZQIXVMP-ULWHTZQDSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-8-oxa-1-azaspiro[5.5]undecane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1C2(COCCC2)CCC[C@H]1C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZNPFWTMZQIXVMP-ULWHTZQDSA-N 0.000 claims 1
• BORABYFZSSBRHD-SPFPWHRZSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-8-thia-1-azaspiro[4.5]decane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1C2(CCSCC2)CC[C@H]1C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 BORABYFZSSBRHD-SPFPWHRZSA-N 0.000 claims 1
• VHPDJPVRYUFCOY-JKXNBNTCSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-9-thia-1-azaspiro[4.5]decane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1C2(CSCCC2)CC[C@H]1C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 VHPDJPVRYUFCOY-JKXNBNTCSA-N 0.000 claims 1
• XPOYQJDBVXPCPP-SPFPWHRZSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]azocane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCCCCC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 XPOYQJDBVXPCPP-SPFPWHRZSA-N 0.000 claims 1
• YWLZRTBTGYTBTI-JDLVMGNASA-N (2s)-1-[(2s)-2-[(2-benzylsulfanyl-1-carboxyethyl)amino]propanoyl]pyrrolidine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(C(O)=O)CSCC1=CC=CC=C1 YWLZRTBTGYTBTI-JDLVMGNASA-N 0.000 claims 1
• OMKGXKUDYQWNDL-QJQMAANRSA-N (2s)-1-[(2s)-2-[(4-ethoxy-4-oxo-3-phenylbutyl)amino]propanoyl]azonane-2-carboxylic acid Chemical compound O=C([C@H](C)NCCC(C(=O)OCC)C=1C=CC=CC=1)N1CCCCCCC[C@H]1C(O)=O OMKGXKUDYQWNDL-QJQMAANRSA-N 0.000 claims 1
• ZYSVWNOPSXCHHW-XIRDDKMYSA-N (2s)-1-[(2s)-2-[[(2s)-1-ethoxy-1-oxo-3-phenylmethoxypropan-2-yl]amino]propanoyl]pyrrolidine-2-carboxylic acid Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)OCC1=CC=CC=C1 ZYSVWNOPSXCHHW-XIRDDKMYSA-N 0.000 claims 1
• KECMOJNAVLOMGT-YGYNJSFOSA-N (2s)-2-[1,3-dioxan-2-ylmethyl-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]amino]propanoic acid Chemical compound N([C@@H](C)C(=O)N(CC1OCCCO1)[C@@H](C)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 KECMOJNAVLOMGT-YGYNJSFOSA-N 0.000 claims 1
• CIGOMLYAIPPEGN-MZQXSQAVSA-N (2s)-2-[1,3-dioxolan-2-ylmethyl-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]amino]propanoic acid Chemical compound N([C@@H](C)C(=O)N(CC1OCCO1)[C@@H](C)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 CIGOMLYAIPPEGN-MZQXSQAVSA-N 0.000 claims 1
• NENGYTOAJHEGQH-YGYNJSFOSA-N (2s)-2-[1,3-dithian-2-ylmethyl-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]amino]propanoic acid Chemical compound N([C@@H](C)C(=O)N(CC1SCCCS1)[C@@H](C)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 NENGYTOAJHEGQH-YGYNJSFOSA-N 0.000 claims 1
• DPCJXYYHKBNRBG-MZQXSQAVSA-N (2s)-2-[1,3-dithiolan-2-ylmethyl-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]amino]propanoic acid Chemical compound N([C@@H](C)C(=O)N(CC1SCCS1)[C@@H](C)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 DPCJXYYHKBNRBG-MZQXSQAVSA-N 0.000 claims 1
• LWIBANSOJGCEHJ-IJXZTRCJSA-N (2s)-2-[2,2-diethoxyethyl-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]amino]propanoic acid Chemical compound CCOC(OCC)CN([C@@H](C)C(O)=O)C(=O)[C@H](C)NC(C(=O)OCC)CCC1=CC=CC=C1 LWIBANSOJGCEHJ-IJXZTRCJSA-N 0.000 claims 1
• WETFHQYPCMZXAM-BEEJXANESA-N (2s)-2-[[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-(thiolan-2-ylmethyl)amino]propanoic acid Chemical compound N([C@@H](C)C(=O)N(CC1SCCC1)[C@@H](C)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 WETFHQYPCMZXAM-BEEJXANESA-N 0.000 claims 1
• ARPVNMIYTVOVEQ-NMBLWERJSA-N (2s)-2-[[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]amino]-3-(2-methyl-1,3-dithian-2-yl)propanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC1(C)SCCCS1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ARPVNMIYTVOVEQ-NMBLWERJSA-N 0.000 claims 1
• XZVIBIOOYKLLSH-NBJLRHFZSA-N (2s)-2-[cyclohexyl-[(2s)-2-[(1-methoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]amino]propanoic acid Chemical compound N([C@@H](C)C(=O)N([C@@H](C)C(O)=O)C1CCCCC1)C(C(=O)OC)CCC1=CC=CC=C1 XZVIBIOOYKLLSH-NBJLRHFZSA-N 0.000 claims 1
• YSEQNZOXHCKLOG-QMMMGPOBSA-N (2s)-2-methyloctanoic acid Chemical compound CCCCCC[C@H](C)C(O)=O YSEQNZOXHCKLOG-QMMMGPOBSA-N 0.000 claims 1
• HWNGLKPRXKKTPK-ONQHYROSSA-N (2s)-3,4-dihydroxypyrrolidine-2-carboxylic acid Chemical compound OC1CN[C@H](C(O)=O)C1O HWNGLKPRXKKTPK-ONQHYROSSA-N 0.000 claims 1
• WYHDGRLNWABGDP-RXQRSOPUSA-N (2s)-4-(dimethoxymethyl)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]pyrrolidine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC(C1)C(OC)OC)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 WYHDGRLNWABGDP-RXQRSOPUSA-N 0.000 claims 1
• UAGFTQCWTTYZKO-WCCKRBBISA-N (2s)-pyrrolidine-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H]1CCCN1 UAGFTQCWTTYZKO-WCCKRBBISA-N 0.000 claims 1
• VGOXYUAJLNRRRS-AVHZRVKJSA-N (3s)-2-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-7-oxa-2-azaspiro[4.5]decane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(C1)COCCC2)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 VGOXYUAJLNRRRS-AVHZRVKJSA-N 0.000 claims 1
• ZGRSXVVEWMYHOH-QJQMAANRSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2-azaspiro[4.5]decane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(C1)CCCCC2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZGRSXVVEWMYHOH-QJQMAANRSA-N 0.000 claims 1
• CCBPBUDHLFHOAS-LLLPINGXSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2-azaspiro[5.5]undecane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2(CCCCC2)C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 CCBPBUDHLFHOAS-LLLPINGXSA-N 0.000 claims 1
• NIOKJHABODAVIK-ZBBQRLJZSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,3a,4,6,7,7a-hexahydro-1h-pyrano[3,4-c]pyrrole-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2COCCC2C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 NIOKJHABODAVIK-ZBBQRLJZSA-N 0.000 claims 1
• SGEAGDRMRRRKCB-NMBLWERJSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-6,10-dioxa-2-azaspiro[4.5]decane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(C1)OCCCO2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 SGEAGDRMRRRKCB-NMBLWERJSA-N 0.000 claims 1
• JOTBUCPVWJSXBV-NMBLWERJSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-6,10-dithia-2-azaspiro[4.5]decane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCCS2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 JOTBUCPVWJSXBV-NMBLWERJSA-N 0.000 claims 1
• CSCVAUQWBWCMOX-SPFPWHRZSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-8-thia-2-azaspiro[4.5]decane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(C1)CCSCC2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 CSCVAUQWBWCMOX-SPFPWHRZSA-N 0.000 claims 1
• WPRDGWPRQXBFPO-QJQMAANRSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-9-oxa-2-azaspiro[5.5]undecane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2(CCOCC2)C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 WPRDGWPRQXBFPO-QJQMAANRSA-N 0.000 claims 1
• XNDDNVPSHVWKEZ-DDPXNHEPSA-N (3s)-4-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,4-thiazocane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@H](CSCCCC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 XNDDNVPSHVWKEZ-DDPXNHEPSA-N 0.000 claims 1
• XAZYXWARXCGTRD-LLLPINGXSA-N (4s)-3-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3-azaspiro[5.5]undecane-4-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(CCCCC2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 XAZYXWARXCGTRD-LLLPINGXSA-N 0.000 claims 1
• ZGGYDMYMFFZKRC-JGWWNCMTSA-N (4s)-5-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-3,3a,4,6,7,7a-hexahydro-1h-thieno[3,4-c]pyridine-4-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2CSCC2CC1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 ZGGYDMYMFFZKRC-JGWWNCMTSA-N 0.000 claims 1
• FJEXDLFFNGRISB-ZKNZNYJQSA-N (4s)-5-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]pyrrole-4-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2COCC2C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 FJEXDLFFNGRISB-ZKNZNYJQSA-N 0.000 claims 1
• QUFDXHDFBQWCOW-SPFPWHRZSA-N (4s)-5-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,5-oxazonane-4-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCOCCCC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 QUFDXHDFBQWCOW-SPFPWHRZSA-N 0.000 claims 1
• GMPSZBNDJUEVMO-ZBBQRLJZSA-N (4s)-5-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,3a,4,6,7,7a-hexahydro-1h-thieno[3,4-c]pyridine-4-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2CSCC2CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 GMPSZBNDJUEVMO-ZBBQRLJZSA-N 0.000 claims 1
• WYBPGCSALLUBCV-HOCLYGCPSA-N (5s)-4-[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]-1,4-thiazonane-5-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCCCSCC1)C(O)=O)C(=O)OCC1=CC=CC=C1 WYBPGCSALLUBCV-HOCLYGCPSA-N 0.000 claims 1
• FNAAEBGFRZDKPW-NMBLWERJSA-N (5s)-4-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-1,4-oxazecane-5-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCCCCOCC1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 FNAAEBGFRZDKPW-NMBLWERJSA-N 0.000 claims 1
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