ZA200505934B - Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors - Google Patents

Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors Download PDF

Info

Publication number
ZA200505934B
ZA200505934B ZA200505934A ZA200505934A ZA200505934B ZA 200505934 B ZA200505934 B ZA 200505934B ZA 200505934 A ZA200505934 A ZA 200505934A ZA 200505934 A ZA200505934 A ZA 200505934A ZA 200505934 B ZA200505934 B ZA 200505934B
Authority
ZA
South Africa
Prior art keywords
formula
product
alkyl
radicals
optionally substituted
Prior art date
Application number
ZA200505934A
Inventor
Patek Marcel
Hittinger Augustin
Bond Daniel
Bouchard Herve
Malleron Jean-Luc
Al-Obeidi Fahad
Strobel Hartmut
Ritter Kurt
Lesuisse Dominique
Nair Anil
Conception Nemecek
Harlow Greg
Mauger Jacques
Palermo Mark
Faitg Thomas
Ruf Sven
El-Ahmad Youssef
Benard Didier
Original Assignee
Aventis Pharma Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Aventis Pharma Sa filed Critical Aventis Pharma Sa
Publication of ZA200505934B publication Critical patent/ZA200505934B/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Neurology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Description

®
The present invention also relates to novel FAK receptor inhibitors that may be used for oncology treatments.
The present invention also relates to novel AKT receptor inhibitors that may be used for oncology treatments. :
Cancer remains a disease for which the existing treatments are clearly insufficient. Certain protein kinases, especially including IGF-1R (Insulin Growth
Factor 1 Receptor), play an important role in many cancers. The inhibition of such protein kinases is potentially important in the chemotherapy of cancers, especially for suppressing the growth or survival of tumors. The present invention thus relates to the E identification of novel products that inhibit such protein kinases. :
Protein kinases participate in signaling events that : control the activation, growth and differentiation of ‘ cells in response either to extracellular mediators or to changes in the environment. In general, these kinases oo belong to two groups: those that preferentially phosphorylate serine and/or threonine residues and those that preferentially phosphorylate tyrosine residues (S.K. Hanks and T. Hunter, FASEB. J., 1995, 9, pages 576- 596]. The serine/threonine kinases are, for example, the isoforms of the protein kinases C [A.C. Newton, J. Biol.
Chem., 1995, 270, pages 28495-28498] and a group of cycline-dependent kinases, for instance cdc2 [J. Pines,
Trends in Biochemical Sciences, 1995, 18, pages 195-197).
Tyrosine kinases comprise growth factor receptors, for instance the epidermal growth factor (EGF) receptor [S. Iwashita and M. Kobayashi, Cellular Signalling, 1992, 4, pages 123-132], and cytosol kinases, for instance pS6tck, p59f¥Yn and ZAP-70 and the kinases csk [C. Chan et. al., Ann. Rev. Immunol., 1994, 12, pages 555-592].
® : . Abnormally high levels of kinase protein activity : have been implicated in many diseases, resulting from abnormal cellular functions. This may arise either directly or indirectly from a dysfunction in the mechanisms for controlling the kinase activity, linked, for example, to a mutation, an overexpression or an inappropriate activation of the enzyme, or an over- or underproduction of cytokines or of growth factors, also involved in the transduction of the signals upstream or downstream of the kinases. In all these cases, a selective inhibition of the action of the kinases offers hope of a beneficial effect.
The type 1 receptor for in the insulin-like growth factor (IGF-I-R) is a transmembrane receptor with tyrosine kinase activity which binds firstly to IGFI, but also to IGFII and to insulin with lower affinity. The binding of IGF1 to its receptor results in oligomerization of the receptor, the activation of tyrosine kinase, intermolecular autophosphorylation and the phosphorylation of cell substrates (main substrates:
IRS1 and Shc). The receptor activated by its ligand induces mitogenic activity in normal cells. However,
IGF-I-R plays an important role in “abnormal” growth.
Several «clinical reports underline the important role of the: IGF-I route in the development of human: cancers:
IGF-I-R is often found overexpressed in many types of tumor (breast, colon, lung, sarcoma, etc.) and its presence 1s often associated with a more aggressive phenotype.
High concentrations of circulating IGF1l are strongly correlated with a risk of prostate cancer, lung cancer and breast cancer.
Furthermore, it has been widely documented that
IGF-I-R is necessary for establishing and maintaining the transformed phenotype in vitro as in vivo [Baserga R,
eo
Exp. Cell. Res., 1999, 253, pages 1-6]. The kinase activity of IGF-I-R is essential for the transformation activity of several oncogenes: EGFR, PDGFR, the large T antigen of the SV40 virus, activated Ras, Raf, and v-Src.
The expression of IGF-I-R in normal fibroblasts induces a neoplastic phenotype, which may then result in the formation of a tumor in vivo. The expression of IGF-I-R plays an important role in substrate-independent growth.
IGF-I-R has also been shown to be a protector in chemotherapy-induced and radiation-induced apoptosis, and cytokine-induced apoptosis. Furthermore, the inhibition of endogenous IGF-I-R with a negative dominant, the formation of a triple helix or the expression of an antisense sequence brings about suppression of the R transforming activity in vitro and reduction of tumor growth in animal models.
Among the kinases for which a modulation of the : activity is desired, FAK (Focal Adhesion Kinase) is also : a preferred kinase.
FAK is a cytoplasmic tyrosine kinase that plays an on important role in tranducing the signal transmitted by the integrins, a family of heterodimeric receptors of cellular adhesion. FAK and the integrins are colocalized in perimembrane structures known as adhesion plaques. It has been shown in many cell types that the activation of
FAK and its phosphorylation on tyrosine residues and in particular its autophosphorylation on tyrosine 397 were dependent on the binding of the integrins to their extracellular ligands and thus induced during cellular adhesion [Kornberg L, and al. J. Biol. Chem. 267(33): 23439-442 (1992)]. The autophosphorylation on tyrosine 397 of FAK represents a binding site for another tyrosine kinase, Src, via its SH2 domain [Schaller et al. Mol.
Cell. Biol. 14 : 1680-1688 1994 ; Xing et al. Mol. Cell.
Biol. 5 : 413-421 1994]. Src can then phosphorylate FAK on tyrosine 925, thus recruiting the adapter protein Grb2 o 5 and. inducing in: certain cells activation of the ras and
MAP kinase pathway involved in controlling cellular proliferation [Schlaepfer et al. Nature ; 372 : 786-791 1994; Schlaepfer et al. Prog. Biophy. Mol. Biol. 71: 435- 478 1999 ; Schlaepfer and Hunter, J. Biol. Chem. 272: 13189-13195 1997].
The activation of FAK can thus induce the jun NH2- terminal kinase (JNK) signaling pathway and result in the progression of the cells to the Gl phase of the cellular cycle [Oktay et al., J. Cell. Biol.145: 1461-1469 1999].
Phosphatidylinositol-3-OH kinase (PI3-kinase) also binds to FAK on tyrosine 397 and this interaction might be necessary for the activation of PI3-kinase [Chen and
Guan, Proc. Nat. Acad. Sci. USA. 91: 10148-10152 1994;
Ling et al. J. Cell. Biochem. 73: 533-544 1999]. The
FAK/Src complex phosphorylates various substrates, for instance paxillin and pl30CAS in fibroblasts ([Vuori et al. Mol. Cell. Biol. 16: 2606-2613 1996].
The results of numerous studies support the hypothesis that FAK inhibitors might be useful in treating cancer. Studies have suggested that FAK might play an important role in in vitro cell proliferation and/or survival. For example, in CHO cells, certain authors have demonstrated that the overexpression of pl25FAK induces an acceleration of the Gl to § transition, suggesting that pl25FAK promotes cellular proliferation (Zhao J.-H et al. J. Cell Biol. 143: 1997- 2008 139%8]. Other authors have shown that tumor cells treated with FAK antisense oligonucleotides lose their adhesion and go into apoptosis (Xu et al, Cell Growth
Differ. 4: 413-418 1996). It has also been demonstrated that FAK promotes the migration of cells in vitro. Thus, fibroblasts that are deficient for the expression of FAK (“knockout” mice for FAK) show a rounded morphology and deficiencies in cell migration in response to chimiotactic signals, and these defects are suppressed by
® reexpression of FAK [DJ. Sieg et al., J. Cell Science. 112: 2677-91 1999]. The overexpression of the C-terminal domain of FAK (FRNK) blocks the stretching of adherent cells and reduces cellular migration in vitro [Richardson
A. and Parsons J.T. Nature. 380: 538-540 1996]. The overexpression of FAK in CHO or COS cells or in human astrocytoma cells promotes migration of the cells. The involvement of FAK in promoting the proliferation and migration of cells in numerous cell types in vitro suggests the potential role of FAK in neoplastic processes. A recent study has effectively demonstrated the increase in the proliferation of tumor cells in vivo after induction of the expression of FAK in human astrocytoma cells [Cary L.A. et al. J. Cell Sci. 109: 1787-94 1996; Wang D et al. J. Cell Sci. 113: 4221-4230 2000]. Furthermore, immunochistochemical studies on human biopsies have demonstrated that FAK is overexpressed in : prostate cancer, breast cancer, thyroid cancer, cancer of the colon, melanoma, brain cancer and lung cancer, the level of expression of FAK being directly correlated to we the tumors having the most aggressive phenotype [Weiner
TM, et al. Lancet. 342 (8878): 1024-1025 1993; Owens et al. Cancer Research. 55: 2752-2755 1995; Maung K. et al.
Oncogene 18: 6824-6828 1999; Wang D et al. J. Cell Sci. 113: 4221-4230 2000].
Protein kinase AKT (also known as PKB) and phosphoinositide 3-kinase (PI3K) are involved in a cell signaling pathway that transmits signals from growth factors activating membrane receptors.
This transduction pathway is involved in numerous cellular functions: regulation of apoptosis, control of transcription and translation, glucose metabolism, angiogenesis and mitochondrial integrity. First identified as an important component of insulin-dependent signaling pathways regulating metabolic responses, serine/threonine kinase AKT was then identified as a
® 7 : mediator playing a key role in survival induced with growth factors. It has been shown that AKT can inhibit death by apoptosis induced by various stimuli, in a certain number of cell types and tumor cells. In accordance with these findings, it has been shown that
AKT can, by phosphorylation of given serine residues, inactivate BAD, GSK3f, caspase-9, and Forkhead transcription factor, and can activate IKKalpha and e-NOS. It is interesting to note that the protein BAD is found hyper-phosphorylated in 11 human tumor cell lines out of 41 studied. Furthermore, it has been shown that hypoxia modulates the induction of VEGF in cells transformed with Ha-ras by activating the PI3K/AKT pathway and by involving the binding sequence of the
HIF-1 (hypoxia inducible factor-1) transcription factor known as HRE for “hypoxy-responsive element”.
AKT plays a very important role in cancer pathologies. The amplification and/or overexpression of
AKT has been reported in many human tumors, for instance gastric carcinoma (amplification of AKT1), ovary carcinoma, breast carcinoma or pancreatic carcinoma (amplification and overexpression of AKT2) and breast carcinomas deficient in estrogen receptors, and also androgen-independent prostate carcinomas (overexpression of AKT3). Furthermore, AKT is constitutively activated in all the PTEN (-/-) tumors, the PTEN phosphatase being deleted or inactivated by mutations in many types of tumors, for instance carcinomas of the ovary, of the prostate, of the endometrium, gliocblastomas and melanomas. AKT is also involved in the oncogenic activation of bcr-abl (references: Khawaja A., Nature 1999, 401, 33-34; Cardone et al. Nature 1998, 282, 1318- 1321; Kitada S. et al., Am J Pathol 1998 Jan; 152(1): 51- 61; Mazure NM et al. Blood 1997, 90, 3322-3331; Zhong H. et al. Cancer Res. 2000, 60, 1541-1545).
: One subject of the present invention is thus the products of general formula (I): : . 5 )
R1 vy
R3 A— ! pal
N Y, " A
A oo 2 v0) §
Y, "10 in which p represents an integer from 0 to 2,
R and Rl, which may be identical or different, represent
O or NH,
R2 and R3, which may be identical or different, represent : hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl which are optionally substituted, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a carbocyclic or heterocyclic radical, these radicals being 3- to 10- membered and the heterocyclic radical containing one or more hetero atoms chosen from O, S, N and NR7, all these radicals optionally being substituted,
Al represents a single bond, an alkyl radical or an allyl or propynyl radical,
® 9
Y and Yl, which may be identical or different, are such that one from among Y and Y1 is chosen from OCF3, -0O-CF2-
CHF2, -0O-CHF2, -0-CH2-CF3, SO2NR5R6, SF5 and -S(0)n-alkyl and the other from among Y and Y1 is chosen from these same values and in addition from the following values: hydrogen, halogen, hydroxyl, alkoxy, nitro, CN, NRSR6, optionally substituted alkyl, optionally substituted aryl and heteroaryl, CF3, O-alkenyl, O-alkynyl, O-cycloalkyl,
S(O)n-alkenyl, S(O)n-alkynyl, S(O)n-cycloalkyl, free, salified or esterified carboxyl and CONRSRE, or alternatively the phenyl radical forms with its substituents ¥ and Y1 the following radicals:
Ae Lo with p representing the integer 2, 3 or 4, the radical thus formed being optionally substituted with one or more alkyl radicals that are themselves optionally substituted,
R5 and Ré6, which may be identical or different, are chosen from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, ‘cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, which are optionally substituted, or alternatively R5 and Ré6 form, with the nitrogen atom to which they are attached, a 3- to 10-membered heterocyclic radical containing one or more hetero atoms chosen from 0, S, N and NR7, which is optionally substituted,
A2, which may be identical to or different from Al, represents the values of Al and CO and S02,
B2 represents a saturated or unsaturated monocyclic or bicyclic heterocyclic radical «containing 1 or more identical or different hetero atoms chosen from 0, S, N and NR7, optionally substituted with one or more
® | 10 : identical or different substitutents chosen from the values of Y2,
R7 represents a hydrogen atom or an alkyl, cycloalkyl, phenyl, acyl, S(0)2Alk, S(0O)2Aryl, S(O)2hetercaryl or
S(0)2NRSR6 radical,
Y2 represents hydrogen, halogen, hydroxyl, cyano, alkyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl, heteroaryl, -0O-alkenyl, -0O-alkynyl, -O-cycloalkyl, -S(0)n-alkyl, -S(0)n-alkenyl, -S(0)n-alkynyl,
S(O)n-cycloalkyl, COOR13, -OCOR13, NRSR6, CONRSRS,
S (O)n-NR5R6, -NR10-CO-R13, -NR10-S02-R13, NH-SO2-NRG5R6, -NR10-CO-NRSR6, -NR10-CS-NR5R6, -NR10-COOR13, all these radicals optionally being substituted, all the alkyl, alkenyl, alkynyl and alkoxy radicals above R being linear or branched and containing not more than 6 carbon atoms, all the cycloalkyl and heterocycloalkyl radicals above containing not more than 7 carbon atoms, ‘ all the aryl and heteroaryl radicals above containing not more than 10 carbon atoms, = all the «carbocyclic and heterocyclic alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and hetercaryl radicals above, and also the ring formed by R5 and R6 with the atom to which they are attached, optionally being substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and cyano, hydroxyl, alkoxy, CF3, nitro, aryl, heteroaryl, -C(=0) -0OR9, -C(=0) -R8, -NR11R1l2, -C(=0) -
NR11R12, -N (R10) -C(=0) -R8, -N(R10)-C(=0)-OR9, N(R10)-C(=0)-NR11R12, -N(R10)-S(O)n-
R8, -S(0O)n-RS8, -N(R10)-S{0)n-NR11R12 or -S(0O)n-NR11R12 radicals, all the aryl and heteroaryl radicals above furthermore being optionally substituted with one or more radicals chosen from alkyl, alkoxy and alkylenedioxy radicals,
® 11 all the cyclic radicals above, and also the ring formed : by R5 and R6 with the atom to which they are attached, being moreover optionally substituted with one or more radicals chosen from oxo and thioxo, n represents an integer from 0 to 2,
R8 represents alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl and heterocarylalkyl,
RS represents the values of R8 and hydrogen,
R10 represents hydrogen or alkyl,
R11 and R12, which may be identical or different, represent hydrogen, C3-Cé6 cycloalkyl, Cl-C4 alkyl and phenyl, optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and cyano, hydroxyl, alkoxy, CF3, nitro, phenyl and free, salified, esterified or amidated carboxyl radicals, or alternatively R11 and R12 form, with the nitrogen atom to which they are attached, a 5- to 7-membered cyclic radical containing one or more hetero atoms chosen from
O, S, N and NR7 and preferably a cyclic amine,
R13, which may be identical to or different than RS or
R6, being chosen from the values of RS5 or R6, it being understood that the products of formula (I) are as defined below from a) to 4d): a) when p represents the integer 0, R represents oxygen,
R1 represents oxygen, Al represents a single bond or alkyl, Y¥ and Yl, which may be identical or different, are such that at least one represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and
R3 do not represent one hydrogen and the other imidazolylalkyl, b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Yi, which may be identical or different, are such that at least one represents OCF3, SOAlk, S{(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain : optionally interrupted with O, 8 or Nalk, always
S substituted with a hydroxamate -CO-NHCH c) when p represents the integer 0, R and Rl. represent oxygen, Al represents a single bond or alkyl, Y and Yl, which may be identical or different, are such that at least one represents S{(O)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or 6- membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, d) when p represents an integer from 0 to 2, R and Rl represent oxygen, Al represents a single bond, Y and Y1, which may be identical or different, are such that one represents SO2Alk or SO2NH2 and the other represents : NRSR6, A2 represents a single bond or alkylene and B2 : represents an optionally substituted 5- to 10-membered heterocyclic radical, then R2 and R3 do not both ws represent hydrogen, said products of formula (I) being in any possible racemic, enantiomeric or diasterecisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (I).
A subject of the present invention is thus the products of general formula (I) as defined above in which p represents an integer from 0 to 2,
R and R1l, which may be identical or different, represent
O or NH,
R2 and R3, which may be identical or different, represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl which are optionally substituted, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a carbocyclic or
® 13 heterocyclic radical, these radicals being 3- to 10- : membered and the heterocyclic radical containing one or more hetero atoms chosen from CO, S, N and NR7, all these radicals optionally being substituted,
Al represents a single bond, an alkyl radical or an allyl or propynyl radical,
Y and Yl, which may be identical or different, are such that one from among Y and Y1 is chosen from OCF3,
S(O)nCF3, S(0)nAlk, SO2CHF2, SO2CF2CF3 and SO02NR5R6 and the other from among Y and Y1 is chosen from these same values and in addition from. the following values: hydrogen, halogen, hydroxyl, alkoxy, NR5R6, optionally substituted alkyl, optionally substituted aryl and heteroaryl, CF3, O-allyl, O-propynyl, O-cycloalkyl,
S(O)n-allyl, S(0O)n-propynyl, S(0O)n-cycloalkyl, free, salified or esterified carboxyl and CONRS5R6 in which R5 and R6, which may be identical or different, are chosen from hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclecalkyl, aryl and heteroaryl, which are optionally substituted, or alternatively R5 and
R6 form, with the nitrogen atom to which they are attached, a 3- to 10-membered heterocyclic radical containing one or more hetero atoms chosen from O, S, N and NR7, which is optionally substituted,
A2, which may be identical to or different from A1, represents the values of Al and CO and S02,
B2 represents a saturated or unsaturated heterocyclic radical containing 1 or more identical or different hetero atoms chosen from O, S, N and NR7, optionally substituted with one or more identical or different substitutents chosen from the values of Y2,
R7 represents a hydrogen atom or an alkyl, cycloalkyl, phenyl, aryl, S(0)2alk, S(0O)2aryl, S(0)2heterocaryl or
S (QO) 2NRSR6 radical,
Y2 represents hydrogen, halogen, hydroxyl, alkyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, O-allyl,
hd 14 : O-propynyl, O-cycloalkyl, S(0)n-alkyl, S(0)n-allyl,
S(O)n-propynyl, S(O)n-cycloalkyl, COORS, OCOR8, NRSR6,
CONR5R6, S(0O)n-R5R6, NHCOR8, NH-S(0O)nR8 or NH-S (0) nCF3 or :
NH-SO2-NR5R6, all these radicals being optionally substituted, all the alkyl, alkenyl, alkynyl and alkoxy radicals above being linear or branched and containing not more than 6 carbon atoms, all the cycloalkyl and heterocycloalkyl radicals above containing not more than 7 carbon atoms, all the aryl and heteroaryl radicals above containing not more than 10 carbon atoms, all the carbocyclic and heterocyclic alkyl, alkenyl, : alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and R heteroaryl radicals above optionally being substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and cyano, hydroxyl, : alkoxy, CF3, nitro, aryl, heteroaryl, -C(=0) -0R9, -C(=0)-R8, -NR11R12, -C(=0)-NR11R12, -N(R10)-C(=0)-RS8, -N(R10)-C(=0)-0R9, N(R10)-C(=0) -NR11R12, -N (R10) -S(0O)n- ne R8, -S(0O)n-RS8, -N(R10)-S(0O)n-NR11R12 or -S(0)n-NR11R12 radicals, all the aryl and heteroaryl radicals above furthermore being optionally substituted with one or more radicals chosen from alkyl and alkylenedioxy radicals, n represents an integer from 0 to 2,
R8 represents alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl and heterocarylalkyl,
R9 represents the values of R8 and hydrogen,
R10 represents hydrogen or alkyl,
R11 and R12, which may be identical or different, represent hydrogen, C3-C6 cycloalkyl, Cl1-C4 alkyl and phenyl, optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms
® 15 : and cyano, hydroxyl, alkoxy, CF3, nitro, phenyl and free, salified, esterified or amidated carboxyl radicals, or alternatively R11 and R12 form, with the nitrogen atom to which they are attached, a 5- to 7-membered cyclic radical containing one or more hetero atoms chosen from 0, 8S, N and NR7 and preferably a cyclic amine, it being understood that the products of formula (I) are as defined below from a) to d): a) when p represents the integer 0, R represents oxygen,
R1 represents oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that at least one represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and
R3 do not represent one hydrogen and the other imidazolylalkyl, b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that at least one represents OCF3, SOAlk, S(0)2alk or SO0O2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk always substituted with a hydroxamate -CO-NHOH : c) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that at least one represents S(O)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or 6- membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, d) when p represents an integer from 0 to 2, R and R1 represent oxygen, Al represents a single bond, Y and Yi, which may be identical or different, are such that one
® 16 : represents SO2Alk or SO2NH2 and the other represents
NRESR6, AZ2 represents a single bond or alkylene and B2 represents an optionally substituted 5- to 10-membered : heterocyclic radical, then R2 and R3 do not both represent hydrogen, | : said products of formula (I) being in any possible racemic, enantiomeric or diasterecisomeric isomer: form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (I).
One subject of the present invention is thus the products of general formula (I) as defined above in which p represents an integer from 0 to 2, | :
R and R1l, which may be identical or different, represent E
O or NH,
R2 and R3, which may be identical or different, represent hydrogen, alkyl, alkenyl, cycloalkyl, phenyl and heteroaryl, which are optionally substituted, or ‘ alternatively R2 and R3 form, together with the carbon atom to which they are attached, a carbocyclic or - heterocyclic radical, these radicals being from 3- to 10-membered and the heterocyclic radical containing one or more hetero atoms chosen from 0, 8S, N and NR7, all these radicals being optionally substituted,
Al represents a single bond, an alkyl radical or an allyl or propynyl radical,
Y and Y1, which may be identical or different, are such that one from among Y and Y1 is chosen from OCF3,
S(0)nCF3, S(0)nAlk, SO2CHF2, SO2CF2CF3 and SO2NR5R6 and the other from among Y and Yl is chosen from these same values and in addition from the following values: hydrogen, halogen, hydroxyl, alkoxy, NR5R6, optionally substituted alkyl and phenyl, and optionally substituted pyrazolyl and pyridyl, with RS5 and Ré6, which may be identical or different, chosen from hydrogen, alkyl, alkenyl, cycloalkyl,
® 17 heterocycloalkyl, phenyl and heteroaryl, which are : optionally substituted, or alternatively RS5 and Ré form, with the nitrogen atom to which they are attached, a 3- to 10-membered heterocyclic radical containing one or more hetero atoms chosen from 0, S, N and NR7, which are optionally substituted,
A2, which may be identical to or different than Al, represents the values of Al and CO and S02,
B2 represents a saturated or unsaturated heterocyclic radical containing one or more identical or different hetero atoms chosen from O, S, N and NR7, optionally substituted with one or more identical or different substituents chosen from the values of Y2, :
R7 represents a hydrogen atom or an alkyl, cycloalkyl or phenyl radical,
Y2 represents hydrogen, halogen, hydroxyl, alkyl, alkoxy, cycloalkyl, heterocycloalkyl, phenyl, heteroaryl,
O-cycloalkyl, S(O)n-alk, S(0O)n-cycloalkyl, COORS, OCORS,
NR5R6, CONRSR6, S{0O)n-R5R6, NHCOR8 and NH-S(0O)nR8, all these radicals being optionally substituted, all the above alkyl, alkenyl, alkynyl and alkoxy radicals being linear or branched and containing up to 6 carbon atoms, all the above cycloalkyl and heterocycloalkyl radicals containing up to 7 carbon atoms, all the above aryl and heteroaryl radicals containing up to 10 carbon atoms, all the above alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, carbocyclic and heterocyclic radicals being optionally substituted with one or more identical or different radicals chosen from halogen atoms and cyano, hydroxyl, alkoxy, CF3, nitro, phenyl, heteroaryl, -C(=0) -ORg9, -C(=0)-R8, -NR11lR12, -C(=0)-NR11R12, -N(R10)-C(=0)-Rs, -N{(R1l0)-C(=0) -0OR9, N (R10) -C(=0) -NR11R12, -N(R10) -
hd 18
S(0)n-R8, -S(0)n-R8, -N(R10)-S(0)n-NR11R12 and -S(0)n- ~ NR11R12, all the aryl and heteroaryl radicals above moreover being optionally substituted with one or more radicals chosen from alkyl and alkylenedioxy radicals, n represents an integer from 0 to 2, :
R8 represents alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, phenyl and phenylalkyl,
RS represents the values of R8 and hydrogen,
R10 represents hydrogen or alkyl,
R11 and R12, which may be identical or different, represent hydrogen, C1-C4 alkyl and phenyl, optionally substituted with one or more identical or different radicals chosen from halogen atoms and hydroxyl, alkoxy, CF3, nitro, phenyl and free, salified, esterified or amidated carboxyl radicals, or alternatively R11 and R12 form, with the nitrogen atom to which they are attached, a 5- to 7-membered cyclic radical containing one or more ans hetero atoms chosen from O, S, N and NR7 and preferably a cyclic amine, it being understood that the products of formula (I) are as defined below from a) to 4d): a) when ©p represents the integer 0, R represents
Oxygen, Rl represents Oxygen, Al represents a single bond or alkyl, Y and Yl, which may be identical or different, are such that at least one represents OCF3 or Salk, a2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and
R3 do not represent a hydrogen for one and imidazolylalkyl for the other, b) when p represents the integer 0, R and R1 represent
Oxygen, Al represents a single bond or alkyl, Y and Yi, which may be identical or different, are such that at least one represents OCF3, SOAlk, S(0C)2alk or SO2NH2, a2
® 19 represents CH2 and B2 represents an optionally : substituted heterocyclic radical, then R2 and R3 do not represent a hydrogen atom for one and, for the other, an alkyl chain optionally interrupted with O, S, Nalk always substituted with a hydroxamate -CO-NHOH, c) when p represents the integer 0, R and Rl represent
Oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that at least one represents S(O)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or 6-membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, d) when p represents an integer from 0 to 2, R and Rl represent oxygen, Al represents a single bond, Y and Y1, which may be identical or different, are such that one represents SO02Alk or SO2NH2 and the other represents
NRSR6, A2 represents a single bond or alkylene and R2 represents an optionally substituted 5- to 10-membered heterocyclic radical, then R2 and R3 do not both represent hydrogen, said products of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (I).
One subject of the present invention is thus the products of formula (I) as defined above in which Y and Y1, which may be identical or different, are such that one from among Y and Yl is chosen from OCF3, -O-CF2-CHF2, -O-CHF2, -0-CH2-CF3, S(O)nCF3, -S-CF2-CF2-CF3, -S(0)n-Alk, -S-Alk-0-Alk, -S-Alk-OH, ~-S-Alk-CN, -S-Alk- heterocycloalkyl, -SO2CHF2, -S02CF2CF3, -SO2NR5R6 and -SF5, with Alk representing an alkyl radical containing from 1 to 4 carbon atoms, and the other from among Y and
® 20 : Yl is chosen from the following values: hydrogen, halogen, nitro, NR5R6, free or esterified carboxyl and
CONRSRE, or alternatively the phenyl radical forms with its substituents Y and Yl one of the following radicals:
A 3 oo (ONNe . © 5 the radical thus formed being optionally substituted with one or more alkyl radicals that are themselves optionally substituted, oo "the other substituents on said products of formula (I) B being chosen from the values defined in claim 1 and it being understood that: : a) when p represents the integer 0, R represents oxygen, Rl represents Oxygen, Al represents a single bond ' or alkyl, Y and Yl, which may be identical or different, are such that one represents hydrogen and the other we represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent hydrogen for one and imidazolylalkyl for the other, b) when p represents the integer 0, R and Rl represent
Oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents OCF3, SOAlk,
S(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent hydrogen for one and, for the other, an alkyl chain optionally interrupted with O, g,
Nalk always substituted with a hydroxamate-CO-NHOH, c) when p represents the integer 0, R and R1 represent
Oxygen, Al represents a single bond or alkyl, Y and Yi, which may be identical or different, are such that one
® 21 represents hydrogen and the other represents S(0O)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or 6-membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, said products of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (I).
A subject of the present. invention is thus the products of general formula (I) as defined above in which one from among Y and Yl represents a hydrogen atom and the other is chosen from OCF3, S(0)nCF3, S(0)nalk,
SO2CHF2, SO2CF2CF3 and SO2NR5R6, the other substituents of said products of formula (I) being chosen from the values defined above, it being understood that: a) when p represents the integer 0, R represents oxygen,
R1 represents oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other imidazolylalkyl, b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Yi, which may be identical or different, are such that one represents hydrogen and the other represents OCF3, SOAlk,
S(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk always substituted with a hydroxamate -CO-NHOH
® 22 c) when p represents the integer 0, R and R1 represent oxygen, Al represents a single bond or alkyl, ¥ and Y1, which may be identical or different, are such that one : represents hydrogen and the other represents S(O)nAlk, AZ represents a single bond and B2 represents an optionally substituted 5- or 6-membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, said products of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (I). | :
A subject of the present invention is thus the products of general formula (I) as defined above in which one from among Y and Y1 represents a hydrogen atom and the other is chosen from S(0)nCF3, S80Alk, S(0)2alk, : SO2CHF2, SO2CF2CF3 and SO2NRG5R6, ' the other substituents of said products of formula (I) being chosen from the values defined above and it being = understood that the products of formula (I) are as defined below in a) and b): a) when p represents the integer 0, R and R1l represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents SOAlk,
S(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk always substituted with a hydroxamate -CO-NHOH b) when p represents the integer 0, R and R1 represent oxygen, Al represents a single bond or alkyl, Y and vi, which may be identical or different, are such that one represents hydrogen and the other represents SOAlk or
S(0)2Blk, A2 represents a single bond and B2 represents
. ® 23 . an optionally substituted 5- or 6-membered aromatic : heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, said products of formula (I) being in any possible racemic, enantiomeric or diastereocisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (I).
A subject of the present invention is thus the products of general formula (I) as defined above in which one from among Y and Y1 represents a hydrogen atom and the other is chosen from S(0)nCF3, SO2CHF2, SO2CF2CF3 and
SO2NRSR6, the other substituents of said products of formula (I) being chosen from the values defined above and it being understood that when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents
SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted by O, S or Nalk, always substituted with a hydroxamate -CO-NHOH said products of formula (I) being in any possible racemic, enantiomeric and diastereoisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (I).
In the products of formula (I) and subsequently, the terms indicated have the following meanings: - the term “Hal”, “Halo” or halogen denotes fluorine, chlorine, bromine or iodine atoms, - the term “alkyl”, “alk”, "“Alk” or “ALK” denotes a linear or branched radical containing not more than 12 carbon atoms, chosen from methyl, ethyl, propyl,
hd 24 : isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, sec-pentyl, tert-pentyl, neopentyl, hexyl, isohexyl, sec-hexyl, tert-hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl radicals, and .also the linear or branched positional isomers thereof.
Mention is made more particularly of alkyl radicals containing not more than 6 carbon atoms, and especially methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, linear or branched pentyl and linear or branched hexyl radicals. - the term “alkenyl radical” denotes a linear or branched radical containing not more than 12 carbon atoms and preferably 4 carbon atoms, chosen, for example, from : " the following values: ethenyl or vinyl, propenyl or R allyl, l-propenyl, n-butenyl, i-butenyl, 3-methyl-2- butenyl, n-pentenyl, hexenyl, heptenyl, ‘octenyl, cyclohexylbutenyl and decenyl, and also the linear or branched positional isomerers thereof. :
Among the alkenyl values that may be mentioned particularly are the values allyl or butenyl. ws - the term “alkynyl radical” denotes a linear or branched radical containing not more than 12 carbon atoms and preferably 4 carbon atoms, chosen, for example, from the following values: ethynyl, propynyl or propargyl, butynvyl, n-butynyl, i-butynyl, 3-methyl-2-butynyl, pentynyl or hexynyl, and also the linear or branched positional isomers thereof.
Among the alkynyl values that are mentioned more particularly is the propargyl value. - the term “alkoxy radical” denotes a linear or branched radical containing not more than 12 carbon atoms and preferably 6 carbon atoms chosen, for example, from methoxy, ethoxy, propoxy, isopropoxy, linear, secondary or tertiary butoxy, pentoxy, hexoxy and heptoxy radicals, and also the linear or branched positional isomers thereof,
® 25 . - the term “alkoxycarbonyl radical” or alkyl-0-CO- : denotes a linear or branched radical containing not more than 12 carbon atoms, in which the alkyl radical has the meaning given above: examples that may be mentioned include methoxycarbonyl and ethoxycarbonyl radicals, - the term “alkylenedioxy radical” or -0O-alkylene-O- denotes a linear or branched radical containing not more than 12 carbon atoms, in which the alkylene radical has the meaning given above: examples that may be mentioned include methylenedioxy and ethylenedioxy radicals, - the term “alkylsulfinyl” or alkyl-SO- denotes a linear or branched radical containing not more than 12 : carbon atoms, in which the alkyl radical has the meaning given above and preferably contains 4 carbon atoms, - the term “alkylsulfonyl” or alkyl-S02- denotes a linear or branched radical containing not more than 12 carbon atoms, in which the alkyl radical has the : meaning given above and preferably contains 4 carbon atoms, : - the term “alkylsulfonylcarbamoyl” or alkyl-SO2-NH-
C(=0)- denotes a linear or branched radical containing not more than 12 carbon atoms, in which the alkyl radical has the meaning given above and preferably contains 4 carbon atoms, - the term “alkylthio” or alkyl-S- denotes a linear. or branched radical containing not more than 12 carbon atoms and especially represents methylthio, ethylthio, isopropylthio and heptylthio radicals, - the term “cycloalkyl radical” denotes a 3- to 10- membered monocyclic or bicyclic carbocyclic radical and especially denotes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl radicals, - the term “-O-cycloalkyl radical” denotes a radical in which the cycloalkyl radical has the meaning given above,

Claims (1)

  1. CLAIMS 1) A product of formula (I): Ri : y NT Y, N A p | R : 0 I | oo Y, - in which p represents an integer from 0 to 2, R and R1l, which may be identical or different, represent O or NH, R2 and R3, which may be identical or different, represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl which are optionally substituted, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a carbocyclic or heterocyclic radical, these radicals being 3- to 10-
    : membered and the heterocyclic radical containing one or more hetero atoms chosen from O, 8S, N and NR7, all these radicals optionally being substituted,
    Al represents a single bond, an alkyl radical or an alkenyl or alkynyl radical, Y and Yl, which may be identical or different, are such that one from among Y and Y1 is chosen from OCF3, -O-CF2- CHF2, -0-CHF2, -0-CH2-CF3, SO2NR5R6, SF5 and ~-S(0O)n-alkyl and the other from among Y and Y1 is chosen from these same values and in addition from the following values: hydrogen, halogen, hydroxyl, alkoxy, nitro, CN, NRS5Reé, optionally substituted alkyl, optionally substituted aryl o 486 and heteroaryl, .CF3, O-alkenyl, O-alkynyl, O-cycloalkyl, S(O)n-alkenyl, S(O)n-alkynyl, S(O)n-cycloalkyl, free, salified or esterified carboxyl and CONRSR6, or alternatively the phenyl radical forms with its substituents Y and Y1 the following radicals:
    CF.
    2P . 0 —O with p representing the integer 2, 3 or 4, the radical : thus formed being optionally substituted with one or more alkyl radicals that are themselves optionally substituted, R5 and R6, which may ‘be identical or different, are chosen from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, which are . optionally substituted, or alternatively R5 and Ré form, with the nitrogen atom to which they are attached, a 3- to 10-membered heterocyclic radical containing one or more hetero atoms chosen from O, S, N and NR7, which is optionally substituted, A2, which may be identical to or different from Al, represents the values of Al and CO and SO2, B2 represents a saturated or unsaturated monocyclic or bicyclic heterocyclic radical containing 1 or more identical or different hetero atoms chosen from 0, S, N and NR7, optionally substituted with one or more identical or different substitutents chosen from the values of Y2, R7 represents a hydrogen atom or an alkyl, cycloalkyl, phenyl, acyl, S(0)2Alk, S(0)2Aryl, S(O)2heteroaryl or S(O) 2NR5R6 radical, Y2 represents hydrogen, halogen, hydroxyl, cyano, alkyl, alkoxy, cyclecalkyl, heterocycloalkyl, aryl, heteroaryl,
    ® 487 O-alkenyl, O-alkynyl, O-cycloalkyl, S(0)n-alkyl, S(0)n- alkenyl, S(O)n-alkynyl, S(O)n-cycloalkyl, COOR13, OCOR13, NRS5R6, CONRSR6, S(0O)n-R5R6, -NR10-CO-R13, -NR10O-S02-R13, : NH-SO2-NRE5R6, -NR10-CO-NRS5R6, -NR10-C5-NR5R6, | _NR10- COOR13, all these radicals optionally being substituted, all the alkyl, alkenyl, alkynyl and alkoxy radicals above being linear or branched and containing not more than 6 carbon atoms, all the cycloalkyl and heterocycloalkyl radicals above containing not more than 7 carbon atoms, all the aryl and hetercaryl radicals above containing not more than 10 carbon atoms, all the carbocyclic and heterocyclic alkyl, alkenyl, ~ alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and heteroaryl radicals above and also the ring formed by R5 and R6 with the atom to which they are attached, optionally being substituted with one or more radicals, : which may be identical or different, chosen from halogen atoms and cyano, hydroxyl, alkoxy, CF3, nitro, aryl, heteroaryl, -C(=0) -0RS9, -C(=0) -R8, -NR11R12, -C({=0) - we NR11R12, -N(R10)-C(=0) -R8, -N (R10) -C(=0) -ORS9, N (R10) - C(=0)-NR11R12, -N (R10) -S(0O)n-RS8, -S(0)n-R8, -N (R10) - S{(0)n-NR11R12 or -S(0)n-NR11lR1l2 radicals, all the aryl and heteroaryl radicals above furthermore being optionally substituted with one or more radicals chosen from alkyl, alkoxy and alkylenedioxy radicals, all the above cyclic radicals, and also the ring formed by R5 and Ré with the atom to which they are attached, being moreover optionally substituted with one or more radicals chosen from oxo and thioxo, n represents an integer from 0 to 2, R8 represents alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, hetercaryl and hetercarylalkyl, R9 represents the values of R8 and hydrogen, R10 represents hydrogen or alkyl,
    ® 488 R11 and R12, .which may be identical or different, represent hydrogen, C3-C6 cycloalkyl, C1-C4 alkyl and phenyl, optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and cyano, hydroxyl, alkoxy, CF3, nitro, phenyl and free, salified, esterified or amidated carboxyl radicals, or alternatively R11 and R12 form, with the nitrogen atom to which they are attached, a 5- to 7-membered cyclic radical containing one or more hetero atoms chosen from
    0, S, N and NR7 and preferably a cyclic amine,
    R13, which may be identical to or different than R5 or R6, being chosen from the values of R5 or Re,
    : it being understood that the product of formula (I) is as defined below from a) to 4d):
    a) when p represents the integer 0, R represents oxygen, R1 represents oxygen, al represents a single bond or alkyl, Y and Y1, which may be identical or different, are : such that at least one represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other imidazolylalkyl,
    b) when p represents the integer 0, R and R1l represent oxygen, Al represents a single bond or alkyl, Y and Y1,
    which may be identical or different, are such that at least one represents OCF3, SOAlk, S(0O)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk always substituted with a hydroxamate -CO-NHOH c¢) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that at least one represents S(O)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or 6-
    ® 489 : : membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, : d) when p represents an integer from 0 to 2, R and R1 represent oxygen, Al represents a single bond, Y and Y1, which may be identical or different, are such that one represents SO2Alk or SO2NH2 and the other represents NRSR6, A2 represents a single bond or alkylene and B2 represents an optionally substituted 5- to 10-membered heterocyclic radical, then R2 and R3 do not both represent hydrogen, said product of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, + and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I). : 2) The product of formula (I) as claimed in claim 1, in which p represents an integer from 0 to 2, ‘ R and R1l, which may be identical or different, represent O or NH,
    a R2 and R3, which may be identical or different, represent hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl which are optionally substituted, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a carbocyclic or heterocyclic radical, these radicals being 3- to 10- membered and the heterocyclic radical containing one or more hetero atoms chosen from O, S, N and NR7, all these radicals optionally being substituted, Al represents a single bond, an alkyl radical or an allyl or propynyl radical, Y and Y1, which may be identical or different, are such that one from among Y and Y1 is chosen from OCF3, S(OYnCF3, S(0)nAlk, SO2CHF2, SO2CF2CF3 and SO0O2NR5Rێ and the other from among Y and Yl is chosen from these same values and in addition from the following values:
    ® 490 hydrogen, halogen, hydroxyl, alkoxy, NRSR6, optionally substituted alkyl, optionally substituted aryl and heteroaryl, CFs, O-allyl, O-propynyl, O-cycloalkyl, S(O)n-allyl, S(O)n-propynyl, S(0)n-cycloalkyl, free, salified or esterified carboxyl and CONRSRE,
    in which R5 and R6, which may be identical or different, are chosen from hydrogen, alkyl, alkenyl, cycloalkyl,
    cycloalkenyl, heterocycloalkyl, aryl and heteroaryl,
    which are optionally substituted, or alternatively R5 and R6 form, with the nitrogen atom to which they are attached, a 3- to 10-membered heterocyclic radical containing one or more hetero atoms chosen from O, S, N
    : and NR7, which is optionally substituted,
    A2, which may be identical to or different from Al, represents the values of Al and CO and S02,
    B2 represents a saturated or unsaturated heterocyclic radical containing 1 or more identical or different :
    hetero atoms chosen from ©O, S and NR7, optionally substituted with one or more identical or different substitutents chosen from the values of Y2,
    R7 represents a hydrogen atom or an alkyl, cycloalkyl,
    phenyl, aryl, S(0)2alk, S(0)2aryl, S(O)hetercaryl and
    S(O) 2NR5R6 radical,
    Y2 represents hydrogen, halogen, hydroxyl, alkyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, O-allyl,
    O-propynyl, O-cycloalkyl, S(O)n-alkyl, S(0O)n-allyl,
    S(O)n-propynyl, S(O)n-cycloalkyl, COORS, OCORS, NRSR6,
    CONRERS6, S(O)n-R5R6, NHCORS, NH-S (0) NR8 or NH-S(0O)nCF3 or
    NH-SO2-NR5R6, all these radicals being optionally substituted,
    all the alkyl, alkenyl, alkynyl and alkoxy radicals above being linear or branched and containing not more than
    6 carbon atoms,
    all the cycloalkyl and heterocycloalkyl radicals above containing not more than 7 carbon atoms,
    all the aryl and heteroaryl radicals above containing not
    ® | 491 : more than 10 carbon atoms, all the carbocyclic and heterocyclic alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and : heteroaryl radicals above optionally being substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and cyano, hydroxyl, alkoxy, CF3, nitro, aryl, heteroaryl, -C(=0) -0R9, -C(=0) -R8, -NR11iR12, -C({=0) -NR11R12, -N{R10) -C(=0) -R8, -N (R10) -C(=0)-0CR9, N(R10)-C(=0) -NR11R12, -N(R10)-S(0O)n- R8, -5(C)n-R8, -N(R10) -S(0)n-NR11R12 or -S(0O)n-NR11R1l2 radicals, all the aryl and heteroaryl radicals above furthermore being optionally substituted with ‘one or more radicals chosen from alkyl and alkylenedioxy radicals, - n represents an integer from 0 to 2, R8 represents alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, : aryl, arylalkyl, heteroaryl and heterocarylalkyl, : R9 represents the values of R8 and hydrogen, R10 represents hydrogen or alkyl, wr R11 and R12, which may be identical or different, represent hydrogen, C3-C6 cycloalkyl, C€1-C4 alkyl and phenyl, optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and cyano, hydroxyl, alkoxy, CF3, nitro, phenyl and free, salified, esterified or amidated carboxyl radicals, or alternatively R11 and R12 form, with the nitrogen atom to which they are attached, a 5- to 7-membered cyclic radical containing one or more hetero atoms chosen from O, 8, N and NR7 and preferably a cyclic amine, it being understood that the product of formula (I) is as defined below from a) to 4d): a) when p represents the integer 0, R represents oxygen, R1 represents oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are
    ® 492 . such that at least one represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other imidazolylalkyl, b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that at least one represents OCF3, SOAlk, S(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain : optionally interrupted with oO, 8 or Nalk always substituted with a hydroxamate -CO-NHOH ¢c) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, ¥Y and Y1, which may be identical or different, are such that at least one represents S(O)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or 6- membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, d) when p represents an integer from 0 to 2, R and Rl represent oxygen, Al represents a single bond, Y and Y1, which may be. identical or different, are such that one. represents SO02Alk or SO2NH2 and the other represents NRGSR6, A2 represents a single bond or alkylene and B2 represents an optionally substituted 5- to 10-membered heterocyclic radical, then R2 and R3 do not both represent hydrogen, said product of formula (I) being in any possible racemic, enantiomeric or diastereocisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I).
    ® | 493 : 3) The product of formula (I) as claimed in claim 1 or 2, in which p represents an integer from 0 to 2, R and R1l, which may be identical or different, represent O or NH, R2 and R3, which may be identical or different, represent hydrogen, alkyl, alkenyl, cycloalkyl, phenyl and heteroaryl, which are optionally substituted, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a carbocyclic or heterocyclic radical, these radicals being 3- to 10- membered and the heterocyclic radical containing one or more hetero atoms chosen from O, S, N and NR7, all these radicals being optionally substituted, Al represents a single bond, an alkyl radical or an allyl : or propynyl radical, Y and Y1, which may be identical or different, are such that one from among Y and Y1 is chosen from OCF3, S(0)nCF3, S(0)nAlk, SO2CHF2, SO2CF2CF3 and SO2NR5R6 and ' the other from Y and Yl is chosen from the same values and in addition from the following values: hydrogen,
    i. halogen, hydroxyl, alkoxy, NR5R6, optionally substituted alkyl and phenyl, and optionally substituted pyrazolyl and pyridyl, in which R5 and R6, which may be identical or different, are chosen from hydrogen, alkyl, alkenyl, cycloalkyl, heterocycloalkyl, phenyl and hetercaryl, which are optionally substituted, or alternatively R5 and Ré form, with the nitrogen atom to which they are attached, a 3- to 10-membered heterocyclic radical containing one or more hetero atoms chosen from O, S, N and NR7, which is optionally substituted, A2, which may be identical to or different from Al, represents the values of Al and CO and SO2, B2 represents a saturated or unsaturated heterocyclic radical containing one or more hetero atoms, which may be identical or different, chosen from O, S, N and NR7,
    ® 494 optionally substituted with one or more substituents, : which may be identical or different, chosen from the values of Y2,
    R7 represents a hydrogen atom or an alkyl, cycloalkyl or phenyl radical,
    Y2 represents hydrogen, halogen, hydroxyl, alkyl, alkoxy,
    cycloalkyl, heterocycloalkyl, phenyl, heteroaryl,
    O-cycloalkyl, S(O0)n-alk, S(O)n-cycloalkyl, COOR9, OCORS,
    NR5R6, CONRSR6, S(0O)n-R5R6, NHCOR8 and NH-S(O)nR8, all these radicals being optionally substituted,
    all the alkyl, alkenyl, alkynyl and alkoxy radicals above being linear or branched and containing not more than 6
    : carbon atoms,
    all the cycloalkyl and heterocycloalkyl radicals above containing not more than 7 carbon atoms,
    all the aryl and heteroaryl radicals above containing not more than 10 carbon atoms, :
    all the carbocyclic and heterocyclic alkyl, alkenyl,
    alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl and heteroaryl radicals above being optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and cyano, hydroxyl,
    alkoxy, CF3, nitro, phenyl, heteroaryl, -C(=0) -0R9,
    -C(=0) -RS8, -NR11R12, -C{(=0) -NR11R12, -N(R10)-C(=0) -RS8, -N (R10) -C(=0)--0OR9, N (R10) -C(=0)-NR11R12, -N(R10)-S(0O)n-
    R8, -S{0)n-R8, -N(R10)-S(O)n-NR11R12 and -S{O)n-NR11lR1l2 radicals,
    all the aryl and heteroaryl radicals above also being optionally substituted with one or more radicals chosen from alkyl and alkylenedioxy radicals,
    n represents an integer from 0 to 2,
    R8 represents alkyl, cycloalkyl, cycloalkylalkyl,
    heterocycloalkyl, heterocycloalkylalkyl, phenyl or phenylalkyl, R9 represents the values of R8 and hydrogen,
    R10 represents hydrogen or alkyl,
    ® 495 ’ R11 and R12, which may be identical or different, represent hydrogen, C1-C4 alkyl and phenyl, which are optionally : substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and hydroxyl, alkoxy, CF3, nitro, phenyl and free,. salified, esterified or amidated carboxyl radicals; or alternatively R11] and R12 form, with the nitrogen atom to which they are attached, a 5- to 7-membered cyclic radical containing one or more hetero atoms chosen from 0, S, N and NR7 and preferably a cyclic amine, it being understood that the products of formula (I) are as defined below from a) to d): a) when p represents the integer 0, R represents oxygen, R1 represents oxygen, Al represents a single bond or alkyl, Y and Y1l, which may be identical or different, are such that at least one represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other we imidazolylalkyl, b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, ¥Y and Y1, which may be identical or different, are such that at least one represents OCF3, SOAlk, S(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk always substituted with a hydroxamate -CO-NHCH c) when p represents the integer 0, R and R1l represent oxygen, Al represents a single bond or alkyl, Y and Yi, which may be identical or different, are such that at least one represents S(O)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or ¢- membered aromatic heterocyclic radical, then R2 and R3
    ® 496 . are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl,
    d) when p represents an integer from 0 to 2, R and Rl represent oxygen, Al represents a single bond, Y and Yl, which may be identical or different, are such that one represents SO2Alk or SO2NH2 and the other represents NRSR6, A2 represents a single bond or alkylene and B2 represents an optionally substituted 5- to 10-membered heterocyclic radical, then R2 and R3 do not both represent hydrogen, said product of formula (I) being in any possible racemic, enantiomeric or diastereoiscmeric isomer form, : and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I). 4) The product of formula (I) as defined in any one of the claims, in which Y and Yl, which may be identical or different, are such that one from among Y and Yl is chosen from OCF3, -O-CF2-CHF2, -0-CRF2, ~-O-CH2-CF3, S(0)nCF3, -S-CF2-CF2-CF3, -S(O)n-Alk, -S-Alk-O-Alk, -S- Alk-OH, -$-Alk-CN, -S-Alk-heterocycloalkyl, (description : morpholino, pyrrolidinyl, piperazinyl, optionally substituted with alk), -SO2CHF2, -SO2CF2CF3, -S0O2NR5R6 and -SFS5, in which Alk represents an alkyl. radical containing from 1 to 4 carbon atoms, and the other from among Y and Y1 is chosen from the following values: hydrogen, halogen, nitro, NRS5R6, free or esterified carboxyl, and CONRS5R6, or alternatively the phenyl radical forms, with its substituents Y and Y1, one of the following radicals: CF, J ;
    ® 497 : : the radical thus formed being optionally substituted with one or more alkyl radicals, which are themselves optionally substituted, _ the other substituents of said products of formula (I) being chosen from the values defined in claim 1, it being understood that: a) when p represents the integer 0, R represents oxygen, R1 represents oxygen, Al represents a single bond or alkyl, Y and Yl, which may be identical or different, are such that one represents hydrogen and the other represents OCF3 or Salk, A2 represents a single bond or alkyl and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other imidazolylalkyl, b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one : represents hydrogen and the other represents OCF3, SOAlk, ' S(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 we and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk always substituted with a hydroxamate -CO-NHOH c¢) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents S(0)nAlk, A2 represents a single bond and B2 represents an optionally substituted 5- or 6-membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, said product of formula (I) being in any possible racemic, enantiomeric or diastereocisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I).
    ° 498 5) The product of formula (I) as defined in any one of the claims, in which one from among Y and Yl represents a hydrogen atom and the other is chosen from OCF3, S(0)nCF3, S(0)nAlk, SO2CHF2, SO2CF2CF3 and SO2NRS5R6,
    the other substituents of said product of formula (I) being chosen from the values defined in claim 1 and it being understood that:
    a) when p represents the integer 0, R represents oxygen, Rl represents oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents OCF3 or Salk, A2 represents a single bond or : alkyl and B2 represents "an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other imidazolylalkyl, b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Yl, : which may be identical or different, are such that one represents hydrogen and the other represents OCF3, SOAlk, S(0O)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk always substituted with a hydroxamate -CO-NHOH
    «¢) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents S(0)nAlk, a2 represents a single bond and B2 represents an optionally substituted 5- or 6-membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, said product of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form,
    and also the addition salts with mineral and organic acids or with mineral and organic bases of said product hd 499 of formula (I). 6) The product of formula (I) as defined in any one of the claims, in which one from among Y and Yl represents a hydrogen atom and the other is chosen from S (0) nCF3, . 5 SOAlk, S{0O)2Alk, SO2CHF2, SO2CF2CF3 and SO2NRSR6, : the other substituents of said product of formula (I) being chosen from the values defined in claim. 1 and it being understood that the product of formula (I) is as defined below in a) and b): a) when p represents the integer 0, R and R1l represent oxygen, Al represents a single bond or alkyl, Y and Yl, which may be identical or different, are such that one represents hydrogen and the other represents SOAlk, S(0)2alk or SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk : always substituted with a hydroxamate -CO-NHOH b) when p represents the integer 0, R and Rl represent oxygen, Al represents a single bond or alkyl, Y and Y1, wr which may be identical or different, are such that one represents hydrogen and the other represents SOAlk or S(0)2Alk, A2 represents a single bond and B2 represents an optionally substituted ©5- or 6-membered aromatic heterocyclic radical, then R2 and R3 are not chosen from hydrogen, alkyl, arylalkyl, aryl and heteroaryl, said product of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I). 7) The product of formula (I) as defined in any one of the claims, in which one from among Y and Y1 represents a hydrogen atom and the other 1s chosen from S(0)nCF3, SO2CHF2, SO2CF2CF3 and SO2NR5R6, the other substituents of said product of formula (I)
    o 500 being chosen from the values defined in claim 1 and it being understood that when p represents the integer 0, R and R1 represent oxygen, Al represents a single bond or alkyl, Y and Y1, which may be identical or different, are such that one represents hydrogen and the other represents SO2NH2, A2 represents CH2 and B2 represents an optionally substituted heterocyclic radical, then R2 and R3 do not represent one hydrogen and the other an alkyl chain optionally interrupted with O, S or Nalk, always substituted with a hydroxamate -CO-NHOH said product of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form,
    and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I). 8) The product of formula (I) as defined in any one of the claims, in which one from among Y and Yl represents a hydrogen atom and the other is chosen from S(0)nCF3, SO2CHF2 and SO2CF2CF3, :
    the other substituents of said product of formula (I) being chosen from the values defined in claim 1, said product of formula (I) being in any possible racemic, enantiomeric or diastereocisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said product. of formula (I).
    9) The product of formula (I) as defined in any one of the claims, such that all the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl radicals defined in claim 1 are optionally substituted with one or more radicals, which may be identical or different, chosen from halogen, cyano, hydroxyl, alkoxy, CF3, nitro, phenyl, carboxyl which is free, salified, esterified with an alkyl radical or amidated with a radical NRllaRl2a,
    -C(=0) -R9a, -NRllaRl2a, -C(=0)-NRllaRl2a, -N(Rl0a)-C(=0)- R9a, -N(R10a) -C(=0) -OR8a, N(R1l0a)-C(=0)-NR1laR1l2a, -
    ® 501 : N(R10a)-S(0)n-R9a, -S(0)n-R9a, -N(R10a)-S(O)n-NRllaRl2a ~ or -(0)n-NRllaRl2a, all the aryl and heteroaryl radicals above furthermore being optionally substituted with an ethylenedioXy
    : 5 radical, :
    R8a represents hydrogen, alkyl, alkenyl, phenyl,
    phenylalkyl, heteroaryl or heterocarylalkyl, : :
    R9%a represents alkyl, cycloalkyl, cycloalkylalkyl,
    heterocycloalkyl, heterocycloalkylalkyl, phenyl, phenylalkyl, heteroaryl or heteroarylalkyl,
    R10a represents hydrogen or alkyl,
    Rlla and R12a, which may be identical or different represent hydrogen, alkyl, cycloalkyl, «cycloalkylalkyl, phenyl,
    phenylalkyl, optionally substituted with one or more substituents, which may be identical or different, chosen from halogen, hydroxyl, Cl-C4 alkyl or Cl-C4 alkoxy, or
    : alternatively Rlla and Rl2a form, with the nitrogen atom ' to which they are attached, a cyclic radical chosen from pyrrolidyl, piperidyl, piperazinyl, morpholinyl,
    we indolinyl, pyrindolinyl, tetrahydroquinolyl, thiazolidinyl and naphthyridyl, said product of formula (I) being in any possible racemic, enantiomeric or diasterecisomeric isomer form,
    and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I). 10) The product of formula (I) as defined in any one of the claims, such that p represents the integer 0, the other substituents of said product of formula (I) having the values defined in any one of the claims.
    11) The product of formula (I) as defined in any one of the claims, such that p represents the integer 1, the other substituents of said product of formula (I) having the values defined in any one of the claims.
    12) The product of formula (I) as defined in any one of
    ® 502 the claims, such that p represents the integer 2, the other substituents of said product of formula (I) having the values defined in any one of the preceding claims.
    13) The product of formula (I) as defined in any one of the claims, such that R1 represents 0, the other substituents of said product of formula (I) having the values defined in any one of the claims. 14) The product of formula (I) as defined in any one of the claims, such that R represents 0, the other substituents of said product of formula (I) having the values defined in any one of the claims. 15) The product of formula (I) as defined in any one of : the claims, such that R2 and R3, which may be identical or different, represent hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, phenyl, phenylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heterocarylalkyl, which are optionally substituted, or : alternatively R2 and R3 form, together with the carbon atom to which they are attached, a carbocyclic or heterocyclic radical, these radicals being 3- to 10- membered and the heterocyclic radical containing one or more hetero atoms chosen from O, S, N and NR7b, all these radicals being optionally substituted, all the above radicals being optionally substituted with 2% one or more radicals chosen from halogen, cyano, hydroxyl, alkyl and alkoxy containing 1 to 4 carbon atoms, CF3, nitro, phenyl, carboxyl which is free, salified, esterified with an alkyl radical or amidated with a radical NR11bR12b, -C(=0)-RSb, -NR11bR1l2b and -C(=0) -NR11bR12b, R7b represents a hydrogen atom, an alkyl radical or a phenyl radical, RS represents hydrogen, alkyl, cycloalkyl, cycloalkyl- alkyl or phenyl, R1lb and R12b, which may be identical or different, represent
    ® 503 : hydrogen, alkyl, cycloalkyl or phenyl, or alternatively " R11b and R12b form, with the nitrogen atom to which they are attached, an optionally substituted piperazinyl radical, the other substituents of said product of formula (I) having the values defined in any one of the claims. 16) The product of formula (I) as defined in any one of the claims, such that R2 and R3, which may be identical or different, are chosen from hydrogen, alkyl,
    phenylalkyl, pyridylalkyl, benzothienylalkyl and thienylbenzothienylalkyl, which are optionally substituted with one or more radicals chosen from halogen atoms and hydroxyl, alkyl and alkoxy radicals containing from one to 4 carbon atoms, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a 3- to 6 -membered cycloalkyl - or heterocycloalkyl radical containing a nitrogen atom, the
    : other substituents of said products of formula (I) having the values defined in any one of the claims.
    17) The product of formula (I) as defined in any one of wee the claims, such that R2 and R3, which may be identical or different, are chosen from hydrogen, alkyl, hydroxyalkyl, phenylalkyl, hydroxyphenylalkyl, pyridylalkyl, benzothienylalkyl or thienylbenzothienylalkyl, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a cycloalkyl radical containing from 3 to 6 carbon atoms or an azetidinyl, pyrrolidyl or piperidyl radical,
    the other substituents of said products of formula (I) having the values defined in any one of the claims.
    18) The product of formula (I) as defined in any one of the claims, such that R2 and R3, which may be identical or different, are chosen from hydrogen, alkyl,
    hydroxyalkyl, phenylalkyl and hydroxyphenylalkyl, or alternatively R2 and R3 form, together with the carbon
    ® 504 atom to which they are attached, a cycloalkyl radical : containing from 3 to 6 carbon atoms.
    19) The product of formula (I) as defined in any one of the claims, such that one from among R2 and R3 is chosen from hydrogen and alkyl, and the other from among R2 and R3 1s chosen from all the values of R2 and R3, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a cycloalkyl radical containing from 3 to 6 carbon atoms,
    the other substituents of said product of formula (I) having the values defined in any one of the claims.
    20) The product of formula (I) as defined in any one of the claims, such that R2 and R3, which may be identical or different, represent hydrogen and alkyl, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a cycloalkyl radical containing from 3 to 6 carbon atoms, the other substituents of said product of formula (I) having the values defined in any one of the claims.
    21) The product of formula (I) as defined in any one of the claims, such that R2 and R3, which may be identical or different, represent hydrogen and CH3, or alternatively R2 and R3 form, together with the carbon atom to which they are attached, a cyclopropyl radical,
    the other substituents of said product of formula (I) having the values defined in any one of the claims.
    22) The product of formula (I) as defined in any one of the claims, such that Al represents a single bond and A2 is chosen from a single bond, a linear or branched alkyl radical containing not more than 6 carbon atoms and allyl, ©propynyl, <C=0 and S02 radicals, the other substituents of said product of formula (I) having the values defined in any one of the claims.
    23) The product of formula (I) as defined in any one of the preceding claims, such that Al represents a single bond and A2 is chosen from a single bond, alkyl, allyl,
    ® | 505 , propynyl, C=0 and S02 radicals, the other substituents of said product of formula (I) having the values defined in any one of the claims. : 24) The product of formula (I) as defined in any one of the claims, such that Al represents a single bond and A2 represents un alkyl or C=0 radical, the other substituents of said product of formula (I) having the values defined in any one of the claims. 25) The product of formula (I) as defined in any one of the claims, such that Al represents a single bond and A2 represents C=0, -CH2-CH2- or -CH2, the other substituents of said product of formula (I) having the values defined in any one of the claims. 26) The product of formula (I) as defined in any one of ~ the claims, such that Al represents a single bond and A2 represents -CH2, the other substituents of said preduct of formula (I) having the values defined in any one of the claims. : 27) The product of formula (I) as defined in any one of the claims, in which Y and Y1 are such that one i. represents a hydrogen atom, a halogen atom or an amino radical and the other is chosen from OCF3, -0O-CF2-CHF2, -O-CHF2, -0-CH2-CF3, -SF5, -S(0)n-CF3, -S (0)n-Aalk, -SO2CHF2, SO2CF2CF3, -SO2NH2, -S-CF2-CF2-CF3, -S-Alk-0O- Alk, -S-Alk-0OH, -S-Alk-CN, -8-Alk-morpholino, -S-Alk- pyrrolidinyl and -S-Alk-piperazinyl, the morpholino, pyrrolidinyl and piperazinyl radicals being optionally substituted with Alk, in which Alk represents an alkyl radical containing from 1 to 4 carbon atoms, the other substituents of said product of formula (I) having the values defined in any one of the claims. 28) The product of formula (I) as defined in any one of the claims, such that Y represents a hydrogen atom and vi is chosen from -0OCF3, S{(O)n-CF3, S(0O)n-CH3, SO2CHF2 and S02-N{(alk)2, the other substituents of said product of formula (I)
    ® 506 having the values defined in any one of the claims. 29) The product of formula (I) as defined in any one of the claims, such that Y represents a hydrogen atom and Y1 is chosen from -OCF3, S{0O)n-CF3 and SO2CHF2,
    the other substituents of said product of formula (I)
    having the values defined in any one of the claims. 30) The product of formula (I) as defined in any one of the claims, such that Y represents a hydrogen atom and Y1 is chosen from -OCF3 and S(0O)n-CF3,
    the other substituents of said product of formula (I) having the values defined in any one of the claims.
    31) The product of formula (I) as defined in any one of : the claims, such that Y represents a hydrogen atom and Y1 is chosen from -OCF3, S-CF3 and S(0)2-CF3,
    the other substituents of said product of formula (I) having the values defined in any one of the claims.
    32) The product of formula (I) as defined in any one of the claims, such that B2 represents a monocyclic or bicyclic heteroaryl radical chosen from pyridyl, pyrimidinyl, quinolyl, azaindolyl, 1H- pyrrolo[2,3-blpyridinyl, guinazolyl, thiazolyl, imidazolyl, pyrazolyl, furazanyl, isoxazolyl, morpholinyl, pyrrolidinyl, furyl, piperidyl, thienyl, chromenyl, oxochromenyl, indolyl, pyrrolyl, purinyl,
    Dbenzoxazinyl, benzimidazolyl and benzofuranyl radicals, these radicals being optionally substituted with one or more radicals chosen from the values of Y2, the other substituents of said product of formula (I) having the values defined in any one of the claims.
    33) The product of formula (I) as defined in any one of the claims, such that B2 represents a heteroaryl radical chosen from 3- or 4-pyridyl, pyrimidinyl, 3- or 4-guinolyl, azaindolyl, gquinazolyl, thiazolyl, imidazolyl, pyrazolyl, furazanyl and isoxazolyl radicals,
    these radicals being optionally substituted with one or more radicals chosen from the values of Y2,
    ® | 507 : the other substituents of said product of formula (I) ~ having the values defined in any one of the claims. 34) The product of formula (I) as defined in any one of oo the claims, such that B2 represents a heteroaryl radical chosen from 3- or 4-pyridyl, pyrimidinyl, 3- or 4-quinolyl, azaindolyl and gquinazolyl radicals, these radicals being optionally substituted with one or more radicals chosen from the values of Y2, the other substituents of said product of formula (I) having the values defined in any one of the claims. 35) The product of formula (I) as defined in any one of the «claims, such that B2 represents 4-pyridyl and 4-quinolyl and 1H-pyrrolo[2,3-blpyrid-3-yl radicals optionally substituted with one or more radicals chosen from the values of Y2 defined in any one of the claims, the other substituents of said product of formula (I) having the values defined in any one of the claims. : 36) The product of formula (I) as defined in any one of the claims, such that Y2 represents hydrogen, halogen, hydroxyl, cyano, alkyl, alkoxy, phenyl, COOH, COCAlk, wr CONRSR6, NRS5R6, -NR10-COOR6, -NR10-CO-R6, -NR10-CS-NR5R6, -NR10-CO-NR5R6 or -NR10-SO2-Ré, all these radicals being optionally substituted, R5 and R6, which may be identical or different, are chosen from hydrogen, alkyl, cycloalkyl, phenyl and 5- or 6-membered heteroaryl radicals containing 1 to 3 hetero atoms chosen from O, N and S, all these radicals being optionally substituted, or alternatively R5 and R6 form, with the nitrogen atom to which they are attached, an optionally substituted pyrrolidinyl, piperidyl, piperazinyl, morpholinyl or quinazolinyl radical, R10 represents hydrogen or alkyl, all the alkyl, alkoxy, cycloalkyl and phenyl radicals above, and also the ring formed by R5 and R6 with the atom to which they are attached, being optionally substituted with one or more radicals, which may be
    ® 508 identical or different, chosen from halogen atoms and the following radicals: cyano; hydroxyl; alkyl; alkoxy; OCF3; CF3; S(0O)n-CF3; nitro; oxo; thioxo; O0OCOAlk; phenyl, itself optionally substituted with one or more radicals chosen from halogen atoms and alkyl and alkoxy radicals; -0COAlk; NH2, NHAlk, N(Alk)2, N (alk) (phenylalkyl), N(Alk) (aminoalkyl), N (Alk) (alkylaminoalkyl) N(Alk) (dialkylaminoalkyl) ; carboxyl in free form or esterified with an alkyl radical,
    all the phenyl radicals above also being optionally substituted with an alkylenedioxy radical, all the alkyl radicals above also being optionally
    : substituted with one or more saturated or partially unsaturated 4- to 7-membered heterocyclic radicals containing at least one nitrogen atom N and also 0 to 2 other hetero atoms chosen from O, N and S, all the pyrrolidinyl and quinazolinyl radicals above also : being optionally substituted with oxo or thioxo, all the alkyl and alkoxy radicals above being linear or branched and containing not more than 6 carbon atoms, all the cycloalkyl radicals above containing not more than 7 carbon atoms, the other substituents of said product of formula (I) having the values defined in any one of the claims.
    37) The product of formula (I) as defined in any one of the claims, such that Y2 represents hydrogen, halogen, hydroxyl, cyano, alkyl, alkoxy, phenyl, CONRSR6, NRERS6, -NR10-COOH, _NR10-COOAlk, -NR10-CO-RS6, -NR10-CS-NR5R6, -NR10-CO-NR5R6 or -NR10-SO2-R6,
    RS and R6, which may be identical or different, are chosen from hydrogen; alkyl; cycloalkyl; phenyl; pyrimidinyl; thienyl; pyridyl; quinolyl; thiazolyl optionally substituted with one or two halogen atoms; pyran optionally substituted with one or more OCOAlk;
    phenyl substituted with one or more radicals chosen from halogen atoms and alkyl, alkoxy, amino, alkylamino,
    ® 509 : : dialkylamino radicals and carboxyl in free form or esterified with an alkyl radical; alkyl substituted with phenyl, which is itself optionally substituted with one or more radicals chosen from halogen atoms, alkyl, oo 5 alkoxy, amino, alkylamino, dialkylamino, carboxyl in free form or esterified with an alkyl radical; alkyl substituted with piperazinyl, which is itself optionally substituted with one or more radicals chosen from AlKk, Alk-OH and pyridyl; alkyl substituted with imidazolyl; alkyl substituted with one or more radicals chosen from NH2, NHAlk, N(Alk) 2, N (alk) (phenylalkyl), N(Alk) (aminocalkyl), N(Alk) (alkylaminoalkyl) and N(Alk) (dialkylaminoalkyl) ; alkyl © substituted with morpholinyl optionally substituted with one or two Alk; alkyl substituted with pyrrolidinyl; alkyl substituted with piperidyl, which is itself optionally substituted with one or two Alk; alkyl substituted with thiomorpholinyl; alkyl substituted with azetidinyl; alkyl substituted with azepanyl, which is optionally substituted with oxo, we or alternatively R5 and Ré form, with the nitrogen atom to which they are attached, a pyrrolidinyl; piperidyl; piperazinyl; morpholinyl; or gquinazolinyl radical, all these radicals being optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and alkyl, hydroxyl and alkoxy radicals, and phenyl radicals the latter of which is itself optionally substituted with one or more radicals chosen from halogen atoms and alkyl and alkoxy radicals, the pyrrolidinyl and quinazolinyl radicals also being optionally substituted with oxo or thioxo, the piperazinyl radical itself being optionally substituted with one or more radicals chosen from Alk, Alk-OH and pyridyl, R10 represents hydrogen or alkyl,
    hg 510 all the alkyl or Alk and alkoxy radicals above being : linear or branched and containing not more than 6 carbon atoms, all the cycloalkyl radicals above containing not more than 7 carbon atoms, all the phenyl radicals also being optionally substituted with a radical chosen from CF3, -QCF3, nitro and alkylenedioxy, the other substituents of said product of formula (I)
    having the values defined in any one of the claims.
    38) The product of formula (I) as defined in any one of the claims, such that Y2 represents V1, halogen, : hydroxyl, _C(=NH)NH2, OV1, 0-CO-V1, COOVl1, COV1, CO-NV1V2, -NV1v2, -NH-CO-V1, -NH-CO0-V1, -NH-NH-CO-V1,
    -NV1-CO-NV1V2, -NV1-CO-NHV1, -NH-CO-NHV1, -NH-S0O2-NHV1 and -NH-S02-V1, in which V1 and V2, which may be identical or different, represent a hydrogen atom, an alkyl, cycloalkyl or phenyl radical or a heterocyclic radical such as pyridinyl,
    pyrazolyl, imidazolyl, dihydroimidazolyl, tetrazolyl, morpholinyl, piperazinyl, piperazinylalkyl, alkylpiperazinyl, phenylpiperazinyl, thienyle, furanyl, piperidyl, methylpiperidyl, pyridyl, pyrrolidyl and pyrrolidylalkyl,
    all the alkyl, phenyl and heterocyclic radicals being optionally substituted with one or more radicals chosen from halogen atoms and hydroxyl, alkyl, alkoxy, CF3, NH2, NHalk, N(alk)2 radicals and a phenyl radical, itself optionally substituted with one or more substituents chosen from halogen atoms and hydroxyl or alkoxy radicals, all the phenyl and heterocyclic radicals above furthermore being optionally substituted with one or more alkyl radicals,
    the phenyl radicals furthermore being optionally substituted with NRS5R6 in which R5 and R6 are as defined
    ® 511 : in claim 1, the other substituents of said product of formula (I) having the values defined in any one of the claims. 39) The product of formula (I) as defined in any one of : 5 the claims, such that Y2 represents hydrogen, halogen, alkyl, cycloalkyl, hydroxyl, alkoxy, carboxyl. which is free or esterified with an alkyl or phenyl radical, NHZ, NHalk, N(alk)2 and phenyl, all the alkyl, alkoxy and phenyl radicals being optionally substituted with one or more radicals chosen from halogen atoms and hydroxyl, CC1-C4 alkyl, C1-C4 alkoxy, CF3, NH2, NHalk and N(alk)2 radicals and a phenyl radical, which is itself optionally substituted with one or more substituents chosen from halogen atoms and : hydroxyl or alkoxy radicals, all the phenyl radicals furthermore being optionally substituted with one or more Cl1-C4 alkyl radicals and : optionally substituted with NRS5R6 in which R5 and R6é are as defined above, the other substituents of said product of formula (I) we having the values defined in any one of the claims. 40) The product of formula (I) as defined in any one of the claims, such that Y2 represents hydrogen, F, Cl, CH3, CH2CH3, OH, OCH3, ©NH2, ©NHAlk and phenyl optionally substituted with NR5R6 in which R5 and R6 are as defined in claim 1, the other substituents of said product of formula (I) having the values defined in any one of the claims. 41) The product of formula (I) as defined in any one of the claims, such that B2 represents 4-pyridyl and 4- guinolyl radicals substituted with one or more radicals chosen from F, Cl, OH and OCH3, the other substituents of said product of formula (I) having the values defined in any one of the claims. 42) The product of formula (I) as defined in any one of the claims, corresponding to formula (IC):
    ® 512 0 LE N R,C PS Cc | | © 1 1c) B,C le in which YC and Y1C are such that one represents a hydrogen atom, a halogen atom or an amino radical and the other is chosen from -OCF3, -O-CF2-CHF2, -0O-CHF2, -O-CH2-
    : CF3, -SF5, -S(O)n-CF3, _s(0)n-Alk, -SO2CHF2, SO2CF2CF3, -SO2NH2, -S-CF2-CF2-CF3, -S-Alk-0-Alk, -S-Alk-OH, -S-Alk-
    CN, -S-Alk-morpholino, -S-Alk-pyrrolidyl and -S-Alk- piperazinyl, the morpholino, pyrrolidyl and piperazinyl radicals being optionally substituted with Alk, with Alk representing an alkyl radical containing from 1 to 4 carbon atoms,
    or alternatively the phenyl radical forms with its substituents YC and Y1C one of the two following radicals:
    5 ® ALK S
    ALK SL with Alk representing an alkyl radical containing from 1 to 4 carbon atoms, R2C and R3C, which may be identical or different, represent hydrogen or optionally substituted alkyl, or alternatively R2C and R3C, which may be identical or different, represent hydrogen or optionally substituted alkyl or alternatively R2C and R3C form, together with
    ® 513 the carbon atom to which they are attached, a C€3-C10 : cycloalkyl or heterocycloalkyl radical,
    A2C represents a single bond or CH2, B2C represents pyridyl, pyrimidyl, quinolyl, azaindolyl,
    quinazolyl, thiazolyl, imidazolyl, pyrazolyl, furazanyl,
    isoxazolyl, morpholinyl, pyrrolidyl, furyl, piperidyl, chromenyl, oxochromenyl, quinazolyl, thienyl, indolyl, pyrrolyl, purinyl, benzoxazinyl, benzimidazolyl or benzofuryl radicals, optionally substituted with one or more radicals chosen from the values of Y2A, Y2CA represents hydrogen, halogen, hydroxyl, cyano, alkyl, alkoxy, phenyl, COOH, COOAlk, CONRS5R6, NRS5R6, : -NR10-COOH, -NR10-CCOAlk, _NR10-CO-R6, -NR10-CS-NR5R6, -NR10-CO-NR5R6 or -NR10-S0O2-R6, all these radicals being optionally substituted, R5 and R6, which may be identical or different, are chosen from hydrogen, alkyl, cycloalkyl, phenyl, pyrimidyl, thienyl, pyridyl, quinolyl, thiazolyl and pyran, all these radicals being optionally substituted,
    or alternatively R5 and Ré form, with the nitrogen atom to which they are attached, an optionally substituted pyrrolidyl, piperidyl, piperazinyl, morpholinyl or quinazolinyl radical, R10 represents hydrogen or alkyl,
    all the alkyl, alkoxy, cycloalkyl and phenyl radicals above, and also the ring formed by R5 and R6 with the atom to which they are attached, being optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and the following radicals: cyano; hydroxyl; alkyl; alkoxy; OCF3; CF3; S(0)n-CF3; nitro; oxo; thioxo; OCOAlk; phenyl, itself optionally substituted with one or more radicals chosen from halogen atoms and alkyl and alkoxy radicals; -OCOAlk; NH2, NHAlk, N (Alk) 2, N(alk) (phenylalkyl),
    N{Alk) (aminoalkyl) N(Alk) (alkylaminocalkyl)
    ® 514 : N(Alk) (dialkylaminoalkyl) ; carboxyl in free form or esterified with an alkyl radical, all the phenyl radicals above also being optionally : substituted with an alkylenedioxy radical, all the alkyl radicals above also being optionally substituted with one or more radicals chosen. from the following radicals: piperazinyl, itself optionally substituted with Alk, Alk-OH and pyridyl; imidazolyl: morpholinyl; pyrrolidyl; piperidyl, itself optionally substituted with one or two alk; azepanyl optionally substituted with oxo, all the pyrrolidyl and gquinazolinyl radicals above also being optionally substituted with oxo or thioxo, all the alkyl and alkoxy radicals above being linear or branched and containing not more than 6 carbon atoms, all the cycloalkyl radicals above containing not more than 7 carbon atoms, n represents an integer from 0 to 2, : J said products of formula (IC) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, es and also the addition salts with mineral and organic acids or with mineral and organic bases of said products of formula (IC). 43) The product of formula (I) as defined in any one of the claims, corresponding to formula (IA):
    [0] N RA A o 1 (1A) BA : I in which:
    ® 515 Y1A represents -OCF3, S{O)n-CF3 and SO2CHF2, . B2a represents 4-quinolyl and 4-pyridyl radicals optionally substituted with one or more radicals chosen from the values of Y2Aa, Y2A has the meaning given in any one of the claims for Y2, R2A and R3A, which may be identical or different, represent hydrogen or optionally substituted alkyl, or alternatively R2A and R3A form, together with the carbon atom to which they are attached, a C3-Cl0 cycloalkyl or heterocycloalkyl radical, all the alkyl and phenyl radicals being optionally substituted with one or more radicals chosen from halogen, OH, alk, Oalk, OCF3, S(0)n-CF3, CF3, NH2, NHAlk and N (alk) 2,
    n represents an integer fom 0 to 2,
    said product of formula (IA) being in any possible : racemic, enantiomeric or diasterecisomeric isomer form,
    and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (IA).
    44) The product of formula (IA) as defined in the preceding claim, in which Y1A, B2a, R2A and R3A have the meanings given above and Y2A represents halogen, -OH,
    -alk, Oalk, + -Oacvyl, -NR5AR6GA, -CO2H, -C02alk, -CO- NRSAR6A, -S(0)n-CF3, -NH-S(O)n-CF3 or phenyl radicals, alk representing a linear or branched alkyl radical containing not more than 6 carbon atoms, all the alkyl, alkoxy and phenyl radicals being optionally substituted,
    RBA and R6A, which may be identical or different, represent hydrogen, alkyl, cycloalkyl or phenyl, the alkyl and phenyl radicals being optionally substituted, or alternatively RS5A and R6A form, with the nitrogen atom to which they are attached, a cyclic radical chosen from pyrrolidyl, piperidyl, piperazinyl, morpholinyl, piperazinyl, indolinyl, pyrindolinyl, tetrahydroquinolyl
    ® 516 : and azetidinyl radicals, all the alkyl, alkoxy and phenyl radicals being optionally substituted with one or more radicals chosen : from halogen, OH, alk, Oalk, OCF3, S(0O)n-CF3, CF3, NH2, NHAlk and N(alk)2, n represents an integer from 0 to 2, said product of formula (IA) being in any. possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (IA).
    45) The product of formula (I) as defined in any one of the claims, corresponding to formula (IA) in which: Y1A represents -OCF3, SCF3 or S(0)2-CF3, ~
    B2a represents a 4-quinolyl or 4-pyridyl radical optionally substituted with one or two radicals chosen from halogen, -OH, alk, -0Oalk, -CO2H, -CO2alk, -NRS5AR6A,
    : -CF3, -OCF3 and optionally substituted phenyl, ‘
    RSA and R6A, which may be identical or different,
    represent hydrogen, alkyl, cycloalkyl or phenyl, the mas alkyl and phenyl radicals being optionally substituted,
    or alternatively R5A and R6A form, with the nitrogen atom to which they are attached, a cyclic radical chosen from pyrrolidyl, piperidyl, piperazinyl, morpholinyl,
    piperazinyl and azetidinyl radicals, R2A and R3A, which may be identical or different,
    represent hydrogen or optionally substituted alkyl, or alternatively R2A and R3A form, together with the carbon atom to which they are attached, a C3-C6 cycloalkyl or heterocycloalkyl radical, all the alkyl and phenyl radicals being optionally substituted with one or more radicals chosen from halogen, OH, alk, Oalk, OCF3, S(O)n-CF3, CF3, NH2, NHalk and N(alk) 2,
    said product of formula (IA) being in any possible, racemic, enantiomeric or diastereoisomeric isomer form,
    ® 517 and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (IA).
    46) The product of formula (I) as defined in any one of the claims, corresponding to formula (IA) in which: Y1A represents -OCF3, SCF3 or S(0)2-CF3, B2a represents a 4-quinolyl or 4-pyridyl radical optionally substituted with one or two radicals chosen from halogen, -OH, alk and -Oalk,
    R2A and R3A, which may be identical or different, represent hydrogen and linear or branched alkyl containing not more than 4 carbon atoms optionally
    : substituted with a hydroxyl radical, or alternatively R2A and R3A form, together with the carbon atom to which they are attached, a C3-Cé cycloalkyl radical, said product of formula (IA) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, : and also the addition salts with mineral and organic acids or with mineral and. organic bases of said product of formula (IA).
    47) The product of formula (I) as defined in any one of the claims, corresponding to formula (IA) in which Yila represents OCF3, SCF3 or S(0)2CF3 and R2A and R3A, which may be identical or different, represent hydrogen and
    CH3, or alternatively R2A and R3A form, together with the carbon atom to which they are attached, a cyclopropyl radical, the other substituents having the values given in any one of the claims,
    said product of formula (IA) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (IA).
    48) The product of formula (I) as defined in any one of the claims, corresponding to formula (IB):
    ht 518 ' 0 ee a, ~~ N R2 A N Oo i" (1B) I" Y, © in which R2, R3, Al, ¥, Yl, A2, B2 and Y2 have the ~ meanings given in any one of the claims, said product of formula (IB) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, : and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (IB). we 49) The product of formula (IB) as defined in the preceding claim, in which Y1 represents OCF3, SCF3 or S(O)2CF3 and R2 and R3, which may be identical or different, represent hydrogen and CH3 or, alternatively R2 and R3 form, together with the carbon atom to which they are attached, a cyclopropyl radical, the other substituents having values given in any one of the claims, said product of formula (IB) being in any possible racemic, enantiomeric or diastereocisomeric isomer form, and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (IB). 50) The product of formula (I) as defined in any one of the claims, the names of which are below: - (8)-5-methyl-l-quinol-4-ylmethyl-3-(4-trifluoromethane-
    ® : :
    sul fonylphenyl)imidazolidine-2,4-dione trifluorcacetate : - (8)-5-methyl-1-pyrid-4-ylmethyl-3-(4-trifluoromethane- sul fonylphenyl)imidazolidine-2,4-dione trifluorocacetate - (S) -5-methyl-1-quinol-4-ylmethyl-3-(4-trifluoromethyl- sulfanylphenyl)imidazolidine-2,4-dione trifluorocacetate - 5,5-dimethyl-1-quinol-4-ylmethyl-3-(4-trifluoromethane- sul fonylphenyl)imidazolidine-2,4-dione trifluoroacetate - (R)-S5-methyl-1-quinol-4-ylmethyl-3-(4-trifluoromethane- sul fonylphenyl)imidazolidine-2,4-dione trifluorocacetate
    - (R)-S5S-methyl-l-guinol-4-ylmethyl-3-(4-trifluoromethyl- sulfanylphenyl)imidazolidine-2,4-dione trifluorocacetate - (R)-5-methyl-1-pyrid-4-ylmethyl-3-(4-trifluoromethane-
    : sulfonylphenyl)imidazolidine-2,4-dione trifluorocacetate - (R)-5-methyl-1-(3-methylpyrid-4-ylmethyl)-3-(4-tri-
    fluoromethanesulfonylphenyl) imidazolidine-2,4-dione trifluorcacetate - (R)-4-methyl-3-gquinol-4-ylmethyl-5-thioxo-1-(4-tri- fluoromethylsulfanylphenyl)imidazolidin-2-one trifluorocacetate :
    - (R)-5-isopropyl-l1-quinol-4-ylmethyl-3-(4-trifluoro- methylsulfanylphenyl) imidazolidine-2,4-dione trifluorocacetate - (R)-5-isopropyl-1-quinol-4-ylmethyl-3-(4-trifluoro- methanesulfonylphenyl)imidazolidine-2, 4-dione trifluorocacetate - (R)-5-(4-hydroxy-benzyl)-1-quinol-4-ylmethyl-3-(4-tri- fluoromethanesul fonylphenyl) imidazolidine-2,4-dione trifluoroacetate - (R)-5- (4-hydroxy-benzyl)-1-pyrid-4-ylmethyl-3-(4-tri-
    fluoromethanesulfonylphenyl)imidazolidine-2,4-dione trifluoroacetate - (R)-5-(1-hydroxy-ethyl)-1-quinol-4-ylmethyl-3-(4-tri- fluoromethanesulfonylphenyl)imidazolidine-2,4-dione trifluoroacetate
    - 4-quinol-4-ylmethyl-6-(4-trifluoromethylsulfanyl- phenyl) -4,6-diazaspiro[2.4]heptane-5,7-dione hg 520 : : trifluorocacetate - 4-quinol-4-ylmethyl-6- (4-trifluoromethanesulfonyl- phenyl) -4,6-diazaspiro(2.4]heptane-5,7-dione trifluorocacetate - 4-pyrid-4-ylmethyl-6-(4-trifluoromethylsulfanylphenyl)- 4,6-diazaspiro [2.4] heptane-5,7-dione trifluoroacetate - 4-pyrid-4-ylmethyl-6-(4-trifluoromethanesulfonyl-- phenyl) -4,6-diazaspiro(2.4]heptane-5,7-dione trifluorocacetate - (R)-1-(3-hydroxypyrid-4-ylmethyl)-5-methyl-3-(4-tri- fluoromethylsulfanylphenyl)imidazolidine-2,4-dione trifluoroacetate - 5,5-dimethyl-1-quinol-4-ylmethyl-3- (4-trifluoromethoxy- phenyl) imidazolidine-2,4-dione trifluorocacetate E - 5,5-dimethyl-l-quinol-4-ylmethyl-3-(4-trifluoromethyl- sulfanylphenyl)imidazolidine-2,4-dione trifluorocacetate - 5,5-dimethyl-1- (3-methylpyrid-4-ylmethyl)-3-(4-tri- : fluoromethoxyphenyl)imidazolidine-2,4-dione trifluorocacetate - 5,5-dimethyl-1-(3-methylpyrid-4-ylmethyl)-3-(4-tri- wn fluoromethylsulfanylphenyl)imidazolidine-2,4-dione trifluorcacetate - 5,5-dimethyl-1- (3-methylpyrid-4-ylmethyl) -3-(4-tri- fluoromethanesulfonylphenyl)imidazolidine-2,4-dione trifluorocacetate - 1- (3-hydroxypyrid-4-ylmethyl)-5,5-dimethyl-3-(4-tri- fluoromethoxyphenyl)imidazolidine-2,4-dione trifluorocacetate - 1- (3-hydroxypyrid-4-ylmethyl)-5,5-dimethyl-3-(4-tri- fluoromethylsulfanylphenyl)imidazolidine-2,4-dione trifluorcacetate - 1- (3-hydroxypyrid-4-ylmethyl)-5,5-dimethyl-3-(4-tri- fluoromethanesulfonylphenyl) imidazolidine-2,4-dione trifluorocacetate - 4-quinol-4-ylmethyl-6-(4-trifluoromethoxyphenyl) -4,6- diazaspiro [2.4] heptane-5,7-dione trifluorocacetate
    ® 521 - 4-(3-methylpyrid-4-ylmethyl)-6-(4-trifluoromethylsulf- : anylphenyl) -4,6-diazaspiro [2.4] heptane-5,7-dione trifluorcacetate - 4- (3-hydroxypyrid-4-ylmethyl)-6-(4-trifluoromethoxy-
    phenyl) -4,6-diazaspiro [2.4] heptane-5,7-dione trifluorocacetate, - 4- (3-hydroxypyrid-4-ylmethyl) -6- (4-trifluoromethylsulf- anylphenyl) -4,6-diazaspiro [2.4] heptane-5,7-dione trifluorocacetate
    - 4- (3-hydroxypyrid-4-ylmethyl) -6-(4-trifluoromethane- sulfonylphenyl)-4,6-diazaspiro [2.4] heptane-5, 7-dione trifluorocacetate, :
    : said product of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form,
    and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I). : 51) The product of formula (I) as defined in any one of the claims, the names of which are given below:
    - {4-[5,5-dimethyl-2,4-dioxo-3-(4-trifluoromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl]lpyrid-2-yl}cyclo- propanecarboxamide trifluoroacetate;
    - 5,5-dimethyl-1-[2- (pyrid-2-ylamino)pyrid-4-ylmeth- yl] -3-(4-trifluoromethylsulfanylphenyl)imidazolidine-2,4-
    dione; compound with trifluoroacetic acid;
    - N-{4-[5,5-dimethyl-2,4-dioxo-3-(4-trifluoromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl] pyrid-2- y1}isobutyramide; compound with trifluoroacetic acid;
    - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl-
    sulfanylphenyl)imidazolidin-1l-ylmethyl]lpyrid-2- yl}propionamide; compound with trifluoroacetic acid;
    - 1-(2-aminopyrid-4-ylmethyl)-5,5-dimethyl-3-(4-tri- fluoromethylsulfanylphenyl)imidazolidine-2,4-dione hydrochloride;
    ® | 522 : : - {4-(5,5-dimethyl-2,4-dioxo-3~ (4-trifluoromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl] pyrid-2-yl}pyrid- ine-2-carboxamide trifluorocacetate; - N-{4-(5,5-dimethyl-2,4-dioxo-3- (4-trifluoyomethyl- sulfanylphenyl)imidazolidin-1-ylmethyllpyrid-2-yl}-3- piperid-1-ylpropionamide trifluoroacetate; :
    - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl]lpyrid-2-yl}-3-[4- (2-hydroxyethyl)piperazin-1-yl]propionamide trifluorocacetate; - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl]pyrid-2-yl}-3- morpholin-4-ylpropionamide trifluorocacetate;
    - N-{4-[5,5-dimethyl-2,4-dioxo-3-(4-trifluoromethyl- ~ sulfanylphenyl)imidazolidin-1-ylmethyllpyrid-2-yl}-3- pyrrolidin-1l-ylpropionamide trifluoroacetate; :
    - N-{4-[5,5-dimethyl-2,4-dioxo-3-(4-trifluoromethyl-
    : sulfanylphenyl)imidazolidin-1-ylmethyl]pyrid-2-yl}-3-(4- ‘ methylpiperazin-1-yl)propionamide trifluoroacetate; - 1-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- i sulfanylphenyl)imidazolidin-1-ylmethyl]lpyrid-2-yl}-3- phenylurea;
    - 1-[2-(6-ethylpyrid-2-ylamino)pyrid-4-ylmethyl] -
    5,5-dimethyl-3-(4-trifluoromethylsulfanylphenyl)imidazol- idine-2,4-dione;
    - 5,5-dimethyl-1-([2-(4-methylpyrid-2-ylamino)pyrid- 4-ylmethyl]-3- (4-trifluoromethylsulfanylphenyl) imid- azolidine-2,4-dione;
    - 5,5-dimethyl-1-[2-(6-methylpyrid-2-ylamino) pyrid-
    4-ylmethyl]l-3-(4-trifluoromethylsulfanylphenyl) imi- dazolidine-2,4-dione;
    - 1-[2-(4,6-dimethylpyrid-2-ylamino)pyrid-4-ylmeth- yl] -5,5-dimethyl-3- (4-trifluoromethylsulfanylphenyl) - ‘ imidazolidine-~2,4-dione;
    ® 523 . - 1-[2-(3,5-dichloropyrid-2-ylamino)pyrid-4-ylmeth- yl] -5,5-dimethyl-3- (4-trifluoromethylsulfanylphenyl) - imidazolidine-2,4-dione; - 5,5-dimethyl-1-[2- (pyrid-4-ylamino)pyrid-4-ylmeth- vyll-3-(4-triflucromethylsulfanylphenyl)imidazolidine-2,4- dione;
    - 5,5-dimethyl-1-[2-(pyrid-3-ylamino)pyrid-4-ylmeth- y1l]l-3-(4-trifluoromethylsulfanylphenyl)imidazolidine-2,4- dione;
    - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl]pyrid-2-yl}-3-(2- oxoazepan-1l-yl)propionamide;
    - 3-(benzylmethylamino) -N-{4-[5,5-dimethyl-2, 4-di- ox0-3-(4-trifluoromethylsulfanylphenyl)imidazolidin-1- ylmethyllpyrid-2-yl}propionamide;
    - 4,5-diacetoxy-6-acetoxymethyl-2-(3-{4-[5,5-dimeth- yl-2,4-dioxo-3-(4-trifluoromethylsulfanylphenyl) - : imidazolidin-1-ylmethyl]lpyrid-2-yl}thioureidoacetic acid;
    - 5,5-dimethyl-1-[2- (5-methylpyrid-2-ylamino)pyri-
    din-4-ylmethyl]-3-(4-trifluoromethylsulfanylphenyl)imid- azolidine-2,4-dione;
    - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl]pyrid-2-yl}-3,5- dimethoxybenzamide trifluoroacetate;
    - 5,5-dimethyl-1-[2- (pyrazin-2-ylamino)pyrid-4-yl-. methyl] -3-(4-trifluoromethylsulfanylphenyl)imidazolidine- 2,4-dione trifluorocacetate; - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- sul fanylphenyl)imidazolidin-1-ylmethyl]pyrid-2-yl}-3-(3-
    methylpiperid-1-yl)propionamide trifluoroacetate;
    - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluocromethyl- sul fanylphenyl)imidazolidin-1-ylmethyl]pyrid-2-yl}-3- (3,5-dimethylpiperid-1-yl)propionamide trifluoroacetate;
    - N-{4-[5,5-dimethyl-2,4-dioxo-3-(4-trifluoromethyl-
    sulfanylphenyl)imidazolidin-1-ylmethyl]pyrid-2-yl}-3- methoxybenzamide trifluorocacetate;
    ® | . : - {4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- sulfanylphenyl) imidazolidin-1-ylmethyl]lpyrid-2-yl}pyzr- azine-2-carboxamide trifluorocacetate; - {4-(5,5-dimethyl-2,4-dioxo-3-(4-trifluoxomethyl- sulfanylphenyl) imidazolidin-1-ylmethyllpyrid-2-yl}thio- phene-2-carboxamide trifluoroacetate; - N-{4-[5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethyl- sulfanylphenyl) imidazolidin-1-ylmethyl]pyrid-2-yl}-4- methylbenzamide; compound with trifluoroacetic acid; - 1-isoquinolin-5-yl-5,5-dimethyl-3-(4-trifluoro- methylsulfanylphenyl)imidazolidine-2,4-dione; - 3-(4-acetylpiperazin-1-yl)-N-{4-[5,5-dimethyl-2,4- dioxo-3- (4-trifluoromethylsulfanylphenyl)imidazolidin-1- © ylmethyllpyrid-2-yl}propionamide; ~ - 3-[4- (2-diethylaminoethyl)piperazin-1-yl] -N-{4- [5,5-dimethyl-2,4-dioxo-3- (4-trifluoromethylsulfanyl- phenyl) imidazolidin-1-ylmethyllpyrid-2-yl}propionamide; : - N-{4-[5,5-dimethyl-2,4-dioxo-3~(4-triflucromethyl- sulfanylphenyl)imidazolidin-1-ylmethyl)pyrid-2-yl}-3- (2,6-dimethylmorpholin-4-yl)propionamide;
    i. - N-{4-(5,5-dimethyl-2,4-dioxo-3-(4-trifluoromethyl- sulfanylphenyl) imidazolidin-1-ylmethyl]l pyrid-2-yl}-3- (4- pyrrolidin-1-ylpiperid-1-yl)propionamide; - N-{4-[5,5-dimethyl-2,4-dioxo-3-(4-trifluoromethyl- sulfanylphenyl) imidazolidin-1-ylmethyl)pyrid-2-yl}-2-(4- pyrrolidin-1l-ylpiperid-1-yl)acetamide; - 5,5-dimethyl-1-[2- (4-methylpyrid-3-ylamino)pyrid- 4-ylmethyl] -3- (4-trifluoromethylsulfanylphenyl) imid- azolidine-2,4-dione; - 5,5-dimethyl-1-[2- (6-morpholin-4-ylpyrid-3-yl- amino) pyrid-4-ylmethyl}-3- (4-trifluoromethylsulfanyl- phenyl) imidazolidine-2,4-dione; . - 1-[2-(2,6-dimethylpyrid-3-ylamino)pyrid-4-ylmeth- y1l]-5,5-dimethyl-3- (4-trifluoromethylsulfanylphenyl)imid- azolidine-2,4-dione;
    hg 525 .- methyl. 5-{4-[5,5-dimethyl-2,4-dioxo-3- (4-tri- fluoromethylsulfanylphenyl)imidazolidin-1-ylmethyl]pyrid- 2-ylamino}pyridine-2-carboxylate; - 1-[2-(2,6-dimethoxypyrid-3-ylamino)pyrid-4-ylmeth- vyl]-5,5-dimethyl-3-(4-trifluoromethylsulfanylphenyl)imid- azolidine-2,4-dione; - 1-[2-(6-fluoropyrid-3-ylamino)pyrid-4-ylmethyl] - 5,5-dimethyl-3-(4-trifluoromethylsulfanylphenyl)imidazol- idine-2,4-dione;
    - 1-[2-(6-methoxypyrid-3-ylamino)pyrid-4-ylmethyl] - 5,5-dimethyl-3-(4-trifluoromethylsulfanylphenyl)imidazol- idine-2,4-dione,
    said products of formula (1) being in any possible racemic, enantiomeric or diastereoisomeric isomer form,
    and also the addition salts with mineral and organic acids or with mineral and organic bases of said product of formula (I). : 52) As a medicinal product, the product of formula (I) as defined in claims 1 to 51, and also the prodrugs thereof, the said product of formula (I) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with pharmaceutically acceptable mineral and organic acids or with pharmaceutically acceptable mineral and organic bases of said product of formula (I). : 53) As a medicinal product, the product of formula (ICQ) as defined in the preceding claims, and also the prodrugs thereof, said product of formula (10) being in any possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with pharmaceutically acceptable mineral and organic acids or with pharmaceutically acceptable mineral and organic bases of said product of formula (IC).
    54) As a medicinal product, the product of formula (Ia)
    as defined in the preceding claims, and also the prodrugs thereof, the said product of formula (IA) being in any hg 526 : possible racemic, enantiomeric or diastereoisomeric isomer form, and also the addition salts with pharmaceutically acceptable mineral and organic acids or with pharmaceutically acceptable mineral and. organic . 5 bases of said product of formula (IA). . 55) As a medicinal product, the product as defined in claim 50 or 51, and the prodrugs thereof,. and the addition salts with pharmaceutically acceptable mineral and organic acids or with pharmaceutically acceptable mineral and organic bases of these products. 56) A pharmaceutical composition containing, as active principle, at least one of the medicinal products as defined in claims 52 to 55. 57) A pharmaceutical composition containing, as active principle, at least one of the medicinal products as defined in claim 44. : 58) The pharmaceutical composition as defined in the claims, also «containing active principles of other chemotherapy medicinal products for combating cancer. 59) The pharmaceutical composition as claimed in any one wn of the claims, characterized in that it is used as a medicinal product, in particular for cancer chemotherapy. 60) The use of the product of formula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of said product of formula (I) for the preparation of medicinal products for inhibiting the activity of protein kinases and especially of a protein kinase. 61) The use of a product of formula (I) as defined in the preceding claim or of pharmaceutically acceptable salts of said product of formula (I) in which the protein kinase is a protein tyrosine kinase. 62) The use of a product of formula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of said product of formula (I), in which the protein kinase is chosen from the following group: EGFR, Fak, FLK-1, FGFR1l, FGFR2, FGFR3, FGFR4, FGFR5, flt-1, IGF-1R,
    he 527 KDR, PLK, PDGFR,. tie2, VEGFR, AKT, Raf. ‘ 63) The use of a product of formula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of the said product of formula (I) in which the protein kinase is IGF1R.
    64) The use of a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I) in which the protein kinase is FAK.
    65) The use of a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I) in which the protein kinase is AKT. 66) The use of a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I) in which the protein kinase is in a cell culture.
    67) The use of a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I) in which the protein kinase is in a mammal.
    68) The use of a product of formula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of said product of formula (I), for the preparation of a medicinal product for preventing or treating a disease characterized by the deregulation of the activity of a protein kinase.
    69) The use of a product of formula (I) as claimed in the preceding claim, in which the disease to be prevented or treated is in a mammal.
    70) The use of a product of formula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of said product of formula (I), for the preparation of a medicinal product for preventing or treating a disease belonging to the following group: disorders of blood vessel proliferation, fibrotic disorders, disorders
    : of mesangial cell proliferation, metabolic disorders, allergies, asthma, thrombosis, diseases. of the nervous system, retinopathy, psoriasis, rheumatoid arthritis, : "diabetes, muscle degeneration, “oncology diseases and cancers. 71) The use of a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I), for the preparation of a medicinal product for treating oncology diseases. 72) The use of a product of formula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of said product of formula (I) for the preparation of a medicinal product for treating cancers. oo © 73) The use of a product of formula (I) as claimed in the preceding claim, in which the disease to be treated is a cancer of solid tumors. : 74) The use of a product of formula (I) as claimed in : the preceding claim, in which the disease to be treated is a cancer that is resistant to cytotoxic agents. 75) The use of a product of formula (I) as defined in i. any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I) for the preparation of a medicinal product for treating cancers including breast cancer, stomach cancer, cancer of the colon, lung cancer, cancer of the ovaries, cancer of the uterus, brain cancer, cancer of the kidney, cancer of the larynx, cancer of the lymphatic system, cancer of the thyroid, cancer of the urogenital tract, cancer of the tract including the seminal vesicle and prostate, bone cancer, cancer of the pancreas and melanomas. 76) The use of a product of formula (I) as claimed in the preceding claim, in which the disease to be treated is a breast cancer, cancer of the colon or lung cancer. 77) The use of a product of formula (I) as defined in any one of the claims, or of a pharmaceutically acceptable salt of said product of formula (I), for the
    , Y PCT/FR2004/000188 preparation of a medicinal product for cancer chemotherapy. 78) The use of a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I), for the preparation of a medicinal product for cancer chemotherapy, used alone or in combination. 79) The use of a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I) for the preparation of a medicinal product to be used alone or in combination with a chemotherapy or radiotherapy, or alternatively in combination with other therapeutic agents. 80) The use of a product of formula (I) as claimed in the preceding claim, in which the therapeutic agents may be commonly used antitumor agents. 81) The product of formula (I) as defined in any one of the claims, &s protein kinase inhibitor, said product of formula (I) being in any possible racemic, enantiomeric or diastereocisomeric isomer form, and also the addition salts with pharmaceutically acceptable mineral and organic acids or with pharmaceutically acceptable mineral and organic bases of said product of Iormula (I), and also prodrugs thereof. 82) The product of formula (I) as defined in any one of the claims, as an IGF1R inhibitor. 83) The product of formula (IA) as defined in the claims, as an IGF1IR inhibitor. 84) A substance or composition for use in a method for inhibiting the activity of protein kinases and especially of a protein kinase, said substance or composition comprising the product oi Iormula (1), as defined in any one cof the claims or of pharmaceutically acceptable salts AMENDED SHEET v PCT/FR2004/000188 of said product of formula (I), and said method comprising administering said substance or composition. 85) A substance or composition for use in a method ZIor preventing or treating a disease characterized by the deregulation of the activity of a protein kinase, said substance or composition comprising a product of formula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of said product of formula (I), and said method comprising administering said substance or composition.
    86) 2A substance or composition for use in a method for preventing or treating a disease belonging to the following group: disorders of blood vessel proliferation, fibrotic disorders, disorders of mesangial cell proliferation, metabolic disorders, allergies, asthma, thrombosis, diseases of the nervous system, retinopathy, psoriasis, rheumatoid arthritis, diabetes, muscle degeneration, oncology diseases and cancers, said substance or composition comprising a product of formula
    (I) as defined in any one of the claims or of pharmaceutically acceptable salts of said product of formula (I), and said method comprising administering said substance or composition.
    87) A substance or composition for use in a method for treating oncclogy diseases, said substance or composition comprising a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I), and said method comprising administering said substance or composition.
    88) A substance or composition for use in a method for Treating cencers, sald substance or composition comprising a proauct of Zorrula (I) as defined in any one of the claims or of pharmaceutically acceptable salts of
    AMENDED SrIET
    \| PCT/FR2004/000188 said product of formula (I), and said method comprising administering said substance or composition. 89) A substance or composition for use in a method for treating cancers including breast cancer, stomach cancer, cancer of the colon, lung cancer, cancer of the ovaries, cancer of the uterus, brain cancer, cancer of the kidney. cancer of the larynx, cancer of the lymphatic system, cancer of the thyroid, cancer of the urogenital tract, cancer of the tract including the seminal vesicle and prostate, bone cancer, cancer of the pancreas and melanomas, said substance or composition comprising a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I), and said method comprising administering said substance or composition. 90) A substance or composition for use in a method for cancer chemotherapy, said substance or composition comprising a product of formula (I) as defined in any one of the claims, or of a pharmaceutically acceptable salt of said product of formula (1), and said method comprising administering said substance or composition. 91) A substance or composition for use in a method for cancer chemotherapy, used alone or in combination, said substance or composition comprising a product of formula (I) as defined in any one of the claims or of a pharmaceutically acceptable salt of said product of formula (I), and said method comprising administering said substance or composition. 82) A substance or composition for use in a method to be used alone or in combination with a chemotherapy or radiotherapy, or alternatively in combination with other therapeutic agents, said substance or composition comprising a product of formula (I) as defined in any one AMENDED SHEET
    “ PCT/FR2004/000188 of the claims or of a pharmaceutically acceptable salt of said product of formula (I), and said method comprising administering said substance or composition. 93) A product of any one of claims 1 to 51 or 81 to 83, substantially as herein described and illustrated. 24) 2A medicinal product of any one of claims 52 to 595, substantially as herein described and illustrated. 95) A composition of any one of claims 56 to 59, substantially as herein described and illustrated.
    96) Use of any one of claims 60 to 80, substantially as herein described and illustrated.
    87) A substance or composition for use in a method of prevention or treatment of any one of claims 84 to 92, substantially as herein described and illustrated.
    98) A new product, a new medicinal product, a new composition, a new use of a product as claimed in any one of claims 1 to 51 or 81 to 83, or a substance or composition for a new use in a method oi treatment or prevention, substantially as herein described.
    AMZINDED SHERT
ZA200505934A 2003-01-31 2005-07-22 Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors ZA200505934B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR0301098A FR2850652B1 (en) 2003-01-31 2003-01-31 NOVEL CYCLIC UREA DERIVATIVES, THEIR PREPARATION AND THEIR PHARMACEUTICAL USE AS INHIBITORS OF KINASES

Publications (1)

Publication Number Publication Date
ZA200505934B true ZA200505934B (en) 2007-06-27

Family

ID=32696243

Family Applications (1)

Application Number Title Priority Date Filing Date
ZA200505934A ZA200505934B (en) 2003-01-31 2005-07-22 Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors

Country Status (24)

Country Link
EP (1) EP1599464B1 (en)
JP (1) JP4604020B2 (en)
KR (1) KR20050098286A (en)
CN (1) CN1768054A (en)
AR (1) AR042936A1 (en)
AT (1) ATE482207T1 (en)
AU (1) AU2004209319A1 (en)
BR (1) BRPI0407091A (en)
CA (1) CA2513631A1 (en)
DE (1) DE602004029236D1 (en)
FR (1) FR2850652B1 (en)
HR (1) HRP20050679A2 (en)
MA (1) MA27651A1 (en)
ME (1) MEP22608A (en)
MX (1) MXPA05007407A (en)
NO (1) NO20054006L (en)
NZ (1) NZ541270A (en)
PE (1) PE20040808A1 (en)
PL (1) PL377811A1 (en)
RS (1) RS20050657A (en)
RU (1) RU2341523C2 (en)
TW (1) TW200505898A (en)
WO (1) WO2004070050A2 (en)
ZA (1) ZA200505934B (en)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2004315596B2 (en) 2003-08-29 2011-11-24 President And Fellows Of Harvard College Inhibitors of cellular necrosis
US7700603B2 (en) 2003-12-15 2010-04-20 Schering Corporation Heterocyclic aspartyl protease inhibitors
US7763609B2 (en) 2003-12-15 2010-07-27 Schering Corporation Heterocyclic aspartyl protease inhibitors
US7592348B2 (en) 2003-12-15 2009-09-22 Schering Corporation Heterocyclic aspartyl protease inhibitors
ATE502298T1 (en) 2003-12-19 2011-04-15 Univ California METHODS AND MATERIALS FOR ASSESSING PROSTATE CANCER THERAPIES
US7718684B2 (en) 2004-02-24 2010-05-18 The Regents Of The University Of California Methods and materials for assessing prostate cancer therapies and compounds
EP1621535A1 (en) * 2004-07-27 2006-02-01 Aventis Pharma S.A. Substituted cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors
EP1621536A1 (en) * 2004-07-27 2006-02-01 Aventis Pharma S.A. Amino cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors
US7709517B2 (en) 2005-05-13 2010-05-04 The Regents Of The University Of California Diarylhydantoin compounds
NZ564223A (en) 2005-05-13 2011-03-31 Univ California Diarylhydantoin compounds for treating hormone refractory prostate cancer
US7709516B2 (en) 2005-06-17 2010-05-04 Endorecherche, Inc. Helix 12 directed non-steroidal antiandrogens
FR2896504B1 (en) * 2006-01-23 2012-07-13 Aventis Pharma Sa NOVEL CYCLIC UREA DERIVATIVES, THEIR PREPARATION AND THEIR PHARMACEUTICAL USE AS INHIBITORS OF KINASES
FR2896503B1 (en) 2006-01-23 2012-07-13 Aventis Pharma Sa NOVEL CYCLIC UREA SULFUR DERIVATIVES, THEIR PREPARATION AND THEIR PHARMACEUTICAL USE AS INHIBITORS OF KINASES
ES2593379T3 (en) 2006-03-27 2016-12-09 The Regents Of The University Of California Androgen receptor modulator for the treatment of prostate cancer and diseases associated with the androgen receptor
JP5350217B2 (en) 2006-03-29 2013-11-27 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Diarylthiohydantoin compounds
EP2061767B1 (en) 2006-08-08 2014-12-17 Sanofi Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use
MX2009006228A (en) 2006-12-12 2009-06-22 Schering Corp Aspartyl protease inhibitors.
UY31432A1 (en) 2007-10-26 2009-05-29 DIARILHIDANTOINE COMPOUNDS
EP2381775A4 (en) 2008-12-23 2012-08-15 Harvard College Small molecule inhibitors of necroptosis
US9108944B2 (en) 2010-02-16 2015-08-18 Aragon Pharmaceuticals, Inc. Androgen receptor modulators and uses thereof
US8685256B2 (en) * 2010-12-21 2014-04-01 Cytec Technology Corp. Microdispersions of hydroxamated polymers and methods of making and using them
US8492556B2 (en) * 2011-11-10 2013-07-23 Allergan, Inc. 2,5-Dioxoimidazolidin-1-yl-3-phenylurea derivatives as formyl peptide receptor like-1 (FPRL-1) receptor modulators
CN104661658A (en) 2012-09-26 2015-05-27 阿拉贡药品公司 Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer
JOP20200097A1 (en) 2013-01-15 2017-06-16 Aragon Pharmaceuticals Inc Androgen receptor modulator and uses thereof
EP2968276A4 (en) 2013-03-15 2017-02-15 President and Fellows of Harvard College Hybrid necroptosis inhibitors
GB201312492D0 (en) * 2013-07-12 2013-08-28 Syngenta Ltd Herbicidal compounds
US10202373B2 (en) 2014-01-14 2019-02-12 Millennium Pharmaceuticals, Inc. Heteroaryls and uses thereof
KR20160122736A (en) 2014-01-14 2016-10-24 밀레니엄 파머슈티컬스 인코퍼레이티드 Heteroaryls and uses thereof
WO2016094846A1 (en) 2014-12-11 2016-06-16 President And Fellows Of Harvard College Inhibitors of cellular necrosis and related methods
TWI726969B (en) 2016-01-11 2021-05-11 比利時商健生藥品公司 Substituted thiohydantoin derivatives as androgen receptor antagonists
CN107619388A (en) * 2016-07-13 2018-01-23 南京天印健华医药科技有限公司 Heterocyclic compound as FGFR inhibitor
CN114014844B (en) * 2016-07-20 2024-10-01 诺华股份有限公司 Aminopyridine derivatives and their use as selective ALK-2 inhibitors
CN111479560A (en) 2017-10-16 2020-07-31 阿拉贡药品公司 Antiandrogen for treating non-metastatic castration-resistant prostate cancer
JP7005779B2 (en) * 2017-10-31 2022-02-10 ペレメッド カンパニー リミテッド Pharmaceutical composition for the prevention or treatment of acute myeloid leukemia or metastatic breast cancer

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2329276A1 (en) * 1975-10-29 1977-05-27 Roussel Uclaf NEW SUBSTITUTES IMIDAZOLIDINES, METHOD OF PREPARATION, APPLICATION AS A MEDICINAL PRODUCT AND COMPOSITIONS CONTAINING THEM
DE4228717A1 (en) * 1992-08-28 1994-03-03 Cassella Ag Imidazolidine derivatives
DE19540027A1 (en) * 1995-10-27 1997-04-30 Gruenenthal Gmbh Substituted imidazolidine-2,4-dione compounds as active pharmaceutical ingredients
ATE233738T1 (en) * 1997-03-03 2003-03-15 Boehringer Ingelheim Pharma SMALL MOLECULES APPLICABLE IN THE TREATMENT OF INFLAMMATORY DISEASES
DE19732928C2 (en) * 1997-07-31 2000-05-18 Gruenenthal Gmbh Use of substituted imidazolidine-2,4-dione compounds as pain relievers
FR2796945B1 (en) * 1999-07-30 2002-06-28 Sod Conseils Rech Applic NOVEL DERIVATIVES OF HYDANTOINS, THIOHYDANTOINS, PYRIMIDINEDIONES AND THIOXOPYRIMIDINONES, PROCESSES FOR THEIR PREPARATION AND THEIR APPLICATION AS MEDICAMENTS
KR100527290B1 (en) * 2000-05-31 2005-11-09 다나베 세이야꾸 가부시키가이샤 INHIBITORS OF αLβ2 MEDIATED CELL ADHESION
PL374162A1 (en) * 2002-05-16 2005-10-03 Bayer Cropscience Gmbh Pyridine carboxamide derivatives and their use as pesticides

Also Published As

Publication number Publication date
CN1768054A (en) 2006-05-03
NO20054006D0 (en) 2005-08-29
FR2850652B1 (en) 2008-05-30
RS20050657A (en) 2007-06-04
PE20040808A1 (en) 2004-12-31
PL377811A1 (en) 2006-02-20
MEP22608A (en) 2010-06-10
RU2005127335A (en) 2006-09-10
DE602004029236D1 (en) 2010-11-04
JP4604020B2 (en) 2010-12-22
AU2004209319A1 (en) 2004-08-19
TW200505898A (en) 2005-02-16
KR20050098286A (en) 2005-10-11
NZ541270A (en) 2008-11-28
MXPA05007407A (en) 2005-09-12
WO2004070050A3 (en) 2005-02-17
CA2513631A1 (en) 2004-08-19
EP1599464B1 (en) 2010-09-22
ATE482207T1 (en) 2010-10-15
MA27651A1 (en) 2005-12-01
WO2004070050A2 (en) 2004-08-19
AR042936A1 (en) 2005-07-06
NO20054006L (en) 2005-10-13
HRP20050679A2 (en) 2006-12-31
BRPI0407091A (en) 2006-01-24
EP1599464A2 (en) 2005-11-30
RU2341523C2 (en) 2008-12-20
JP2006517569A (en) 2006-07-27
FR2850652A1 (en) 2004-08-06

Similar Documents

Publication Publication Date Title
ZA200505934B (en) Cyclic urea derivatives, preparation method thereof and pharmaceutical use of same as kinase inhibitors
US20240139194A1 (en) Preparation and methods of use for ortho-aryl 5-membered heteroaryl-carboxamide containing multi-targeted kinase inhibitors
US7642278B2 (en) Indazole benzimidazole compounds
US7064215B2 (en) Indazole benzimidazole compounds
US7186716B2 (en) 3-Pyrrol-pyridopyrazoles and 3-pyrrolyl-indazoles as novel kinase inhibitors
KR101675984B1 (en) Thienodiazepine derivatives or pharmaceutically acceptable salt thereof, and pharmaceutical composition comprising the same as an active ingredient
BR112019008061A2 (en) methods of using indazol-3-carboxamides and their use as inhibitors of the wnt / b-catenin signaling pathway
CN113646307B (en) Pyrido [3,4-d ] pyrimidin-8-one derivatives having protein kinase inhibitory activity and pharmaceutical compositions thereof
WO2014004863A2 (en) Compounds, compositions, and therapeutic uses thereof
EP3010503A2 (en) Novel bicyclic bromodomain inhibitors
JP2001508800A (en) Phthalazine having angiogenesis inhibitory activity
JP2016520116A (en) Imidazopyrrolidinone derivatives and their use in the treatment of diseases
JP2015514802A (en) Methods and compositions for RAF kinase mediated diseases
TW200303863A (en) Substituted indazoles, compositions comprising them, manufacturing process and use
US11304929B2 (en) Tosylacetate based compounds and derivatives thereof as PHGDH inhibitors
JP2016537384A (en) Pyrrolopyrrolone derivatives and their use as BET inhibitors
WO2016115869A1 (en) Novel inhibitor of flt3 kinase and use thereof
JP7285249B2 (en) Novel [1,6]naphthyridine compounds and derivatives as CDK8/CDK19 inhibitors
RU2780168C1 (en) NEW DERIVATIVE OF PYRIDO [3,4-d] PYRIMIDINE-8-ONE WITH PROTEIN KINASE INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION FOR PREVENTING, ALLEVIATING, OR TREATING CANCER, CONTAINING ABOVE DERIVATIVE
TWI759829B (en) Heterocyclic pyrazole derivatives as type iii receptor tyrosine kinase inhibitors
US20240217968A1 (en) Pharmaceutical compound
EP4377304A1 (en) Srpk inhibitors
AU2010319382A1 (en) Kinase inhibitors