Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
  • A61P27/06—Antiglaucoma agents or miotics
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
  • C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups

Definitions

• Glaucoma is a disease of the eye characterized by increased intraocular pressure. On the basis of its etiology, glaucoma has been classified as primary or secondary. For example, primary glaucoma in adults (congenital glaucoma) may be either open-angle or acute or chronic angle-closure. Secondary glaucoma results from pre-existing ocular diseases such as uveitis, intraocular tumor or an enlarged cataract. Glaucoma occurs in about 2% of all persons over the age of 40 and may be asymptotic for years before progressing to rapid loss of vision.
• Secondary glaucoma is caused by any interference with the flow of aqueous humor from the posterior chamber into the anterior chamber and subsequently, into the canal of Schlemm. Inflammatory disease of the anterior segment may prevent aqueous escape by causing complete posterior synechia in iris bombe, and may plug the drainage channel with exudates. Other common causes are intraocular tumors, enlarged cataracts, central retinal vein occlusion, trauma to the eye, operative procedures and intraocular hemorrhage.
• prostaglandins and prostamides have recently become the first line treatments of glaucoma.
• Certain eicosanoids and their derivatives are currently commercially available for use in glaucoma management.
• Eicosanoids and derivatives include numerous biologically important compounds such as prostaglandins and their derivatives.
• Prostaglandins can be described as derivatives of prostanoic acid which have the following structural formula:
• prostaglandins are known, depending on the structure and substituents carried on the alicyclic ring of the prostanoic acid skeleton. Further classification is based on the number of unsaturated bonds in the side chain indicated by numerical subscripts after the generic type of prostaglandin [e.g. prostaglandin Ej (PGEi), prostaglandin E 2 (PGE2)], and on the configuration of the substituents on the alicyclic ring indicated by ⁇ or ⁇ [e.g. prostaglandin F2 ⁇ (PGF2 ⁇ )].
• PGEi prostaglandin Ej
• PGE2 prostaglandin E 2
• PPF2 ⁇ prostaglandin F2 ⁇
• Y has from 0 to 14 carbon atoms and is: an organic acid functional group, or an amide or ester thereof; hydroxymethyl or an ether thereof; or a tetrazolyl functional group;
• Z is halo, -OH, -OR, -SH, -CF 3 , or -CN; each R 1 is independently O, S, CH 2 , or if R 1 forms a double bond to another R 1 , then both are CH, provided that 0-0, S-O, and O-S are not present, and each R is independently -H, Ci -6 alkyl, Ci -6 hydroxyalkyl, or acyl.
• These compounds are also useful for growing hair, including one or more of: increasing the number of individual hairs, increasing the length of individual hairs, and increasing the width or thickness of individual hairs. These compounds are also useful for improving the appearance of hair, including increasing its gloss, shine, or other properties related to the reflection or dispersion of light, as well as changing the color of hair, including changing hair from grey or white to the color the hair was before it turned grey or white, such as red, brown, or black.
• the compound could be dissolved or suspended in an aqueous solution or emulsion that is buffered to an appropriate pH, and administered topically to an eye of a mammal (see US 7,091,231).
• “treat,” “treating,” or “treatment” refer to the use of a compound, composition, therapeutically active agent, or drug in the diagnosis, cure, mitigation, treatment, or prevention of disease or other undesirable condition.
• a pharmaceutically acceptable salt is any salt of the parent compound that is suitable for administration to an animal or human.
• a pharmaceutically acceptable salt also refers to any salt which may form in vivo as a result of administration of an acid, another salt, or a prodrug which is converted into an acid or salt.
• a salt comprises one or more ionic forms of the compound, such as a conjugate acid or base, associated with one or more corresponding counter-ions. Salts can form from or incorporate one or more deprotonated acidic groups (e.g. carboxylic acids), one or more protonated basic groups (e.g. amines), or both (e.g. zwitterions).
• a prodrug is a compound which is converted to a therapeutically active compound after administration. For example, conversion may occur by hydrolysis of an ester group or some other biologically labile group.
• Prodrug preparation is well known in the art. For example, "Prodrugs and Drug Delivery Systems,” which is a chapter in Richard B. Silverman, Organic Chemistry of Drug Design and Drug Action, 2d Ed., Elsevier Academic Press: Amsterdam, 2004, pp. 496-557, provides further detail on the subject. In particular, alkyl esters having such as methyl, ethyl, isopropyl, and the like are contemplated. Also contemplated are prodrugs containing a polar group such as hydroxyl or morpholine. Examples of such prodrugs include
• Tautomers are isomers that are in rapid equilibrium with one another. For example, tautomers may be related by transfer of a proton, hydrogen atom, or hydride ion.
• a structure is intended to include every possible stereoisomer, both pure or in any possible mixture.
• Alternate solid forms are different solid forms than those that may result from practicing the procedures described herein. For example, alternate solid forms may be polymorphs, different kinds of amorphous solid forms, glasses, and the like.
• Non-covalent complexes are complexes that may form between the compound and one or more additional chemical species that do not involve a covalent bonding interaction between the compound and the additional chemical species. They may or may not have a specific ratio between the compound and the additional chemical species. Examples might include solvates, hydrates, charge transfer complexes, and the like.
• a dashed line represents the presence or absence of a bond.
• Y is an organic acid functional group, or an amide or ester thereof; or Y is hydroxymethyl or an ether thereof; or Y is a tetrazolyl functional group.
• Y is limited to from 0 to 14 carbon atoms, from 0 to 5 oxygen atoms, from 0 to 2 nitrogen atoms, from 0 to 2 sulfur atoms, from 0 to 1 phosphorous, and any necessary hydrogen atoms.
• organic acid functional group is an acidic functional group on an organic molecule. While not intending to be limiting, organic acid functional groups may comprise an oxide of carbon, sulfur, or phosphorous. Thus, while not intending to limit the scope of the invention in any way, in certain compounds Y is a carboxylic acid, sulfonic acid, or phosphonic acid functional group.
• Esters and amides of organic acid functional groups contain have a nitrogen or an oxygen atom directly attached to the acidic core atom, where the oxygen atom is not part of an -OH moiety.
• the acidic core atom is the atom that is bonded to -OH or -SH in the organic acid functional group.
• esters of amides of carboxylic acids, sulfonic acid, and phosphonic acid functional groups are depicted below.
• An amide may also have an -SO 2 - moiety.
• the amide - CONHSO 2 R 3 wherein R 3 is a hydrocarbyl of from 1 to 14 carbon atoms, is contemplated.
• R, R 1 , R 2 , and R 3 are hydrocarbyl subject to the constraint that Y may not have more than 14 carbon atoms.
• Hydrocarbyl is a moiety consisting of carbon and hydrogen, including, but not limited to: a. alkyl, which is hydrocarbyl that contains no double or triple bonds, such as:
• linear alkyl e.g. methyl, ethyl, o-propyl, «-butyl, /i-pentyl, /7-hexyl, etc.
• branched alkyl e.g. iso-p ⁇ opyl, t-butyl and other branched butyl isomers, branched pentyl isomers, etc.
• cycloalkyl e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.
• alkenyl which is hydrocarbyl having 1 or more double bonds, including linear, branched, or cycloalkenyl
• alkynyl which is hydrocarbyl having 1 or more triple bonds, including linear, branched, or cycloalkynyl
• d unsubstituted or hydrocarbyl substituted phenyl
• e combinations of alkyl, alkenyl, and/or akynyl
• Ci- 6 hydrocarbyl is hydrocarbyl having 1, 2, 3, 4, 5, or 6 carbon atoms.
• Ci- 6 alkyl is alkyl having 1, 2, 3, 4, 5, or 6, carbon atoms such as methyl, ethyl, propyl isomers, butyl isomers, pentyl isomer, and hexyl isomers, etc.
• R 2 is Ci-C 6 alkyl, phenyl, or biphenyl
• other isomeric forms of the tetrazolyl functional group such as the one shown below are also possible, unsubstituted and hydrocarbyl substituted tetrazolyl up to Ci 4 are considered to be within the scope of the term "tetrazolyl.”
• Y is -CO 2 R 4 , -CONR 5 R 6 , -CON(CH 2 CH 2 QH) 2 , - CONH(CH 2 CH 2 OH), -CH 2 OH, -P(O)(OH) 2 , -CONHSO 2 R 4 , -SO 2 NR 5 R 6 ,
• R 4 ' R 5 and R 6 are independently H, Ci-C 6 alkyl, Ci -6 hydroxyalkyl, unsubstituted phenyl, or unsubstituted biphenyl, provided that Y has no more than 14 carbon atoms.
• Z is halo, -OH, -OR, -SH, -CF 3 , or -CN.
• Each R 1 is independently O, S, CH 2 , or if R 1 forms a double bond to another R 1 , then both are CH, provided that O-O, S-O, and O-S are not present.
• the chain formed by the R 1 groups may be one of those shown below.
• Each R is independently -H, Ci -6 alkyl, Cj -6 hydroxyalkyl, or Ci -6 acyl.
• Hydroxyalkyl is alkyl having a hydroxyl attached. The hydroxyl could be attached at any position.
• Ci -6 hydroxyalkyl has from 1 to 6 carbon atoms.
• Acyl is , wherein Rx is hydrocarbyl.
• Ci -6 acyl has from 1 to 6 carbon atoms.
• X is Cl.
• Z is OH.
• Z is OH.
• Another embodiment is a compound represented by the formula
• R 10 is H or Ci -6 alkyl.
• Another embodiment is a compound represented by the formula
• Another embodiment is a compound represented by the formula
• Another embodiment is a compound represented by the formula
• Another embodiment is method of reducing intraocular pressure comprising administering a compound disclosed herein to a mammal in need thereof.
• Another embodiment is a method of treating glaucoma or ocular hypertension comprising administering a compound disclosed herein to a mammal in need thereof.
• Another embodiment is a method of growing hair or improving the appearance of hair comprising administering a compound disclosed herein to a mammal in need thereof.
• Another embodiment is use of a compound disclosed herein in the manufacture of a medicament for the treatment of glaucoma or ocular hypertension.
• Another embodiment is use of a compound disclosed herein in the manufacture of a medicament for growing hair or improving the appearance of hair.
• the syringe containing the aldehyde 5 was rinsed with 2 mL of THF to complete the addition and the mixture was stirred at 25 0 C for 3 h.
• the reaction was worked up with addition of saturated aqueous ammonium chloride (50 mL) and the aqueous layer was extracted with ethyl acetate (2x75 mL). The ethyl acetate layers were combined and washed with brine, dried over 30 g of anhydrous sodium sulfate, filtered and concentrated in vacuo to yield 920 mg of crude products.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Ophthalmology & Optometry (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Dermatology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Priority Applications (9)

Applications Claiming Priority (4)

Publications (1)

Family

ID=40932327

Family Applications (1)

Country Status (12)

Families Citing this family (2)

Citations (4)

Family Cites Families (14)

• 2009
  • 2009-02-02 US US12/363,996 patent/US8455547B2/en active Active
  • 2009-02-03 KR KR1020107019695A patent/KR20100119787A/ko not_active Ceased
  • 2009-02-03 JP JP2010545948A patent/JP5566912B2/ja not_active Expired - Fee Related
  • 2009-02-03 EP EP09708693A patent/EP2245005A1/en not_active Withdrawn
  • 2009-02-03 WO PCT/US2009/032943 patent/WO2009100057A1/en not_active Ceased
  • 2009-02-03 AU AU2009212570A patent/AU2009212570B2/en not_active Ceased
  • 2009-02-03 CN CN2009801079234A patent/CN101959854A/zh active Pending
  • 2009-02-03 BR BRPI0907913-0A patent/BRPI0907913A2/pt not_active IP Right Cessation
  • 2009-02-03 CA CA2713958A patent/CA2713958A1/en not_active Abandoned
  • 2009-02-03 EP EP12167472A patent/EP2487153A1/en not_active Withdrawn
  • 2009-02-03 RU RU2010135795/04A patent/RU2505530C2/ru not_active IP Right Cessation
  • 2009-02-03 MX MX2010008589A patent/MX2010008589A/es active IP Right Grant
• 2010
  • 2010-08-02 IL IL207354A patent/IL207354A0/en unknown

Patent Citations (4)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events