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CN107737125A - A kind of medicine of medicine post-abortion metrorrhagia - Google Patents

A kind of medicine of medicine post-abortion metrorrhagia Download PDF

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Publication number
CN107737125A
CN107737125A CN201710964667.7A CN201710964667A CN107737125A CN 107737125 A CN107737125 A CN 107737125A CN 201710964667 A CN201710964667 A CN 201710964667A CN 107737125 A CN107737125 A CN 107737125A
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alkyl
group
medicine
hydrogen
substituent
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王玉美
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a kind of medicine of medicine post-abortion metrorrhagia, the medicine includes：Structural formula compound and its pharmaceutically acceptable salt described herein, the ester or prodrug of effective dose；And pharmaceutically acceptable carrier, wherein R1 are hydrogen, C1‑6Alkyl, single or multiple halo C1‑6Alkyl, the C substituted by one or two oh group1‑6Alkyl or the C substituted by a substituent1‑6Alkyl, the substituent are selected from the group, and the group is made up of the following：Cyano group and C1‑4Alkyl oxy；R2 is hydrogen, C1‑6Alkyl, single or multiple halo C1‑6Alkyl, the C substituted by one or two oh group1‑6Alkyl or the C substituted by a substituent1‑6Alkyl, the substituent are selected from the group, and the group is made up of the following：Cyano group and C1‑4Alkyl oxy；R3 is hydrogen, C1‑4Alkyl oxy, hydroxyl, cyano group, C1‑4Alkyl or halogen；R4 is hydrogen, C1‑4Alkyl oxy, hydroxyl, cyano group, C1‑4Alkyl or halogen.The medicine of the present invention has anastalsis to postabortal uterine hemorrhage.

Description

A kind of medicine of medicine post-abortion metrorrhagia
Technical field
The present invention relates to field of medicaments, and specifically, the present invention relates to a kind of medicine of medicine post-abortion metrorrhagia Thing.
Background technology
Drug abortion refers to by drug administration and the method for No operation terminal pregnancy, because of its convenient, painful small, curative effect Significantly, welcome by vast Women of Childbearing Age, clinically extensive use.But hemorrhage after drug abortion time lengthening, bleeding Amount increases as its major complications, turns into the problem of clinical letter is to be solved.
The content of the invention
It is an object of the invention to provide a kind of medicine of medicine post-abortion metrorrhagia.
In order to realize the purpose of the present invention, the present invention provides a kind of medicine of medicine post-abortion metrorrhagia, described Medicine includes：Effective dose has following structural compound and its pharmaceutically acceptable salt, ester or prodrug；Pharmaceutically Acceptable carrier：
,
Wherein R1 is hydrogen, C1-6Alkyl, single or multiple halo C1-6Alkyl, the C substituted by one or two oh group1-6Alkyl, Or the C substituted by a substituent1-6Alkyl, the substituent are selected from the group, and the group is made up of the following：Cyano group and C1-4Alkane Base epoxide；
R2 is hydrogen, C1-6Alkyl, single or multiple halo C1-6Alkyl, the C substituted by one or two oh group1-6Alkyl or by The C of one substituent substitution1-6Alkyl, the substituent are selected from the group, and the group is made up of the following：Cyano group and C1-4Alkyl oxygen Base；
R3 is hydrogen, C1-4Alkyl oxy, hydroxyl, cyano group, C1-4Alkyl or halogen；
R4 is hydrogen, C1-4Alkyl oxy, hydroxyl, cyano group, C1-4Alkyl or halogen.
Preferably, R1 is hydrogen.
Preferably, R2 is hydrogen.
Preferably, R3 is hydrogen.
Preferably, R4 is hydrogen.
The present invention also provides the compound with following structural and is preparing the medicine of medicine post-abortion metrorrhagia In purposes：
,
Wherein R1 is hydrogen, C1-6Alkyl, single or multiple halo C1-6Alkyl, the C substituted by one or two oh group1-6Alkyl, Or the C substituted by a substituent1-6Alkyl, the substituent are selected from the group, and the group is made up of the following：Cyano group and C1-4Alkane Base epoxide；
R2 is hydrogen, C1-6Alkyl, single or multiple halo C1-6Alkyl, the C substituted by one or two oh group1-6Alkyl or by The C of one substituent substitution1-6Alkyl, the substituent are selected from the group, and the group is made up of the following：Cyano group and C1-4Alkyl oxygen Base；
R3 is hydrogen, C1-4Alkyl oxy, hydroxyl, cyano group, C1-4Alkyl or halogen；
R4 is hydrogen, C1-4Alkyl oxy, hydroxyl, cyano group, C1-4Alkyl or halogen.
Preferably, R1 is hydrogen.
Preferably, R2 is hydrogen.
Preferably, R3 is hydrogen.
Preferably, R4 is hydrogen.
Before further describing the invention, it should be appreciated that the invention is not restricted to described embodiment, because it Certainly may change.It should also be understood that the purpose of terms used herein is only description embodiment, it is not used to form limit System, because the scope of the present invention is only limited by the appended claims.
Unless otherwise indicated, all scientific and technical terminologies used herein are managed with one skilled in the art of the present invention The usual implication of solution is identical.All patents referred to herein, application, published application and other publications are all in full with reference to knot Together in herein.If definition listed in this paper patent, application and other publications is included in definition in the part with reference Opposite or inconsistent, the definition in the part, which will overwhelm, quotes the definition for including this paper.
Herein and the singulative used in appended claims "one", " one kind " and " described " include plural indicate Thing, unless the context.It should also be noted that claims can be formulated as excluding any optional key element.Together Sample, this explanation application make reference claim element and relatively use this kind of removing property term, such as " only having ", " only ", Or use the antecedent basis of " negative " limitation.
Terms used herein "comprising", " containing " and " comprising " are used with its opening, infinite implication.
To provide conciser description, without using term " about " before some quantitative expressions herein.It should be understood that either No clearly to use term " about ", each content herein represents the numerical value actually given, and it is also represented by being based on ability The approximation for the given numerical value that domain ordinary skill can rationally infer, including due to this kind of caused by experiment and/or measuring condition The equivalent value and approximation of given numerical value.No matter when as a percentage during yield, this kind of yield represents specifically changing Learn metering and can be obtained the maximum amount of ratio with same entity for calculating the entity quality of yield than under the conditions of.Percentage The concentration of form represents quality ratio, unless otherwise indicated.
Unless otherwise indicated, all scientific and technical terminologies used herein are managed with one skilled in the art of the present invention The usual implication of solution is identical.Implement or test with similar or equivalent any method described herein and material although can also use The present invention, but preferable method and material are described below.All publications being mentioned above are totally incorporated herein by reference, with Cited publication, which is associated, comes these methods of disclosure and description and/or material.
Unless otherwise indicated, the methods and techniques of embodiment of the present invention typically follow conventional method well known in the art Carry out described in bibliography simultaneously such as some in generals or particularly, the bibliography is quoted and begged for through this specification By.See, e.g., Loudon, OrganicChemistry (《Organic chemistry》), fourth edition；New York：Oxford University Press (OxfordUniversityPress), 2002,360-361,1084-1085 page；Smith and March, March ' sAdvancedOrganicChemistry：Reactions, Mechanisms, andStructure (《Numb chi is advanced to organise Learn：Reaction, mechanism and structure》), the 5th edition, Wei Li scientific companies (Wiley-Interscience), 2001.
It is used to name the nomenclature of motif compound in the embodiments herein to illustrate herein.The nomenclature typically uses Commercially available AutoNom softwares (the MDL companies of Andrew in the sage of California), version 12.0.2 are obtained.
It should be understood that for clarity, some features of the invention described in the content of single each embodiment are also It may be incorporated in single embodiment and provide.Conversely, in the content of single embodiment Short Description it is of the invention Each feature can also be provided separately or be provided in the form of any suitable sub-portfolio.With the chemistry represented by changeable-shaped All combinations of the related embodiment of group are specific to be included in the scope of the invention and by being disclosed herein, just as single herein Disclose solely and clearly each and each combination (that is, can divide down to such combination comprising itself for the compound of stable compound From, characterize and detection biological activity compound).In addition, chemistry listed in describing the embodiment of such changeable-shaped All sub-portfolios of group are also specifically included in the scope of the invention and by being disclosed herein, just as herein individually and clearly public Open each and each such sub-portfolio of chemical group.
" pharmaceutically acceptable salt " is intended to indicate that the free acid of compound illustrated herein or the salt of alkali, its do not have toxicity, It can biologically tolerate or biologically be suitable to be administered to object.Generally referring to, S.M.Berge etc., “PharmaceuticalSalts(《Pharmaceutical salts》) " J.Pharm.Sci., 1977,66,1-19.It is preferable pharmaceutically acceptable Salt be pharmaceutically effectively and be adapted for contact with object tissue without excessive toxicity, stimulate or it is anaphylactoid those. Compound as described herein can have group acid enough, the enough group of alkalescence, two kinds of functional group or exceed It is a kind of all types of and therefore pharmaceutically acceptable to be formed with a variety of inorganic or organic base, and inorganic and organic acid reaction Salt.
The example of pharmaceutically acceptable salt includes sulfate, pyrosulfate, disulfate, sulphite, bisulfite Salt, phosphate, dibasic alkaliine, dihydric phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetic acid Salt, propionate, caprate, caprylate, acrylates, formates, isobutyrate, caproate, enanthate, propiolate, grass Hydrochlorate, malonate, succinate, suberate, sebacate, fumarate, maleate, Isosorbide-5-Nitrae-acetylenedicarboxylic acid salt, 1, 6- hexyndioic acids salt, benzoate, chloro benzoate, methyl benzoic acid salt, dinitro-benzoate, hydroxy benzoate, first P-methoxybenzoic acid salt, phthalate, sulfonate, metilsulfate, propyl sulfonic acid salt, benzene sulfonate, xylene monosulfonic acid Salt, naphthalene -1- sulfonate, naphthalene-2-sulfonic acid salt, phenyl acetate salt, phenylpropionic acid salt, PB, citrate, lactate, Gamma hydroxybutyrate, glycollate, tartrate and mandelate.The list of other suitable pharmaceutically acceptable salts can See Remington ' sPharmaceuticalSciences (《Remington pharmaceutical science》), the 17th edition, Pennsylvania The Mack Publishing Company (MackPublishingCompany) of Easton, 1985.
It may also include and one or more pharmaceutically may be used for the pharmaceutical composition of therapeutic purposes, including compound described herein The excipient of receiving.Pharmaceutically acceptable excipient refers to no toxicity and is biologically suitable to the material being administered to object.This Class excipient promotes the administration process of compound described herein and compatible with active component.Pharmaceutically acceptable excipient Example includes stabilizer, lubricant, surfactant, diluent, antioxidant, binding agent, colouring agent, swelling agent, emulsification Agent or flavor enhancement.In a preferred embodiment, the pharmaceutical composition of the invention is aseptic composite.Art technology can be used Personnel are known or the complex technique that can use prepares pharmaceutical composition.
The present invention also relates to aseptic composite, including meet the country for determining said composition and the composition of local code.
The conventional method prepared according to a variety of formulations are used in this area, pharmaceutical composition and compound described herein can Solution, emulsion, supensoid agent or the dispersant being formulated as in appropriate drug solvent or supporting agent, or pill, tablet, lozenge, bolt Agent, wafer, sugar-coat agent, granule, powder agent, the powder agent for reconstruction or the capsule together with solid carriers.The present invention's Pharmaceutical composition can be given by appropriate route of delivery, such as oral, parenteral, rectum, intranasal, part or through eye on the way Footpath, or pass through suction.Preferably, said composition is formulated as being used for administered intravenously or orally.
For being administered orally, compound of the invention can (such as tablet or capsule) or solution, emulsion in solid form Or the form of supensoid agent provides.To prepare Orally administered composition, compound of the invention can be prepared to form such as daily about 0.01 To about 50mg/kg or daily about 0.05 to about 20mg/kg or daily about 0.1 to about 10mg/kg dosage.Other dosage bags Include daily about 0.1mg to 1g, daily about 1mg to about 10mg, daily about 10mg to about 50mg, daily about 50mg to about 250mg, Or daily about 250mg to 1g.Oral tablet may include and compatible pharmaceutically acceptable excipient (such as diluent, disintegration Agent, binding agent, lubricant, sweetener, flavor enhancement, colouring agent and preservative) mixing active component.Suitable inert filler Including sodium carbonate and calcium carbonate, sodium phosphate and calcium phosphate, lactose, starch, sugar, glucose, methylcellulose, magnesium stearate, Mannitol, D-sorbite etc..Exemplary fluids oral vehicle includes ethanol, glycerine, water etc..Starch, polyvinylpyrrolidone (PVP), Explotab, microcrystalline cellulose and alginic acid are exemplary disintegrants.Bonding agent may include starch and gelatin. If it does, lubricant can be magnesium stearate, stearic acid or talcum.If desired, certain material can be used (as list is hard Glycerol or distearin) coating tablet is with the absorption in delaying stomach and intestine road, or uses enteric coating peridium.
Capsule for oral administration includes hard and Perle.To prepare hard gelatin capsule, can by active component with Solid, semisolid or liquid diluent mixing.Perle can be by by active component and water, oil (such as peanut oil or olive Olive oil), atoleine, the mixture of the list of short chain fatty acids and two glyceride, the side of polyethylene glycol 400 or mixed with propylene glycol It is prepared by formula.
Liquid for oral administration can be the form of supensoid agent, solution, emulsion or syrup, or can be The dry products rebuild before use with water or other suitable supporting agents.This kind of fluid composition is optional to be included：It is pharmaceutically acceptable Excipient, such as suspending agent (such as D-sorbite, methylcellulose, mosanom, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose Element, aluminium stearate gel etc.)；Non-aqueous supporting agent, for example, oily (such as apricot kernel oil or fractionated coconut oil), propane diols, ethanol or Water；Preservative (such as methyl p-hydroxybenzoate or propylparaben or sorbic acid)；Wetting agent (such as lecithin)； And (if desired) flavor enhancement or colouring agent.
The composition of the present invention can be formulated as suppository and be used for rectally.(including intravenous, flesh is used for parenteral Meat is interior, intraperitoneal, intranasal or subcutaneous route), reagent of the invention can be buffered to conjunction with aseptic aqueous solution agent or supensoid agent Suitable pH and isotonicity or by it is parenteral it is acceptable it is oily in the form of provide.Suitable aqueous carrier includes Ringer's solution And isotonic sodium chloride.This kind of form can be unit dosage form (such as ampoule or disposable injection device), multiple dose form (medicine bottle that can be such as taken out suitable dose) or solid form or available for the pre-concentration liquid for preparing injectable formulation. In several minutes of the time to a couple of days, the scope of exemplary infusion dosage is about 1 to 1000 μ g/kg/ minutes and drug-carrier The reagent of mixing.
For intranasal, suction or oral administration, the spray agent for for example also including suitable carrier can be used to give this hair Bright pharmaceutical composition.
For local use, the compound of the present invention is preferably formulated as emulsifiable paste or ointment or suitable for being locally administered Similar supporting agent.For local administration, the compound of the present invention can be mixed with drug-carrier, concentration is that medicine accounts for supporting agent About 0.1% to about 10%.Another pattern for giving the reagent of the present invention is to reach the effect of transdermal delivery using patch formulation Fruit.
Terms used herein " treatment " or " processing " include " preventative " and " therapeutic " treatment." preventative " treatment refers to Postpone the development of disease, disease symptomses or medical conditions, the symptom that suppression is likely to occur or reduce disease or symptom development or multiple The risk of hair." therapeutic " treatment includes reducing existing disease, the order of severity of symptom or illness or suppresses its deterioration.Therefore, The essence that treatment includes improving or prevents the deterioration of existing disease symptomses, prevents other symptoms, improves or prevent symptom System reason, suppress imbalance or disease, such as prevent imbalance or advancing of disease, mitigate imbalance or disease, promote imbalance or disease Row, mitigation disease or the illness caused by imbalance of retiring due to illness stop disease or the symptom of imbalance.
Term " object " refers to the mammalian subject for needing the treatment, such as people.
In the treatment method according to the present invention, " effective dose " refers to needed for the object acquisition for being enough to make this kind for the treatment of of needs The amount or dosage for the treatment of benefit.The effective dose or dosage of the compound of the present invention can be by conventional methods (as modeling, dosage are passed Increasing or clinical test) determine, wherein consider conventional factors, such as pattern or approach, the medicine generation of reagent of administration or medicine delivery Dynamics, the order of severity of infection and process, the judgement of the health status of object, the state of an illness and body weight and the doctor in charge.Show The scope of example property dosage is daily per Kilogram subject body weight about 1ug to 2mg active agent, and preferably from about 0.05 to 100mg/kg/ My god or about 1 to 35mg/kg/ days or about 0.1 to 10mg/kg/ days.In other embodiments, the scope of exemplary dose is About 1mg was to about 1g/ days, or about 1-500,1-250,1-100,1-50,50-500 or 250-500mg/ days.Accumulated dose can be with Single or separated dosage device (such as BID, TID, QID) is given.
Once the disease of patient improves, you can regulating dosage is used for preventative or maintaining treatment.For example, administration Dosage or frequency or both can change to be down to symptom keeps the required level for treating or preventing effect.Certainly, if disease Shape has mitigated to proper level, can stop treating.But during any symptom recurrence, between patient can be required in long-term basis Have a rest treatment.Patient may also need to the long-term treatment on the basis of long time-histories.
Retouched by reference to specific embodiment with the schematic synthetic schemes of general preparative methods in this article and afterwards State Exemplary chemical entity useful in the method for the present invention.Those skilled in the art will appreciate that to obtain herein more Kind compound, can suitably be selected parent material, so as to which the reaction scheme protected by suitably with or without makes With final required substituent to generate required product.Or, it may be necessary to or want in final required substituent position Put using the proper group that can be carried by reaction scheme and can be substituted in due course by required substituent.In addition, this area The order that technical staff should be understood that the conversion shown in following scheme and arbitrarily can hold with specific side base function phase is carried out.It is logical Preferably carried out with each reaction described in scheme under about 0 DEG C to the reflux temperature of organic solvent used.All material leads to Bought at Chang Kecong market supply business.
The medicine of the present invention can shorten the prothrombin time of aborting rat, thrombin time, and plasma fibrinogen increases Add, show that there is anastalsis to postabortal uterine hemorrhage.
Brief description of the drawings
Fig. 1 is rat uterus blastaea form, wherein A：Normal pregnancy group；B：Model control group； C：Positive controls；D、 E、F：The basic, normal, high dosage group of medicine of the present invention.
Embodiment
Below by way of the description of embodiment, the invention will be further described, but this is not to the present invention Limitation, those skilled in the art are according to the basic thought of the present invention, and various modifications may be made or improves, as long as but not taking off From the present invention basic thought, within the scope of the present invention.
Experimental example
The structural formula of medical compounds of the present invention is：
The SD female rats 90 of healthy unpregnancy are only pressed 2 with male rat:1 ratio mates, and morning next day carries out vaginal smear inspection Look into, to find to have sperm to be pregnant 1st day.Successfully female mice 60 that mate are chosen, 6 groups, every group 10 are randomly divided into by weight Only, respectively normal pregnancy group, model control group, positive controls (Gongxuening capsule, have purchased from Yunnan Baiyao medicine company share Limit company) and the basic, normal, high dosage group of medicine of the present invention.In addition to normal pregnancy group, remaining each group fills on the 7th day respectively in gestation Stomach mifepristone 12.50mg/kg (9:And Misoprostol 0.12mg/kg (17 00):00), while in intravaginal insert quantitative Cotton balls one (cotton balls weighs 90 mg).Next day is respectively at 9:00 and 17:00 takes out cotton balls, is wrapped up with preservative film, is put into plastics It is closed stored refrigerated in bag；A new cotton balls is replaced simultaneously in intravaginal, continuously to the 14th day.After modeling success, next day the (the 8th My god), the daily gavage of positive controls gives Gongxuening capsule content 0.15g/kg, the basic, normal, high dosage group of medicine of the present invention Daily gavage gives 1.2mg/kg, 2.4mg/kg and 4.8mg/kg, and normal pregnancy group and model control group are given distilled water, given Medicine body product is 2mL/100g.Each group 1 time a day, continuous 7d.
With 3% 0.5ml/ intraperitoneal injection of anesthesia of yellow Jackets after last dose 24h, taken entirely through abdominal aorta Blood (adds anti-coagulants), 1500r/min centrifugation 15min, takes supernatant.When determining factor using automatic coagulation analyzer Between (PT), thrombin time (TT), plasma fibrinogen (FIB).Statistical analysis is carried out with the softwares of SPSS 17.0.Data with Mean ± standard deviationRepresent, more group differences use variance analysis, and two groups of group differences are examined with Dunnett-t.P <0.05 represents that difference is statistically significant.As a result see the table below.
Rat uterus are completely cut after taking blood, rat uterus morphology is carried out and visually observes, as a result see Fig. 1.Observation knot Fruit shows that normal pregnancy group uterus is expanded in nodositas, and color and luster is red, and blood supply is enriched, and embryo number 5~10, embryo is seen after dissection It is intact；See extravasated blood in the uterine cavity of model group uterus, embryo is imperfect, there is residual, is incomplete abortion；Administration group uterus is except indivedual Embryo or obvious extravasated blood are had no outside congested.
Note：Compared with normal pregnancy group, * P<0.05；Compared with model control group, * * P<0.05；With positive controls ratio Compared with Δ P<0.05.

Claims (1)

1. purposes of the compound with following structural in the medicine for preparing medicine post-abortion metrorrhagia：
,
Wherein R1 is the C substituted by one or two oh group1-6Alkyl；R2 is substituted by one or two oh group C1-6Alkyl；R3 is hydrogen；R4 is hydrogen.
CN201710964667.7A 2016-11-26 2016-11-26 A kind of medicine of medicine post-abortion metrorrhagia Withdrawn CN107737125A (en)

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CN201611057383.1A CN106580982B (en) 2016-11-26 2016-11-26 A medicine for treating uterine bleeding after medical abortion

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106132967A (en) * 2014-03-27 2016-11-16 詹森药业有限公司 4,5,6,7 tetrahydro-pyrazoles being replaced also [1,5 a] pyrimidine derivatives and 2,3 dihydro 1H imidazo [1,2 b] pyrazole derivatives as ROS1 inhibitor

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GT200600381A (en) * 2005-08-25 2007-03-28 ORGANIC COMPOUNDS
US7655683B2 (en) * 2006-02-10 2010-02-02 Janssen Pharmaceutica Nv Imidazolopyrazole derivatives useful as selective androgen receptor modulators

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106132967A (en) * 2014-03-27 2016-11-16 詹森药业有限公司 4,5,6,7 tetrahydro-pyrazoles being replaced also [1,5 a] pyrimidine derivatives and 2,3 dihydro 1H imidazo [1,2 b] pyrazole derivatives as ROS1 inhibitor

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