- PIPERIDINYL- AND PIPERAZINYL-SUBSTITUTED HETEROAROMATIC CARBOXAMIDES AS MODULATORS OF GPR6
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Disclosed are compounds of Formula 1 and pharmaceutically acceptable salts thereof, wherein L, R4, R5, R8, R10, R11, X1, X2, X3, X9, X12, and Z are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with GPR6.
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Paragraph 0302; 0308
(2018/10/25)
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- SUBSTITUTED IMIDAZOLES AS N-TYPE CALCIUM CHANNEL BLOCKERS
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Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, and G are defined herein.
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Page/Page column 50
(2015/02/25)
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- SUBSTITUTED IMIDAZOLES AS N-TYPE CALCIUM CHANNEL BLOCKERS
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Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, and G are defined herein.
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Paragraph 0316-0317
(2015/02/25)
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- MTP INHIBITING TETRAHYDRO-NAPHTHALENE-1-CARBOXYLIC ACID DERIVATIVES
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The present invention is concerned with novel tetrahydro-naphthalene-1-carboxylic acid derivatives having apoB secretion/MTP inhibiting activity and concomitant lipid lowering activity. The invention further relates to methods for preparing such compounds
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Page/Page column 29; 30; 31; 32
(2008/12/05)
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- Novel potent and selective Ca2+ release-activated Ca2+ (CRAC) channel inhibitors. Part 3: Synthesis and CRAC channel inhibitory activity of 4′-[(trifluoromethyl)pyrazol-1-yl]carboxanilides
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From a series of 4'-[(trifluoromethyl)pyrazol-1-yl]carboxanilides derived from 4-methyl-4'-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,3-thiadiazole-5-carboxanilide, one inhibited thapsigargin-induced Ca2+ influx in Jurkat T cells (IC50 = 77 nM) and exhibited high selectivity for the CRAC channel over the VOC channel (index: >130). Another acted as an inhibitor for both T lymphocyte activation-induced diseases and ovalbumin-induced airway eosinophilia in rats (ED50 = 1.3 mg/kg) p.o.
- Yonetoku, Yasuhiro,Kubota, Hirokazu,Miyazaki, Yoji,Okamoto, Yoshinori,Funatsu, Masashi,Yoshimura-Ishikawa, Noriko,Ishikawa, Jun,Yoshino, Taiji,Takeuchi, Makoto,Ohta, Mitsuaki
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experimental part
p. 9457 - 9466
(2009/04/07)
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- PIPERIDINE OR PIPERAZINE SUBSTITUTED TETRAHYDRO-NAPHTHALENE-1-CARBOXYLIC ACID MTP INHIBITING COMPOUNDS
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The present invention is concerned with novel piperidine or piperazine substituted tetrahydro-naphthalene-1-carboxylic acid derivatives having apoB secretion/MTP inhibiting activity and concomitant lipid lowering activity. The invention further relates to
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Page/Page column 37
(2008/12/05)
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- (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6- (trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (YM580) as an orally potent and peripherally selective nonsteroidal androgen receptor antagonist
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A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that compound 33 was a potent AR antagonist, and subsequent optical resolution provided (+)-(2R,5S)4-[4-cyano-3-(trifluoromethyl)phenyl]-2, 5-dimethyl-N-[6(triflouromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound 33a decreased the weight of rat ventral prostate in a dose-dependent manner (ED50 = 2.2 mg/kg/day), and induced the maximum antiandrogenic effect, comparable to that of surgical castration, without significantly affecting serum testosterone levels. Compound 33a is a promising clinical candidate for prostate cancer monotherapy.
- Kinoyama, Isao,Taniguchi, Nobuaki,Toyoshima, Akira,Nozawa, Eisuke,Kamikubo, Takashi,Imamura, Masakazu,Matsuhisa, Akira,Samizu, Kiyohiro,Kawanimani, Eiji,Niimi, Tatsuya,Hamada, Noritaka,Koutoku, Hiroshi,Furutani, Takashi,Kudoh, Masafumi,Okada, Minoru,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
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p. 716 - 726
(2007/10/03)
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