IE53802B1

IE53802B1 - Carboxyalkyl dipertides, process for their production and pharmaceutical compositions containing them

Carboxyalkyl dipertides, process for their production and pharmaceutical compositions containing them

Info

Publication number: IE53802B1
Authority: IE; Ireland
Prior art keywords: alanyl; carboxylic acid; phenylpropyl; lower alkyl; carboethoxy
Prior art date: 1980-10-23

Application number

IE2475/81A

Other languages

English (en)

Other versions

IE812475L (en

Original Assignee

Schering Corp

Priority date

1980-10-23

Filing date

1981-10-21

Publication date

1989-03-01

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26895254&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IE53802(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1981-10-21 Application filed by Schering Corp filed Critical Schering Corp

1982-04-23 Publication of IE812475L publication Critical patent/IE812475L/xx

1989-03-01 Publication of IE53802B1 publication Critical patent/IE53802B1/en

Links

238000000034 method Methods 0.000 title claims abstract description 42
230000008569 process Effects 0.000 title claims description 18
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
125000004181 carboxyalkyl group Chemical group 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 143
125000000217 alkyl group Chemical group 0.000 claims abstract description 73
125000003545 alkoxy group Chemical group 0.000 claims abstract description 28
239000001257 hydrogen Substances 0.000 claims abstract description 27
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 16
150000001413 amino acids Chemical class 0.000 claims abstract description 14
150000002431 hydrogen Chemical class 0.000 claims abstract description 13
108010016626 Dipeptides Proteins 0.000 claims abstract description 11
235000001014 amino acid Nutrition 0.000 claims abstract description 11
125000004104 aryloxy group Chemical group 0.000 claims abstract description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
238000009833 condensation Methods 0.000 claims abstract description 7
230000005494 condensation Effects 0.000 claims abstract description 7
125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
125000000304 alkynyl group Chemical group 0.000 claims abstract description 4
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
229910052720 vanadium Inorganic materials 0.000 claims abstract description 4
229910052727 yttrium Inorganic materials 0.000 claims abstract description 4
125000002947 alkylene group Chemical group 0.000 claims abstract description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 9
-1 diloweralkylamino Chemical group 0.000 claims description 63
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 34
238000002360 preparation method Methods 0.000 claims description 30
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 14
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 13
125000003282 alkyl amino group Chemical group 0.000 claims description 9
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 9
239000005977 Ethylene 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 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
125000004442 acylamino group Chemical group 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
125000001769 aryl amino group Chemical group 0.000 claims description 6
125000005110 aryl thio group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
239000011593 sulfur Substances 0.000 claims description 6
150000001735 carboxylic acids Chemical class 0.000 claims description 5
125000002541 furyl group Chemical group 0.000 claims description 5
125000001041 indolyl group Chemical group 0.000 claims description 5
230000009467 reduction Effects 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 5
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
229910052721 tungsten Inorganic materials 0.000 claims description 4
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
206010020772 Hypertension Diseases 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
125000001072 heteroaryl group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
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 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
125000003302 alkenyloxy group Chemical group 0.000 claims description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims description 2
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 3
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
125000003107 substituted aryl group Chemical group 0.000 claims 1
229940030600 antihypertensive agent Drugs 0.000 abstract description 3
239000002220 antihypertensive agent Substances 0.000 abstract description 3
239000003112 inhibitor Substances 0.000 abstract description 3
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 abstract description 2
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 abstract description 2
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 abstract description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 84
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
239000000203 mixture Substances 0.000 description 64
239000012141 concentrate Substances 0.000 description 49
235000008504 concentrate Nutrition 0.000 description 49
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
239000002253 acid Substances 0.000 description 45
239000000243 solution Substances 0.000 description 36
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 31
238000003756 stirring Methods 0.000 description 30
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
229960003767 alanine Drugs 0.000 description 25
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
235000019439 ethyl acetate Nutrition 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
239000011347 resin Substances 0.000 description 20
229920005989 resin Polymers 0.000 description 20
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
125000004494 ethyl ester group Chemical group 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
150000004702 methyl esters Chemical class 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
239000003921 oil Substances 0.000 description 14
235000019198 oils Nutrition 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
239000000047 product Substances 0.000 description 13
229960000583 acetic acid Drugs 0.000 description 11
125000001980 alanyl group Chemical group 0.000 description 11
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 11
239000007787 solid Substances 0.000 description 11
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000000908 ammonium hydroxide Substances 0.000 description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
239000012230 colorless oil Substances 0.000 description 9
239000012362 glacial acetic acid Substances 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 9
239000002904 solvent Substances 0.000 description 9
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
125000004356 hydroxy functional group Chemical group O* 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
229940024606 amino acid Drugs 0.000 description 7
125000004122 cyclic group Chemical group 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
229920002261 Corn starch Polymers 0.000 description 6
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000008120 corn starch Substances 0.000 description 6
WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
238000009472 formulation Methods 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
239000002808 molecular sieve Substances 0.000 description 6
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
KUSYIGBGHPOWEL-VIFPVBQESA-N (2s)-2-methylnonanoic acid Chemical compound CCCCCCC[C@H](C)C(O)=O KUSYIGBGHPOWEL-VIFPVBQESA-N 0.000 description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
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 description 5
229920002472 Starch Polymers 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
239000008101 lactose Substances 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
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 description 5
239000008188 pellet Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 4
230000032050 esterification Effects 0.000 description 4
238000005886 esterification reaction Methods 0.000 description 4
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 description 4
STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 description 4
239000008187 granular material Substances 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
239000005457 ice water Substances 0.000 description 4
239000008107 starch Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
239000001506 calcium phosphate Substances 0.000 description 3
UOQACRNTVQWTFF-UHFFFAOYSA-N decane-1,10-dithiol Chemical compound SCCCCCCCCCCS UOQACRNTVQWTFF-UHFFFAOYSA-N 0.000 description 3
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 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 description 3
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
239000002245 particle Substances 0.000 description 3
229960002429 proline Drugs 0.000 description 3
229940107700 pyruvic acid Drugs 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
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 description 2
KEDYTOTWMPBSLG-JGWWNCMTSA-N (2s)-1-[(2s)-2-[(1-carboxy-3-phenylpropyl)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)=O)CCC1=CC=CC=C1 KEDYTOTWMPBSLG-JGWWNCMTSA-N 0.000 description 2
SRCSNTPZUAEFEI-ZETCQYMHSA-N (2s)-2-(2,2-diethoxyethylamino)propanoic acid Chemical compound CCOC(OCC)CN[C@@H](C)C(O)=O SRCSNTPZUAEFEI-ZETCQYMHSA-N 0.000 description 2
VHOVPEFSJKDBIQ-AKGZTFGVSA-N (2s)-4-formylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CC(C=O)CN1 VHOVPEFSJKDBIQ-AKGZTFGVSA-N 0.000 description 2
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 description 2
JZQMYZYHNUBBGW-FHNOQDHRSA-N (8s)-7-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2-thia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(CSCC2)C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 JZQMYZYHNUBBGW-FHNOQDHRSA-N 0.000 description 2
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 description 2
DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 2
SRXRBNCPSVMKIE-UHFFFAOYSA-N 2-azaspiro[4.4]nonane-3-carboxylic acid Chemical compound C1NC(C(=O)O)CC11CCCC1 SRXRBNCPSVMKIE-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
241000478345 Afer Species 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
229930195722 L-methionine Natural products 0.000 description 2
229930182821 L-proline Natural products 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
239000002585 base Substances 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
239000012267 brine Substances 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
150000001768 cations Chemical class 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
239000002934 diuretic Substances 0.000 description 2
229940030606 diuretics Drugs 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
238000003801 milling Methods 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229940097258 other antihypertensives in atc Drugs 0.000 description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
PHICBFWUYUCFKS-UHFFFAOYSA-N spiro[4.4]nonane Chemical compound C1CCCC21CCCC2 PHICBFWUYUCFKS-UHFFFAOYSA-N 0.000 description 2
CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 description 2
229910001220 stainless steel Inorganic materials 0.000 description 2
239000010935 stainless steel Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
CWJNJELEEDZCTI-SPFPWHRZSA-N (10s)-9-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,5-dioxa-9-azaspiro[5.5]undecane-10-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(CC1)OCCCO2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 CWJNJELEEDZCTI-SPFPWHRZSA-N 0.000 description 1
LQFCEJMYZZJAQP-ULWHTZQDSA-N (10s)-9-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2-oxa-9-azaspiro[5.5]undecane-10-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(COCCC2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 LQFCEJMYZZJAQP-ULWHTZQDSA-N 0.000 description 1
OFQMLPFMHSGCGO-PNWOJRQDSA-N (1s)-1-[(2s)-2-[(1-carboxy-2-phenylethyl)amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroisoindole-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)[C@@]1(C2CCCCC2CN1)C(O)=O)C(C(O)=O)CC1=CC=CC=C1 OFQMLPFMHSGCGO-PNWOJRQDSA-N 0.000 description 1
OLMPXRUAQBIBRA-ZKNZNYJQSA-N (1s)-2-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-1,3,3a,4,5,6,7,7a-octahydroisoindole-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2CCCCC2C1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 OLMPXRUAQBIBRA-ZKNZNYJQSA-N 0.000 description 1
AYECQRAXWBGXSZ-WJGSZSDCSA-N (1s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,3,3a,4,5,6,7,7a-octahydroisoindole-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2CCCCC2C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 AYECQRAXWBGXSZ-WJGSZSDCSA-N 0.000 description 1
ZPMLPGJPBCGJEE-DDPXNHEPSA-N (1s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-6,10-dioxa-2-azaspiro[4.5]decane-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2(OCCCO2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZPMLPGJPBCGJEE-DDPXNHEPSA-N 0.000 description 1
ZSVWLZABTMDGGY-NMBLWERJSA-N (1s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-6,10-dithia-2-azaspiro[4.5]decane-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@H](C2(SCCCS2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZSVWLZABTMDGGY-NMBLWERJSA-N 0.000 description 1
ZWYARZRADGJOSY-DGLPSNNLSA-N (1s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-7-oxa-2-azaspiro[4.4]nonane-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2(COCC2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZWYARZRADGJOSY-DGLPSNNLSA-N 0.000 description 1
ZNDSVVDQVJWXPU-NHVNWABUSA-N (1s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-8-oxa-2-azaspiro[5.5]undecane-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2(COCCC2)CCC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZNDSVVDQVJWXPU-NHVNWABUSA-N 0.000 description 1
DDKIPPYUPQTBSB-BJASNALYSA-N (1s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-9-thia-2-azaspiro[4.5]decane-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2(CSCCC2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 DDKIPPYUPQTBSB-BJASNALYSA-N 0.000 description 1
AGTXRFGPDRZBSU-SOLGRHFHSA-N (1s)-3-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,2,3,3a,4,6,7,7a-octahydrothiopyrano[3,4-c]pyrrole-1-carboxylic acid Chemical compound N([C@@H](C)C(=O)C1C2CSCCC2[C@H](N1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 AGTXRFGPDRZBSU-SOLGRHFHSA-N 0.000 description 1
DFIBNXVAHCBWNY-LYAPFXNSSA-N (2S)-1-[(2S)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-4-(dimethoxymethyl)pyrrolidine-2-carboxylic acid Chemical compound C(=O)(O)C(CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1[C@H](C(=O)O)CC(C1)C(OC)OC DFIBNXVAHCBWNY-LYAPFXNSSA-N 0.000 description 1
YBJMVTZCCQCBHN-FJSDZJTPSA-N (2S)-1-[(2S)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-4-(oxan-2-yl)pyrrolidine-2-carboxylic acid Chemical compound C(=O)(O)C(CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1[C@H](C(=O)O)CC(C1)C1OCCCC1 YBJMVTZCCQCBHN-FJSDZJTPSA-N 0.000 description 1
OUFSXRHCTCKMDW-MQFTVXPDSA-N (2S)-1-[(2S)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-4-(oxan-2-yl)pyrrolidine-2-carboxylic acid Chemical compound C(=O)(OCC)C(CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1[C@H](C(=O)O)CC(C1)C1OCCCC1 OUFSXRHCTCKMDW-MQFTVXPDSA-N 0.000 description 1
AAWISURHYKTGKD-XWAAWYQISA-N (2S)-1-[(2S)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-4-(oxolan-2-yl)pyrrolidine-2-carboxylic acid Chemical compound C(=O)(OCC)C(CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1[C@H](C(=O)O)CC(C1)C1OCCC1 AAWISURHYKTGKD-XWAAWYQISA-N 0.000 description 1
ZWUABRPGCONAIA-XRVVJQKQSA-N (2S)-2,3,3a,4,6,6a-hexahydro-1H-furo[3,4-b]pyrrole-2-carboxylic acid Chemical compound N1C2C(C[C@H]1C(=O)O)COC2 ZWUABRPGCONAIA-XRVVJQKQSA-N 0.000 description 1
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 description 1
YSBGEWDPKVVBTF-RXQRSOPUSA-N (2S)-4-(1,3-dithiolan-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)C1SCCS1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 YSBGEWDPKVVBTF-RXQRSOPUSA-N 0.000 description 1
PCVPDXHZOGCZFY-RLHVNXBHSA-N (2S)-4-[bis(ethylsulfanyl)methyl]-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(SCC)SCC)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 PCVPDXHZOGCZFY-RLHVNXBHSA-N 0.000 description 1
YZVYEXCSLONNSI-GOEBONIOSA-N (2r)-1-[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]azocane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@H](CCCCCC1)C(O)=O)C(=O)OCC1=CC=CC=C1 YZVYEXCSLONNSI-GOEBONIOSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 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 description 1
YZVYEXCSLONNSI-HOCLYGCPSA-N (2s)-1-[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]azocane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCCCCC1)C(O)=O)C(=O)OCC1=CC=CC=C1 YZVYEXCSLONNSI-HOCLYGCPSA-N 0.000 description 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 description 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 description 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 description 1
AHVSFLISGWKNPQ-QJQMAANRSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1-azaspiro[4.5]decane-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1C2(CCCCC2)CC[C@H]1C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 AHVSFLISGWKNPQ-QJQMAANRSA-N 0.000 description 1
QPPJXNUAKMKLBS-OTTZHXMRSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2,3,3a,4,6,6a-hexahydrothieno[3,4-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2CSCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 QPPJXNUAKMKLBS-OTTZHXMRSA-N 0.000 description 1
RMRFPJHLTBRSCV-XWAAWYQISA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2,3,4,4a,5,6,8,8a-octahydrothiopyrano[3,4-b]pyridine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2CCSCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 RMRFPJHLTBRSCV-XWAAWYQISA-N 0.000 description 1
RCOUZSKNKNCSEK-DKKDMOBXSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,3-dimethoxypyrrolidine-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C(OC)(OC)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 RCOUZSKNKNCSEK-DKKDMOBXSA-N 0.000 description 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 description 1
IFTYGOMODVBUPL-ZBBQRLJZSA-N (2s)-1-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-3,3a,4,6,7,7a-hexahydro-2h-thiopyrano[4,3-b]pyrrole-2-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2CSCCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 IFTYGOMODVBUPL-ZBBQRLJZSA-N 0.000 description 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 description 1
BZUUFZKMSQKDNY-GSCOYNGXSA-N (2s)-1-[(2s)-2-[(1-methoxy-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)OC)CCC1=CC=CC=C1 BZUUFZKMSQKDNY-GSCOYNGXSA-N 0.000 description 1
DBAQBRAQKYAQEO-ZKNZNYJQSA-N (2s)-1-[(2s)-2-[(1-methoxy-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)OC)CCC1=CC=CC=C1 DBAQBRAQKYAQEO-ZKNZNYJQSA-N 0.000 description 1
ITPIYTPAZKXJMW-WJGSZSDCSA-N (2s)-1-[(2s)-2-[(1-methoxy-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)OC)CCC1=CC=CC=C1 ITPIYTPAZKXJMW-WJGSZSDCSA-N 0.000 description 1
VINNCWIYGPLXOA-YYPSJVGGSA-N (2s)-1-[(2s)-2-[[4-(4-chlorophenyl)-1-ethoxy-1-oxobutan-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=C(Cl)C=C1 VINNCWIYGPLXOA-YYPSJVGGSA-N 0.000 description 1
GWUUTVZHEFRRQG-DNBGNTRDSA-N (2s)-1-[(2s)-2-aminopropanoyl]-2,3,3a,4,6,6a-hexahydrofuro[3,4-b]pyrrole-2-carboxylic acid Chemical compound C1OCC2C[C@@H](C(O)=O)N(C(=O)[C@@H](N)C)C21 GWUUTVZHEFRRQG-DNBGNTRDSA-N 0.000 description 1
DATPFTPVGIHCCM-BYPYZUCNSA-N (2s)-2-(ethylamino)propanoic acid Chemical compound CCN[C@@H](C)C(O)=O DATPFTPVGIHCCM-BYPYZUCNSA-N 0.000 description 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 description 1
SCJYBEPFUOGAME-PPHPATTJSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;6-chloro-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O SCJYBEPFUOGAME-PPHPATTJSA-N 0.000 description 1
SAOSCTYRONNFTC-JTQLQIEISA-N (2s)-2-methyldecanoic acid Chemical compound CCCCCCCC[C@H](C)C(O)=O SAOSCTYRONNFTC-JTQLQIEISA-N 0.000 description 1
YSEQNZOXHCKLOG-QMMMGPOBSA-N (2s)-2-methyloctanoic acid Chemical compound CCCCCC[C@H](C)C(O)=O YSEQNZOXHCKLOG-QMMMGPOBSA-N 0.000 description 1
PFFITEZSYJIHHR-NSHDSACASA-N (2s)-2-methylundecanoic acid Chemical compound CCCCCCCCC[C@H](C)C(O)=O PFFITEZSYJIHHR-NSHDSACASA-N 0.000 description 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 description 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 description 1
RKEYKDXXZCICFZ-AKGZTFGVSA-N (2s)-5-hydroxypiperidine-2-carboxylic acid Chemical compound OC1CC[C@@H](C(O)=O)NC1 RKEYKDXXZCICFZ-AKGZTFGVSA-N 0.000 description 1
UAGFTQCWTTYZKO-WCCKRBBISA-N (2s)-pyrrolidine-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H]1CCCN1 UAGFTQCWTTYZKO-WCCKRBBISA-N 0.000 description 1
ODSNARDHJFFSRH-OCAPTIKFSA-N (3as,7ar)-2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical compound C1CCC[C@@H]2CNC[C@@H]21 ODSNARDHJFFSRH-OCAPTIKFSA-N 0.000 description 1
WLDMPODMCFGWAA-OLQVQODUSA-N (3as,7ar)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1CCC[C@@H]2C(=O)NC(=O)[C@@H]21 WLDMPODMCFGWAA-OLQVQODUSA-N 0.000 description 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 description 1
JELSMELPOHWINJ-SPFPWHRZSA-N (3s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2-azaspiro[4.4]nonane-3-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(CCCC2)C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 JELSMELPOHWINJ-SPFPWHRZSA-N 0.000 description 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 description 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 description 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 description 1
CRHGLJLBPLFGHZ-NMBLWERJSA-N (3s)-2-[(2s)-2-[(1-methoxy-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)OC)CCC1=CC=CC=C1 CRHGLJLBPLFGHZ-NMBLWERJSA-N 0.000 description 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 description 1
ZUIYCYHOKOSLLL-IUCAKERBSA-N (5s)-4-[(2s)-2-aminopropanoyl]-1,4-thiazonane-5-carboxylic acid Chemical compound C[C@H](N)C(=O)N1CCSCCCC[C@H]1C(O)=O ZUIYCYHOKOSLLL-IUCAKERBSA-N 0.000 description 1
DGYYJOWZRWLDNN-ZKNZNYJQSA-N (6s)-7-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-1,3,4,4a,5,6,8,8a-octahydropyrano[3,4-c]pyridine-6-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2CCOCC2C1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 DGYYJOWZRWLDNN-ZKNZNYJQSA-N 0.000 description 1
ZAJRYOBUCLQLIK-DKKDMOBXSA-N (6s)-7-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,4-dioxa-7-azaspiro[4.4]nonane-6-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2(OCCO2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZAJRYOBUCLQLIK-DKKDMOBXSA-N 0.000 description 1
XYCBWACIUMDNAI-YKOWGRMDSA-N (6s)-7-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-6-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@H](C2(SCCS2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 XYCBWACIUMDNAI-YKOWGRMDSA-N 0.000 description 1
ZBGBJCQQOUPLAK-CJKWIIOHSA-N (7s)-2-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2-azaspiro[4.5]decane-7-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1CC2(CC1)C[C@H](CCC2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ZBGBJCQQOUPLAK-CJKWIIOHSA-N 0.000 description 1
SIWPDOPZGDIFIM-WJGSZSDCSA-N (7s)-6-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,3,4,4a,5,7,8,8a-octahydropyrano[4,3-c]pyridine-7-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2COCCC2C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 SIWPDOPZGDIFIM-WJGSZSDCSA-N 0.000 description 1
TYMZNESRKPFSQX-WJGSZSDCSA-N (7s)-6-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,3,4,4a,5,7,8,8a-octahydrothiopyrano[4,3-c]pyridine-7-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2CSCCC2C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 TYMZNESRKPFSQX-WJGSZSDCSA-N 0.000 description 1
LLAOXLKYDOOLHH-JKXNBNTCSA-N (7s)-6-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-2-oxa-6-azaspiro[4.5]decane-7-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1C2(COCC2)CCC[C@H]1C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 LLAOXLKYDOOLHH-JKXNBNTCSA-N 0.000 description 1
MTLUOIASMAGAPX-JKXNBNTCSA-N (7s)-8-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1-oxa-8-azaspiro[4.5]decane-7-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(OCCC2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 MTLUOIASMAGAPX-JKXNBNTCSA-N 0.000 description 1
SXJBVDKLTHFKFI-LLTTWOEGSA-N (8S)-7-[2-[(1-ethoxy-1-oxo-3-phenylbutan-2-yl)amino]acetyl]-2-thia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound C=1C=CC=CC=1C(C)C(C(=O)OCC)NCC(=O)N([C@@H](C1)C(O)=O)CC21CCSC2 SXJBVDKLTHFKFI-LLTTWOEGSA-N 0.000 description 1
OZYDFNHNZMMLDH-JQCDREMPSA-N (8s)-3-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-7-azaspiro[4.5]decane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)C1CC2(CC1)CN[C@@H](CC2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 OZYDFNHNZMMLDH-JQCDREMPSA-N 0.000 description 1
HZKJIRVHPFEEPF-ZETCQYMHSA-N (8s)-7-(2-oxopropanoyl)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)C(=O)C)CC21SCCS2 HZKJIRVHPFEEPF-ZETCQYMHSA-N 0.000 description 1
NHRSVYAQPCAFDK-YMNIQAILSA-N (8s)-7-(2-oxopropanoyl)-2-thia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)C(=O)C)CC11CSCC1 NHRSVYAQPCAFDK-YMNIQAILSA-N 0.000 description 1
DUJDRZPFIVUVNN-JSGCOSHPSA-N (8s)-7-[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)C(=O)OCC1=CC=CC=C1 DUJDRZPFIVUVNN-JSGCOSHPSA-N 0.000 description 1
CLCFKVWSQFNBOZ-GGXMVYKUSA-N (8s)-7-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-2-thia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(CSCC2)C1)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 CLCFKVWSQFNBOZ-GGXMVYKUSA-N 0.000 description 1
KDFAHXNYGFPCQQ-WJGSZSDCSA-N (8s)-7-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,3,4,4a,5,6,8,8a-octahydropyrano[3,4-c]pyridine-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2COCCC2CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 KDFAHXNYGFPCQQ-WJGSZSDCSA-N 0.000 description 1
BWDIZLMPBYAHGW-WJGSZSDCSA-N (8s)-7-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,3,4,4a,5,6,8,8a-octahydrothiopyrano[3,4-c]pyridine-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](C2CSCCC2CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 BWDIZLMPBYAHGW-WJGSZSDCSA-N 0.000 description 1
HRWCVUIFMSZDJS-YKOWGRMDSA-N (8s)-7-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 HRWCVUIFMSZDJS-YKOWGRMDSA-N 0.000 description 1
IXOLTUISSICXBZ-FHNOQDHRSA-N (8s)-7-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1-oxa-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(OCCC2)C1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 IXOLTUISSICXBZ-FHNOQDHRSA-N 0.000 description 1
KKSQMTJMNALLFX-LOACHALJSA-N (8s)-7-[2-[(1-carboxy-3-phenylpropyl)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)O)CCC1=CC=CC=C1 KKSQMTJMNALLFX-LOACHALJSA-N 0.000 description 1
QBRHHUXJSQBAGT-DKTYTTGXSA-N (8s)-7-[2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]acetyl]-2-thia-7-azaspiro[4.4]nonane-8-carboxylic acid Chemical compound N1([C@@H](CC2(CSCC2)C1)C(O)=O)C(=O)CNC(C(=O)OCC)CCC1=CC=CC=C1 QBRHHUXJSQBAGT-DKTYTTGXSA-N 0.000 description 1
FHJYMEFAZOQJLH-NZEUDUFCSA-N (8s)-9-[(2s)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]-1,4-dithia-9-azaspiro[4.5]decane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2(C1)SCCS2)C(O)=O)C(C(O)=O)CCC1=CC=CC=C1 FHJYMEFAZOQJLH-NZEUDUFCSA-N 0.000 description 1
ADJKKZUIUDDEPY-NMBLWERJSA-N (8s)-9-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,4-dioxa-9-azaspiro[4.5]decane-8-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2(C1)OCCO2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 ADJKKZUIUDDEPY-NMBLWERJSA-N 0.000 description 1
YNDSKPMAIBHSLN-SPFPWHRZSA-N (9s)-8-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-1,5-dithia-8-azaspiro[5.5]undecane-9-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2(C1)SCCCS2)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 YNDSKPMAIBHSLN-SPFPWHRZSA-N 0.000 description 1
KMQKVLVPFMFEID-QJQMAANRSA-N (9s)-8-[(2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]-8-azaspiro[4.5]decane-9-carboxylic acid Chemical compound N([C@@H](C)C(=O)N1[C@@H](CC2(CCCC2)CC1)C(O)=O)C(C(=O)OCC)CCC1=CC=CC=C1 KMQKVLVPFMFEID-QJQMAANRSA-N 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
ADKDJHASTPQGEO-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrole Chemical compound C1CNC2CCCC21 ADKDJHASTPQGEO-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
PIINXYKJQGMIOZ-UHFFFAOYSA-N 1,2-dipyridin-2-ylethane-1,2-dione Chemical compound C=1C=CC=NC=1C(=O)C(=O)C1=CC=CC=N1 PIINXYKJQGMIOZ-UHFFFAOYSA-N 0.000 description 1
ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
STNNRJFAZZAILC-UHFFFAOYSA-N 1,5-oxazocane-4-carboxylic acid Chemical compound OC(=O)C1CCOCCCN1 STNNRJFAZZAILC-UHFFFAOYSA-N 0.000 description 1
REKCOCMOYWUZED-UHFFFAOYSA-N 1-(3,3-dimethoxypropyl)-1-nitrocyclopentane Chemical compound COC(OC)CCC1([N+]([O-])=O)CCCC1 REKCOCMOYWUZED-UHFFFAOYSA-N 0.000 description 1
KWENTBKLBHHLNV-UHFFFAOYSA-N 1-(3,3-dimethoxypropyl)cyclopentan-1-amine Chemical compound COC(OC)CCC1(N)CCCC1 KWENTBKLBHHLNV-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
ZXMYUPJTDAGGFW-UHFFFAOYSA-N 1-azaspiro[4.4]nonane-2-carboxylic acid Chemical compound N1C(C(=O)O)CCC11CCCC1 ZXMYUPJTDAGGFW-UHFFFAOYSA-N 0.000 description 1
UIOORSWZRBWXCD-ZDUSSCGKSA-N 1-o-benzyl 2-o-ethyl (2s)-4-oxopyrrolidine-1,2-dicarboxylate Chemical compound CCOC(=O)[C@@H]1CC(=O)CN1C(=O)OCC1=CC=CC=C1 UIOORSWZRBWXCD-ZDUSSCGKSA-N 0.000 description 1
HCUARRIEZVDMPT-UHFFFAOYSA-M 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)[O-])=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-M 0.000 description 1
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
ODSNARDHJFFSRH-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical compound C1CCCC2CNCC21 ODSNARDHJFFSRH-UHFFFAOYSA-N 0.000 description 1
QFKVQNJEBLYEAH-UHFFFAOYSA-N 2,3,3a,4,6,6a-hexahydro-1h-furo[3,4-b]pyrrole Chemical compound C1OCC2NCCC21 QFKVQNJEBLYEAH-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
PPKAIMDMNWBOKN-UHFFFAOYSA-N 2-Oxo-4-phenylbutyric acid Chemical compound OC(=O)C(=O)CCC1=CC=CC=C1 PPKAIMDMNWBOKN-UHFFFAOYSA-N 0.000 description 1
LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 description 1
PNSAYTGWJPRUTD-UHFFFAOYSA-N 3-(1-nitrocyclopentyl)propanal Chemical compound O=CCCC1([N+](=O)[O-])CCCC1 PNSAYTGWJPRUTD-UHFFFAOYSA-N 0.000 description 1
DRZCPHGVEATLFR-UHFFFAOYSA-N 4,4-diethoxybutanenitrile Chemical compound CCOC(OCC)CCC#N DRZCPHGVEATLFR-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
101100119767 Caenorhabditis elegans fat-4 gene Proteins 0.000 description 1
101100468762 Caenorhabditis elegans ric-3 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
239000001116 FEMA 4028 Substances 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
239000003810 Jones reagent Substances 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
150000008575 L-amino acids Chemical class 0.000 description 1
239000004201 L-cysteine Substances 0.000 description 1
235000013878 L-cysteine Nutrition 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
CEXDJDXDWBWRSA-AWVGZIQVSA-N N([C@@H](C)C(=O)N1[C@@H](CCC2CCCCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=C(Cl)C=C1 Chemical compound N([C@@H](C)C(=O)N1[C@@H](CCC2CCCCC21)C(O)=O)C(C(=O)OCC)CCC1=CC=C(Cl)C=C1 CEXDJDXDWBWRSA-AWVGZIQVSA-N 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 1
GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
239000002262 Schiff base Substances 0.000 description 1
150000004753 Schiff bases Chemical class 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
159000000021 acetate salts Chemical class 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
229960002576 amiloride Drugs 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000003945 anionic surfactant Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
LPHNXQDGAWZOCU-UHFFFAOYSA-N azocane-2-carboxylic acid hydrate Chemical compound O.N1C(CCCCCC1)C(=O)O LPHNXQDGAWZOCU-UHFFFAOYSA-N 0.000 description 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
235000011175 beta-cyclodextrine Nutrition 0.000 description 1
125000003460 beta-lactamyl group Chemical group 0.000 description 1
229960004853 betadex Drugs 0.000 description 1
239000000872 buffer Substances 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
239000003093 cationic surfactant Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
235000013339 cereals Nutrition 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
229940005991 chloric acid Drugs 0.000 description 1
229960002303 citric acid monohydrate Drugs 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
RDXABLXNTVBVML-UHFFFAOYSA-N diethoxyphosphanyl diethyl phosphite Chemical compound CCOP(OCC)OP(OCC)OCC RDXABLXNTVBVML-UHFFFAOYSA-N 0.000 description 1
125000002474 dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
229950010030 dl-alanine Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
229960003199 etacrynic acid Drugs 0.000 description 1
PGEVGMOTJUZUKY-MERQFXBCSA-N ethyl (2r)-2-amino-3-benzylsulfanylpropanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)CSCC1=CC=CC=C1 PGEVGMOTJUZUKY-MERQFXBCSA-N 0.000 description 1
GLOHKOSMRJUOTO-RXQRSOPUSA-N ethyl (2s)-1-[(2s)-2-(phenylmethoxycarbonylamino)propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylate Chemical compound N([C@@H](C)C(=O)N1C2CCCCC2C[C@H]1C(=O)OCC)C(=O)OCC1=CC=CC=C1 GLOHKOSMRJUOTO-RXQRSOPUSA-N 0.000 description 1
UVPOIPYHTOFDIB-MERQFXBCSA-N ethyl (2s)-2-amino-3-phenylmethoxypropanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](N)COCC1=CC=CC=C1 UVPOIPYHTOFDIB-MERQFXBCSA-N 0.000 description 1
RVMNHKXJDVRAPE-HNNXBMFYSA-N ethyl (8s)-7-[2-(phenylmethoxycarbonylamino)acetyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate Chemical compound C([C@H](N(C1)C(=O)CNC(=O)OCC=2C=CC=CC=2)C(=O)OCC)C21SCCS2 RVMNHKXJDVRAPE-HNNXBMFYSA-N 0.000 description 1
WGXQJCFTGHCJJL-UHFFFAOYSA-N ethyl 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline-2-carboxylate Chemical compound C1CCCC2NC(C(=O)OCC)CCC21 WGXQJCFTGHCJJL-UHFFFAOYSA-N 0.000 description 1
ZWKOTRNANCDLSE-UHFFFAOYSA-N ethyl 1,2,3,4,4a,5,7,7a-octahydrofuro[3,4-b]pyridine-2-carboxylate Chemical compound N1C(C(=O)OCC)CCC2COCC21 ZWKOTRNANCDLSE-UHFFFAOYSA-N 0.000 description 1
SUWTYCOTEIUZTF-UHFFFAOYSA-N ethyl 1,4-thiazonane-5-carboxylate Chemical compound CCOC(=O)C1CCCCSCCN1 SUWTYCOTEIUZTF-UHFFFAOYSA-N 0.000 description 1
QQXQAEWRSVZPJM-UHFFFAOYSA-N ethyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1 QQXQAEWRSVZPJM-UHFFFAOYSA-N 0.000 description 1
WNKOJUVNRGYDPP-UHFFFAOYSA-N ethyl 2,3,3a,4,6,6a-hexahydro-1h-thieno[3,4-b]pyrrole-2-carboxylate Chemical compound C1SCC2NC(C(=O)OCC)CC21 WNKOJUVNRGYDPP-UHFFFAOYSA-N 0.000 description 1
DKWAALUXJAKCRQ-UHFFFAOYSA-N ethyl 2-oxo-3-phenylbutanoate Chemical compound CCOC(=O)C(=O)C(C)C1=CC=CC=C1 DKWAALUXJAKCRQ-UHFFFAOYSA-N 0.000 description 1
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
239000001761 ethyl methyl cellulose Substances 0.000 description 1
235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
229960003883 furosemide Drugs 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
230000005484 gravity Effects 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
229960002003 hydrochlorothiazide Drugs 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
150000004715 keto acids Chemical class 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000012528 membrane Substances 0.000 description 1
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
KCUNTYMNJVXYKZ-JTQLQIEISA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 KCUNTYMNJVXYKZ-JTQLQIEISA-N 0.000 description 1
IXKUPTBCNCVFCM-VIFPVBQESA-N methyl (4s)-5-(2-oxopropanoyl)-1,5-oxazocane-4-carboxylate Chemical compound COC(=O)[C@@H]1CCOCCCN1C(=O)C(C)=O IXKUPTBCNCVFCM-VIFPVBQESA-N 0.000 description 1
GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
CJSZWOGCKKDSJG-UHFFFAOYSA-N nitrocyclopentane Chemical compound [O-][N+](=O)C1CCCC1 CJSZWOGCKKDSJG-UHFFFAOYSA-N 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
238000005192 partition Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 1
LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000006894 reductive elimination reaction Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
229960004605 timolol Drugs 0.000 description 1
229940078499 tricalcium phosphate Drugs 0.000 description 1
235000019731 tricalcium phosphate Nutrition 0.000 description 1
229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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 description 1
239000008158 vegetable oil Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1