JP2010532383A

JP2010532383A - カリウムａｔｐチャネル開口薬の塩およびその使用

カリウムａｔｐチャネル開口薬の塩およびその使用 Download PDF

Info

Publication number: JP2010532383A
Authority: JP; Japan
Prior art keywords: formula; formulation; group; salt; subject
Prior art date: 2007-07-02
Legal status : Pending

Application number

JP2010515241A

Other languages

English (en)

Japanese (ja)

Other versions

JP2010532383A5 (OSRAM

Inventor

コーウェン，ネイル，エム．

デュークス，レイン

Original Assignee

エッセンシャリス，インク．

Priority date

2007-07-02

Filing date

2008-07-01

Publication date

2010-10-07

2008-07-01 Application filed by エッセンシャリス，インク． filed Critical エッセンシャリス，インク．

2010-10-07 Publication of JP2010532383A publication Critical patent/JP2010532383A/ja

2011-08-18 Publication of JP2010532383A5 publication Critical patent/JP2010532383A5/ja

Status Pending legal-status Critical Current

Links

150000003839 salts Chemical class 0.000 title claims abstract description 393
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 title description 11
239000011591 potassium Substances 0.000 title description 11
229910052700 potassium Inorganic materials 0.000 title description 11
238000000034 method Methods 0.000 claims abstract description 245
FCTRVTQZOUKUIV-MCDZGGTQSA-M potassium;[[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound [K+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)([O-])=O)[C@@H](O)[C@H]1O FCTRVTQZOUKUIV-MCDZGGTQSA-M 0.000 claims abstract description 224
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 55
230000000694 effects Effects 0.000 claims abstract description 47
238000011282 treatment Methods 0.000 claims abstract description 40
230000002411 adverse Effects 0.000 claims abstract description 20
239000000203 mixture Substances 0.000 claims description 415
238000009472 formulation Methods 0.000 claims description 393
108091006146 Channels Proteins 0.000 claims description 294
150000001875 compounds Chemical class 0.000 claims description 207
239000003814 drug Substances 0.000 claims description 106
150000001450 anions Chemical class 0.000 claims description 102
229940079593 drug Drugs 0.000 claims description 100
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 98
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 70
150000001768 cations Chemical class 0.000 claims description 58
125000003277 amino group Chemical group 0.000 claims description 55
238000013270 controlled release Methods 0.000 claims description 54
125000001424 substituent group Chemical group 0.000 claims description 54
229910052783 alkali metal Inorganic materials 0.000 claims description 46
YLLWQNAEYILHLV-UHFFFAOYSA-N 7-chloro-3-methyl-1$l^{6},2,4-benzothiadiazin-2-ide 1,1-dioxide;2-hydroxyethyl(trimethyl)azanium Chemical group C[N+](C)(C)CCO.C1=C(Cl)C=C2S(=O)(=O)[N-]C(C)=NC2=C1 YLLWQNAEYILHLV-UHFFFAOYSA-N 0.000 claims description 45
230000001965 increasing effect Effects 0.000 claims description 43
150000003512 tertiary amines Chemical class 0.000 claims description 41
210000004369 blood Anatomy 0.000 claims description 38
239000008280 blood Substances 0.000 claims description 38
150000001340 alkali metals Chemical class 0.000 claims description 37
QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 37
102000004877 Insulin Human genes 0.000 claims description 35
108090001061 Insulin Proteins 0.000 claims description 35
229940125396 insulin Drugs 0.000 claims description 35
235000012000 cholesterol Nutrition 0.000 claims description 30
239000003112 inhibitor Substances 0.000 claims description 28
239000003472 antidiabetic agent Substances 0.000 claims description 26
239000003795 chemical substances by application Substances 0.000 claims description 26
230000003914 insulin secretion Effects 0.000 claims description 26
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 26
229920000642 polymer Polymers 0.000 claims description 24
229940125708 antidiabetic agent Drugs 0.000 claims description 21
150000003626 triacylglycerols Chemical class 0.000 claims description 19
206010020772 Hypertension Diseases 0.000 claims description 18
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 17
230000002218 hypoglycaemic effect Effects 0.000 claims description 16
235000012054 meals Nutrition 0.000 claims description 15
230000002829 reductive effect Effects 0.000 claims description 15
208000013016 Hypoglycemia Diseases 0.000 claims description 14
229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 14
230000005856 abnormality Effects 0.000 claims description 14
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 14
208000032928 Dyslipidaemia Diseases 0.000 claims description 13
208000017170 Lipid metabolism disease Diseases 0.000 claims description 13
108010091821 Sulfonylurea Receptors Proteins 0.000 claims description 12
102000018692 Sulfonylurea Receptors Human genes 0.000 claims description 12
201000010065 polycystic ovary syndrome Diseases 0.000 claims description 11
239000000333 selective estrogen receptor modulator Substances 0.000 claims description 11
229940095743 selective estrogen receptor modulator Drugs 0.000 claims description 11
238000008214 LDL Cholesterol Methods 0.000 claims description 10
HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 claims description 9
108010011459 Exenatide Proteins 0.000 claims description 9
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 9
229960001519 exenatide Drugs 0.000 claims description 9
230000016087 ovulation Effects 0.000 claims description 9
229940044551 receptor antagonist Drugs 0.000 claims description 9
239000002464 receptor antagonist Substances 0.000 claims description 9
SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical group COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 8
108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 claims description 8
208000031226 Hyperlipidaemia Diseases 0.000 claims description 8
239000003098 androgen Substances 0.000 claims description 8
229950004994 meglitinide Drugs 0.000 claims description 8
208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 8
206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 8
102000004217 thyroid hormone receptors Human genes 0.000 claims description 8
108090000721 thyroid hormone receptors Proteins 0.000 claims description 8
102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims description 7
FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 claims description 7
229940123464 Thiazolidinedione Drugs 0.000 claims description 7
229960000698 nateglinide Drugs 0.000 claims description 7
OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 claims description 7
229960002354 repaglinide Drugs 0.000 claims description 7
108010017464 Fructose-Bisphosphatase Proteins 0.000 claims description 6
YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 6
230000002641 glycemic effect Effects 0.000 claims description 6
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
230000001939 inductive effect Effects 0.000 claims description 6
229920000609 methyl cellulose Polymers 0.000 claims description 6
235000010981 methylcellulose Nutrition 0.000 claims description 6
239000001923 methylcellulose Substances 0.000 claims description 6
229960003365 mitiglinide Drugs 0.000 claims description 6
WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 claims description 6
230000027758 ovulation cycle Effects 0.000 claims description 6
HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 6
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 5
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 claims description 5
239000001856 Ethyl cellulose Substances 0.000 claims description 5
229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 5
208000035150 Hypercholesterolemia Diseases 0.000 claims description 5
108010069201 VLDL Cholesterol Proteins 0.000 claims description 5
239000012190 activator Substances 0.000 claims description 5
229920002678 cellulose Polymers 0.000 claims description 5
239000001913 cellulose Substances 0.000 claims description 5
235000010980 cellulose Nutrition 0.000 claims description 5
235000019325 ethyl cellulose Nutrition 0.000 claims description 5
229920001249 ethyl cellulose Polymers 0.000 claims description 5
206010061666 Autonomic neuropathy Diseases 0.000 claims description 4
108010001394 Disaccharidases Proteins 0.000 claims description 4
229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 4
206010033645 Pancreatitis Diseases 0.000 claims description 4
150000002016 disaccharides Chemical class 0.000 claims description 4
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 4
235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
239000001863 hydroxypropyl cellulose Substances 0.000 claims description 4
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 4
208000006575 hypertriglyceridemia Diseases 0.000 claims description 4
239000004031 partial agonist Substances 0.000 claims description 4
MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 claims description 4
229960004034 sitagliptin Drugs 0.000 claims description 4
XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 3
LBXCUWNYHJDGKP-UHFFFAOYSA-N 7-chloro-3-methyl-2h-1,2,4-benzothiadiazine Chemical compound C1=C(Cl)C=C2SNC(C)=NC2=C1 LBXCUWNYHJDGKP-UHFFFAOYSA-N 0.000 claims description 3
229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
229940126033 PPAR agonist Drugs 0.000 claims description 3
229960002632 acarbose Drugs 0.000 claims description 3
XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims description 3
235000019577 caloric intake Nutrition 0.000 claims description 3
239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims description 3
230000036961 partial effect Effects 0.000 claims description 3
239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 claims description 3
229960005095 pioglitazone Drugs 0.000 claims description 3
229960004586 rosiglitazone Drugs 0.000 claims description 3
QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 claims description 3
108010033693 saxagliptin Proteins 0.000 claims description 3
229960004937 saxagliptin Drugs 0.000 claims description 3
SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 claims description 3
229960001254 vildagliptin Drugs 0.000 claims description 3
WMUIIGVAWPWQAW-DEOSSOPVSA-N (2s)-2-ethoxy-3-{4-[2-(10h-phenoxazin-10-yl)ethoxy]phenyl}propanoic acid Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCN1C2=CC=CC=C2OC2=CC=CC=C21 WMUIIGVAWPWQAW-DEOSSOPVSA-N 0.000 claims description 2
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims description 2
108010019598 Liraglutide Proteins 0.000 claims description 2
IRLWJILLXJGJTD-UHFFFAOYSA-N Muraglitazar Chemical compound C1=CC(OC)=CC=C1OC(=O)N(CC(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRLWJILLXJGJTD-UHFFFAOYSA-N 0.000 claims description 2
FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 claims description 2
OGWAVGNOAMXIIM-UHFFFAOYSA-N albiglutide Chemical compound O=C(O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)CNC(=O)C(N)CC=1(N=CNC=1))CCC(=O)O)C(O)C)CC2(=CC=CC=C2))C(O)C)CO)CC(=O)O)C(C)C)CO)CO)CC3(=CC=C(O)C=C3))CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCN)CCC(=O)O)CC4(=CC=CC=C4))C(CC)C)C)CC=6(C5(=C(C=CC=C5)NC=6)))CC(C)C)C(C)C)CCCCN)CCCNC(=N)N OGWAVGNOAMXIIM-UHFFFAOYSA-N 0.000 claims description 2
229960004733 albiglutide Drugs 0.000 claims description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
QLZHNIAADXEJJP-UHFFFAOYSA-L dioxido-oxo-phenyl-$l^{5}-phosphane Chemical group [O-]P([O-])(=O)C1=CC=CC=C1 QLZHNIAADXEJJP-UHFFFAOYSA-L 0.000 claims description 2
JGCMEVUWRCNKKE-KBPBESRZSA-N ethyl (2s)-2-[[[5-[2-amino-5-(2-methylpropyl)-1,3-thiazol-4-yl]furan-2-yl]-[[(2s)-1-ethoxy-1-oxopropan-2-yl]amino]phosphanyl]amino]propanoate Chemical compound O1C(P(N[C@@H](C)C(=O)OCC)N[C@@H](C)C(=O)OCC)=CC=C1C1=C(CC(C)C)SC(N)=N1 JGCMEVUWRCNKKE-KBPBESRZSA-N 0.000 claims description 2
229940125753 fibrate Drugs 0.000 claims description 2
229960002701 liraglutide Drugs 0.000 claims description 2
229950001135 muraglitazar Drugs 0.000 claims description 2
AHLKSOXEVRYIRD-UHFFFAOYSA-N n-phenylquinazolin-2-amine Chemical compound N=1C=C2C=CC=CC2=NC=1NC1=CC=CC=C1 AHLKSOXEVRYIRD-UHFFFAOYSA-N 0.000 claims description 2
229950008257 ragaglitazar Drugs 0.000 claims description 2
235000021055 solid food Nutrition 0.000 claims description 2
239000004059 squalene synthase inhibitor Substances 0.000 claims description 2
238000010254 subcutaneous injection Methods 0.000 claims description 2
239000007929 subcutaneous injection Substances 0.000 claims description 2
GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 claims description 2
229960001641 troglitazone Drugs 0.000 claims description 2
GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 claims description 2
102000012195 Fructose-1,6-bisphosphatases Human genes 0.000 claims 2
208000001145 Metabolic Syndrome Diseases 0.000 claims 1
102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 1
229940122054 Peroxisome proliferator-activated receptor delta agonist Drugs 0.000 claims 1
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
229960003512 nicotinic acid Drugs 0.000 claims 1
235000001968 nicotinic acid Nutrition 0.000 claims 1
239000011664 nicotinic acid Substances 0.000 claims 1
CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 claims 1
229950004704 tesaglitazar Drugs 0.000 claims 1
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 abstract description 152
229960004042 diazoxide Drugs 0.000 abstract description 141
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 28
201000010099 disease Diseases 0.000 abstract description 19
230000002503 metabolic effect Effects 0.000 abstract description 12
208000035475 disorder Diseases 0.000 abstract description 9
230000001225 therapeutic effect Effects 0.000 abstract description 8
241000282414 Homo sapiens Species 0.000 abstract description 7
230000003285 pharmacodynamic effect Effects 0.000 abstract description 6
230000007774 longterm Effects 0.000 abstract description 4
208000031295 Animal disease Diseases 0.000 abstract 1
125000000217 alkyl group Chemical group 0.000 description 103
229910052739 hydrogen Inorganic materials 0.000 description 51
239000001257 hydrogen Substances 0.000 description 51
208000008589 Obesity Diseases 0.000 description 47
235000020824 obesity Nutrition 0.000 description 47
-1 nucleoside diphosphate Chemical class 0.000 description 45
125000001072 heteroaryl group Chemical group 0.000 description 44
125000000623 heterocyclic group Chemical group 0.000 description 37
125000000753 cycloalkyl group Chemical group 0.000 description 34
125000005346 substituted cycloalkyl group Chemical group 0.000 description 34
238000000634 powder X-ray diffraction Methods 0.000 description 33
239000003826 tablet Substances 0.000 description 33
239000013543 active substance Substances 0.000 description 29
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 28
206010012601 diabetes mellitus Diseases 0.000 description 27
229910052736 halogen Inorganic materials 0.000 description 26
150000002367 halogens Chemical class 0.000 description 26
150000002431 hydrogen Chemical class 0.000 description 26
125000003107 substituted aryl group Chemical group 0.000 description 26
230000015572 biosynthetic process Effects 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
125000000547 substituted alkyl group Chemical group 0.000 description 24
125000003118 aryl group Chemical group 0.000 description 23
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 22
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 22
239000002904 solvent Substances 0.000 description 22
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
239000008103 glucose Substances 0.000 description 21
230000005764 inhibitory process Effects 0.000 description 21
229920001577 copolymer Polymers 0.000 description 20
239000011159 matrix material Substances 0.000 description 20
125000004429 atom Chemical group 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
241001465754 Metazoa Species 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
125000003545 alkoxy group Chemical group 0.000 description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 18
108010010234 HDL Lipoproteins Proteins 0.000 description 17
102000015779 HDL Lipoproteins Human genes 0.000 description 17
206010033307 Overweight Diseases 0.000 description 17
229910052757 nitrogen Inorganic materials 0.000 description 17
235000020825 overweight Nutrition 0.000 description 17
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 17
239000000126 substance Substances 0.000 description 17
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
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 16
229910052708 sodium Inorganic materials 0.000 description 16
239000011734 sodium Substances 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
206010022489 Insulin Resistance Diseases 0.000 description 15
125000002252 acyl group Chemical group 0.000 description 15
230000002496 gastric effect Effects 0.000 description 15
150000002632 lipids Chemical class 0.000 description 15
230000009467 reduction Effects 0.000 description 15
239000000556 agonist Substances 0.000 description 14
125000004414 alkyl thio group Chemical class 0.000 description 14
238000005755 formation reaction Methods 0.000 description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
238000002360 preparation method Methods 0.000 description 14
229940002612 prodrug Drugs 0.000 description 14
239000000651 prodrug Substances 0.000 description 14
101000760570 Homo sapiens ATP-binding cassette sub-family C member 8 Proteins 0.000 description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
206010061216 Infarction Diseases 0.000 description 13
208000010125 myocardial infarction Diseases 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
239000004381 Choline salt Substances 0.000 description 12
241000700159 Rattus Species 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
239000002775 capsule Substances 0.000 description 12
235000019417 choline salt Nutrition 0.000 description 12
201000009104 prediabetes syndrome Diseases 0.000 description 12
125000001453 quaternary ammonium group Chemical group 0.000 description 12
150000003248 quinolines Chemical class 0.000 description 12
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 12
208000011580 syndromic disease Diseases 0.000 description 12
238000002560 therapeutic procedure Methods 0.000 description 12
102100024645 ATP-binding cassette sub-family C member 8 Human genes 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
235000019441 ethanol Nutrition 0.000 description 11
239000000499 gel Substances 0.000 description 11
230000007574 infarction Effects 0.000 description 11
238000004519 manufacturing process Methods 0.000 description 11
239000007787 solid Substances 0.000 description 11
210000001519 tissue Anatomy 0.000 description 11
102000004190 Enzymes Human genes 0.000 description 10
108090000790 Enzymes Proteins 0.000 description 10
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
102000004257 Potassium Channel Human genes 0.000 description 10
238000010521 absorption reaction Methods 0.000 description 10
125000003710 aryl alkyl group Chemical group 0.000 description 10
239000002585 base Substances 0.000 description 10
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 10
230000037396 body weight Effects 0.000 description 10
229940088598 enzyme Drugs 0.000 description 10
201000008980 hyperinsulinism Diseases 0.000 description 10
229910052751 metal Inorganic materials 0.000 description 10
239000002184 metal Substances 0.000 description 10
239000011859 microparticle Substances 0.000 description 10
108020001213 potassium channel Proteins 0.000 description 10
102000005962 receptors Human genes 0.000 description 10
108020003175 receptors Proteins 0.000 description 10
150000003573 thiols Chemical class 0.000 description 10
102100021177 ATP-sensitive inward rectifier potassium channel 11 Human genes 0.000 description 9
101000614701 Homo sapiens ATP-sensitive inward rectifier potassium channel 11 Proteins 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
125000004390 alkyl sulfonyl group Chemical group 0.000 description 9
230000027455 binding Effects 0.000 description 9
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 9
229960001231 choline Drugs 0.000 description 9
125000004415 heterocyclylalkyl group Chemical group 0.000 description 9
210000002381 plasma Anatomy 0.000 description 9
239000000047 product Substances 0.000 description 9
239000000243 solution Substances 0.000 description 9
239000010409 thin film Substances 0.000 description 9
230000004580 weight loss Effects 0.000 description 9
NDGLGOGSZCDCPI-UHFFFAOYSA-N 5-amino-n'-[2-(2-chlorophenyl)ethyl]-n-cyanopyridine-3-carboximidamide Chemical compound NC1=CN=CC(C(NCCC=2C(=CC=CC=2)Cl)=NC#N)=C1 NDGLGOGSZCDCPI-UHFFFAOYSA-N 0.000 description 8
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
125000004644 alkyl sulfinyl group Chemical group 0.000 description 8
206010003119 arrhythmia Diseases 0.000 description 8
230000006793 arrhythmia Effects 0.000 description 8
239000011248 coating agent Substances 0.000 description 8
238000000576 coating method Methods 0.000 description 8
238000007906 compression Methods 0.000 description 8
230000006835 compression Effects 0.000 description 8
239000003925 fat Substances 0.000 description 8
235000019197 fats Nutrition 0.000 description 8
125000005842 heteroatom Chemical group 0.000 description 8
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
238000007254 oxidation reaction Methods 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
239000000825 pharmaceutical preparation Substances 0.000 description 8
230000002685 pulmonary effect Effects 0.000 description 8
208000002815 pulmonary hypertension Diseases 0.000 description 8
229910052717 sulfur Inorganic materials 0.000 description 8
229920003176 water-insoluble polymer Polymers 0.000 description 8
VZJFGSRCJCXDSG-UHFFFAOYSA-N Hexamethonium Chemical compound C[N+](C)(C)CCCCCC[N+](C)(C)C VZJFGSRCJCXDSG-UHFFFAOYSA-N 0.000 description 7
150000008044 alkali metal hydroxides Chemical class 0.000 description 7
125000004656 alkyl sulfonylamino group Chemical group 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
239000013078 crystal Substances 0.000 description 7
230000003111 delayed effect Effects 0.000 description 7
235000005911 diet Nutrition 0.000 description 7
239000002552 dosage form Substances 0.000 description 7
210000002216 heart Anatomy 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
238000001990 intravenous administration Methods 0.000 description 7
239000006186 oral dosage form Substances 0.000 description 7
150000002894 organic compounds Chemical class 0.000 description 7
229940073108 proglycem Drugs 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
230000004044 response Effects 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
159000000000 sodium salts Chemical class 0.000 description 7
210000002784 stomach Anatomy 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 6
NFLLKCVHYJRNRH-UHFFFAOYSA-N 8-chloro-1,3-dimethyl-7H-purine-2,6-dione 2-(diphenylmethyl)oxy-N,N-dimethylethanamine Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Cl)=N2.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 NFLLKCVHYJRNRH-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
208000002705 Glucose Intolerance Diseases 0.000 description 6
206010018429 Glucose tolerance impaired Diseases 0.000 description 6
241000282412 Homo Species 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
206010020710 Hyperphagia Diseases 0.000 description 6
239000002202 Polyethylene glycol Substances 0.000 description 6
208000001280 Prediabetic State Diseases 0.000 description 6
230000009471 action Effects 0.000 description 6
210000001789 adipocyte Anatomy 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
239000011575 calcium Substances 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
210000004413 cardiac myocyte Anatomy 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
230000008859 change Effects 0.000 description 6
238000005538 encapsulation Methods 0.000 description 6
XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 6
230000006870 function Effects 0.000 description 6
230000014509 gene expression Effects 0.000 description 6
125000004475 heteroaralkyl group Chemical group 0.000 description 6
230000001976 improved effect Effects 0.000 description 6
238000010606 normalization Methods 0.000 description 6
230000003204 osmotic effect Effects 0.000 description 6
235000020830 overeating Nutrition 0.000 description 6
229940044601 receptor agonist Drugs 0.000 description 6
239000000018 receptor agonist Substances 0.000 description 6
238000007634 remodeling Methods 0.000 description 6
210000002966 serum Anatomy 0.000 description 6
UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 6
238000001228 spectrum Methods 0.000 description 6
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 6
208000024891 symptom Diseases 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
229940086542 triethylamine Drugs 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 5
206010016807 Fluid retention Diseases 0.000 description 5
206010060378 Hyperinsulinaemia Diseases 0.000 description 5
102000004882 Lipase Human genes 0.000 description 5
108090001060 Lipase Proteins 0.000 description 5
108010013563 Lipoprotein Lipase Proteins 0.000 description 5
102000043296 Lipoprotein lipases Human genes 0.000 description 5
102000004895 Lipoproteins Human genes 0.000 description 5
108090001030 Lipoproteins Proteins 0.000 description 5
102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 5
108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 5
102100040918 Pro-glucagon Human genes 0.000 description 5
206010064911 Pulmonary arterial hypertension Diseases 0.000 description 5
108010062497 VLDL Lipoproteins Proteins 0.000 description 5
230000036982 action potential Effects 0.000 description 5
230000004872 arterial blood pressure Effects 0.000 description 5
230000015556 catabolic process Effects 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
230000007423 decrease Effects 0.000 description 5
230000037213 diet Effects 0.000 description 5
230000037406 food intake Effects 0.000 description 5
239000012458 free base Substances 0.000 description 5
229940088597 hormone Drugs 0.000 description 5
239000005556 hormone Substances 0.000 description 5
201000001421 hyperglycemia Diseases 0.000 description 5
230000003451 hyperinsulinaemic effect Effects 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000004615 ingredient Substances 0.000 description 5
NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 5
210000004185 liver Anatomy 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
239000002245 particle Substances 0.000 description 5
201000008312 primary pulmonary hypertension Diseases 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
125000005415 substituted alkoxy group Chemical group 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
102100031786 Adiponectin Human genes 0.000 description 4
108010076365 Adiponectin Proteins 0.000 description 4
208000024827 Alzheimer disease Diseases 0.000 description 4
201000001320 Atherosclerosis Diseases 0.000 description 4
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
229920000858 Cyclodextrin Polymers 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
102000027487 Fructose-Bisphosphatase Human genes 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 4
102000051325 Glucagon Human genes 0.000 description 4
108060003199 Glucagon Proteins 0.000 description 4
108010007622 LDL Lipoproteins Proteins 0.000 description 4
102000007330 LDL Lipoproteins Human genes 0.000 description 4
102000016267 Leptin Human genes 0.000 description 4
108010092277 Leptin Proteins 0.000 description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
208000001871 Tachycardia Diseases 0.000 description 4
ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
210000000577 adipose tissue Anatomy 0.000 description 4
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
230000002280 anti-androgenic effect Effects 0.000 description 4
230000003178 anti-diabetic effect Effects 0.000 description 4
239000000051 antiandrogen Substances 0.000 description 4
229940030600 antihypertensive agent Drugs 0.000 description 4
239000002220 antihypertensive agent Substances 0.000 description 4
229910052791 calcium Inorganic materials 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
230000001413 cellular effect Effects 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
125000004093 cyano group Chemical group *C#N 0.000 description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
230000001419 dependent effect Effects 0.000 description 4
238000000113 differential scanning calorimetry Methods 0.000 description 4
239000002934 diuretic Substances 0.000 description 4
235000012631 food intake Nutrition 0.000 description 4
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 4
229960004666 glucagon Drugs 0.000 description 4
239000008187 granular material Substances 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
125000004446 heteroarylalkyl group Chemical group 0.000 description 4
239000000017 hydrogel Substances 0.000 description 4
239000003456 ion exchange resin Substances 0.000 description 4
229920003303 ion-exchange polymer Polymers 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
229940039781 leptin Drugs 0.000 description 4
235000019626 lipase activity Nutrition 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
229910000000 metal hydroxide Inorganic materials 0.000 description 4
150000004692 metal hydroxides Chemical class 0.000 description 4
229940100692 oral suspension Drugs 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
229940127557 pharmaceutical product Drugs 0.000 description 4
230000008569 process Effects 0.000 description 4
235000000891 standard diet Nutrition 0.000 description 4
239000011593 sulfur Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
230000002459 sustained effect Effects 0.000 description 4
238000013268 sustained release Methods 0.000 description 4
239000007916 tablet composition Substances 0.000 description 4
230000006794 tachycardia Effects 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
GYLUMIIRFKDCKI-UHFFFAOYSA-L trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;dihydroxide Chemical compound [OH-].[OH-].C[N+](C)(C)CCCCCC[N+](C)(C)C GYLUMIIRFKDCKI-UHFFFAOYSA-L 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
229940122815 Aromatase inhibitor Drugs 0.000 description 3
210000002237 B-cell of pancreatic islet Anatomy 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
108010004103 Chylomicrons Proteins 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
SQSPRWMERUQXNE-UHFFFAOYSA-N Guanylurea Chemical class NC(=N)NC(N)=O SQSPRWMERUQXNE-UHFFFAOYSA-N 0.000 description 3
206010019233 Headaches Diseases 0.000 description 3
208000007976 Ketosis Diseases 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
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 3
206010028813 Nausea Diseases 0.000 description 3
206010030113 Oedema Diseases 0.000 description 3
108010016731 PPAR gamma Proteins 0.000 description 3
102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 3
229940127315 Potassium Channel Openers Drugs 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
102100037997 Squalene synthase Human genes 0.000 description 3
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 3
229930006000 Sucrose Natural products 0.000 description 3
208000021017 Weight Gain Diseases 0.000 description 3
238000009825 accumulation Methods 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000004913 activation Effects 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
150000001342 alkaline earth metals Chemical class 0.000 description 3
238000010171 animal model Methods 0.000 description 3
230000000561 anti-psychotic effect Effects 0.000 description 3
238000013459 approach Methods 0.000 description 3
239000003886 aromatase inhibitor Substances 0.000 description 3
230000008901 benefit Effects 0.000 description 3
210000004204 blood vessel Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229940111134 coxibs Drugs 0.000 description 3
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 3
230000003247 decreasing effect Effects 0.000 description 3
238000006731 degradation reaction Methods 0.000 description 3
230000001934 delay Effects 0.000 description 3
238000003745 diagnosis Methods 0.000 description 3
229940030606 diuretics Drugs 0.000 description 3
206010015037 epilepsy Diseases 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
230000029142 excretion Effects 0.000 description 3
238000013265 extended release Methods 0.000 description 3
239000010408 film Substances 0.000 description 3
239000012530 fluid Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
235000013305 food Nutrition 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
239000003349 gelling agent Substances 0.000 description 3
231100000869 headache Toxicity 0.000 description 3
230000002440 hepatic effect Effects 0.000 description 3
230000003834 intracellular effect Effects 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
201000005857 malignant hypertension Diseases 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
229960003194 meglumine Drugs 0.000 description 3
239000012528 membrane Substances 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
230000002107 myocardial effect Effects 0.000 description 3
210000004165 myocardium Anatomy 0.000 description 3
210000001087 myotubule Anatomy 0.000 description 3
230000008693 nausea Effects 0.000 description 3
239000002773 nucleotide Substances 0.000 description 3
125000003729 nucleotide group Chemical group 0.000 description 3
230000037361 pathway Effects 0.000 description 3
239000003614 peroxisome proliferator Substances 0.000 description 3
230000000704 physical effect Effects 0.000 description 3
239000004036 potassium channel stimulating agent Substances 0.000 description 3
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 3
210000001147 pulmonary artery Anatomy 0.000 description 3
JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 3
150000003335 secondary amines Chemical class 0.000 description 3
230000028327 secretion Effects 0.000 description 3
239000002002 slurry Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
239000012730 sustained-release form Substances 0.000 description 3
229940095064 tartrate Drugs 0.000 description 3
DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 3
238000002211 ultraviolet spectrum Methods 0.000 description 3
230000002861 ventricular Effects 0.000 description 3
230000004584 weight gain Effects 0.000 description 3
235000019786 weight gain Nutrition 0.000 description 3
KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
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 2
HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 description 2
YIUIVFFUEVPRIU-UHFFFAOYSA-N 8-chlorotheophylline Chemical class O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21 YIUIVFFUEVPRIU-UHFFFAOYSA-N 0.000 description 2
208000004998 Abdominal Pain Diseases 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 2
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 2
241000282472 Canis lupus familiaris Species 0.000 description 2
102000018208 Cannabinoid Receptor Human genes 0.000 description 2
108050007331 Cannabinoid receptor Proteins 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
208000028698 Cognitive impairment Diseases 0.000 description 2
208000008020 Cohen syndrome Diseases 0.000 description 2
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 2
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 2
206010012735 Diarrhoea Diseases 0.000 description 2
108010039731 Fatty Acid Synthases Proteins 0.000 description 2
241000282326 Felis catus Species 0.000 description 2
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
229930091371 Fructose Natural products 0.000 description 2
239000005715 Fructose Substances 0.000 description 2
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
208000001021 Hyperlipoproteinemia Type I Diseases 0.000 description 2
208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 2
201000010252 Hyperlipoproteinemia Type III Diseases 0.000 description 2
206010058179 Hypertensive emergency Diseases 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
206010023379 Ketoacidosis Diseases 0.000 description 2
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 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
206010026749 Mania Diseases 0.000 description 2
150000001204 N-oxides Chemical class 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
206010033557 Palpitations Diseases 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
201000010769 Prader-Willi syndrome Diseases 0.000 description 2
206010063837 Reperfusion injury Diseases 0.000 description 2
FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229930182558 Sterol Natural products 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
208000025569 Tobacco Use disease Diseases 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical group NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 2
TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 2
206010047700 Vomiting Diseases 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
239000000205 acacia gum Substances 0.000 description 2
229940100228 acetyl coenzyme a Drugs 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000004423 acyloxy group Chemical group 0.000 description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
229940025084 amphetamine Drugs 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
229940127003 anti-diabetic drug Drugs 0.000 description 2
229940124599 anti-inflammatory drug Drugs 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
239000001961 anticonvulsive agent Substances 0.000 description 2
239000000935 antidepressant agent Substances 0.000 description 2
229940005513 antidepressants Drugs 0.000 description 2
239000002830 appetite depressant Substances 0.000 description 2
125000004658 aryl carbonyl amino group Chemical group 0.000 description 2
125000004657 aryl sulfonyl amino group Chemical group 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
238000003556 assay Methods 0.000 description 2
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
125000005605 benzo group Chemical group 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
230000017531 blood circulation Effects 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
125000003739 carbamimidoyl group Chemical class C(N)(=N)* 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
230000006727 cell loss Effects 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 2
229960002023 chloroprocaine Drugs 0.000 description 2
229940075419 choline hydroxide Drugs 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
230000007012 clinical effect Effects 0.000 description 2
RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 2
239000005516 coenzyme A Substances 0.000 description 2
229940093530 coenzyme a Drugs 0.000 description 2
208000010877 cognitive disease Diseases 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
239000003431 cross linking reagent Substances 0.000 description 2
229940097362 cyclodextrins Drugs 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
230000009089 cytolysis Effects 0.000 description 2
230000006378 damage Effects 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 2
238000001514 detection method Methods 0.000 description 2
150000001982 diacylglycerols Chemical class 0.000 description 2
230000035487 diastolic blood pressure Effects 0.000 description 2
230000003205 diastolic effect Effects 0.000 description 2
GDLBFKVLRPITMI-UHFFFAOYSA-N diazoxide Chemical compound ClC1=CC=C2NC(C)=NS(=O)(=O)C2=C1 GDLBFKVLRPITMI-UHFFFAOYSA-N 0.000 description 2
230000000378 dietary effect Effects 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
238000009792 diffusion process Methods 0.000 description 2
229960004993 dimenhydrinate Drugs 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
229940099182 dramamine Drugs 0.000 description 2
201000006549 dyspepsia Diseases 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
201000001386 familial hypercholesterolemia Diseases 0.000 description 2
201000011110 familial lipoprotein lipase deficiency Diseases 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
239000007888 film coating Substances 0.000 description 2
238000009501 film coating Methods 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
230000014101 glucose homeostasis Effects 0.000 description 2
238000000227 grinding Methods 0.000 description 2
239000003111 growth hormone derivative Substances 0.000 description 2
125000005224 heteroarylcarbonylamino group Chemical group 0.000 description 2
125000005553 heteroaryloxy group Chemical group 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 2
230000013632 homeostatic process Effects 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
150000004679 hydroxides Chemical class 0.000 description 2
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
208000020887 hyperlipoproteinemia type 3 Diseases 0.000 description 2
208000000522 hyperlipoproteinemia type IV Diseases 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
229960003943 hypromellose Drugs 0.000 description 2
230000006872 improvement Effects 0.000 description 2
125000001041 indolyl group Chemical group 0.000 description 2
230000003993 interaction Effects 0.000 description 2
208000003243 intestinal obstruction Diseases 0.000 description 2
210000001596 intra-abdominal fat Anatomy 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
230000037356 lipid metabolism Effects 0.000 description 2
229960001078 lithium Drugs 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000008018 melting Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000008368 mint flavor Substances 0.000 description 2
150000002772 monosaccharides Chemical class 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
239000002105 nanoparticle Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
150000002892 organic cations Chemical class 0.000 description 2
AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 2
229960001243 orlistat Drugs 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
239000008188 pellet Substances 0.000 description 2
235000019371 penicillin G benzathine Nutrition 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
230000001766 physiological effect Effects 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
159000000001 potassium salts Chemical class 0.000 description 2
230000002265 prevention Effects 0.000 description 2
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
229960004919 procaine Drugs 0.000 description 2
238000012545 processing Methods 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
238000011160 research Methods 0.000 description 2
229960003015 rimonabant Drugs 0.000 description 2
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
201000000980 schizophrenia Diseases 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
229960004425 sibutramine Drugs 0.000 description 2
239000007962 solid dispersion Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
238000001694 spray drying Methods 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
150000003432 sterols Chemical class 0.000 description 2
235000003702 sterols Nutrition 0.000 description 2
230000004936 stimulating effect Effects 0.000 description 2
230000035488 systolic blood pressure Effects 0.000 description 2
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 2
125000001302 tertiary amino group Chemical group 0.000 description 2
238000012360 testing method Methods 0.000 description 2
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
238000002411 thermogravimetry Methods 0.000 description 2
150000001467 thiazolidinediones Chemical class 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
125000005309 thioalkoxy group Chemical group 0.000 description 2
229940116269 uric acid Drugs 0.000 description 2
230000008673 vomiting Effects 0.000 description 2
238000011684 zucker rat (obese) Methods 0.000 description 2
AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
229930182837 (R)-adrenaline Natural products 0.000 description 1
KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
WWASAZBMXLYJCT-KTKRTIGZSA-N (z)-1-aminoicos-11-en-2-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCC(O)CN WWASAZBMXLYJCT-KTKRTIGZSA-N 0.000 description 1
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 description 1
SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 1
VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
229940124801 5-HT6 antagonist Drugs 0.000 description 1
WZTBJUYSQNCMJG-UHFFFAOYSA-N 7-methoxy-1,1-dioxo-n-propan-2-yl-4h-1$l^{6},2,4-benzothiadiazin-3-amine Chemical compound N1C(NC(C)C)=NS(=O)(=O)C2=CC(OC)=CC=C21 WZTBJUYSQNCMJG-UHFFFAOYSA-N 0.000 description 1
239000005541 ACE inhibitor Substances 0.000 description 1
102100021240 ATP-sensitive inward rectifier potassium channel 8 Human genes 0.000 description 1
206010060954 Abdominal Hernia Diseases 0.000 description 1
208000004611 Abdominal Obesity Diseases 0.000 description 1
102000000452 Acetyl-CoA carboxylase Human genes 0.000 description 1
108010016219 Acetyl-CoA carboxylase Proteins 0.000 description 1
208000010444 Acidosis Diseases 0.000 description 1
229920000178 Acrylic resin Polymers 0.000 description 1
239000004925 Acrylic resin Substances 0.000 description 1
102000004539 Acyl-CoA Oxidase Human genes 0.000 description 1
108020001558 Acyl-CoA oxidase Proteins 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
208000022309 Alcoholic Liver disease Diseases 0.000 description 1
201000004384 Alopecia Diseases 0.000 description 1
201000000736 Amenorrhea Diseases 0.000 description 1
206010001928 Amenorrhoea Diseases 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
102100032187 Androgen receptor Human genes 0.000 description 1
229940123413 Angiotensin II antagonist Drugs 0.000 description 1
102100033367 Appetite-regulating hormone Human genes 0.000 description 1
101710111255 Appetite-regulating hormone Proteins 0.000 description 1
208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
102100026189 Beta-galactosidase Human genes 0.000 description 1
108010018763 Biotin carboxylase Proteins 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
208000032841 Bulimia Diseases 0.000 description 1
206010006550 Bulimia nervosa Diseases 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
108010075254 C-Peptide Proteins 0.000 description 1
229940124802 CB1 antagonist Drugs 0.000 description 1
QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
229940121981 Carboxypeptidase inhibitor Drugs 0.000 description 1
101710127041 Carboxypeptidase inhibitor Proteins 0.000 description 1
208000004652 Cardiovascular Abnormalities Diseases 0.000 description 1
102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 description 1
108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
208000002177 Cataract Diseases 0.000 description 1
206010065941 Central obesity Diseases 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
206010010071 Coma Diseases 0.000 description 1
AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
241000766026 Coregonus nasus Species 0.000 description 1
208000001778 Coronary Occlusion Diseases 0.000 description 1
206010011086 Coronary artery occlusion Diseases 0.000 description 1
TVZCRIROJQEVOT-CABCVRRESA-N Cromakalim Chemical compound N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-CABCVRRESA-N 0.000 description 1
DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
229940127193 DGAT1 inhibitor Drugs 0.000 description 1
KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
208000002249 Diabetes Complications Diseases 0.000 description 1
208000001380 Diabetic Ketoacidosis Diseases 0.000 description 1
206010012655 Diabetic complications Diseases 0.000 description 1
DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
229940097420 Diuretic Drugs 0.000 description 1
206010014476 Elevated cholesterol Diseases 0.000 description 1
206010014486 Elevated triglycerides Diseases 0.000 description 1
206010014733 Endometrial cancer Diseases 0.000 description 1
206010014759 Endometrial neoplasm Diseases 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
229920003139 Eudragit® L 100 Polymers 0.000 description 1
229920003135 Eudragit® L 100-55 Polymers 0.000 description 1
229920003141 Eudragit® S 100 Polymers 0.000 description 1
229920003134 Eudragit® polymer Polymers 0.000 description 1
208000004930 Fatty Liver Diseases 0.000 description 1
229940123469 Fatty acid synthase inhibitor Drugs 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
206010056465 Food craving Diseases 0.000 description 1
102100031416 Gastric triacylglycerol lipase Human genes 0.000 description 1
208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
101800001586 Ghrelin Proteins 0.000 description 1
102400000442 Ghrelin-28 Human genes 0.000 description 1
101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 description 1
108010051696 Growth Hormone Proteins 0.000 description 1
229920002907 Guar gum Polymers 0.000 description 1
108010023302 HDL Cholesterol Proteins 0.000 description 1
206010061209 Hip deformity Diseases 0.000 description 1
101100054314 Homo sapiens ABCC9 gene Proteins 0.000 description 1
101000614717 Homo sapiens ATP-sensitive inward rectifier potassium channel 8 Proteins 0.000 description 1
101100400966 Homo sapiens MED23 gene Proteins 0.000 description 1
229920000869 Homopolysaccharide Polymers 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
206010020864 Hypertrichosis Diseases 0.000 description 1
206010020880 Hypertrophy Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
102000003746 Insulin Receptor Human genes 0.000 description 1
108010001127 Insulin Receptor Proteins 0.000 description 1
208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
206010062061 Knee deformity Diseases 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
108010059881 Lactase Proteins 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
239000004367 Lipase Substances 0.000 description 1
206010067125 Liver injury Diseases 0.000 description 1
229920000161 Locust bean gum Polymers 0.000 description 1
101150104680 MCH1 gene Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
208000037093 Menstruation Disturbances Diseases 0.000 description 1
206010027339 Menstruation irregular Diseases 0.000 description 1
101710140999 Metallocarboxypeptidase inhibitor Proteins 0.000 description 1
IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
102000002568 Multienzyme Complexes Human genes 0.000 description 1
108010093369 Multienzyme Complexes Proteins 0.000 description 1
150000001200 N-acyl ethanolamides Chemical class 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
102000029748 Neuropeptide Y2 receptor Human genes 0.000 description 1
108010046593 Neuropeptide Y5 receptor Proteins 0.000 description 1
102000028582 Neuropeptide Y5 receptor Human genes 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
108020005497 Nuclear hormone receptor Proteins 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
208000004166 Obesity Hypoventilation Syndrome Diseases 0.000 description 1
206010030124 Oedema peripheral Diseases 0.000 description 1
206010031127 Orthostatic hypotension Diseases 0.000 description 1
102400000319 Oxyntomodulin Human genes 0.000 description 1
101800001388 Oxyntomodulin Proteins 0.000 description 1
102100029909 Peptide YY Human genes 0.000 description 1
108010088847 Peptide YY Proteins 0.000 description 1
208000018262 Peripheral vascular disease Diseases 0.000 description 1
206010035004 Pickwickian syndrome Diseases 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
101710184309 Probable sucrose-6-phosphate hydrolase Proteins 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
101100382379 Rattus norvegicus Cap1 gene Proteins 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
241000220010 Rhode Species 0.000 description 1
229940083324 Selective androgen receptor modulator Drugs 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
102000005157 Somatostatin Human genes 0.000 description 1
108010056088 Somatostatin Proteins 0.000 description 1
102100038803 Somatotropin Human genes 0.000 description 1
102000000019 Sterol Esterase Human genes 0.000 description 1
108010055297 Sterol Esterase Proteins 0.000 description 1
102400000472 Sucrase Human genes 0.000 description 1
101710112652 Sucrose-6-phosphate hydrolase Proteins 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
244000299461 Theobroma cacao Species 0.000 description 1
229940121792 Thiazide diuretic Drugs 0.000 description 1
AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102100029677 Trehalase Human genes 0.000 description 1
108010087472 Trehalase Proteins 0.000 description 1
102000008316 Type 4 Melanocortin Receptor Human genes 0.000 description 1
108010021436 Type 4 Melanocortin Receptor Proteins 0.000 description 1
206010046543 Urinary incontinence Diseases 0.000 description 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
241000269370 Xenopus <genus> Species 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
HPFVBGJFAYZEBE-XNBTXCQYSA-N [(8r,9s,10r,13s,14s)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] 3-cyclopentylpropanoate Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CCC(=O)C=C3CC2)C)CC[C@@]11C)CC1OC(=O)CCC1CCCC1 HPFVBGJFAYZEBE-XNBTXCQYSA-N 0.000 description 1
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
125000000218 acetic acid group Chemical group C(C)(=O)* 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
229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 description 1
230000007950 acidosis Effects 0.000 description 1
208000026545 acidosis disease Diseases 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
239000000808 adrenergic beta-agonist Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
102000016679 alpha-Glucosidases Human genes 0.000 description 1
108010028144 alpha-Glucosidases Proteins 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
230000001668 ameliorated effect Effects 0.000 description 1
231100000540 amenorrhea Toxicity 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
229960002932 anastrozole Drugs 0.000 description 1
YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
108010080146 androgen receptors Proteins 0.000 description 1
229940030486 androgens Drugs 0.000 description 1
239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
239000006053 animal diet Substances 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
230000003556 anti-epileptic effect Effects 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
239000003524 antilipemic agent Substances 0.000 description 1
239000013011 aqueous formulation Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
210000002565 arteriole Anatomy 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
239000000305 astragalus gummifer gum Substances 0.000 description 1
238000007681 bariatric surgery Methods 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
108010005774 beta-Galactosidase Proteins 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000008512 biological response Effects 0.000 description 1
230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
230000036765 blood level Effects 0.000 description 1
230000036770 blood supply Effects 0.000 description 1
238000009534 blood test Methods 0.000 description 1
230000036760 body temperature Effects 0.000 description 1
230000006931 brain damage Effects 0.000 description 1
231100000874 brain damage Toxicity 0.000 description 1
208000029028 brain injury Diseases 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000000872 buffer Substances 0.000 description 1
210000005252 bulbus oculi Anatomy 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
229910052792 caesium Inorganic materials 0.000 description 1
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
239000000480 calcium channel blocker Substances 0.000 description 1
235000021236 calorie-restricted diet Nutrition 0.000 description 1
239000007894 caplet Substances 0.000 description 1
239000007963 capsule composition Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
230000005961 cardioprotection Effects 0.000 description 1
150000001767 cationic compounds Chemical class 0.000 description 1
230000019522 cellular metabolic process Effects 0.000 description 1
229920003086 cellulose ether Polymers 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
210000000038 chest Anatomy 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
235000019219 chocolate Nutrition 0.000 description 1
235000014651 chocolate spreads Nutrition 0.000 description 1
201000001883 cholelithiasis Diseases 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
238000009535 clinical urine test Methods 0.000 description 1
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
229960003608 clomifene Drugs 0.000 description 1
238000010367 cloning Methods 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
210000001608 connective tissue cell Anatomy 0.000 description 1
238000007596 consolidation process Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
229950004210 cromakalim Drugs 0.000 description 1
125000002993 cycloalkylene group Chemical group 0.000 description 1
DUSHUSLJJMDGTE-ZJPMUUANSA-N cyproterone Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DUSHUSLJJMDGTE-ZJPMUUANSA-N 0.000 description 1
229960003843 cyproterone Drugs 0.000 description 1
GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical class NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
235000013367 dietary fats Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
102000038379 digestive enzymes Human genes 0.000 description 1
108091007734 digestive enzymes Proteins 0.000 description 1
125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
229940126534 drug product Drugs 0.000 description 1
229940088679 drug related substance Drugs 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
235000005686 eating Nutrition 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000002621 endocannabinoid Substances 0.000 description 1
210000003158 enteroendocrine cell Anatomy 0.000 description 1
229960005139 epinephrine Drugs 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
229950009769 etabonate Drugs 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
229960002568 ethinylestradiol Drugs 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000009093 first-line therapy Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
229940028334 follicle stimulating hormone Drugs 0.000 description 1
238000012395 formulation development Methods 0.000 description 1
229910052730 francium Inorganic materials 0.000 description 1
KLMCZVJOEAUDNE-UHFFFAOYSA-N francium atom Chemical compound [Fr] KLMCZVJOEAUDNE-UHFFFAOYSA-N 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
208000001130 gallstones Diseases 0.000 description 1
108010091264 gastric triacylglycerol lipase Proteins 0.000 description 1
208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
GNKDKYIHGQKHHM-RJKLHVOGSA-N ghrelin Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CN)COC(=O)CCCCCCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 GNKDKYIHGQKHHM-RJKLHVOGSA-N 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
230000001890 gluconeogenic effect Effects 0.000 description 1
230000004153 glucose metabolism Effects 0.000 description 1
150000002314 glycerols Chemical class 0.000 description 1
239000004247 glycine and its sodium salt Substances 0.000 description 1
235000013905 glycine and its sodium salt Nutrition 0.000 description 1
150000002332 glycine derivatives Chemical class 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
239000003324 growth hormone secretagogue Substances 0.000 description 1
235000010417 guar gum Nutrition 0.000 description 1
239000000665 guar gum Substances 0.000 description 1
229960002154 guar gum Drugs 0.000 description 1
229920000591 gum Polymers 0.000 description 1
230000003779 hair growth Effects 0.000 description 1
230000003676 hair loss Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
231100000234 hepatic damage Toxicity 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
125000005549 heteroarylene group Chemical group 0.000 description 1
125000005419 heteroarylsulfonylamino group Chemical group 0.000 description 1
102000050710 human ABCC8 Human genes 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000002102 hyperpolarization Effects 0.000 description 1
230000002267 hypothalamic effect Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
239000012729 immediate-release (IR) formulation Substances 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
208000000509 infertility Diseases 0.000 description 1
230000036512 infertility Effects 0.000 description 1
231100000535 infertility Toxicity 0.000 description 1
230000006749 inflammatory damage Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229940090044 injection Drugs 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000006362 insulin response pathway Effects 0.000 description 1
210000002660 insulin-secreting cell Anatomy 0.000 description 1
235000011073 invertase Nutrition 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
150000008040 ionic compounds Chemical class 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
230000001788 irregular Effects 0.000 description 1
208000037906 ischaemic injury Diseases 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
230000009916 joint effect Effects 0.000 description 1
230000004140 ketosis Effects 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
210000003127 knee Anatomy 0.000 description 1
229940116108 lactase Drugs 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
239000010410 layer Substances 0.000 description 1
229960003881 letrozole Drugs 0.000 description 1
HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
230000004130 lipolysis Effects 0.000 description 1
108010022197 lipoprotein cholesterol Proteins 0.000 description 1
230000008604 lipoprotein metabolism Effects 0.000 description 1
230000008818 liver damage Effects 0.000 description 1
208000019423 liver disease Diseases 0.000 description 1
230000004807 localization Effects 0.000 description 1
235000010420 locust bean gum Nutrition 0.000 description 1
239000000711 locust bean gum Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
206010025482 malaise Diseases 0.000 description 1
229940049920 malate Drugs 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
LTYOQGRJFJAKNA-IJCONWDESA-N malonyl-coenzyme a Chemical compound O[C@@H]1[C@@H](OP(O)(O)=O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-IJCONWDESA-N 0.000 description 1
238000007726 management method Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
230000012241 membrane hyperpolarization Effects 0.000 description 1
230000005906 menstruation Effects 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
230000006609 metabolic stress Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229960003105 metformin Drugs 0.000 description 1
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
230000003228 microsomal effect Effects 0.000 description 1
229960001110 miglitol Drugs 0.000 description 1
210000003470 mitochondria Anatomy 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
PXZWGQLGAKCNKD-DPNMSELWSA-N molport-023-276-326 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 PXZWGQLGAKCNKD-DPNMSELWSA-N 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
210000002464 muscle smooth vascular Anatomy 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
GNVRJGIVDSQCOP-UHFFFAOYSA-N n-ethyl-n-methylethanamine Chemical compound CCN(C)CC GNVRJGIVDSQCOP-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229950006327 napsilate Drugs 0.000 description 1
230000022001 negative regulation of insulin secretion Effects 0.000 description 1
PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
229950001628 netoglitazone Drugs 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
239000002658 neuropeptide Y receptor agonist Substances 0.000 description 1
108010089579 neuropeptide Y2 receptor Proteins 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
230000000422 nocturnal effect Effects 0.000 description 1
102000006255 nuclear receptors Human genes 0.000 description 1
108020004017 nuclear receptors Proteins 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
208000001797 obstructive sleep apnea Diseases 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
210000000287 oocyte Anatomy 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
229940100691 oral capsule Drugs 0.000 description 1
238000007410 oral glucose tolerance test Methods 0.000 description 1
239000008203 oral pharmaceutical composition Substances 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
125000004316 oxathiadiazolyl group Chemical group O1SNN=C1* 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
238000012856 packing Methods 0.000 description 1
210000002571 pancreatic alpha cell Anatomy 0.000 description 1
208000021255 pancreatic insulinoma Diseases 0.000 description 1
238000010951 particle size reduction Methods 0.000 description 1
239000002304 perfume Substances 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000036581 peripheral resistance Effects 0.000 description 1
210000002824 peroxisome Anatomy 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
229960003562 phentermine Drugs 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
229960002310 pinacidil Drugs 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
229920001993 poloxamer 188 Polymers 0.000 description 1
229940044519 poloxamer 188 Drugs 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
239000011148 porous material Substances 0.000 description 1
230000000291 postprandial effect Effects 0.000 description 1
230000003823 potassium efflux Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
210000000229 preadipocyte Anatomy 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
238000004321 preservation Methods 0.000 description 1
238000003825 pressing Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
QAQREVBBADEHPA-IEXPHMLFSA-N propionyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QAQREVBBADEHPA-IEXPHMLFSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
230000004224 protection Effects 0.000 description 1
229940121649 protein inhibitor Drugs 0.000 description 1
239000012268 protein inhibitor Substances 0.000 description 1
230000006916 protein interaction Effects 0.000 description 1
230000005588 protonation Effects 0.000 description 1
230000036593 pulmonary vascular resistance Effects 0.000 description 1
235000021251 pulses Nutrition 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
KNXKVYCVGXFLES-UHFFFAOYSA-N pyridine-2-carboximidamide Chemical compound NC(=N)C1=CC=CC=N1 KNXKVYCVGXFLES-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
238000011555 rabbit model Methods 0.000 description 1
229960003401 ramipril Drugs 0.000 description 1
HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
208000036273 reactive airway disease Diseases 0.000 description 1
108091006084 receptor activators Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000000306 recurrent effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000033904 relaxation of vascular smooth muscle Effects 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
210000005241 right ventricle Anatomy 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
235000003441 saturated fatty acids Nutrition 0.000 description 1
150000004671 saturated fatty acids Chemical class 0.000 description 1
230000037390 scarring Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000012106 screening analysis Methods 0.000 description 1
230000000580 secretagogue effect Effects 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
239000000849 selective androgen receptor modulator Substances 0.000 description 1
239000003751 serotonin 6 antagonist Substances 0.000 description 1
230000035939 shock Effects 0.000 description 1
238000004088 simulation Methods 0.000 description 1
238000010583 slow cooling Methods 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
229940029258 sodium glycinate Drugs 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
WUWHFEHKUQVYLF-UHFFFAOYSA-M sodium;2-aminoacetate Chemical compound [Na+].NCC([O-])=O WUWHFEHKUQVYLF-UHFFFAOYSA-M 0.000 description 1
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
229960000553 somatostatin Drugs 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
238000005507 spraying Methods 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
229940114926 stearate Drugs 0.000 description 1
102000005969 steroid hormone receptors Human genes 0.000 description 1
108020003113 steroid hormone receptors Proteins 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000003860 storage Methods 0.000 description 1
210000004003 subcutaneous fat Anatomy 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
229940071103 sulfosalicylate Drugs 0.000 description 1
230000001629 suppression Effects 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
230000008961 swelling Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
229950001362 tebutate Drugs 0.000 description 1
150000003505 terpenes Chemical class 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
229960003604 testosterone Drugs 0.000 description 1
229940063296 testosterone and estrogen Drugs 0.000 description 1
BJQWBACJIAKDTJ-UHFFFAOYSA-N tetrabutylphosphanium Chemical compound CCCC[P+](CCCC)(CCCC)CCCC BJQWBACJIAKDTJ-UHFFFAOYSA-N 0.000 description 1
DFQPZDGUFQJANM-UHFFFAOYSA-M tetrabutylphosphanium;hydroxide Chemical compound [OH-].CCCC[P+](CCCC)(CCCC)CCCC DFQPZDGUFQJANM-UHFFFAOYSA-M 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
239000003451 thiazide diuretic agent Substances 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
230000008719 thickening Effects 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
239000005495 thyroid hormone Substances 0.000 description 1
229940036555 thyroid hormone Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
230000007704 transition Effects 0.000 description 1
230000005945 translocation Effects 0.000 description 1
230000032258 transport Effects 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
150000004684 trihydrates Chemical class 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
229920003169 water-soluble polymer Polymers 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
239000008096 xylene Substances 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
238000011680 zucker rat Methods 0.000 description 1
238000011683 zucker rat (lean) Methods 0.000 description 1