- SUBSTITUTED BICYCLE HETEROCYCLIC DERIVATIVES USEFUL AS ROMK CHANNEL INHIBITORS
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Disclosed are compounds of Formula (I) or a salt thereof, wherein R1 is (II) or (III); each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3, L1, L2, R1a, R1b, R1c, and n are define herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
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Page/Page column 112; 113
(2018/06/06)
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- SUBSTITUTED NITROGEN CONTAINING COMPOUNDS
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Disclosed are compounds of Formula (I): or a salt thereof, Formula (II) wherein R1 is: or; each W is independently NR1b or O; Z is a bond or CHR1d; and R1, R2, Rd, R3a, R3b, L1, B, V, Y, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of ROMK, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating cardiovascular diseases.
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Page/Page column 90; 91
(2019/01/05)
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- 2,3-DIARYL- OR HETEROARYL-SUBSTITUTED 1,1,1-TRIFLUORO-2-HYDROXYPROPYL COMPOUNDS
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The present invention relates to compounds of formula I wherein R1a to R1c, R2, R3 and R5 are as defined in the description and claims and R4 signifies a bicyclic heteroaryl group or a cyanophenyl group, as well as pharmaceutically acceptable salts thereof. The compounds are glucocorticoid receptor antagonists useful for the treatment and/or prevention of diseases such as diabetes, dyslipidemia, obesity, hypertension, cardiovascular diseases, adrenal imbalance or depression.
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Page/Page column 64
(2010/10/19)
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- Cancer chemotherapy: A paclitaxel prodrug for ADEPT (Antibody-Directed Enzyme Prodrug Therapy)
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A glucuronide-based prodrug of paclitaxel (taxol) has been synthesized for use in antibody-directed enzyme prodrug therapy (ADEPT). This three-component prodrug was obtained by coupling a glucuronyl derivative of N-methylamino 4-nitrophenol (10) to the 2′-hydroxy group of the side-chain of paclitaxel through an aromatic carbamate. Once deprotected, prodrug 2 was shown to be relatively stable in human serum, and to be significantly less cytotoxic (IC50 = 65 μM and 90 nM, respectively) than the parent drug. As expected, compound 2 efficiently releases taxol in the presence of β-glucuronidase.
- Schmidt, Frederic,Ungureanu, Ioana,Duval, Romain,Pompon, Alain,Monneret, Claude
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p. 2129 - 2134
(2007/10/03)
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- Glucuronide prodrugs of hydroxy compounds for antibody directed enzyme prodrug therapy (adept): A phenol nitrogen mustard carbamate
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A prodrug consisting of a β-D-glucuronic acid linked to a self-immolative spacer (a N-(ortho-hydroxyphenyl)-N-methylcarbamate) and a phenolic nitrogen mustard was synthesised. As this prodrug was easily cleaved by a β-glucuronidase enzyme and displayed lo
- Schmidt,Florent,Monneret,Straub,Czech,Gerken,Bosslet
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p. 1071 - 1076
(2007/10/03)
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