WO2001082877A2 - Verwendung von parp-inhibitoren in kosmetischen zubereitungen - Google Patents
Verwendung von parp-inhibitoren in kosmetischen zubereitungen Download PDFInfo
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- WO2001082877A2 WO2001082877A2 PCT/EP2001/004838 EP0104838W WO0182877A2 WO 2001082877 A2 WO2001082877 A2 WO 2001082877A2 EP 0104838 W EP0104838 W EP 0104838W WO 0182877 A2 WO0182877 A2 WO 0182877A2
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- alkyl
- phenyl
- benzimidazole
- hydrogen
- carboxamide
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- 0 CCCCCNCC* Chemical compound CCCCCNCC* 0.000 description 16
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/004—Aftersun preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
- A61K8/066—Multiple emulsions, e.g. water-in-oil-in-water
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
- A61K8/068—Microemulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/28—Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q15/00—Anti-perspirants or body deodorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/001—Preparations for care of the lips
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/006—Antidandruff preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/12—Preparations containing hair conditioners
Definitions
- the present invention relates to the use of PARP inhibitors in cosmetic preparations, in particular use in after-sun creams.
- the invention also relates to cosmetic preparations which contain a PARP inhibitor and a UV absorber.
- Human skin is subject to certain aging processes, which are partly due to intrinsic processes (chronoaging) and partly to exogenous factors (environmental, e.g. photoaging).
- aging processes which are partly due to intrinsic processes (chronoaging) and partly to exogenous factors (environmental, e.g. photoaging).
- environmental, e.g. photoaging there are temporary or permanent changes in the skin, such as acne, oily or dry skin, keratoses, rosaceae, photosensitive, inflammatory, erythematous, allergic or autoimmune-reactive reactions such as dermatoses, photodermatoses and others, their exact causes and factors that influence them. are often only incompletely understood.
- the exogenous factors include, in particular, sunlight or artificial radiation sources with a comparable spectrum, as well as compounds that can arise from the radiation, such as undefined reactive photo products, which can also be radical or ionic.
- these factors also include harmful or reactive compounds such as ozone, free radicals such as the hydroxyl radical, singlet oxygen and other reactive oxygen or nitrogen compounds, cigarette smoke, natural and synthetic toxins, and others that disrupt the natural physiology or morphology of the skin.
- harmful or reactive compounds such as ozone, free radicals such as the hydroxyl radical, singlet oxygen and other reactive oxygen or nitrogen compounds, cigarette smoke, natural and synthetic toxins, and others that disrupt the natural physiology or morphology of the skin.
- the influence of these factors leads, among other things, to direct damage to the DNA of the skin cells and the collagen, elastin or glycosaminoglycan molecules of the extracellular matrix, which are responsible for the firmness of the skin.
- MMPs matrix metalloproteinases
- TIMPs tissue inhibitor of matrix etalloproteinases
- the skin's ability to regenerate is reduced.
- inflammatory reactions can occur.
- immunoregulatory compounds such as interleukins, prostaglandins and histamines are released.
- the consequences of aging are thinning of the skin, weaker interlocking of the epidermis and the is, reduction in the number of cells and the supplying blood vessels.
- the aging processes lead to the formation of fine lines and wrinkles, the skin becomes leathery, yellowish and sagging, and pigment disorders occur.
- Cosmetic or dermatological care products with proprietary properties that counteract the described or comparable processes or that reduce or reverse their harmful effects are often characterized by specific properties; among other things, they are radical-trapping, antioxidant, anti-inflammatory or moisturizing; they prevent or reduce the activity of the matrix-degrading enzymes or regulate the new synthesis of collagen, elastin or proteoglycans.
- specific properties among other things, they are radical-trapping, antioxidant, anti-inflammatory or moisturizing; they prevent or reduce the activity of the matrix-degrading enzymes or regulate the new synthesis of collagen, elastin or proteoglycans.
- numerous other mechanisms of action are conceivable.
- UV light ultraviolet light
- UVA 320 to 400 n
- UVB 290 to 320 nm
- UVC 10 to 290 nm
- the ultraviolet radiation component in sunlight is able to produce both physiological and pathological effects in the skin.
- the effects of UV radiation can be divided into acute and chronic. Acute effects are e.g. the sunburn, chronic close e.g. certain forms of skin cancer.
- Processes in turn induce or intensify the inflammatory reaction, which in turn leads to an intensification of the harmful oxidative processes already described.
- the use of compounds that positively influence these processes would therefore be extremely advantageous and in the sense of a cosmetic or dermatological application.
- Sunburn is a UV-induced skin erythema caused by vasodilation of dermal vessels. This is mediated by cyclo-oxygenase and lipoxygenase products of arachidonic acid. The production and release of prostaglandins is also associated with UVB erythema and develops in the first 6 to 12 hours after UV exposure. The effect can be prevented by topical application of NSAIDs (NSAID: nonsteroidal anti-inflammatory drugs, for example indomethacin). However, these anti-inflammatory drugs have no effect on the delayed, late erythema that delays in 24 h after exposure Appearance occurs. This is modulated by lipoxygenase products. Selective inhibitors of the cyclooxygenase and lipoxygenase pathways may be useful in the prevention and therapy of the sunburn rhythm.
- the skin is an important organ of immunological activity.
- the immune system can be influenced by the interaction with UV light. UV light influences e.g. the Langerhans see cells and changes their immunological function. Even low doses of UVB light reduce Langerhans's cells' ability to present antigens. UV light blocks the normal effector path and creates a misdirected immune response by activating T suppressor cells. The mechanism of this photo-suppression is still largely unclear. The release of soluble immune system regulators from destroyed keratinocytes is discussed. Photoimmune suppression appears to have an important role in the development of skin cancer. Animal experiments have shown that implanted, UV-induced tumors can be rejected in non-UV-exposed animals. However, the tumor is not rejected in UV-exposed animals. Immunosuppression is therefore an essential factor in the development and development of skin cancer (Fisher and Kripke (1990) Science 216, 1133-1134.).
- UV light can produce serious morphological changes in all parts of the skin (with the exception of perhaps the subcutaneous layers) (sagging, wrinkling, dermis, blotchy (de) pigmentation). Changes affect the aberrant tissue, changes in keratinocytes and melanocytes and functional changes in Langerhanssehe cells.
- a sun-exposed epidermis can have a doubled thickness compared to sun-protected skin and also shows clear signs of disorganization (hyperkeratosis, parakeratosis and acanthosis).
- sensitivity to sun and / or UV light there may also be an increased sensitivity to sun and / or UV light. This can be done by genetic or acquired diseases, genetic predisposition, certain medications, age-related factors etc.
- Hereditary sensitivity to sun radiation is, for example, Xeroderma pigmentosum, Blooms syndrome, Rothmund-Thomson syndrome, porphyrias, phenylketonuria, dysplastic Nevus syndrome, basal cells Nevussy syndrome.
- the rather acquired light sensitivities include, for example, a persistent light reaction, actinic reticuloid (also actinoreticulosis or actinic-reticular hyperplasia), polymorphic light eruption (polymorphic light eruption, PMLE), solar urticaria, actinic prurigo, lupus erythematosus, hidroidroidiniforma vaccine disease and disseminated superficial actinic parakeratosis. Photosensitization with an unknown mechanism exists, for example, in lupus erythomatosus or polymorphic light dermatosis (PMLE).
- actinic reticuloid also actinoreticulosis or actinic-reticular hyperplasia
- polymorphic light eruption polymorphic light eruption
- solar urticaria actinic prurigo
- lupus erythematosus hidroidroidiniforma vaccine disease
- disseminated superficial actinic parakeratosis disseminated
- IC50 33 ⁇ M, Banasik et al., (1992) J. of Biological Chemistry 267: 1569
- the compound was added to the cells 24-48 hours before the irradiation in high concentrations (15 mM) (Baich et al. (1997) Pigmented Cell Res 10: 391).
- Beatrix-Farkas and Szekeres showed that pretreatment of mouse skin with 0- (3-piperidino-2-hydroxy-l-propyl) -nicotinic acid amidoxime dihydrochloride and subsequent, acute UV radiation with 2-fold MED, clinical and histological signs of one sunburn prevents (2 nd European Congress of Pharmacology; Budapest Hungary, 3-July 7, 1999). .
- the authors suggested that the protective effects described on a down-regulation of excessive activation polymerase enzyme poly (ADP-ribose) ⁇ ( PARP) rest.
- PARP catalyzes the binding of ADP-Ribose to DNA-associated core proteins, eg histones, with the formation of poly (ADP-Ribose) chains.
- ATP and NAD are used. If the DNA is severely damaged, for example after massive radical formation or UV radiation, PARP is overactivated, too much energy (ATP / NAD) is consumed, which leads to cell death.
- the present invention relates to the production and use of cosmetic and dermatological preparations with an effective content of a PARP inhibitor.
- the present invention relates to cosmetic and dermatological preparations which offer effective protection
- the advantageous effect is due to the fact that the active substances used as PARP inhibitors prevent undesired cell death and the associated undesirable secondary reactions, such as e.g. prevent or reduce the inflammatory reactions.
- the present invention relates to active substances and preparations containing such active substances for cosmetic and dermatological treatment or prevention of undesired changes in the skin appearance, such as
- PUVA is a combination of treatment with Psoralens (P) and subsequent irradiation of the skin with long-wave UV light (UVA).
- Psoralens are compounds that occur in many plants and cause the skin to be temporarily sensitized to UVA light.
- Psoralen or its derivatives can be administered systemically (orally) (eg Methoxsalen capsules) or topically (eg Tripsor PUVA, methoxsalen baths).
- the therapy is used for various skin diseases including psoriasis, para-psoriasis, atopic dermatitis, polymorphic light dermatosis and "mycosis fungoides" (MF), vitiligo, generalized eczema, lying planus, generalized granuloma annulare.
- Chronic polymorphic light eruption or light rash is a very common, very itchy, polymorphic (papular, vesicular, eczematous, lupus-like, lichenoid) light sensation disorder on the exposed parts of the body.
- the light rash often appears as reddening as a result of photosensitization.
- Polymorphic means the fact that the rash can take various forms (see above). The most common are piles of pink or red, raised pimples 2 to 5 mm in diameter on the arms, chest and lower legs.
- the light rash is usually perceived as a burn and is associated with itching that lasts for several days.
- the light rash is thought to be caused by an immune response to a compound altered by sun exposure in the skin.
- This photodermatosis is essentially influenced by the action of sun, UV, UR light or by ionizing rays, i.e. it is a skin disease dependent on a light reaction.
- Pathomechanisms a) excessive radiation (dermatitis solaris, cheilitis actinica); b) skin hypersensitivity, i.e. Lowered stimulus threshold either as a result of a photo allergy (e.g. acne prurigo, light rash, spring dermatitis, Hidroa aestivalis) or phototoxically after photochemical sensitization by tar, mineral or mountain amotte oil, furanocoumarin, porphyrins etc. (e.g.
- the clinical picture also includes any skin disease triggered or exacerbated by light (e.g. lupus erythematosus, pellagra).
- Eye damage (keratitis, cataracts) can with insufficient protection. Long-term damage is premature skin aging (increased dryness, wrinkles and wrinkles) and skin cancer. The risk is increased especially for people with light skin tones. There are no serious concerns in normal patients with PUVA therapy for 2-3 months. In the case of long-term therapy, the skin should be examined for abnormal changes every 6 months.
- PUVA therapy is also used in severe forms of psoriasis mostly in older patients or in those who do not respond to other therapies. In 90% of all cases, PUVA therapy has a positive effect on the disease and suppresses the symptoms as long as the therapy is used.
- Psoriasis is a common, hereditary skin disease that can vary greatly in severity and intensity. Neither phototherapy nor any other established treatment methods allow permanent healing.
- Vitiligo Patients with vitiligo have areas of skin that are completely depigmented. PUVA therapy can produce a certain amount of repigmentation (especially with vitiligo in the facial region or with dark-skinned patients).
- Possible PARP inhibitors for the purposes of the invention are the following groups, which include a non-exhaustive list. If the compounds are new, they can be synthesized by the method known to the person skilled in the art. In particular, reference is made to WO 97/04771.
- the first group of PARP inhibitors relates to substituted 2-phenylbenzimidazoles of the general formula I or II
- R 1 is hydrogen, branched and unbranched C 1 -C 6 -alkyl, where a C atom of the alkyl radical can also carry OR 11 or a group R 5 , where R 11 is hydrogen or C 1 -C 4 -alkyl, and
- R 2 is hydrogen, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NHCOR 21 , NR 22 R 23 OH, 0 -CC-C 4 -alkyl, 0-C ⁇ -C 4 -alkylphenyl, NH 2 , phenyl , where the phenyl rings can also be substituted with a maximum of two radicals R 24 , and R 21 and R 22 independently of one another are hydrogen or C 1 -C 4 -alkyl and R 23 is hydrogen, C 1 -C 4 -alkyl or phenyl, and R 24 OH, Ci-C ß- alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH, and
- x can be 0, 1 and 2 and
- R 3 denotes -D- (F 1 ) P - (E) g- (F 2 ) r -G, where p, q and r cannot simultaneously be 0, or -E- (D) U - (F 2 ) s - (G) v , where the radical E can still be substituted by one or two radicals A, or R 3 is B and
- R 4 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Ce-alkyl, OH, nitro, CF 3 , CN, NR 41 R 42 , NH-CO-R 43 , 0 -CC-C 4 alkyl , where R 41 and R 42 are independently hydrogen or
- C 1 -C 4 alkyl and R 43 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkyl-phenyl or
- Phenyl mean, and DS and 0
- F 1 is a chain of 1 to 8 carbon atoms, where a carbon atom of the chain can also carry an OH or 0 -CC 4 alkyl group and
- F 2 is a chain of 1 to 8 carbon atoms, a carbon atom of the chain can also carry an OH or 0 -CC 4 alkyl group and
- p can mean 0 and 1 and
- u can be 0 and 1 and
- v can be 0 and 1
- R 51 is hydrogen and branched and unbranched -CC 6 alkyl, (CH 2 ) t -K means and R 52 is hydrogen, branched and unbranched Ci-Cg-alkyl, phenyl,
- R 53 branched or unbranched O-Ci-Cg-alkyl, phenyl, branched or unbranched C ⁇ -C 4 alkyl-phenyl, wherein in R 52 and R 53 independently of one another a hydrogen of the Ci-Cg-alkyl radical is substituted by one of the following radicals can be: OH, 0-C !
- R 33 is hydrogen, -CC 4 alkyl or phenyl, and can be
- R 31 is hydrogen, -CC 6 alkyl, (CH 2 ) t -K and
- R 33 is hydrogen and C -C 4 ⁇ alkyl
- K phenyl which can still carry a maximum of two radicals R, NR l R 2 (with R kl or R k2 with the same meanings as R 41 or R 42 ), NH-C ⁇ -C-alkyl-phenyl, pyrrolidine, piperidine , 1,2,5, 6-tetrahydropyridine, morpholine, trihydroazepine, piperazine, which can still be substituted with an alkyl radical Ci-Cg-alkyl, and Ho opiperazin, which is still substituted with an alkyl radical Ci-Cg-alkyl can be and
- R 5 is hydrogen, -CC 6 alkyl, NR 7 R 9 and
- R 7 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 4 -alkyl-phenyl, phenyl, where the ring can also be substituted by up to two R 71 radicals, and
- R 71 OH, -CC 6 alkyl, 0 -CC 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH 2 , and R 8 is hydrogen, Ci-C ß alkyl, phenyl, C ⁇ -C 4 -alkyl-phenyl, wherein the ring may be substituted with up to two radicals R 81, and
- R 81 OH, -C -C 6 alkyl, 0 -C -C alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH, and
- R 9 is hydrogen, C0CH 3 , CO-0 -CC-C-alkyl, C0CF 3 , branched and unbranched Ci-C ß- alkyl, where one or two hydrogens of the C ⁇ -C 6 alkyl radical are each substituted by one of the following radicals can: OH, 0-C 4 ⁇ alkyl and phenyl and the phenyl ring can also carry one or two of the following radicals: iodine, chlorine, bromine, fluorine, branched and unbranched Ci-C ß alkyl, nitro, A ino, -C 4 alkylamino, -C 4 dialkylamino, OH, OC 1 -C 4 alkyl, CN, CF 3 / S0 2 -C 4 -C 4 alkyl, can mean, and
- R 1 is hydrogen, branched and unbranched C 1 -C 6 -alkyl, where a C atom of the alkyl radical can also carry OR 11 or a group R 5 , where
- R 11 is hydrogen or CC 4 alkyl
- R 2 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched -CC 6 alkyl, nitro, CF 3 , CN, NR 21 R 22 , NH-CO-R 23 , OR 21 , wherein
- R 21 and R 22 are independently hydrogen or C ⁇ -C 4 alkyl
- R 23 is hydrogen, -C ⁇ C 4 alkyl or phenyl
- R 31 is hydrogen, C 1 -C 4 -alkyl, OH and 0 -C 1 -C 4 alkyl,
- n denotes 1, 2, 3 or 4
- R 4 is hydrogen, branched and unbranched Ci-C ⁇ alkyl, chlorine, bromine fluorine, nitro, cyano, NR 41 R 42 , NH-CO-R 43 , OR 41 , where
- R 41 and R 42 are independently hydrogen or -CC 4 alkyl and
- R 43 is -C 4 alkyl or phenyl
- R 51 is hydrogen and branched and unbranched Ci-Cg-alkyl
- R 52 is hydrogen, branched and unbranched Ci-C ß alkyl, phenyl, o
- R 53 branched or unbranched 0 -CC 6 alkyl, phenyl, branched or unbranched C 1 -C 4 -alkyl phenyl, where in R 52 and R 53 independently of one another a hydrogen of the -C 6 alkyl radical by one of the following Residues can be substituted: OH, 0 -CC-C 4 ⁇ alkyl, cyclohexyl, cyclopentyl, tetrahydronaphthyl, cyclopropyl, cyclobutyl, cycloheptyl, naphthyl and phenyl, the carbocycles of the radicals R 52 and R 53 independently of one another or can carry two of the following radicals: branched or unbranched C 1 -C 6 -alkyl, branched or unbranched 0-C 1 -C 4 alkyl, OH, F, Cl, Br, J, CF 3 , NO 2 , NH 2
- Particularly preferred positions for the radical R 2 in the general formula I or II are the 3-position and the 4-position relative to the benzimidazole ring.
- the 3-position or 4-position relative to the benzimidazole ring is also preferred for the radical R 3 .
- R 1 is hydrogen
- R 2 is hydrogen, branched or unbranched Ci-Cg-alkyl, nitro, CN, NH, 0-C ⁇ -C 4 alkyl.
- R 3 is -0- (CH 2 ) pR 5 with p equal to 2, 3 or 4.
- R 5 preferably denotes a 6-membered ring, in particular piperazine,
- R 52 preferably denotes an optionally substituted one
- Phenyl ring especially if R 5 is a 6-membered ring.
- R 4 is hydrogen
- R 1 is hydrogen, branched and unbranched C 1 -C 6 -alkyl, where a C atom of the alkyl radical can also carry OR 11 or a group R 5 , where Rii is hydrogen or C 1 -C 4 -alkyl, and
- R 2 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, nitro, CF 3 , CN, NR 21 R 22 , NH-CO-R 23 , OR 21 , wherein
- R 21 and R 22 are independently hydrogen or -CC 4 alkyl and
- R 23 is hydrogen, -CC 4 alkyl or phenyl, and R 3
- R 31 is hydrogen, CHO and - (CH 2 ) 0 - (CHR 3 ) m - (CH 2 ) n ⁇ R5, where
- R 32 is hydrogen, -CC 4 alkyl, OH and 0 -CC 4 alkyl, m, o is independently 0, 1 or 2 and n is 1, 2, 3 or 4, and
- R 4 is hydrogen, branched and unbranched Ci-Cg-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR 1 R 42 , NH-CO-R 43 , OR 41 , where
- R 41 and R 42 independently of one another are hydrogen or C 1 -C 4 -alkyl and R 43 are C 1 -C 4 -alkyl or phenyl, and
- R 51 is hydrogen and branched and unbranched Ci-Cg-alkyl
- R 52 hydrogen, C0CH 3 , CO-0 -CC 4 -alkyl, C0CF 3 , branched and unbranched Ci-Cg-alkyl, where a hydrogen of the Ci-Cg-alkyl radical can be substituted by one of the following radicals: OH,
- C 1 -C 4 -alkyl and phenyl and the phenyl ring can also carry one or two of the following radicals: chlorine, bromine, fluorine, branched and unbranched C 1 -C 4 -alkyl, nitro, amino, C 1 -C 4 - Alkylamino, -C-C 4 -dialkylamino, OH, 0-C ⁇ -C 4 -alkyl, CN,
- S0 2 -C-C 4 alkyl means. Particularly preferred positions for the radical R 2 in the general formula I or II are the 3-position and the 4-position relative to the benzimidazole ring. The 3-position or 4-position relative to the benzimidazole ring is also preferred for the radical R 3 .
- R 1 is hydrogen
- R 2 is hydrogen, branched or unbranched Ci-Cg-alkyl, nitro, CN, NH 2 , 0-C ⁇ -C 4 alkyl.
- R 2 is particularly preferably hydrogen.
- R 31 is hydrogen or - (CH 2 ) p -R 5 , wherein
- p 1 or 2
- R 52 is hydrogen, branched and unbranched Ci-Cg-alkyl, where a hydrogen of the Ci-Cg-alkyl radical can be substituted by one of the following radicals:
- OH, C 1 -C 4 -alkyl and phenyl and the phenyl ring can also carry one or two of the following radicals: chlorine, bromine, fluorine, branched and unbranched C 1 -C 4 -alkyl, nitro, amino, C 1 - C 4 -Alkyla1td.no, C 1 -C 4 -dialkylanu.no, OH, 0-C ⁇ ⁇ C 4 alkyl, CN, S0 2 -C-C 4 alkyl, may mean.
- R 31 is hydrogen or - (CH 2 ) P -R 5 , wherein
- p 1 or 2
- R 52 is hydrogen, branched and unbranched Ci-Cg-alkyl, where a hydrogen of the Ci-Cg-alkyl radical can be substituted by one of the following radicals: OH, 0-C ⁇ -C 4 alkyl and phenyl and the phenyl ring another or can carry two of the following radicals: chlorine, bromine, fluorine, branched and unbranched C ⁇ -C 4 alkyl, nitro, Amino, C 1 -C 4 -Alkyl11d.no, -C-C 4 -dialkylamino, OH, 0-C-C 4 -alkyl, CN, S0 2 -C-C4-alkyl, can mean.
- R 52 is hydrogen, branched and unbranched Ci-Cg-alkyl, where a hydrogen of the Ci-Cg-alkyl radical can be substituted by one of the following radicals: OH, 0-C ⁇ -C 4 alkyl and phenyl and the phenyl ring another or carry two of the following residues: chlorine,
- Bromine, fluorine, branched and unbranched C ⁇ -C 4 alkyl, nitro, amino, C 1 -C 4 -Alkyl1ru.no, -C-C 4 -dialkylamino, OH, 0-C ⁇ -C 4 -alkyl, CN, S0 2 -C ⁇ -C 4 alkyl may mean.
- R 4 is hydrogen
- the compounds of the formula I can be used as racemates, as enantiomerically pure compounds or as diastereomers. If enantiomerically pure compounds are desired, these can be obtained, for example, by carrying out a classical resolution with the compounds of the formula I or their intermediates using a suitable optically active base or acid.
- the invention also relates to compounds of the formula I which are mesomeric or tautomeric.
- Example 5 2 (3 (2- (N, N-Dimethylamino) eth-1-yloxy) phenyl) benzimidazole-4-carboxylic acid amide
- Example 61 2 (4 (4-Isopropyl-homopiperazin-l-yl) phenyl) benzimidazole-4-carboxylic acid amide
- Example 62 (4-Isopropyl-homopiperazin-l-yl) phenyl) benzimidazole-4-carboxylic acid amide
- Another group of PARP inhibitors relates to substituted benzodiazepine derivatives of the general formula I.
- A is a chain C 1 -C 3 , where each carbon atom can also carry one or two of the following substituents: -CC 4 -alkyl, OH, 0 -CC-C-alkyl, COOH, COO -CC-C 4 - Alkyl and
- X 1 can be S, 0 and NH and
- X 2 is a carbon atom that can still carry a chain C 1 -C 4 , and N and
- X 3 can be N and CR 2 , where
- R 2 is hydrogen, branched and unbranched Ci-Cg-alkyl, -C-C 4 alkyl phenyl, phenyl and
- R 1 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched C 1 -C 6 -alkyl, OH, nitro, CF 3 , CN, NR ⁇ R 12 , NH-CO-R 13 , 0-C ⁇ -C 4 ⁇ Alkyl, where R 11 and R 12 are independent of one another
- R 13 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-phenyl or phenyl, and
- B is an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 15 carbon atoms, such as, for example, phenyl, naphthalene, tetrahydronaphthalene, indane, carbazole, fluorene, cyclohexane, an unsaturated, saturated or partially-unsaturated mono- , bi- or tricyclic ring with a maximum of 14 carbon atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms or 0 to 2 sulfur atoms such as pyridine, thiophene, quinoline, quinoxaline, furan, idazole, pyrrole, indole, benzene can mean imidazole, pyrimidine, pyrazine, benzofuran, benzothiophene, thiophene, quinaxoline and isoxazole, which are each still substituted by one R 4 and a maximum
- F 2 has the same meaning as F 1 regardless of F 1
- G 1 represents a bond or an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 15 carbon atoms such as, for example, phenyl, naphthalene, tetrahydronaphthalene, indane, carbazole, fluorene, cyclohexane, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 14 carbon atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms or 0 to 2 sulfur atoms such as pyridine, thiophene, quinoline, quinoxaline, furan, imidazole, pyrrole, indole, benzimidazole, pyrimidine , Pyrazine, benzofuran, benzothiophene, thiophene, quinaxoline and isoxazole, can mean, which are each still substituted with a maximum of 3 different or identical radical
- p can mean 0 and 1 and
- q can be 0 and 1 and
- r can be 0 and 1
- R 41 is hydrogen, Ci-Cg-alkyl, phenyl, the maximum of two
- R 6 can carry, and (CH) tK and
- R 43 is hydrogen and -C 4 alkyl
- R 5 hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1: L R 12 , NH-CO-R 13 , 0-C ⁇ - C 4 alkyl, phenyl
- R 5 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1: L R 12 , NH-CO-R 13 , 0-C ⁇ -C 4 alkyl
- R 7 is hydrogen, Ci-Cg-alkyl, phenyl, where the ring can also be substituted with up to two radicals R 71 , and an amine NR 1: L R 12 or a cyclic saturated amine with 3 to 7 members, such as pyrrolidine, Piperidine, 1, 2, 5, 6-tetrahydropyridine, morpholine, homopiperidine, piperazine, which can still be substituted by an alkyl radical Ci-Cg-alkyl, and homopiperazine, which still has an alkyl radical Ci-Cg- Alkyl can be substituted, and where K, R 5 , R 6 and R 7 the radicals R 11 , R 12 and R 13 can independently assume the same meaning as in R 1 , and
- R 71 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH, and
- R 8 Ci-Cg-alkyl, phenyl, -C-C 4 alkyl-phenyl, where the ring can still be substituted with up to two radicals R 81 , and
- R 81 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH, and
- R 9 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 4 -alkyl-phenyl and phenyl, where the phenyl rings can also be substituted by up to two R 91 radicals, and
- R 91 can be OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH,
- A is a C chain which may be substituted
- X 1 represents 0
- X 2 and X 3 each represent an N atom
- R 1 is hydrogen
- A is a C 2 chain, which may be substituted
- X 1 represents 0
- X 2 and X 3 each represent an N atom
- R 1 is hydrogen
- B can be phenyl, cyclohexyl, piperidine, pyridine, pyrimidine, pyrazine, naphthalene, piperazine and quinoline.
- R 1 , X 1 and A have the same meaning as above
- X 2 and X 3 each represent a nitrogen atom
- B Can represent hydrogen and an alkyl chain -C ⁇ C.
- C0NH and the other radical A 2 or A 1 are hydrogen, chlorine, fluorine, bromine, iodine, Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1: L R 12 , NH-CO-R 13 , 0 -C -C-alkyl, and
- X 1 can be N and CR 2 and
- X 2 can be independent of X 1 , N and CR 2 and
- R 2 is hydrogen, Ci-Cg-alkyl, -C ⁇ C-alkyl-phenyl, phenyl and
- R 1 is hydrogen, chlorine, fluorine, bromine, iodine, Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1: L R 12 , NH-CO-R 13 , 0-C ⁇ -C 4 alkyl, where R 11 and R 12 independently of one another are hydrogen or C 1 -C 4 -alkyl and R 13 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-phenyl or phenyl, and
- B is an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 15 carbon atoms such as, for example, phenyl, naphthalene, tetrahydronaphthalene, indane, carbazole, fluorene, cyclohexane, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 14 carbon atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms or 0 to 2 sulfur atoms such as pyridine, thiophene, quinoline, quinoxaline, furan, imidazole, pyrrole, indole, benzene can mean imidazole, pyrimidine, pyrazine, benzofuran, benzothiophene, thiophene, quinaxoline and isoxazole, each of which can be substituted by an R 4 and a maximum of 3 identical or
- R 4 denotes hydrogen and - (D) p - (E) s - (F) q -G, where
- p can mean 0 and 1 and
- F can be a Ci-Cg alkyl chain
- q can be 0 and 1 and
- R 41 is hydrogen, Ci-Cg-alkyl, Ci-Cg-alkyl-phenyl, phenyl, where the rings can still carry a maximum of two radicals R 6 , and (CH 2 ) r -H and
- R 43 is hydrogen and -C 4 alkyl
- H NR 1 L R 12 , NR 1J —C ⁇ -C 4 alkylphenyl, pyrrolidine, piperidine, 1, 2, 5, 6-tetrahydropyridine, morpholine, homopiperidine, homopiperazine, piperazine, which are still with a Ci-Cg- Alkyl radical or can still be substituted with a Ci-Cg-alkyl-phenyl radical and the phenyl ring with a maximum of two R 81 , and
- R 5 hydrogen, chlorine, fluorine, bromine, iodine, Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1: L R 12 , NH-CO-R 13 , 0 -CC-C 4 alkyl
- R 6 hydrogen, chlorine, fluorine, bromine, iodine, Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1 ⁇ 12 , NH-CO-R 13 , 0-C ⁇ ⁇ C 4 alkyl
- R 7 is hydrogen, Ci-Cg-alkyl, phenyl, where the ring can also be substituted with up to two identical or different radicals R 71 , and an amine NR 1: L R 12 or a cyclic saturated amine having 3 to 7 members, such as pyrrolidine, piperidine, etc., and
- R 71 OH, -CC 6 alkyl, 0 -CC 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH 2 , and
- R 8 Ci-Cg-alkyl, phenyl, CC 4 -alkyl-phenyl, where the ring can also be substituted with up to two radicals R 81 , and
- R 81 OH, -C -C 6 alkyl, 0 -C -C alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH, and
- R 9 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 4 -alkyl-phenyl and phenyl, where the phenyl rings can also be substituted with up to two identical or different R 91 radicals, and
- R 91 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro and NH can be.
- radicals R 11 , R 12 and R 13 can assume the different meanings independently of one another and independently of the respective meaning in the case of another radical (for example A 1 , R 1 , R 5, etc.).
- C x -C y alkyl is always understood to mean, where possible, branched and unbranched C x -C y alkyl.
- X 1 represents an N atom
- X 2 represents CH and
- R 1 is hydrogen
- a 1 represents C0NH 2 and
- a 2 represents hydrogen
- X 1 represents an N atom
- X 2 represents CH and
- R 1 is hydrogen
- a 1 represents CONH 2 and
- a 2 represents hydrogen
- B represents phenyl, pyridine or piperidine, each of which may also be substituted by a radical R 4 and R 5 and
- R 1 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1; L R 12 , NH-CO-R 13 , 0-C ⁇ -C 4 ⁇ Alkyl, wherein R 11 and R 12 are independent of each other
- R 13 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-phenyl or phenyl, and A 1 is a straight-chain or branched Co-Cg-alkyl radical and
- R 2 is hydrogen and Ci-Cg-alkyl
- a 3 is an aromatic or heteroaromatic one or two-membered ring, each with 5 or 6 ring atoms and up to 3 heteroatoms, selected from N, 0, S, for example. Phenyl, thiophene, pyridine, pyrimidine, naphthalene, indole,
- Imidazole which can also be substituted by R 4 and one or two R 3 , where R 3 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 11 .
- Example 5 (N (3-trifluoromethylphenyl) aminomethyl) -2H-phthalazin-l-one
- Example 6
- A means naphthalene, aromatic heteromonocycle, aromatic or partially aromatic heterobicyclic and heterotricyclic, where the ring systems contain a maximum of 15 carbon atoms and up to 4 heteroatoms selected from the group N, 0, S and can additionally carry up to 2 oxo groups and A with - can be substituted to three different or identical radicals R 3 and additionally a radical R 4 and
- R 1 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, OH, nitro, CF 3 , CN, R 1 ⁇ 12 , NH-CO-R 13 , 0-C ⁇ -C4-alkyl, where R 11 and R 12 independently of one another are hydrogen or C 1 -C 4 -alk l and R 13 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkylphenyl or phenyl, and
- R 2 is hydrogen, branched and unbranched Ci-Cg-alkyl
- R 3 is hydrogen, chlorine, bromine, iodine, fluorine, CF 3 , 0CF 3 , nitro, NH,
- CO-R 8 , C0 -R 8 , S0 2 -R 8 , OH, O-C1-C4-alkyl, 0-Co-C-alkyl-phenyl, a C ⁇ ⁇ Cg chain that is saturated, unsaturated or partially unsaturated may be, and may also be substituted by one R 33 radical, phenyl, where the phenyl rings may also be substituted by up to three identical or different R 31 radicals, and pyridyl, which may be substituted by up to three R 32 radicals , and
- R 31 OH, Ci-Cg-alkyl, 0-C ⁇ -C alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH, and
- R 32 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH 2 , CN, and
- R 33 CO-NH-R 8 , OH, O-Ci-Cg-alkyl, 0-CO-R 8 ' , and R 4 means - (D) p - (E) s - (CH 2 ) q -B, where
- p can mean 0 and 1 and
- q can be 0, 1, 2, 3 or 4, and
- R 41 is hydrogen, Ci-Cg-alkyl, (CH 2 ) r -G and
- R 41 and R 42 can form a phthaloyl radical
- R 43 is hydrogen and -CC 4 ⁇ alkyl
- G phenyl which can still carry a maximum of two radicals R, NR 1 ⁇ 12 , NH-C ⁇ -C 4 alkylphenyl, pyrrolidine, piperidine, 1, 2, 5, 6-tetrahydropyridine, morpholine, homopiperidine, piperazine, which can still be substituted with an alkyl radical Ci-Cg-alkyl, and homopiperazine, which can still be substituted with an alkyl radical Ci-Cg-alkyl, and
- R 7 is hydrogen, Ci-Cg-alkyl, phenyl, where the ring can also be substituted with up to two radicals R 71 , and R 71 OH, Ci-Cg-alkyl, OC 1 -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH 2 , and
- R 8 Ci-Cg-alkyl, CF 3 , NR 1: L R 12 , phenyl, -C-C 4 alkyl phenyl, where the ring can still be substituted with up to two radicals R 81 , and
- R 8 OH, Ci-Cg-alkyl, 0-C ⁇ -C-alkyl, chlorine, bromine, iodine, fluorine, CF 3 ,
- R 9 is hydrogen, CO-R 8 , S0 2 -R 8 , C0 2 -R 8 , Ci-Cg-alkyl, -C-C 4 alkyl-
- R 91 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NH 2 , and can be
- R 9 can be hydrogen, CC 4 alkyl and Co-C 4 alkyl phenyl.
- A Preferred meanings of A are indole, benzimidazole, pyrrole, imidazole, furan, thiophene, benzothiophene, benzofuran, pyrazole, thiazole, benzothiazole, phthalimide, indazole, benzotriazole,
- Pyridine, thiophene, thiazole, furan, indole, oxazole, pyrazole, pyrrole, benzofuran, imidazole, benzothiophene, isoxazole, pyrazine, pyrimidine, pyridazine, quinoline, and the heterocycle can be substituted with up to three radicals R 3 and one radical R 4 , in which R 3 is hydrogen, chlorine, bromine, iodine, fluorine, COR 8 , C0 2 R 8 , S0R 8 , a Ci-Cg chain which can be saturated, unsaturated or partially unsaturated, and also with a group 0-CO-R 8 can be substituted, Ci-Cg-alkyl-phenyl, phenyl, where the phenyl rings can also be substituted with up to three identical or different radicals R 31 , and pyridyl, which can be substituted with up to three radicals R 32 , and
- R 4 is hydrogen and (D) p - (E) s - (CH 2 ) q -B, and R 3 and R 4 are not simultaneously hydrogen.
- Pyridine, pyrazine, pyrimidine, pyridazine, quinoline, thiazole, thiophene, pyrrole and pyrazole and the heterocycle can be substituted by a radical R 3 and a radical R 4 , where
- R 3 is hydrogen, chlorine, bromine, iodine, fluorine, -CC 4 alkyl, and
- R 4 is (D) p - (E) s - (CH 2 ) g -B.
- A can be pyridine, thiophene and thiazole and the heterocycle is substituted by a radical R 4 , where R 4 is (D) p - (E) s - (CH 2 ) q -B and R 3 is hydrogen.
- Example 106 2- (4- (4-chlorophenyl-carbonyl) -l-methyl-pyrrol-2-yl) -benzimidazole-4-carboxamide
- Example 107 2- (4- (4-chlorophenyl-carbonyl) -l-methyl-pyrrol-2-yl) -benzimidazole-4-carboxamide
- Another group of PARP inhibitors relates to substituted benzimidazoles of the general formulas I and II
- A denotes a saturated or monounsaturated carbocycle with 3 to 8 carbon atoms, which may additionally have fused on a benzene ring, the rings being able to be substituted with one or two different or identical radicals R 3 and the radical R 4 , and
- R 1 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, OH, nitro, CF 3 , CN, NR 1 ⁇ 12 , NH-CO-R 13 , 0-C ⁇ -C4-alkyl, in which
- R 11 and R 12 independently of one another are hydrogen or C 1 -C 4 -alkyl and
- R 13 is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkylphenyl or phenyl, and
- R 2 is hydrogen, branched and unbranched Ci-Cg-alkyl, -CC 4 alkyl phenyl and
- R 3 Ci-Cg-alkyl, OH, 0-C ⁇ -C 4 alkyl, 0-C ⁇ -C 4 alkyl phenyl, NR 11 12 , phenyl, C ⁇ -C 4 alkyl phenyl, CF 3 , COOH, C00 -C-alkyl, C0NH-C ⁇ -C4-alkyl, C0NH 2 , where the phenyl rings can be substituted with a maximum of two identical or different radicals R 31 , and
- R 31 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NR ⁇ R 2 , and R 4 means - (0) p - (CH 2 ) g -B, where
- p can mean 0 and 1 and
- R 41 is hydrogen, Ci-Cg-alkyl, (CH 2 ) r -E and
- E phenyl which can still carry a maximum of two radicals R 72 , and, if r - 0.1, also NR U R 12 , NH -CC 4 -alkylphenyl, pyrrolidine, piperidine, dihydropiperidine, morpholine, homopiperidine, Piperazine, which can still be substituted with Ci-Cg-alkyl and C ⁇ ⁇ C 4 -alkyl-phenyl, and homopiperazine, which can still be substituted with Ci-Cg-alkyl and C ⁇ -C 4 ⁇ alkyl-phenyl, and
- R 7 is hydrogen, Ci-Cg-alkyl, phenyl, where the ring can also be substituted with up to two identical or different radicals R 71 , and
- R 71 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NR l -i 12 , and
- R 72 OH, Ci-Cg-alkyl, 0-C ⁇ -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NR 1: L R 12 , and R 8 Ci-Cg-alkyl, phenyl, -C-C 4 -alkyl-phenyl-0-C ⁇ -C-alkyl-phenyl, where the ring can still be substituted with up to two identical or different radicals R 81 , and
- R 81 OH, Ci-Cg-alkyl, O-Ci- alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NR 1: L R 12 , and
- R 9 is hydrogen, Ci-Cg-alkyl, -CC 4 alkyl phenyl, phenyl, where the rings can be substituted with up to two radicals R 91 , and
- R 91 OH, Ci-Cg-alkyl, 0-C ! -C 4 alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro, NR 1: L R 12 , and can be.
- carbocycles which are at least monosubstituted.
- Preferred carbocycles are: tetralin, indane, cycloheptane, cyclohexane, cyclopentane, cyclobutane and cyclopropane.
- R 1 , R 2 and R 3 is hydrogen and R 4 has the meaning as above, where p is 0 and 1 and q is 0.1 and 2 , R 41 and R 42, independently of one another, hydrogen and C ⁇ -C 4 alkyl, R 7 are hydrogen, C ⁇ 4 alkyl and phenyl, R 9 are hydrogen, C 4 alkyl, and C ⁇ ⁇ C 2 alkyl -Phenyl, and R 4 in 3- and 4-pitch on the cyclohexane ring, both the ice and the trans forms or mixtures thereof being included.
- A is a cyclohexane ring and R 1 , R 2 and R 4 are hydrogen and R 4 has the meaning as above, where p 0 and 1 and q 0, 1 and 2, R 41 and R 42 , independently of one another, are hydrogen and C 1 -C 4 -alkyl, R 7 is hydrogen, R 9 is hydrogen, C 1 -C 4 -alkyl and benzyl, and R 4 in the 4-position on the cyclohexane Ring can stand, both the ice and the trans forms and their mixtures are included.
- R 4 is hydrogen, branched and unbranched Ci-Cg-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR 8 R 9 , NH-CO-R 10 , OR 8 , where R 8 and R 9 independently of one another are hydrogen or C ⁇ - C 4 alkyl and NR 8 R 9 together can be a cyclic amine having 4 to 8 ring atoms, the ring still being a radical (branched and unbranched Ci-Cg-alkyl, C -C 7 cycloalk -CC-C-alkyl , CO-R 41 ' COOR 41 and phenyl), and R 10 can be hydrogen, C 1 -C 4 -alkyl or phenyl and R 41 can have the same meanings as R 21 ,
- A is a saturated or monounsaturated heterocyclic, 4- to 8-membered ring, which contains one or two nitrogen atoms, in which case an oxygen or sulfur atom can also be incorporated, which is substituted by the substituents R 2 and R 3 is where
- -C-C 4 alkyl nitro, CF 3 , cyano, - (CH 2 ) 0 - 2 -NR 24 R 25 , NH-CO-R 10 , OR 10 , COOR 10 , S0-C ⁇ -C 4 alkyl, S0 2 Ph, S0 2 NH, NHS0 2 -C ⁇ -C-alkyl, NHS0Ph and CF 3 , where R 24 and R 25 independently represent hydrogen or -CC 4 alkyl and NR 24 R 25 together is a cyclic amine with 4 can be up to 8 ring atoms, the ring still being a radical branched and unbranched Ci-Cg-alkyl, C 3 -C 7 cycloalk -CC-C-alkyl ,.
- CO-R 22 ⁇ COOR 22 (with R 22 being hydrogen, branched or unbranched Ci-Cg-alkyl, C 3 -C 7 cycloalk-C ⁇ -C-alkyl, phen-C ⁇ -C 4 alkyl, C 3 -C 7- Cycloalkyl and phenyl) and phenyl can carry, and R 10 is hydrogen, -CC 4 alkyl or phenyl, and
- R 23 denotes NR 2 6R2 7 , where R 26 and R 27 are hydrogen, Ci-Cg-alkyl, Co-C 4 -alkyl-phenyl, the phenyl ring also having up to 3 radicals Cl, F, Br, J, C ⁇ - C-alkyl, CF 3 , CN, S0 2 -C-C-alkyl, S0 2 -phenyl, N0 2 , NH 2 , NHC0-C ⁇ -C 4 ⁇ alkyl, NHCO-phenyl, OH, 0-C ⁇ -C 4th -Alkyl, 0-C ⁇ -C 4 alkyl phenyl may be substituted, and NR 26 R 27 can also be a cyclic amine having 3 to 8 members, which may also contain a further heteroatom such as 0, N and S and the ring can also be substituted by a radical R 28 , where R 28 C 1 -C 4 alkyl and C 1 -C 4 alkyl phen
- R 3 is hydrogen, branched and unbranched Ci-Cs-alkyl optionally substituted by Ci-Cg-alkyl substituted C 3 -C 7 -cycloalkyl-alk C ⁇ -C 4 alkyl optionally substituted by Ci-Cg-alkyl substituted C 3 -Cv-cycloalkyl, where a C atom of the radical can also carry a phenyl ring, which in turn can be substituted with 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and unbranched C 1 -C 4 -alkyl, nitro, CF 3 , cyano, (CH 2 ) o- 2 ⁇ R 32 R 33 , NH-CO-R 10 , OR 10 , COOR 10 , S0 2 -C ⁇ -C 4 alkyl, S0 2 Ph , CH 3 , S0 2 NH, NHS0 2 -C ⁇ -C-alkyl, NHS0 2
- R 1 , R 2 and R 4 are hydrogen and A is piperidine which is bonded to the 4-position on the benzimidazole and R 3 is hydrogen, Ci-Cg-alkyl, benzyl and phenethyl means and is bound in the 1-position on the piperidine ring.
- R 5 to R 10 in the radicals R 1 to R 4 are independent of one another.
- NR 8 R 9 , NR 24 R 25 and NR 32 R 33 are piperidine, pyrrolidine, piperazine and homopiperazine.
- the ring can preferably also carry a radical of branched and unbranched Ci-Cg-alkyl, C -C 7 -cycloalk-C ⁇ -C 4 alkyl, CO-R 7 and phenyl.
- A is piperidine, pyrrolidine, piperazine, morpholine or homopiperazine.
- A means N or CH
- R 1 is hydrogen, branched and unbranched C 1 -C 6 -alkyl, where a C atom of the alkyl radical can also carry OR 11 or a group R 5 , where
- R 11 is hydrogen or -CC alkyl
- R 2 is hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched Ci-Cg-alkyl, nitro, CF 3 , CN, NR 21 R 22 , NH-CO-R 23 , OR 21 , wherein
- R 21 and R 22 independently of one another are hydrogen or C 1 -C 4 -alkyl and
- R 23 is hydrogen, -C ⁇ C 4 alkyl or phenyl
- R 3 is - (CH 2 ) q -NR 31 R 32 , (CH 2 ) q -NR 33 R 34 , where q can be 0, 1, 2 or 3,
- R 31 denotes hydrogen, Ci-Cg-alkyl, (CH 2 ) r NR 33 R 34 R 32 means (CH) r NR 33 R 34 ,
- R 31 and R 32 independently of one another are r 2, 3, 4, 5 or 6 and R 33 and R 34 independently of one another are hydrogen, Ci-Cg-alkyl, together with the nitrogen is a ring of 3 to 8 atoms which is a additional heteroatom selected from 0, N -CC-C-alkyl, NC 0 -C 2 -phenyl or NH can carry, phenyl -CC 4 -alkyl, the phenyl ring having up to 3 identical or different substituents selected from the group Ci-Cg-alkyl, halogen, nitro, S0 2 NR 35 R 36 (with R 35 , R 36 independently of one another are hydrogen, C ⁇ -C 4 ⁇ alkyl or together with the nitrogen is a ring of 3 to 8 atoms, which is an additional Heteroatom selected from 0, S, S0 2 , NC 1 -C 4 alkyl, N-Co-C 2 phenyl or NH can wear), -C ⁇ C 4 alkoxy, S
- R 4 is hydrogen, branched and unbranched Ci-Cg-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR 1 R 42 , NH-CO-R 43 , OR 41 , where
- R 41 and R 42 are independently hydrogen or -CC 4 alkyl and
- R 43 is -C 4 alkyl or phenyl
- Preferred positions for the radical R 2 in the general formula I are the 3-position and the 4-position relative to the benzimidazole ring.
- the 3-position or 4-position relative to the benzimidazole ring is also preferred for the radical R 3 .
- R 1 is hydrogen
- R 2 is hydrogen, branched or unbranched Ci-Cg-alkyl, nitro, CN, NH 2 , 0-C ⁇ ⁇ C-alkyl.
- R 2 is particularly preferably hydrogen.
- R 3 is (CH 2 ) 1 , NR 35 R 36 and
- R 37 can be hydrogen and -CC alkyl
- R 35 and R 36 independently of one another hydrogen and -CC alkyl and together as NR 35 R 36 can also be cyclic aliphatic amines such as piperidine, pyrrolidine, azepine and piperazine, where the piperazine on the second N atom can also be substituted by hydrogen or C 1 -C 4 -alkyl.
- the preferred meaning of R 4 is hydrogen.
- the cosmetic and dermatological formulations according to the invention can be composed as usual and can be used for the treatment, care and cleaning of the skin or hair and as a make-up product in cosmetics. They preferably contain 1 ocg / 100 g to 10% by weight of the active ingredient.
- the composition depends on the effectiveness of the inhibitor, the penetration properties of the active substance through the stratum corneum and its ability to form a depot in the skin.
- the use of the PARP inhibitor according to the invention is advantageously carried out by regular application, e.g. in the form of a cosmetic or dermatological preparation, over a period of time.
- the duration of use in the sense of the invention is the one-time application, but preferably a period of at least one day, particularly preferably over three days to three months, particularly preferably over one to two weeks.
- the cosmetic or dermatological preparation of the PARP inhibitors be present in an amount of 0.1 ug / cm 2 to 2 mg / cm 2 , between once a week and 4 to 5 times a day, preferably 3 times to be applied topically per week up to 3 times a day, particularly preferably once or twice a day.
- Both the Ki and the corresponding IC 50 values can be used to determine the effectiveness of the active substance.
- an IC50 value is determined in such a way that the active ingredient is only added after the relevant time.
- Active substances intended for after-sun applications advantageously have penetration properties which enable the substance to penetrate the skin quickly. In contrast, a quick penetration is not important for applications with a "preconditioning" character, but the ability to build up a depot in the skin is an advantage.
- an effective treatment is also a prevention of
- prematurely aged skin eg wrinkles, age spots, telangiectasias, pigment disorders
- prematurely aged skin appendages e.g wrinkles, age spots, telangiectasias, pigment disorders
- Photosensitive, inflammatory, erythematous, allergic or autoimmune-reactive changes in the skin and / or the appendages in particular acne, oily or dry skin, keratoses, rosaceae, dermatoses, atopic eczema, seborrheic eczema, photodermatoses, polymorphic light dermatosis
- the active ingredient according to the invention or cosmetic and dermatological preparations according to the invention also serve in a surprising and unpredictable manner
- the cosmetic and dermatological preparations according to the invention are applied to the skin and / or the hair in a sufficient amount in the manner customary for cosmetics.
- the active substances according to the invention are used in cosmetic compositions for cleaning the skin, such as bar soaps,
- skin cosmetic preparations such as W / O or O / W skin and body creams, day and night creams, eye creams, light protection agents, after sun products, hand care products, face creams, multiple emulsions, jellies, microemulsions, liposome preparations, Niosome preparations, anti-wrinkle creams, facial oils, lipogels, sports gels, moisturizing creams, bleaching creams, vitamin creams, skin lotions, care lotions, ampoules, after-shave lotions, pre-shaves, moisturizing lotions, Tanning lotions, cellulite creams, depigmenting agents, massage preparations, body powder, facial tonic, face masks, deodorants, antiperspirants, nose strips, anti-acne agents, repellants, shaving agents, hair removers, intimate hygiene products, foot care products, baby care products and others.
- skin cosmetic preparations such as W / O or O / W skin and body creams, day and night creams, eye creams, light
- the active compounds according to the invention can be used in cosmetic products for hair care, such as hair treatments, hair lotions, hair rinses, hair emulsions, tip fluids, leveling agents for perms, hot oil treatment preparations, conditioners, setting lotions, shampoos, hair tinting and coloring agents, hair sprays, hair lotions setting agents, gloss sprays, Brilliant hair, hair styling products, hair tonic, alopecie care products and others can be used.
- cosmetic products for hair care such as hair treatments, hair lotions, hair rinses, hair emulsions, tip fluids, leveling agents for perms, hot oil treatment preparations, conditioners, setting lotions, shampoos, hair tinting and coloring agents, hair sprays, hair lotions setting agents, gloss sprays, Brilliant hair, hair styling products, hair tonic, alopecie care products and others can be used.
- the active compounds according to the invention are also suitable for use in cosmetic preparations for decorative cosmetics, for example as make-up, powder, blush, eyeshadow, eye pencils, eyeliner, eye foundation cream, lipsticks, eyebrow pencils, contour pencils, masking pencils, theatrical make-up, mascara, eyelash tint , staining, make-up removal products and others.
- the cosmetic, hygienic, dermatological or pharmaceutical preparations can be prepared as a spray (pump spray or aerosol), foam, gel, gel spray, lotion, cream, mousse, ointment, suspensions or powder.
- active ingredients in an encapsulated form, e.g. encapsulated as cellulose, in gelatin, with polyamides, in niosomes, wax matrices, with cyclodextrins or liposomally encapsulated.
- Preparations according to the invention can contain cosmetic auxiliaries as are usually used in such preparations, e.g. Preservatives, bactericides, perfumes, substances to prevent foaming, dyes, pigments, thickeners, surface-active substances, emulsifiers, softening substances, softeners, fats, oils, waxes or other usual components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers , Solubilizers, electrolytes, organic acids, organic solvents or silicone derivatives.
- cosmetic auxiliaries e.g. Preservatives, bactericides, perfumes, substances to prevent foaming, dyes, pigments, thickeners, surface-active substances, emulsifiers, softening substances, softeners, fats, oils, waxes or other usual components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers , Solubilizers, electrolytes, organic acids, organic solvents or silicone derivative
- the preparations can contain further compounds which have an anti-oxidative effect, as a radical scavenger, moisturize or moisturize the skin, have anti-rythematous, anti-inflammatory or anti-allergic properties to complement or enhance their effect.
- these compounds can be selected from the group of vitamins, plant extracts, alpha and beta hydroxy acids, ceramides, anti-inflammatory, anti-microbial or UV-filtering substances, as well as their derivatives and mixtures thereof.
- the antioxidants are advantageously selected from the group consisting of amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. ⁇ -carotene, ⁇ -carotene, lycopene) and their derivatives, chlorogenic acid and their derivatives, lipoic acid and their derivatives (e.g.
- amino acids e.g. glycine, histidine, tyrosine, tryptophan
- imidazoles e.g. urocanic acid
- peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine)
- thiols e.g. thioredoxin, Glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, ⁇ -linoleyl, cholesteryl and glyceryl esters
- salts dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (eg buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfate
- (Metal) chelators e.g. oc-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), OC-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated Fatty acids and their derivatives (e.g. ⁇ -linolenic acid, linoleic acid, oleic acid), folic acid and their derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives (e.g.
- ascorbyl palmitate Mg-ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g. vitamin -E-acetate), vitamin A and derivatives (vitamin A palmitate) as well as coniferyl benzoate of benzoic resin, rutinic acid and its derivatives, butylated hydroxytoluene, butylated hydroxyanisole, norihydrogua ac resinic acid, nordihydroguajaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose Derivatives, sesamol, sesamolin, zinc and their derivatives (eg ZnO, ZnS04), selenium and their derivatives (eg selenium methionine), stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide) and the derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipid
- Preparations according to the invention can also advantageously contain substances which absorb UV radiation in the UV-B and / or UV-A range.
- the Total amount of filter substances e.g. 0.1% by weight to 30% by weight, preferably 0.5 to 15% by weight, in particular 1 to 10% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations, that protect the skin from the entire range of ultraviolet radiation.
- Light stabilizers which can be used alone or as a mixture together with the compounds of the formula I are e.g.
- UV filters which can be used in combination with the active compound combinations according to the invention, is of course not intended to be limiting.
- the total amount of the filter substances is generally 0.1% by weight to 30% by weight, preferably 0.5 to 15% by weight, in particular 1 to 10% by weight, based on the total weight of the preparations, to provide cosmetic preparations that protect the skin from the entire range of ultraviolet radiation.
- the lipid phase is advantageously selected from the group of substances of mineral oils, mineral waxes, branched and / or unbranched hydrocarbons and waxes, triglycerides of saturated and / or unsaturated, branched and / or unbranched Cs-C 24 -alkane-5-carboxylic acids; they can be selected from synthetic, semi-synthetic or natural oils such as olive oil, palm oil, almond oil or mixtures; Oils, fats or waxes, esters of saturated and / or unsaturated, branched and / or unbranched C 3 -C 3 o-alkane carboxylic acids and saturated and / or unsaturated, branched and / or unbranched C 3 -C 3
- the aqueous phase of the preparations according to the invention optionally advantageously contains alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol monoethyl ether.
- Preferred emulsifiers are known W / 0, but also O / W emulsifiers such as polyglycerol esters, sobitan esters or partially esterified glycerides.
- Suitable solubilizers are, in particular, ethoxylated sorbitan esters, ethoxylated lanolin alcohols and ethoxylated castor oil.
- Typical native and synthetic thickeners or gel formers in formulations are crosslinked polyacrylic acids and their derivatives, polysaccharides such as xanthan gum or alginates, carboxymethyl cellulose or hydroxycarboxymethyl cellulose, hydrocolloids such as gum arabic or motmorillonite minerals such as bentonites or fatty alcohols, polyvinyl alcohol and polyvinylpyronolidone.
- Suitable propellants for aerosols according to the invention are the customary propellants, for example propane, butane, pentane and others.
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
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Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2001258381A AU2001258381A1 (en) | 2000-05-04 | 2001-04-30 | Use of parp inhibitors in cosmetic preparations |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2000121468 DE10021468A1 (de) | 2000-05-04 | 2000-05-04 | Verwendung von PARP-Inhibitoren in kosmetischen Zubereitungen |
DE10021468.1 | 2000-05-04 |
Publications (2)
Publication Number | Publication Date |
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WO2001082877A2 true WO2001082877A2 (de) | 2001-11-08 |
WO2001082877A3 WO2001082877A3 (de) | 2002-03-14 |
Family
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Application Number | Title | Priority Date | Filing Date |
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PCT/EP2001/004838 WO2001082877A2 (de) | 2000-05-04 | 2001-04-30 | Verwendung von parp-inhibitoren in kosmetischen zubereitungen |
Country Status (3)
Country | Link |
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AU (1) | AU2001258381A1 (de) |
DE (1) | DE10021468A1 (de) |
WO (1) | WO2001082877A2 (de) |
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1247514A2 (de) * | 2001-04-03 | 2002-10-09 | Faber-Castell AG | Flüssigkeit zur Lippenpflege und Lippenfärbung |
WO2006067327A2 (fr) * | 2004-12-20 | 2006-06-29 | L'oreal | Antagonistes des recepteurs peripheriques des benzodiazepines pour le traitement des peaux seches |
WO2006067328A2 (fr) * | 2004-12-20 | 2006-06-29 | L'oreal | Utilisation de ligands du recepteur des benzodiazepines pour lutter contre les signes du vieillissement |
US7462724B2 (en) | 2005-11-15 | 2008-12-09 | Abbott Laboratories | Substituted 1H-benzimidazole-4-carboxamides are potent PARP inhibitors |
JP2009510106A (ja) * | 2005-09-29 | 2009-03-12 | アボット・ラボラトリーズ | 2位においてフェニルによって置換された1h−ベンズイミダゾール−4−カルボキサミドは強力なparp阻害薬である |
US7550603B2 (en) | 2005-04-11 | 2009-06-23 | Abbott Laboratories Inc. | 1H-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position are potent PARP inhibitors |
US7728026B2 (en) | 2005-04-11 | 2010-06-01 | Abbott Laboratories, Inc. | 2-substituted-1 h-benzimidazile-4-carboxamides are PARP inhibitors |
US7781596B1 (en) | 1998-11-03 | 2010-08-24 | Abbott Laboratories | Substituted 2-phenylbenzimidazoles, the production thereof and their use |
JP2010533728A (ja) * | 2007-07-16 | 2010-10-28 | アボット・ラボラトリーズ | ベンズイミダゾール系ポリ(adp−リボース)ポリメラーゼ阻害薬 |
US7999117B2 (en) | 2006-05-02 | 2011-08-16 | Abbott Lab | Substituted 1H-benzimidazole-4-carboxamides are potent PARP inhibitors |
WO2011107504A1 (de) | 2010-03-04 | 2011-09-09 | Bayer Cropscience Ag | Fluoralkyl- substituierte 2 -amidobenzimidazole und deren verwendung zur steigerung der stresstoleranz in pflanzen |
US8093396B2 (en) | 2009-01-19 | 2012-01-10 | Abbott Laboratories | Benzthiazole inhibitors of poly(ADP-ribose)polymerase |
EP2561759A1 (de) | 2011-08-26 | 2013-02-27 | Bayer Cropscience AG | Fluoralkyl-substituierte 2-amidobenzimidazole und ihre Wirkung auf das Pflanzenwachstum |
WO2014037340A1 (de) | 2012-09-05 | 2014-03-13 | Bayer Cropscience Ag | Verwendung substituierter 2-amidobenzimidazole, 2-amidobenzoxazole und 2-amidobenzothiazole oder deren salze als wirkstoffe gegen abiotischen pflanzenstress |
CN104030987A (zh) * | 2009-04-02 | 2014-09-10 | 默克雪兰诺有限公司 | 二氢乳清酸脱氢酶抑制剂 |
CN104230893A (zh) * | 2007-10-12 | 2014-12-24 | 艾伯维巴哈马有限公司 | 2-((r)-2-甲基吡咯烷-2-基)-1h-苯并咪唑-4-甲酰胺晶形2 |
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US7781596B1 (en) | 1998-11-03 | 2010-08-24 | Abbott Laboratories | Substituted 2-phenylbenzimidazoles, the production thereof and their use |
EP1247514A3 (de) * | 2001-04-03 | 2003-12-17 | Faber-Castell AG | Flüssigkeit zur Lippenpflege und Lippenfärbung |
EP1247514A2 (de) * | 2001-04-03 | 2002-10-09 | Faber-Castell AG | Flüssigkeit zur Lippenpflege und Lippenfärbung |
WO2006067327A2 (fr) * | 2004-12-20 | 2006-06-29 | L'oreal | Antagonistes des recepteurs peripheriques des benzodiazepines pour le traitement des peaux seches |
WO2006067328A2 (fr) * | 2004-12-20 | 2006-06-29 | L'oreal | Utilisation de ligands du recepteur des benzodiazepines pour lutter contre les signes du vieillissement |
WO2006067327A3 (fr) * | 2004-12-20 | 2007-03-01 | Oreal | Antagonistes des recepteurs peripheriques des benzodiazepines pour le traitement des peaux seches |
WO2006067328A3 (fr) * | 2004-12-20 | 2007-03-29 | Oreal | Utilisation de ligands du recepteur des benzodiazepines pour lutter contre les signes du vieillissement |
US8217070B2 (en) | 2005-04-11 | 2012-07-10 | Abbott Laboratories | 2-substituted-1H-benzimidazole-4-carboxamides are PARP inhibitors |
US7550603B2 (en) | 2005-04-11 | 2009-06-23 | Abbott Laboratories Inc. | 1H-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position are potent PARP inhibitors |
US7728026B2 (en) | 2005-04-11 | 2010-06-01 | Abbott Laboratories, Inc. | 2-substituted-1 h-benzimidazile-4-carboxamides are PARP inhibitors |
JP2009510106A (ja) * | 2005-09-29 | 2009-03-12 | アボット・ラボラトリーズ | 2位においてフェニルによって置換された1h−ベンズイミダゾール−4−カルボキサミドは強力なparp阻害薬である |
US7462724B2 (en) | 2005-11-15 | 2008-12-09 | Abbott Laboratories | Substituted 1H-benzimidazole-4-carboxamides are potent PARP inhibitors |
US7595406B2 (en) | 2005-11-15 | 2009-09-29 | Abbott Laboratories Inc. | Substituted 1H-benzimidazole-4-carboxamides are potent PARP inhibitors |
US7999117B2 (en) | 2006-05-02 | 2011-08-16 | Abbott Lab | Substituted 1H-benzimidazole-4-carboxamides are potent PARP inhibitors |
JP2010533728A (ja) * | 2007-07-16 | 2010-10-28 | アボット・ラボラトリーズ | ベンズイミダゾール系ポリ(adp−リボース)ポリメラーゼ阻害薬 |
US8067613B2 (en) | 2007-07-16 | 2011-11-29 | Abbott Laboratories | Benzimidazole poly(ADP ribose)polymerase inhibitors |
JP2014237665A (ja) * | 2007-07-16 | 2014-12-18 | アッヴィ・インコーポレイテッド | ベンズイミダゾール系ポリ(adp−リボース)ポリメラーゼ阻害薬 |
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US8093396B2 (en) | 2009-01-19 | 2012-01-10 | Abbott Laboratories | Benzthiazole inhibitors of poly(ADP-ribose)polymerase |
CN104030987A (zh) * | 2009-04-02 | 2014-09-10 | 默克雪兰诺有限公司 | 二氢乳清酸脱氢酶抑制剂 |
CN104030987B (zh) * | 2009-04-02 | 2017-04-12 | 默克雪兰诺有限公司 | 二氢乳清酸脱氢酶抑制剂 |
WO2011107504A1 (de) | 2010-03-04 | 2011-09-09 | Bayer Cropscience Ag | Fluoralkyl- substituierte 2 -amidobenzimidazole und deren verwendung zur steigerung der stresstoleranz in pflanzen |
EP2561759A1 (de) | 2011-08-26 | 2013-02-27 | Bayer Cropscience AG | Fluoralkyl-substituierte 2-amidobenzimidazole und ihre Wirkung auf das Pflanzenwachstum |
WO2014037340A1 (de) | 2012-09-05 | 2014-03-13 | Bayer Cropscience Ag | Verwendung substituierter 2-amidobenzimidazole, 2-amidobenzoxazole und 2-amidobenzothiazole oder deren salze als wirkstoffe gegen abiotischen pflanzenstress |
Also Published As
Publication number | Publication date |
---|---|
DE10021468A1 (de) | 2001-11-08 |
AU2001258381A1 (en) | 2001-11-12 |
WO2001082877A3 (de) | 2002-03-14 |
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