- COMPOSITION AND METHODS OF USE OF TETRAHYDROISOQUINOLINE SMALL MOLECULES TO BIND AND MODULATE PCSK9 PROTEIN ACTIVITY
-
This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds
- -
-
Page/Page column 40; 41
(2017/03/14)
-
- IMMUNE ADJUSTMENT COMPOUND, USE THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
-
The present invention provides a compound represented by formula I, wherein R is a halogen element or a C1-C6 alkyl group. The compound has S1 P1 receptor agonist activity and selective specificity and has obviously-shortened half-life in-vivo, and therefore the compound is a high-quality second-generation S1P1 receptor agonist. The present invention also provides a use of the compound in preparing medicine for treating diseases or symptoms mediated by an S1P1 receptor, a pharmaceutical composition comprising the compound, and uses of the compound and the pharmaceutical composition in treating diseases or symptoms mediated by the S1 P1 receptor.
- -
-
Paragraph 0091; 0092
(2016/08/29)
-
- SPIROCYCLIC COMPOUNDS AS TRYPTOPHAN HYDROXYLASE INHIBITORS
-
The present invention is directed to spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.
- -
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Page/Page column 263; 264
(2015/03/28)
-
- Modulators of methyl modifying enzymes, compositions and uses thereof
-
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
- -
-
Page/Page column 175; 176
(2015/12/26)
-
- PYRROLIDINE GPR40 MODULATORS
-
The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, or a solvate thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.
- -
-
Page/Page column 55
(2015/11/27)
-
- 4-{4-[(1 E)-4-(2,9-DIAZASPIRO[5.5]UNDEC-2-YL)BUT-1 -EN-1 -YL]-2-METHYLBENZYL}-5-(PROPAN-2-YL)-1 H-PYRAZOL-3-YL BETA-D- GLUCOPYRANOSIDE ACETATE
-
The present invention provides a compound of Formula I or hydrate thereof, useful for the treatment of diabetes.
- -
-
Page/Page column 8
(2015/05/26)
-
- SERINE/THREONINE KINASE INHIBITORS
-
Compounds having the formula I wherein R1, R2, R3, R4, R5, Ra, Rb, Rc, Rd, Re, n, r, s and t are as defined herein and which compounds are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.
- -
-
Paragraph 0333; 0332
(2015/02/19)
-
- FUSED TRICYCLIC AMIDE COMPOUNDS AS MULTIPLE KINASE INHIBITORS
-
Provided are fused tricyclic amide compounds, pharmaceutical compositions comprising at least one such fused tricyclic compound, processes for the preparation thereof, and the use thereof in therapy. Disclosed herein are certain tricyclic amide compounds that can be useful for inhibiting multiple (specifically BRAF and/or EGFR-T790M) kinases and for treating disorders mediated thereby.
- -
-
Page/Page column 114
(2015/01/16)
-
- PAR2 RECEPTOR ANTAGONISTS
-
Compounds of formula (I) or pharmaceutically acceptable salts, solvates or hydrates thereof wherein P, Q, X, Y, R1, R2, R3, R10, R11, and R12 are as defined in the claims, and the use those compounds in medicine.
- -
-
Page/Page column 33
(2014/02/16)
-
- RECEPTOR ANTAGONISTS
-
N-(4-carbamimidoylphenyl)-amide derivatives having utility in therapy as PAR2 receptor antagonists.
- -
-
Page/Page column 19
(2014/02/16)
-
- DIHYDROPYRAZOLE GPR40 MODULATORS
-
The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.
- -
-
Paragraph 00280
(2014/06/11)
-
- NOVEL UREA COMPOUNDS
-
The present invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0020; 0022
(2014/04/18)
-
- 8-ETHYL-6-(ARYL)PYRIDO [2,3-D]PYRIMIDIN-7(8H) -ONES FOR THE TREATMENT OF NERVOUS SYSTEM DISORDERS AND CANCER
-
Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders or neurofibromatosis. Also described herein are methods of utilizing PAK inhibitors for the treatment of cancer.
- -
-
Paragraph 00618
(2013/04/10)
-
- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
-
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein
- -
-
Paragraph 00357; 00358
(2013/06/05)
-
- NOVEL PYRAZOLE COMPOUNDS
-
The present invention provides a compound of Formula II: wherein X represents the following: or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0024; 0025
(2013/11/19)
-
- Oxidative cyclizations, the synthesis of aryl-substituted c-glycosides, and the role of the second electron transfer step
-
Anodic oxidation reactions have been used to synthesize aryl- and biaryl-substituted C-glycosides. The reactions take advantage of the tendency for alcohol nucleophiles to trap nonpolar radical cations. The addition of the alcohol to the radical cation appears to be reversible, and the success of the cyclizations is dependent on the ease with which the resulting benzylic radical is oxidized.
- Smith, Jake A.,Moeller, Kevin D.
-
supporting information
p. 5818 - 5821
(2013/12/04)
-
- ALPHA, ALPHA - DI SUBSTITUTED GLYCINE ESTER DERIVATIVES AND THEIR USE AS HDAC INHIBITORS
-
Compounds selected from the following group and their salts are inhibitors of HDAC activity, useful in the treatment of, inter alia, cell proliferative disease and inflammation: Cyclopentyl 1 -[({5-[(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]pyridin-2- yl}methy)amino]cyclopropanecarboxylate; Cyclopentyl 1 -[({5-[(1E)-3-(hydroxyamino)-3- oxoprop-1-en-1-yl]pyridin-2-yl}methy)amino]cyclobutanecarboxylate; Cyclopentyl 1-[({5- [(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]pyridin-2yl}methyl)amino]- cyclopentanecarboxylate; Cyclopentyl 1-[({5-[(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1- yl]pyridin-2-yl}methyl)amino]cyclohexanecarboxylate; Cyclopentyl 4-[({5-[(1E)-3- (hydroxyamino)-3-oxoprop-1 -en-1 -yl]pyridin-2-yl}methyl)amino]tetrahydro-2H-pyran-4- carboxylate; Cyclopentyl 4-[({6-[(1E)-3-{[1 -(2-methylpropoxy)ethoxy]amino}-3-oxoprop-1 - en-1 -yl]pyridin-3-yl}methyl)amino]tetrahydro-2H-pyran-4-carboxylate; Cyclopentyl 1 -({4- [(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]-2-methylbenzyl}amino)- cyclohexanecarboxylate; Cyclopentyl 1-({4-[(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]- 2-methylbenzyl}amino)cyclopentanecarboxylate; Cyclopentyl 1-({4-[(1E)-3- (hydroxyamino)-3-oxoprop-1-en-1-yl]-2-methylbenzyl}amino)cyclobutanecarboxylate; Methylcyclopentyl 4-[({6-[(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]pyridin-3- yl}methyl)amino]tetrahydro-2H-pyran-4-carboxylate; Cyclopentyl 4-{[1 -({6-[(1E)-3- (hydroxyamino)-3-oxoprop-1-en-1-yl]pyridin-3-yl}methyl)piperidin-4-yl]amino}tetrahydro- 2H-pyran-4-carboxylate; Cyclopentyl 4-{[1-({5-[(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1- yl]pyridin-2-yl}methyl)piperidin-4-yl]amino}tetrahydro-2H-pyran-4-carboxylate; Cyclopentyl 4-({4-[(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]benzyl}amino)tetrahydro- 2H-pyran-4-carboxylate; Cyclopentyl 4-({3-[(1E)-3-(hydroxyamino)-3-oxoprop-1 -en-1 - yl]benzyl}amino)tetrahydro-2H-pyran-4-carboxylate; and (3R)-Tetrahydrofuran-3-yl N-{4- [(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]benzyl}-2-methyl-D-leucinate.
- -
-
Page/Page column 30
(2012/03/26)
-
- Novel Spiropiperidine Compounds
-
A compound of the formula: or a pharmaceutically acceptable salt thereof as well as a pharmaceutical composition, and a method for treating diabetes.
- -
-
Page/Page column 11
(2011/05/03)
-
- C-LINKED HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS
-
The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.
- -
-
Page/Page column 39-40
(2011/05/05)
-
- THIAZOLE COMPOUNDS AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE
-
Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, C1-4alkyl, C1-4alkoxy, CF3 and OCF3; -Y- represents formula (IA) R3 represents hydrogen, fluoro, chloro or C1-4alkyl; R4a and R4b each independently represent hydrogen, C1-4alkyl, C1-4alkoxy, CF3 or halo; and R5 represents a group Z-X; wherein Z is absent or represents (CH2)2 or O; and X represents formula (IB) wherein: J and L both represent CH, or one of J and L represents CH and the other represents N; when both J and L represent CH, R6 represents hydrogen, halo, CF3, C1-4alkyl or C1-4alkoxy in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, OCF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; or when one of J or L represents N, R6 represents hydrogen or halo in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; and R8 and R9 are independently selected from hydrogen and C1-4alkyl; or salts thereof which activate soluble guanylate cyclase (sGC), pharmaceutical compositions containing them, their use in medicine, and processes for their preparation.
- -
-
Page/Page column 37
(2010/04/03)
-
- PYRIMIDINE DERIVATIVES AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE
-
Disclosed are compounds of formula (I) and or salts thereof which activate soluble guanylate cyclase (sGC), pharmaceutical compositions containing them, their use in the manufacture of a medicament for teating cardiovascular diseases, and processes for their preparation.
- -
-
Page/Page column 40
(2010/04/03)
-
- OXADIAZOLE DERIVATIVES
-
The invention relates to compounds of formula (I); wherein R1, R2, Ra, Rb, W, Q and S have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple
- -
-
Page/Page column 91
(2010/11/03)
-
- SUBSTITUTED IMIDAZOLONE DERIVATIVES, PREPARATIONS AND USES
-
The present invention relates to polysubstituted imidazolone derivatives, to the pharmaceutical compositions comprising them and to the therapeutic uses thereof in the human and animal health fields. The present invention also relates to a process for preparing these derivatives.
- -
-
Page/Page column 59-60; 64
(2010/02/16)
-
- Theramutein modulators
-
This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.
- -
-
Page/Page column 191
(2010/02/17)
-
- NOVEL COMPOUNDS AS ANTAGONISTS OR INVERSE AGONISTS FOR OPIOID RECEPTORS
-
This invention relates to novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy.
- -
-
Page/Page column 92
(2010/09/07)
-
- 2,6-DISUBSTITUTED PYRIDINES AS SOLUBLE GUANYLATE CYCLASE ACTIVATORS
-
Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, CF3, C1-4alkyl and allyl; Y represents (II), (III), (IV) or (V) wherein R3 represents CF3 or C1-4alkyl; and R3a represents CF3 or C1-4alkyl.
- -
-
Page/Page column 66
(2009/07/17)
-
- RENIN INHIBITORS
-
The present invention relates to biphenyl compounds of formula (I). These compounds are renin inhibitors of a non- peptidic nature and of low molecular weight. The invention further relates to a pharmaceutical composition containing said compounds, as wel
- -
-
Page/Page column 23
(2009/04/25)
-
- HETEROCYCLIC COMPOUND
-
[Object] To provide a novel compound having an excellent immunosuppressive activity with low toxicity or a pharmacological salt thereof. [Means to achieve the object] A compound having general formula (I) shown below or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable prodrug thereof [wherein A represents a carboxyl group, or the like, B represents a hydrogen atom, or the like, V represents a single bond, a methylene group, or the like, n represents an integer of from 0 to 2, W represents a 5- to 7-membered heterocyclic group, or the like, Z represents a group selected from Substituent group A, or the like, and Substituent group A represents the group consisting of a halogen atom, a C1-C6 alkyl group, a C3-C7 cycloalkyl group.
- -
-
Page/Page column 97
(2010/11/29)
-
- BENZIMIDAZOLE DERIVATIVES USEFUL IN TREATMENT OF VALLINOID RECE TOR TRPVL RELATED DISORDERS
-
The claimed invention provides benzimidazole derivatives antagonists of VRl, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds of Formula I may be used in the treatment of osteoarthritis,
- -
-
Page/Page column 61
(2008/06/13)
-
- ARYLSULFONYL PYRROLIDINES AS 5-HT6 INHIBITORS
-
This invention relates to substituted pyrrolidine compounds of the formula I wherein m, n, Ar, R1 and R2 are as defined herein. Methods of making the compounds and using the compounds are disclosed.
- -
-
Page/Page column 54
(2008/12/05)
-
- THERAMUTEIN MODULATORS
-
This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.
- -
-
Page/Page column 225
(2008/12/07)
-
- QUINOXALINE DERIVATIVES AS INHIBITORS OF THE TYROSINE KINASE ACTIVITY OF JANUS KINASES
-
The present invention relates to quinoxaline compound of the formula (I): wherein R1 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R7; R2 is carbocyclyl or heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R8; R3, R4, R5 and R6 are each independently hydrogen or R9; and R7, R8 and R9 are each independently selected from organic and inorganic substituents, their use in therapy of diseases, in particular diseases mediated by the tyrosine kinase activity of Janus kinases, including JAK-2 and JAK-3 kinases
- -
-
Page/Page column 38
(2009/01/24)
-
- 5-Aryl-indan-1-ol and analogs useful as progesterone receptor modulators
-
Compounds of formula I are provided, wherein R1-R9 and n are defined herein, and pharmaceutical compositions and kits containing these compounds. Also provided are methods of inducing contraception, providing hormone replacement ther
- -
-
Page/Page column 17
(2010/11/26)
-
- BENZENE COMPOUND HAVING 2 OR MORE SUBSTITUENTS
-
A superior LXR modulator is provided. A compound represented by the general formula (I): [wherein R1: -COR9 (wherein R9: alkyl, optionally substituted alkoxy or optionally substituted amino); R2: H, OH, alkoxy, optionally substituted amino, etc.; R3: H, optionally substituted alkyl, cycloalkyl, optionally substituted alkoxy, optionally substituted amino, halogeno, etc.; R4 and R5: H, optionally substituted alkyl, halogeno, etc.; R6 and R7: H, alkyl; R8: -X2R10 [wherein R10: -COR11 (wherein R11 : OH, optionally substituted alkoxy, optionally substituted amino, etc.), -SO2R12 (wherein R12: optionally substituted alkyl, optionally substituted amino, etc.), tetrazol-5-yl, etc.; X2: single bond, optionally substituted alkylene, etc.]; X1: -NH-, -O-, -S-, etc.; Y1: optionally substituted phenyl, optionally substituted 5- to 6-membered aromatic heterocyclyl; Y2: optionally substituted aryl, optionally substituted heterocyclyl, etc.] and the like is provided.
- -
-
-
- INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME
-
The present invention provides compounds of formula (4), and their pharmaceutically acceptable salts and solvates, which are useful as inhibitors of the Hepatitis C virus (HCV) polymerase enzyme and are also useful for the treatment of HCV infections in HCV-infected mammals. The present invention also provides pharmaceutical compositions comprising compounds of formula (4), their pharmaceutically acceptable salts and solvates. Furthermore, the present invention provides intermediate compounds and methods useful in the preparation of compounds of formula (4).
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-
Page/Page column 163-164
(2008/06/13)
-
- Optimization of sulfonamide derivatives as highly selective EP1 receptor antagonists
-
A series of 4-[(2-{isobutyl[(5-methyl-2-furyl)sulfonyl]amino}phenoxy)methyl]benzoic acids and 4-({2-[isobutyl(1,3-thiazol-2-ylsulfonyl)amino]phenoxy}methyl)benzoic acids were synthesized and evaluated for their EP receptor affinities and EP1 receptor anta
- Naganawa, Atsushi,Matsui, Toshiaki,Ima, Masaki,Yoshida, Koji,Tsuruta, Hiroshi,Yamamoto, Shingo,Yamamoto, Hiroshi,Okada, Hiroki,Maruyama, Takayuki,Nakai, Hisao,Kondo, Kigen,Toda, Masaaki
-
p. 7774 - 7789
(2007/10/03)
-
- PYRAZOLE DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF, AND INTERMEDIATE FOR PRODUCTION THEREOF
-
The present invention provides pyrazole derivatives represented by the general formula: wherein R1 represents H, an optionally substituted C1-6 alkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted C1-6 alkyl group etc.; R2 represents H, a halogen atom, OH, an optionally substituted C1-6 alkyl group etc.; X represents a single bond, O or S; Y represents a single bond, a C1-6 alkylene group etc. ; Z represents CO or SO2; R4 and R5 represent H, an optionally substituted C1-6 alkyl group etc.; and R3, R6 and R7 represent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.
- -
-
Page/Page column 46
(2008/06/13)
-
- PYRAZOLE DERIVATIVES, MEDICINAL COMPOSITION CONTAINING THE SAME, MEDICINAL USE THEREOF, AND INTERMEDIATE FOR PRODUCTION THEREOF
-
The present invention provides pyrazole derivatives represented by the general formula: wherein R1 represents H, an optionally substituted C1-6 alkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted C1-6 alkyl group etc.; R2 represents H, a halogen atom, OH, an optionally substituted C1-6 alkyl group etc.; X represents a single bond, O or S; Y represents an optionally substituted C1-6 alkylene group etc.; Z represents -RB, -CORC etc. in which RB represents an optionally substituted C1-6 alkyl group etc.; and RC represents an optionally substituted C1-6 alkyl group etc.,; R4 represents H, an optionally substituted C1-6 alkyl group etc.; and R3, R5 and R6 represent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, impaired glucose tolerance, impaired fasting glycemia, diabetic complications or obesity, and a disease associated with the increase of blood galactose level such as galactosemia, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.
- -
-
Page/Page column 108
(2010/02/12)
-
- AROYL-PIPERAZINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS TACHYKININ ANTAGONISTS
-
This invention relates to piperazine derivatives of formula (I), wherein Y is bond or lower alkylene, R1 is aryl which may have substituent(s), R2 is aryl or indolyl, each of which may have substituent(s), R3 is hydrogen or lower alkyl, and R4 is as defined in the description, and its pharmaceutically acceptable salt, to processes for preparation thereof, to pharmaceutical composition comprising the same, and to a use of the same for treating or preventing Tachykinin-mediated diseases in human beings or animals. 1
- -
-
-
- Compounds having activity as inhibitors of cytochrome P450RAI
-
Compounds having Formula 1 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.
- -
-
Page column 120
(2010/01/31)
-
- Compounds having activity as inhibitors of cytochrome P450RAI
-
Compounds having Formula 2 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.
- -
-
Page column 118
(2010/01/31)
-
- Compounds having activity as inhibitors of cytochrome P450RAI
-
Compounds having Formula 8 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.
- -
-
Page column 43, 119
(2010/11/29)
-
- Methods of providing and using compounds having activity as inhibitors of cytochrome P450RAI
-
Novel compounds having the Formulas 1 through 8, wherein the symbols have the meaning defined in the specification, and certain previously known compounds have been discovered to act as inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids. The compound can also be used in co-treatment with retinoids.
- -
-
-
- Compounds having activity as inhibitors of cytochrome P450RAI
-
Compounds having Formula 1 wherein the symbols have the meaning defined in the specification are inhibitors of the cytochrome P450RAI (retinoic acid inducible) enzyme, and are used for treating diseases responsive to treatment by retinoids.
- -
-
-
- Trisubstituted biphenyls
-
Antihypertensive and antiatherosclerotic trisubstituted biphenyls of the formula STR1 in which R1 represents a carboxyl radical or represents a C1 -C8 -alkoxycarbonyl radical, R2 represents straight-chain or bra
- -
-
-
- Conformationally Restricted Retinoids
-
A series of conformationally restricted retinoids was synthesized and screened in two assays used to measure the ability of retinoids to control cell differentiation, namely, the reversal of keratinization in tracheal organ culture from vitamin A deficient hamsters and the inhibition of the induction of mouse epidermal ornithine decarboxylase by a tumor promoter.These compounds had bonds corresponding to selected bonds of the E-tetraene chain of retinoic acid (1) held in a planar cisoid conformation by inclusion in an aromatic ring.The meta-substituted analogue 3 of 4-benzoic acid (2) was far less active than 2 in both assays.In contrast, the vinyl homologue of 2 (4) and the 7,8-dihydro and 7,8-methano analogues (5 and 6) had activity comparable to that of 2.Analogues of 4-benzoic acid (7) were also screened.Replacement of the tetrahydronaphthalene ring of 7 by a benzonorbornenyl group (9) significantly reduced activity, as did removal of the vinylic methyl group from 9 (10).Replacement of the propenyl group of 9 by a cyclopropane ring (12) also reduced activity.Replacement of the tetrahydronaphthalene ring of 7 by 4,4-dimethyl-3,4-dihydro-2H-1-benzopyran and -benzothiopyran rings (13 and 14) also decreased activity.Inclusion of the 7,9 double bond system of 1 in an aromatic ring (15 and 16) reduced activity, whereas inclusion of the 5,7 double bond system in an aromatic ring enhanced activity (7 and 19).Inclusion of the 11,13 and 9,11,13 double bond systems in aromatic rings (2 and 18) also reduced activity below that of 1.Retinoic acid, 7, 13, 14, and 19 inhibited papilloma tumor formation in mice.Toxicity testing indicated that 7 was more toxic than 1, 13, 14, and 19, 19 was more toxic than 1, and 13 and 14 were less toxic than 1.
- Dawson, Marcia I.,Hobbs, Peter D.,Derdzinski, Krzysztof,Chan, Rebecca L.-S.,Gruber, John,et al.
-
p. 1516 - 1531
(2007/10/02)
-