JP2000504672A - Balanol analogues - Google Patents

Abstract

  (57) [Summary] The present invention relates to a solid phase methodology for the production of a combinatorial library of structural analogs of natural products balanol (opiocordin, azepinostatin), which are inhibitors of protein kinase C (PKC) and protein kinase A (PKA). The method consists of solid-phase synthesis of analogous variants of balanol, which leads to high molecular diversity. The synthetic scheme is based on a retrosynthesis analysis of the native structure and three major building blocks have been shown to be suitable as templates for modification. The dicarboxy-functional moiety is fixed to the polymer support as a monoallyl ester or as an intramolecular anhydride. Libraries produced by this method are particularly suitable for high throughput screening of potential drug candidates for treatment of mammals, especially humans.

Description

DETAILED DESCRIPTION OF THE INVENTION         Balanol analogues Field of the invention         The present invention utilizes a specially developed combinatorial library scheme. , A new method for synthesizing balanol analogs. The plan is It is also particularly suitable for library synthesis of balanol analogs. The present invention is of interest Providing a means to obtain a new group of compounds having certain surprising structures and functional features, Therefore, the present invention relates to the use of libraries for screening purposes and the treatment of various diseases. The use of the novel compounds as Background of the Invention         In traditional medicinal chemistry, appropriate pharmacological and toxicological properties are In the process of finding one active ingredient (drug) to have, on average 10,000 different Compounds are synthesized and tested. A series of analytical, crystallographic, organic synthetic and computational Gathering combined experience from chemical technology, the whole "logical drug design "It was founded as a new field often called. These methods are new Has been expected to speed up and facilitate the search for So far, it has not been shown to be very effective. Today, one new drug The average cost is still about 250-350,000,000 US dollars and one new drug It takes an average of 12 years to get to the market. In addition, the last 20 years Despite the white scientific progress, many diseases have no cure or cure for them. Still threatening humanity due to inadequate therapy I have. These clearly include AIDS, cardiovascular disease and human cancer, as well as neurodegenerative disorders. Diseases associated with harm (eg, Alzheimer's disease), metabolic disorders (type 2 diabetes) And other diseases that affect the quality as well as the length of life.         New chemistry / minute to facilitate the search for new biologically active compounds Analytical techniques have been developed. This research area often involves combinatorial chemistry. Is one of the fastest-developed research fields in modern organic chemistry. You. With the synthesis and screening of large and diverse libraries of small molecules, In addition to reaching new drugs, new synthetic receptors, new substances or new It can also be very important to find the right catalyst. Statements reported in this area Most of the contributions involve libraries of small peptides and oligonucleotides. This is because synthetic plans for solid-phase synthesis of these molecules have been around for decades. Because it is optimized for However, small molecules are Finding a bigger challenge and finding a potential lead in the drug discovery process Have the potential.         Creating Chemical Diversity Using Combinatorial Chemistry Is one of the most active fields in modern organic chemistry. Initially, the research was Focused on peptide and nucleotide library synthesis, but more recently- Anesthetics, [such as sedative sleeping pills, anticonvulsants, neuroleptics and anxiolytics] Transsystemic depressants, drugs or skeletons to treat neuromuscular abnormalities [like antiparkinsonian drugs] Muscle relaxants, analgesics, central nervous system stimulants, local anesthetics, cholinergic drugs, acetylcholine Phosphorus esterase inhibitors or cholinergic antagonists, adrenergic drugs, [Like cardiac glycosides, antianginal drugs, antiarrhythmic drugs] cardiovascular drugs, anticoagulants, coagulants And plasma expanders, diuretics, antiallergic and antiulcer drugs, antilipidemic drugs, Non-steroidal anti-inflammatory drugs, drugs that affect glucose metabolism, anti-mycobacterial drugs, Raw material or antibacterial, antifungal; insecticide, preservative or disinfectant; hormone antagonist Antitumor agents, antiviral agents for cancer chemotherapy or photochemotherapy; or HIV-sensitivity Find molecules that have activity in other fields, such as potential dyes and AIDS drugs Because it is ambiguous that it may be a drug-a library of non-peptide small molecules -Synthesis is primarily attracting attention and resources in this area.         Protein kinase C (PKC) is used for signal transduction, cell growth and Serine / threonine specific kinases involved in various processes including vesicular differentiation It belongs to the family of Ze. Activated PKC is involved in many disease processes Therefore, drugs that inhibit PKC have a wide range of therapeutic potential. These include cancer, inflammation, Such as cardiovascular dysfunction, diabetic complications, asthma, central nervous system disorders and HIV infection It contains a wide range of severe diseases.         Balanol is a metabolite of fungi and has a high PKC inhibitory activity. Attention. In addition, balanol is a known PKC inhibitor It has a relatively good therapeutic index compared to staurosporin. Sentence A total synthesis example of several balanols in solution [Lampe, J.W .; Hughes, P.F .;   Bigger, C.K .; Smith, S.H; Hu, H.J.Org.Chem. 1994, 59, 5147-5148; Lamp e, J.W .; Hughes, P.F .; Bigger, C.K .; Smith, S.H .; Hu, H. J. Org. Chem. 1996,   61, 4572-4581; Niclolaou, K.C .; Bunnage, M.E .; Koide, K.J.J.Am.Chem.S oc., 1994, 116, 8402-8403; Adams, C.P .; Fairway, S.M .; Hardy, C.J .; Hibbs, D. E .; Hursthouse, M.B .; Morley, A.D .; Sharp.B.W .; Vicker, N; Warner, I.J.Che m.Soc.Perkjn Trans. I, 1995, 2355-2362] and similar with improved selectivity [Lai, Y.-S .; Stamper, M. Bioorg. Med. Chem. Lett. 1995, 5, 2147-2150; Lai, Y.-S .; Menaldino, D.S .; Nichols, J.B .; Jagdmann, G.E.J. ; Mylott, F .; Gillespie, J; Hall, S.E. Bioorg. Med. Chem. Lett. 1995, 5, 21. 51-2154; Nicolaou, K.C .; Koide, K; Bunnage, M.E.Chem. Eur. J. 1995, 1, 454- 466] have been reported. However, all of these syntheses are And applied chemistry that is not compatible with solid-phase organic synthesis or combinatorial chemistry It contains some level of complexity. Summary of the Invention         It is an object of the present invention to provide for the synthesis of balanol analogs using solid phase synthesis methodology. To provide a simplified synthesis plan for For the synthesis of balanol analogues The new solid-phase method makes it easier to obtain known analogs and It is believed that no balanol analog could be provided. The synthesis plan also Enables easy synthesis of combinatorial libraries of balanol analogs Will do.         Therefore, the present invention provides the following general formula I:         K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D I Wherein K—C (-O) — represents a carboxy group or a derivative thereof; Each means an organic diradical; L¹And L^TwoAre each independently -NR^Five-Ma Or -O- [wherein each R^FiveIs hydrogen, optionally substituted C_1-20-Alkyl, optionally substituted Done C_1-20Alkenyl, optionally substituted C_1-20-Alkadienyl, optionally C replaced_1-20-Alkatrienyl, optionally substituted aryl, and optional Independently selected from heteroaryl substituted with^ThreeIs additive to B A bond (so that B becomes a three-terminal free radical)]; and D Means optionally substituted aryl or optionally substituted heteroaryl ] A method for producing a balanol derivative of The method involves the following steps: (A) A molecule with an optionally protected functional group immobilized on a solid support material -C (= O) -A-C (= O) -M¹ [Wherein, -C (= O) -M¹Means a carboxy group or a derivative thereof] And (B) Bifunctional moiety L 'optionally protected with a functional group¹-B-L '^TwoWith the fixed molecule -C ( = O) -A-C (= O) -M¹Terminal of -C (= O) -M¹And optionally protected functional groups Fragment -C (= O) -A-C (= O) -L¹-B-L '^TwoTo form (C) Arbitrarily protected functional group D-C (= O) -M^Two[Where C (= O) -M^TwoIs carboxy Represents a group or a derivative thereof] -C (= O) -A-C (= O) -L¹-B-L '^TwoL '^Two Compound -C (= O) -A-C (= O) -L bound to the terminal and optionally protected with a functional group¹- B-L^Two-C (= O) -D [this step is L '^TwoDeprotection of any protecting groups contained in Include), and (D) Compound K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D can be cleaved from the solid support material. And [The process entrusts the deprotection of one or more functional groups attached to A, B and / or D Include Consists of         The invention also relates to at least four compounds each having the general formula I described above. And preferably in the range of 6-200 compounds, more preferably 6-100 Multi-order of compounds {A}-{B}-{D} in the range of compounds, especially in the range of 8-64 compounds A method is also provided for synthesizing the original array. The method involves the following steps: (A) m molecules immobilized on a solid support material and optionally protected with functional groups -C (= O) -A- C (= O) -M¹[Wherein, -C (= O) -M¹Represents a carboxy group or a derivative thereof]] A} (B) n bifunctional group moieties L 'optionally protected with functional groups¹-B-L '^TwoArray {B} of Immobilized molecule -C (= O) -A-C (= O) -M¹Terminal of -C (= O) -M¹To M * n fragments with optionally protected functional groups -C (= O) -A-C (= O) -L¹-B-L '^TwoNo Forming ray {A}-{B} (C) o-parts optionally protected with a functional group D-C (= O) -M^TwoArray of {D} [where C (= O) -M^TwoRepresents a carboxy group or a derivative thereof.] The immobilized fragment -C (= O) -A-C (= O) -L¹-B-L '^TwoL '^TwoM * n * o immobilized immobilized functional groups attached to the ends Compound -C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D to form an array {A}-{B}-{D} Is L '^TwoArbitrarily includes the deprotection of any protecting group contained in (D) Compound K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D array {A}-{B}-{D} Cleaving from the material [the process was bound to individual A, B and / or D Optionally including deprotection of one or more functional groups] Consists of         Some of the new analogs have no structural similarity to the original balanol molecule. Therefore, no biological effects are expected at a glance, but such compounds Is useful as a drug that is expected to have higher specificity than balanol itself. It is thought that.         Therefore, the present invention relates to the use of a library for screening purposes and its use as a drug. The use of all individual compounds is also provided. Detailed description of the invention Definition         In the text, the term "C_1-20`` Alkyl '' refers to methyl, ethyl, propyl, iso- Propyl, cyclopropyl, butyl, tert-butyl, iso-butyl, cyclobutyl , Pentyl, cyclopentyl, hexyl, cyclohexyl, hexadecyl, hep 1 such as tadecyl, octadecyl, nonadecyl A linear, cyclic or branched hydrocarbon group having up to 20 carbon atoms is meant. As well The term "C_1-6-Alkyl '' means methyl, ethyl, propyl, iso-propyl, 1 to 6 carbon atoms such as methyl, cyclopentyl, hexyl, cyclohexyl Means a linear, cyclic or branched hydrocarbon group having_1-4-Alkyl '' Is methyl, ethyl, propyl, iso-propyl, cyclopropyl, butyl, is Lines having 1 to 4 carbon atoms, such as o-butyl, tert-butyl, cyclobutyl Means a cyclic, cyclic or branched hydrocarbon group.         "C_1-6-Alkyl '' is preferably methyl, ethyl, propyl , Iso-propyl, butyl, tert-butyl, iso-butyl, pentyl, cyclopent Hexyl, cyclohexyl, especially methyl, ethyl, propyl, iso- Propyl, tert-butyl, iso-butyl and cyclohexyl. "C_1-4-Arki Preferred examples of methyl '', methyl, ethyl, propyl, iso-propyl, butyl, tert -Butyl and iso-butyl.         Also the term "C_2-20 Alkenyl "," C_4-20Alkadienyl "and" C_6-20 "Alkatrienyl" refers to 2-20, 4-20 and 6-20 carbon atoms, respectively. And linear, cyclic or branched, each containing 1, 2 and 3 unsaturated bonds Mean hydrocarbon group. Examples of alkenyl groups are vinyl, allyl, butenyl, Pentenyl, hexenyl, heptenyl, octenyl, heptadecaenyl. Examples of alkadienyl groups include butadienyl, pentadienyl, hexadienyl, And heptadecadienyl. An example of an alkatrienyl group is hexa Trienyl, heptatrienyl, octatrienyl and heptadecatrienyl It is. Preferred examples of alkenyl are vinyl, allyl, butenyl, especially allyl is there.         Also the term "C_2-20"Alkynyl" has 2 to 20 carbon atoms, And a linear or branched hydrocarbon group containing one triple bond. Examples of this are ethynyl, propynyl, butynyl, octynyl and dodecainyl. is there.         In the text, the terms "alkyl", "alkenyl", "alkadie" The terms "optionally substituted" with respect to "nil", "alkatrienyl" and "alkynyl" "Is" means that the group of interest is one or several times, preferably 1 to 3 times, (When attached to an unsaturated carbon atom, it may be represented in a tautomeric keto form), C_1-6 -Alkoxy (ie alkyloxy), C_2-6-Alkenyloxy, carboxy , Oxo (forming keto or aldehyde functionality), C_1-6-Alkoxycarbonyl , C_1-6-Alkylcarbonyl, formyl, aryl, aryloxycarbonyl , Aryloxy, arylcarbonyl, heteroaryl, heteroaryloxy Cyclocarbonyl, heteroaryloxy, heteroarylcarbonyl, amino, No and di (C_1-6 -Alkyl) amino; carbamoyl, mono and di (C_1-6 -A Alkyl) aminocarbonyl, amino-C_1-6-Alkyl-aminocarbonyl, mono-  And di (C_1-6-Alkyl) amino-C_1-6 -Alkyl-aminocarbonyl, C_1-6- Alkylcarbonylamino, guanidino, carbamide, C_1-6-Alkanoyl oki Si, sulfono, C_1-6-Alkylsulfonyloxy, nitro, sulfanyl, C_1-6- Alkylthio, trihalogen-C_1-4-Alkyl, fluorine, chlorine, bromine or iodine Halogens such as [aryl and heteroaryl are “optionally substituted aryl and And heteroaryl "may be substituted as described above. Means that it can be replaced.         Substituents are hydroxy, C_1-6-Alkoxy, carboxy, C_1-6-Alkoki Cicarbonyl, C_1-6-Alkylcarbonyl, formyl, aryl, aryloxy Cycarbonyl, arylcarbonyl, heteroaryl, amino, mono- and di ( C_1-6 -Alkyl) amino, carbamoyl, mono- and J (C_1-6-Alkyl) aminocarbonyl, amino-C_1-6-Alkyl-aminocarbonyl , Mono- and di (C_1-6-Alkyl) amino-C_1-6-Alkyl-aminocarbonyl, C_{1- 6} -Alkylcarbonylamino, carbamide, trihalogen-C_1-6-Alkyl, fu Halogen such as nitrogen, chlorine, bromine or iodine [aryl and heteroaryl are 1 -5, preferably 1-3, C_1-4-Alkyl, C_1-4-Alkoxy, nitro, a Which can be substituted by mino or halogen]. Especially preferred Examples are hydroxy, C_1-6-Alkoxy, carboxy, aryl, heteroaryl Le, amino, mono- and di (C_1-6-Alkyl) amino and fluorine, chlorine, bromine Or halogen such as iodine [aryl and heteroaryl are 1-3_1-4-A Lucil, C_1-4-Can be substituted by alkoxy, nitro, amino or halogen] is there.         As used herein, the term "aryl" refers to a fully or partially aromatic carbocycle. Means a formula ring or ring system, e.g., phenyl, naphthyl, 1,2,3,4-tetrahydrona Futyl, anthracyl, phenanthracyl, pyrenyl, benzopyrenyl, fluoro There are lenyl and xanthenyl, of which phenyl is a preferred example.         The term “heteroaryl” means that one or more carbon atoms is a heteroatom, for example, Nitrogen (= N- or -NR^Five-[R^FiveIs hydrogen and C_1-4-Alkyl)]), Fully or partially aromatic carbon substituted by sulfur and / or oxygen atoms Means a cyclic ring or ring system. Examples of such heteroaryl groups are oxazolyl , Isoxazolyl, thiazolyl, isothiazolyl, pyrrolyl, imidazolyl, Pyrazolyl, pyridinyl, pyrazinyl, pyridazinyl, piperidinyl, cumaryl , Furyl, quinolyl, benzothiazolyl, benzotriazolyl, benzodiazoli , Benzoxazolyl, phthalazinyl, phthalanyl, triazolyl, tetrazo Ryl, isoquinolyl, acridinyl, carbazolyl, dibenzazepinyl, i And benzopyrazolyl and phenoxazonyl. Preferred Hetero Allies The radicals are pyridinyl, benzopyrazolyl and imidazolyl.         In the present text, the term "non-aromatic carbocyclic and heterocyclic groups" refers to Consisting of only carbon atoms (carbocyclic) or of carbon atoms with heteroatoms (Heterocyclic) means a ring. Heteroatoms are typically nitrogen, oxygen and sulfur Selected from. Such groups contain no unsaturated bonds or one or several It contains unsaturated bonds and, if present, however, creates an aromatic π-electron system. It is located in a manner that does not harm. The position of the radical is a two-terminal liberation resulting from such a group In the case of a group, it should be considered to be located directly on the ring.         Particular examples of non-aromatic carbocyclic and heterocyclic groups include oxaze Oxazetane, diazetan, thiazetan, oxazolan, imidazolidine, Thiazolan, oxaziran, hexahydropyridazine, thiaziran, oxazepa , Diazepan, thiazepan, oxazocane, diazocane, Azocaine, tetrahydrofuran, dihydrofuran, pyrrolidine, tetrahydro Thiophene, tetrahydropyran, piperidine, tetrahydrothiopyran, oki Sepang (oxepane), azepan, thiepane, oxocane, azocane, thiosilicate , Cyclopropane, oxirane, aziridine, cyclopropane, azirine, Clobutane, oxetane, azetidine, thietane, 2-azetidinone, 1,3-lacto , Pyrrolidine, pyrroline, pyrrole, cyclopentene, cyclopentadiene, Pyrrolidion, pyrrolidone, cyclohexyl, oxirane, dioxirane, mole Folin, piperidine, 1,5-lactone, 1,5-lactam, cyclohexene, cyclo Hexadiene, piperidione, tropane, 1,6-laclone (tropolone), 1,6-la Kutam, azepine, dihydroaze There are pins, tetrahydroazepine and hexahydroazepine. Especially preferred Examples include oxirane, aziridine, azirine, oxetane, 2-azetidinone , 1,3-lactone, pyrrolidine, pyrroline, pyrrole, pyrrolidone, pyrrolidione , Oxirane, dioxirane, morpholine, piperidine, δ-valerolactam (2 -Piperidone), 1,5-lactone, piperidione, tropolone, 1,6-lactam, aze With pin, dihydroazepine, tetrahydroazepine and hexahydroazepine is there. Particularly preferred examples include 2-azetidinone, 1,3-lactone, pyrrolidone, 1,5-lactam, 1,5-lactone, tropolone, 1,6-lactam, azepine, dihydro Azepine, tetrahydroazepine and hexahydroazepine.         In the text, the terms "aryl", "heteroaryl" and "non- The term "optionally substituted" with respect to "aromatic carbocyclic and heterocyclic groups" refers to When one or several, preferably 1-5, especially 1-3, Droxy (when present in the enol system, it may be shown in a tautomeric keto form) , C_1-6-Alkyl, C_1-6-Alkoxy, oxo (shown in tautomeric enol form Carboxy, C_1-6-Alkoxycarbonyl, C_1-6-Alkylcarbonyl , Formyl, aryl, aryloxy, aryloxycarbonyl, aryl Carbonyl, heteroaryl, amino, mono- and di (C_1-6-Alkyl) amino; Carbamoyl, mono- and di (C_1-6-Alkyl) aminocarbonyl, amino-C_1-6 -Alkyl-aminocarbonyl, mono- and di (C_1-6-Alkyl) amino-C_1-6-Al Kill-aminocarbonyl, C_1-6-Alkylcarbonylamino, guanidino, carb Mid, C_1-6-Alkanoyloxy, sulfono, C_1-6-Alkylsulfonyloxy, Nitro, sulfanyl, dihalogen-C_1-4-Alkyl, trihalogen-C_1-4-Arki Groups selected from halogens such as chloro, fluoro, chloro, bromo or iodo [substituted Aryl or heteroaryl representing a group] Means that it can be replaced by Preferred examples are hydroxy, C_1-6-Alkyl, C_1-6 -Alkoxy, carboxy, C_1-6-Alkoxycarbonyl, C_1-6-Alkylcal Bonyl, aryl, amino, mono- and di (C_1-6-Alkyl) amino and fluorine Halogen, such as chlorine, bromine or iodine [aryl and heteroaryl May be substituted as described above].         In the text, the synonyms "organic biradical" and "biradical" are It has the meaning generally associated with it. Therefore, such two-terminal radicals are Two hydrogen atoms (theoretically, without binding to one prototype) are also removed from the prognosis. By leaving, you can actually be guided. In the text, an interesting two-ended release The group may be linear or cyclic, and a linear or cyclic half-terminal free radical (sub-bira dical) consists of two or more domains. Both linear and cyclic properties An example of a two-terminal free radical consisting of a domain having Carbonyl-phenylene, methylene-phenylene-methyleneoxy and methylene There is n-phenylene.         Examples of linear or bonded two-terminal free radical domains include: Optionally O, S and NR^FiveInterrupted by one or more heteroatoms selected from One or several, preferably 1-5, especially 1- 5 arbitrarily substituted Cs_1-6-Alkyl, optionally substituted C_2-6-Alkenyl , Optionally substituted C_4-8-Alkadienyl, optionally substituted C_6-8-Arcatri Enyl, hydroxy, oxo, thereby forming keto or aldehyde functionality ), -O-R⁶, Formyl, -C (= O) -R⁶, -O-C (= O) -R⁶, Carboxy, -C (= O) -O-R⁶, Optionally substituted heteroaryl, optionally substituted heteroaryloxy, optional Optionally substituted aryl, optionally substituted aryloxy, fluorine, chlorine, odor Elementary and iodine Elemental halogens, nitro, cyano, -N (R^Five)_Two, -N (R⁷) -CO-R⁶, Carbamoyl , Mono- or di (C_1-6-Alkyl) aminocarbonyl, sulfanyl, optionally substituted Done C_1-6-Alkylthio, optionally substituted C_1-6-Alkylthio-C_1-6-Arki , (Optionally substituted aryl) thio, guanidino, sulfono (-SO_ThreeH), Rufino (-SO_TwoH), halosulfonyl, -OS (O)_m-R⁶[M is 2 or 3], -N (R⁷) S (O)_m-R⁶[M is 2 or 3], -S (O)_m-N (R⁷)_Two[M is 2 or 3], -S (O)_m-NH (R⁷ ) [M is 2 or 3], -S (O)_m-NH_Two[M is 2 or 3], isocyano, isothio Cyano, thiocyano, -OP (O)_p(R⁶)_q[p is 1, 2 or 3, q is 1 or 2, and And p + q are 3, 4 or 5] and -N (R⁷) P (O)_p(R⁶)_q[p is 1, 2 or 3, q is 1 Or 2, and p + q is a substituent selected from 3, 4 or 5] [each R^FiveAnd each R⁶Is , Hydrogen, optionally substituted C_1-20-Alkyl, optionally substituted C_2-20-Alkenyl , Optionally substituted C_4-20-Alkadienyl, optionally substituted C_6-20-Arca Trienyl, optionally substituted aryl, and optionally substituted heteroaryl Selected independently from the R; each R⁷Is hydrogen and C_1-4-Selected from alkyl] Has an optionally substituted alkylene chain of 1-20 carbon atoms.         Particularly preferred for domains of linear or linked two-radicals Examples are arbitrarily O, S and NR^FiveOne or two heteroatoms selected from More interrupted and / or terminated, optionally substituted C_1-6-Alkyl, Optionally substituted C_2-6-Alkenyl, hydroxy, oxo (so keto or Forms an aldehyde functionality), -O-R⁶, Formyl, -C (= O) -R⁶, -O-C (= O) -R⁶ , Carboxy, -C (= O) -O-R⁶An optionally substituted heteroaryl, an optionally substituted Heteroaryloxy, optionally substituted aryl, optionally substituted ant Halogen, such as oxy, fluorine, chlorine, bromine and iodine, cyano, -N (R^Five )_Two, -N (R⁷) -CO-R⁶, Carbamoyl, mono- or di (C_1-6-Alkyl) aminocar Bonil, C_1-6-A Substituent selected from alkylthio [each R^FiveAnd each R⁷Is independently hydrogen and C_1-4-A Each R⁶Is hydrogen, optionally substituted C_1-6-Alkyl, optional Commutated C_2-6-Alkenyl, optionally substituted aryl, and optionally substituted 1-3 independently selected from heteroaryl], optionally substituted May have an alkylene chain of 1-6 carbon atoms.         Two-terminal radicals may also include one or more cyclic moieties, especially 5- or 6- or 7-membered rings. It may consist of or include a formula component. Each such cyclic component is independently May be saturated, unsaturated or fully or partially aromatic; it may be carbocyclic or Well; or 1, 2, 3 or 4 typically nitrogen (= N- or -NR^Five-[In the formula , R^FiveIs a linear two-terminal radical as defined above)), and It may be a heterocyclic ring containing a telo atom. If some cyclic components are present, They may be linked via a single or double bond, or may be condensed , Or a combination thereof.         Examples of cyclic biterminal radicals are optionally substituted non-aromatic carbocyclic and In addition to the two terminal radicals of the telocyclic group, optionally substituted aryl groups and optionally substituted It is a two-terminal radical of a substituted heteroaryl group.         As is evident from the general formula 1 and the related definitions, And depending on the nature of the possible substituents, compound I may have one or several asymmetric Carbon may be present. See below. The compounds synthesized according to the method of the present invention are essentially , But their mixtures also include racemic mixtures, Includes all of the individual molecules and all stereoisomers resulting from the presence of any isomer It is a thing.         In addition, the compounds of general formula I, including their possible salts, are pharmaceutically acceptable. It is believed that the salts to be carried out are particularly suitable. Salts include acid addition and base salts . Examples include hydrochloride, sodium salt, calcium Salts and potassium salts. Pharmaceutically acceptable salts include, for example, Remington's Pharma ceutical Sciences [17.Ed. Alfonso R. Gennaro (Ed.), Mack Publishing Comp any, Easton, PA, U.S.A., 1985]. Furthermore, the final product is water It can also exist in the form of Japanese products. Construction of compounds of general formula I         The principle of the method of the present invention is shown in FIG. Baranol Retrosynthesis Analysis showed that the mono-protected aromatic diacid, amino alcohol, respectively. And the three main building blocks or synthons that are benzoic acid derivatives Is identified. [Method diagram 1]         Therefore, many changes are possible with reference to the method diagram 1 and It is feasible within the scope of the description. For example, the balanol molecules each have -L^Two-C (= O)- And -C (= O) -L¹-Contains one amide bond and one ester bond corresponding to You. However, analogs that can be within the scope of the present invention include two amide bonds or two It may contain ester bonds, Or their bonds may be interchanged, so that the ester bond is -L^Two-C (= O)-, amide bond is -C (= O) -L¹-Corresponds to. Furthermore, benzoic acid bildi The blocking block may be represented by any aromatic and heteroaromatic carboxylic acid. Diacids can be any other linear, cyclic, non-aromatic or aromatic derived diacid. A carboxylic acid may be used.         The molecule K-C (= O)-in the general formula I means a carboxylic acid (K = OH) or a derivative thereof. I do. Any carboxylic acid derivative known in the art falls within the definition of the invention It is thought that. However, if the molecule -C (= O) -K is (compound I synthesized according to the present invention) And) that portion typically occurs when compound I is cleaved from the solid phase resin, Free acid form (-COOH; K = OH) or carboxylate form (-COO^-; K = O^-) On is an alkali metal such as sodium or potassium, or an alkali such as calcium. Lithium metal and ammonium ions (N (R)_TwoR^Two)], Or Mid (-CONH_Two, -CONHR, -C0NRR '; each K = NH_Two, NHR, NRR '), hydroxyl Amide (-CON (OH) H; K = N (OH) H), hydrazide (-CONHNH_Two, CONHNHR '' '; each K = NHNH_Two, NHNHR '' ') or an ester (-COOR "; K = R") wherein R, R', R "and R" 'Is each optionally substituted C_1-20-Alkyl, optionally substituted C_2-20-Al Kenyl, optionally substituted C_4-20-Alkadienyl, optionally substituted C_6-20-A Lucatrienyl, optionally substituted aryl, or optionally substituted heteroaryl Reel means independently]. In addition, C-terminal carboxyl The acid may be reduced in the cleavage step to the corresponding aldehyde (K = H) No. Preferably, K is OH, O^-, OR ", NH_Two, NHR or NRR ', especially OH, Toxi, or NH_Two[R and R 'are C_1-6-Selected from alkyl and benzyl, where R "is C_1-6-Alkyl, C_2-6-Selected from alkenyl, phenyl and benzyl] To taste.         For a two-terminal radical A, this is the formula                            − (CR^ThreeR^Four)_n− (Ie, an alkylene chain that does not have a heteroatom that interrupts or terminates) n is 1-20, preferably 1-12, especially 2-8, and Each R^ThreeAnd R^FourIs hydrogen, optionally substituted C_1-6-Alkyl, optionally substituted C_2-6- Alkenyl, optionally substituted C_4-8-Alkadienyl, optionally substituted C_6-8- Alkatrienyl, hydroxy, oxo (so keto or aldehyde functional Form), -O-R⁶, Formyl, -C (= O) -R⁶, -O-C (= O) -R⁶, Carboxy, -C ( = O) -O-R⁶Optionally substituted heteroaryl, optionally substituted heteroaryl Oxy, optionally substituted aryl, optionally substituted aryloxy, fluorine Halogens such as, chlorine, bromine and iodine, nitro, cyano, -N (R^Five)_Two, -N (R⁷ ) -CO-R⁶, Carbamoyl, mono- or di (C_1-6-Alkyl) aminocarbonyl, Ruphanyl, optionally substituted C_1-6-Alkylthio, optionally substituted C_1-6-A Lucircio-C_1-6-Alkyl, (optionally substituted aryl) thio, guanidino, Sulfono (-SO_ThreeH), sulfino (-SO_TwoH), halosulfonyl, -OS (O)_m-R⁶[M is 2 or 3], -N (R⁷) S (O)_m-R⁶[M is 2 or 3], -S (O)_m-N (R⁷)_Two[M is 2 Or 3], -S (O)_m-NH (R⁷) [M is 2 or 3], -S (O)_m-NH_Two[M is 2 or 3] , Isocyano, isothiocyano, thiocyano, -OP (O)_p(R⁶)_q[P is 1, 2 or 3, q is 1 or 2, and p + q is 3, 4 or 5] and -N (R⁷) P (O)_p(R⁶)_q[ p is 1, 2 or 3, q is 1 or 2, and p + q is 3, 4 or 5] And select [each R^FiveAnd each R⁶Is hydrogen, optionally substituted C_1-20-Alkyl, any C replaced_2-20-Alkenyl, optionally substituted C_4-20-Alkadienyl, Optionally substituted C_6-20-Alkatrienyl, optionally substituted aryl, and Independently selected from heteroaryl and optionally substituted heteroaryl; each R⁷Is hydrogen and C_{1 -Four} -Alkyl), up to 5, preferably up to 3 substituents R^ThreeAnd R^Four Is different from hydrogen] May be an aliphatic two-terminal free radical.         Substituent R^ThreeAnd R^FourIs the optionally substituted C_1-6-Alkyl, optionally substituted  C_2-6-Alkenyl, hydroxy, oxo (with keto or aldehyde function ), -O-R⁶, Formyl, -C (= O) -R⁶, -O-C (= O) -R⁶, Carboxy, -C ( = O) -O-R⁶Optionally substituted heteroaryl, optionally substituted heteroaryl Oxy, optionally substituted aryl, optionally substituted aryloxy, fluorine , Halogens such as chlorine, bromine and iodine, cyano, -N (R^Five)_Two, -N (R⁷) -CO-R⁶ , Carbamoyl, mono- or di (C_1-6-Alkyl) aminocarbonyl, C_1-6-Al Kirthio [each R^FiveAnd each R⁷Is hydrogen and C_1-4-Independently selected from alkyl, Each R⁶Is hydrogen, optionally substituted C_1-6-Alkyl, optionally substituted C_2-6-Arche From nil, optionally substituted aryl, and optionally substituted heteroaryl Independently selected].         Alternatively, the two-terminal free radical A is designated as a fragment -C (= O) -A-C (= O)-, for example, For example, an aliphatic or aromatic dicarbonyl functionalized molecule as shown in FIGS. [Where X is> NR^Five,> NH, -O-, -S-, -Se-, -Te-, -CR¹R^Two-,> C = O,> C = S Selected from the group, Y¹, Y^Two, R¹And R^TwoIs independently aryl and hetero Y represents a substituent defined as an optional substituent of aryl (as described above); or Y¹ Is Y^TwoWith, along with the atoms present between these substituents, 4-, 5-, 6-, 7- or 8-membered ring (optionally substituted non-aromatic carbocyclic or heteroaromatic ring or optional Which may be an aromatic or heteroaromatic ring substituted with May form a group; each Z¹And Z^TwoAre independently = N-, = N⁺R^Five-Means] derived from Can be.         Preferred examples of the two-terminal free radical A include the following free radicals: Phenyl, naphthyl, anthracyl, pyrenyl, benzopyrenyl, Noxazonyl, N⁸-Phenoxazonyl, quinolyl, benzophenazinyl, ethidium And fluorenyl: two-terminal radicals containing or consisting of cyclic two-terminal radicals of Is a leaving group. Particularly preferred examples include naphthyl, benzopyrenyl, and phenoxy. Sazonil, N⁸-Phenoxazonyl, quinolyl, benzophenazinyl, ethidium And / or fluorenyl; and / or the formula-(CR^ThreeR^Four)_n− [Where each R^ThreeAnd R^FourIs , Optionally substituted C_1-6-Alkyl, optionally substituted C_2-6-Alkenyl, hydr Roxy, oxo (thus forming keto or aldehyde functionality), -O-R⁶ , Formyl, -C (= O) -R⁶, -O-C (= O) -R⁶, Carboxy, -C (= O) -O-R⁶, Optionally replace Heteroaryl, optionally substituted heteroaryloxy, optionally substituted Aryl, optionally substituted aryloxy, fluorine, chlorine, bromine and Halogen such as iodine, cyano, -N (R^Five)_Two, -N (R⁷) -CO-R⁶, Carbamoyl, mono- Or di (C_1-6-Alkyl) aminocarbonyl, C_1-6-Alkylthio, sulfono (- SO_ThreeH), sulfino (-SO_TwoH) selected independently of each other^FiveAnd each R⁷Is hydrogen and And C_1-4-Each R independently selected from alkyl⁶Is hydrogen, optionally substituted C_1-6-A Rukill, optionally substituted C_2-6-Alkenyl, optionally substituted aryl, and Independently selected from heteroaryl and optionally substituted heteroaryl]] May comprise or consist of groups.         These aromatic and heteroaromatic diradicals, A, are aryl or heteroaromatic. Substituted with one or more groups selected from the same groups as defined above for the substituents on the reel group It may be.         With regard to the carbonyl groups adjacent to A of formula I, these carbonyl groups are An essential part of the starting material for producing compound I or a library of compound I It is believed that there is. Therefore, in most cases, two carboxylic acid groups [1- One in an optionally protected form and the other in the free acid or activated form] or Two carboxylic acids in the form of intramolecular anhydrides It is advantageous to use cyclic moieties having a boxy group. In this way, A is easy To the solid phase material.         Dicarboxylic acid functionality showing fragment -C (= O) -A-C (= O)-after insertion into compound I Examples of compounds are as follows:         Aromatic and heteroaromatic: 2,2'-biquinoline-4,4'-dicarboxylic acid, 5-nitro-isophthalic acid, 2-amino- Phthalic acid, 2-bromo-terephthalic acid, 2-nitro-terephthalic acid, 3,6-dichloro -Phthalic anhydride, 4,5-dichloro-phthalic anhydride, 3-nitro-phthalic anhydride , 4-Nitro-phthalic anhydride, homophthalic acid, 4,4'-biphenyl-dicarboxylic acid , 2,2'-biphenyl-dicarboxylic acid, 2,3-naphthalene-dicarboxylic acid, 2,6-naph Taren-dicarboxylic acid, 1,8-naphthalene-dicarboxylic anhydride, 3-nitro-1,8- Naphthalene-dicarboxylic anhydride, 1,2-phenylene-dioxy-diacetic acid (diaceti c acid), embonic acid, 5,5'-dithiobis- (2-nitrobenzoic acid) ( 3,3'-6), 2,2'-dithiobenzoic acid, glutamic acid-5- (3-carboxy-4-nitro- Anilide), alizarin-3-methyliminodiacetic acid, 1,4-phenylene-diacetic acid, 2,4 '-Benzophenone-dicarboxylic acid, 2,4'-benzophenyl-dicarboxylic acid, Ridamic acid (chelidamic acid), 2,3-pyridine-dicarboxylic acid, 2,4-pyridine- Dicarboxylic acid, 2,5-pyridine-dicarboxylic acid, 2,6-pyridine-dicarboxylic acid, 3, 4-pyridine-dicarboxylic acid, 3,5-pyridine-dicarboxylic acid, 4,5-pyridine-dica Rubonic acid, imidazole-4,5-dicarboxylic acid, 3,4,5,6-tetrachloro-phthalic acid , 2-amino-4,6-pyrimidine-dicarboxylic acid, 9,10-anthracene-dicarboxylic acid Acid, 1,4-didroxy-naphthalene-2,3-dicarboxylic acid, benzimidazole-5,6 -Dicarboxylic acid, benzophenone-4,4'-dicarboxylic acid, 4-methoxy-phthalic acid, Naphthidine-3,3'-dicarboxylic acid, naphthalene-1,2-di Carboxylic acid, naphthalene-1,3-dicarboxylic acid, naphthalene-1,4-dicarboxylic acid, Naphthalene-1,5-dicarboxylic acid, naphthalene-1,6-dicarboxylic acid, naphthalene-1 , 7-dicarboxylic acid, naphthalene-1,8-dicarboxylic acid, naphthalene-2,3-dicarbo Acid, naphthalene-2,4-dicarboxylic acid, naphthalene-2,5-dicarboxylic acid, naphthalene Len-2,7-dicarboxylic acid, naphthalene-2,8-dicarboxylic acid, pyrimidine-4,6-di Carboxylic acid, pyrazole-3,6-dicarboxylic acid and 1,10-phenanthroline-5 2,6-dicarboxylic acid; particularly preferred are phthalic acid, isophthalic acid, terephthalic acid , 5-nitro-isophthalic acid, 2,6-naphthalenedicarboxylic acid, 1,2-naphthalenedica Rubonic acid, 2,3-naphthalenedicarboxylic acid, biphenyl-4,4'-dicarboxylic acid, bifu Phenyl-2,4'-dicarboxylic acid, 4-methoxy-biphenyl-2,4'-dicarboxylic acid, 2,2 ' -Benzophenone dicarboxylic acid, 3,3'-benzophenone dicarboxylic acid, 4,4'-ben Zophenone dicarboxylic acid, benzophenone-2,4'-dicarboxylic acid, 2-methoxy- Nzophenone-2'-5-dicarboxylic acid, 2-methoxy-benzophenone-4'-5-dicarbo Acid 6,2 ', 6'-trihydroxy-2,4'-dicarboxy-bisphenylmethane, 1,1- ( 6 ', 2 ", 6" -trihydroxy-2', 4 "-dicarboxy-diphenyl) -ethene, 6,2 ', 6'- Trihydroxybenzophenone-2,4'-dicarboxylic acid, 6,2 ', 6'-trimethoxy- Nzophenone-2,4'-dicarboxylic acid, 2-carboxamide-6,2 ', 6'-trihydroxy Benzophenone-4'-carboxylic acid, 2-carboxyethyl-6,2 ', 6'-trihydroxy Benzophenone-4'-carboxylic acid, 2-carboxymethyl-6,2 ', 6'-trihydroxy Benzophenone-4'-carboxylic acid, 6,2 ', 6'-trifluorobenzophenone-2,4'-di Carboxylic acid, 2 ', 6'-dimethoxy-6-hydroxybenzophenone-2,4'-dicarboxylic Is an acid; and         Linear and non-aromatic: Oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, Suberic acid, azelaic acid, sebacic acid, undecanedioicacid , Dodecanoic acid, tetradecandioic acid, hexadecandioic acid docosantioic acid, tolan , Trans-muconic acid, methyl maleic acid, methyl maleic anhydride, (+) And (-)-Camphoric acid, 1,3-acetonedicarboxylic acid, N- (acetamido) -iminodiacetic acid , L-aspartic acid, S-carboxymethyl-L-cysteine, 2,2 '-(ethylenedithi E) -Diacetic acid, malic acid (+ and-), D-penicillamine, phenylsuccinic acid, N- (e (Suphonomethyl) -iminodiacetic acid, tetrahydrofolate, (+ or-) 0,0'-dibenzyl- 2-tartaric acid, (3-thienyl) -malonic acid, N-phthaloyl-1-glutamic acid, dife Nilmaleic anhydride, cis-1,2,3,6-tetrahydrophthalic acid, 3,4,5,6-tetra Hydrophthalic acid, pyrazine-2,3-dicarboxylic acid, ticaricillin, Heliconic acid, glycine cresol red, cyclopropane-1,1'-dicarboxylic acid, cyclohexane Lobutane-1,1'-dicarboxylic acid, 1-cyclopentene-1,2-dicarboxylic anhydride, 1, 1'-azobis- (cyclohexane-carboxylic acid), cyclopropane-1,2-dicarbo Acid, (cis + trans) -1,4-cyclohexanedicarboxylic acid, pyrazine-2,5- Dicarboxylic acid, piperidine-2,6-dicarboxylic acid, piperidine-3,3-dicarboxylic acid , Pyrroline-N-oxide-5,5-dicarboxylic acid, γ-pyrone-2,6-dicarboxylic acid and And piperazine-2,6-dicarboxylic acid.         For a two-terminal radical B, this is the formula                             − (CR^ThreeR^Four)_n− [Where R^Three, R^FourAnd n is the same as defined in A). Seems good.         Alternatively, B may be an aliphatic or aromatic amino acid such as shown in FIG. Rucol [where X is> NR⁶,> NH, -O-, -S-, -Se-, -Te-, -CR¹R^Two-,> C = O,> C = S Selected from the group consisting of¹, Y^Two, R¹And R^TwoAre Substituents defined as optional substituents on reel and heteroaryl (as described above) Independently means; or Y¹Is Y^TwoTogether with the atoms present between these substituents Together with a 4-, 5-, 6-, 7- or 8-membered ring (optionally substituted non-aromatic carbocyclic or Is a heteroaromatic ring or an optionally substituted aromatic or heteroaromatic ring, May form a two-terminal free radical; each Z¹And Z^TwoAre independently = N-, = N⁺ R^Five-Means].         Preferred examples of the two-terminal radical B include, for example, the following non-aromatic carbocyclic Compound free radicals: cyclopropane, cyclobutane, cyclopentane, cyclopent Ten, cyclopentadiene, cyclohexane, cycloheptane and cyclooctene Tan; the following aromatic or non-aromatic heterocyclic compounds: epoxide, aziridi Thioepoxide, oxazetan, diazetan, thiazetan, oxazolan, Imidazolidine, thiazolan, oxazirane, hexahydropyridazine, thiazi Orchid, oxazepane, diazepane, thiazepane, oxazocane, diazocane , Thiazocane, tetrahydrofuran, dihydrofuran, pyrrolidine, tetrahi Drothiophene, tetrahydropyran, piperidine, tetrahydrothiopyran, Oxepan, azepan, tiepan, oxocane, azocane, thiocane, Clopropane, oxirane, aziridine, cyclopropene, azirine, cyclobu Tan, oxetane, azetidine, thietane, 2-azetidinone, 1,3-lactone, Loridine, pyrroline, pyrrole, pyrrolidione, pyrrolidone, oxirane, geo Xylan, morpholine, piperidine, 1,5-lactone, 1,5-lactam, cyclohexane Xen, cyclohexadiene, piperidione, tropane, 1,6-laclone (tropo Ron), 1,6-lactam, azepine, dihydroazepine, tetrahydroazepine and And hexahydroazepine.         As is clear from the above, each L¹And L^TwoIs -NR^Five-Or -O- [wherein each R^FiveIs hydrogen, optionally substituted C_1-20-Alkyl, optionally substituted C_2-20-Al Kenyl, optionally substituted C_4-20-Alkadienyl, optionally substituted C_6-20-A Lucatrienyl, optionally substituted aryl, and optionally substituted heteroaryl Selected independently of the reel or R^FiveMeans an additional bond to B (that B becomes a three-terminal free radical)]]. R^FiveIs hydrogen, C_1-4-Arki Preferably, it refers to an additional bond to thiol or B. Above all, L¹And L^TwoOne One is -O- and the other is -NR^Five-[Where R^FiveIs hydrogen, C_1-4-Addition to alkyl or B Meaning binding].         Therefore, interesting and very suitable starting materials for the synthesis of compound I are , 1-amino-ω-hydroxy- (optionally substituted) -C_1-6-Alkylene wherein C_{1- 6} -Alkylene is C_1-6-Is a two-terminal radical of the radical defined by alkyl, optional The substituents are as defined for “alkyl”.         Amino alcohols are non-aromatic carbocyclic or heterocyclic compounds When selected from the group of the hydroxy- and amino-functional groups, where applicable, They can be located 1,2-, 1,3-, 1,4- or 1,5- relative to each other, and likewise have an amino group and an amino group. The stereochemical environment of the rucol group is in the cis-configuration [two substituents are on the same side of the ring] Or trans configuration [two substituents on different sides of the ring] Can be. In addition, different enantiomers (mirror images) and diastereomers Present in non-aromatic carbocyclic or heterocyclic compounds so substituted The natural consequences of chirality exist. Therefore, a particularly preferred example is The hydroxy and amino functions are 1,2 or 1,3 relative to each other, especially 1,2 Derived from non-aromatic carbocyclic and heterocyclic compounds located at There is Rucol.         Specific examples of amino alcohols derived from non-aromatic carbocyclic compounds Are 2-aminoethanol, 1-amino-2-propanol, 3-amino-1-propanol Ethanol, 2-amino-1-propanol, 2-amino-2-methyl-1-propanol, 1-a Mino-2-methyl-2-propanol, 3-amino-2-methyl-1-propanol, 2-amino 1-butanol, 1-amino-2-butanol, 3-amino-3-butanol, 3-amino-1- Butanol, 4-amino-2-butanol, cis-2-amino-1-cyclobutanol, tran s-2-amino-1-cyclobutanol, 5-amino-1-pentanol, 2-amino-1-pen Tanol, 3-amino-2-pentanol, 2-amino-3-pentanol, 1-amino- 2-pentanol, cis-2-amino-1-cyclopentanol, trans-2-amino-1-cy Clopentanol, 6-amino-1-hexanol, trans-4-amino-1-cyclohexa Nol, cis-4-amino-1-cyclohexanol, trans-2-amino-1-cyclohexanol Nol, cis-2-amino-1-cyclohexanol, cis-2-amino-1-cyclohexano Cis, cis-2-amino-4-methyl-1-cyclohexanol, cis-2-amino-5-methyl- 1-cyclohexanol, trans-2-amino-1-cycloheptanol, cis-2-amino- 1-cycloheptanol, trans-2-amino-1-cyclooctanol, cis-2-amino- There is 1-cyclooctanol.         Specific examples of amino alcohols derived from heterocyclic compounds include Cis-4-amino-3-hydroxypyrrolidine, trans-4-amino-3-hydroxypyrroli Gin, cis-4-amino-3-hydroxy-tetrahydrofuran, trans-4-amino-3-h Droxy-tetrahydrofuran, cis-4-amino-3-hydroxy-tetrahydrothio Phen, trans-4-amino-3-hydroxy-tetrahydrothiophene, cis-3-amino -4-hydroxy-piperidine, trans-3-amino-4-hydroxy-piperidine, cis-4- Amino-3-hydroxy-piperidine, trans-4-amino-3-hydroxy-piperidine, cis-5-amino -3-hydroxy-piperidine, trans-5-amino-3-hydroxy-piperidine, cis-4- Amino-3-hydroxy-tetrahydro-2H-pyran, trans-4-amino-3-hydroxy- Tetrahydro-2H-pyran, cis-4-amino-3-hydroxy-tetrahydro-2H-thiopi Orchid, trans-4-amino-3-hydroxy-tetrahydro-2H-thiopyran, cis-5-amido No-4-hydroxy-2-piperidone, trans-5-amino-4-hydroxy-2-piperidone, trans-3-amino-4-hydroxy-azepan, cis-3-amino-4-hydroxy-azepan , Trans-4-amino-3-hydroxy-azepan, cis-4-amino-3-hydroxy-azepa Trans-5-amino-4-hydroxy-azepane, cis-5-amino-4-hydroxy-azene Bread, trans-3-amino-4-hydroxy-oxepane, cis-3-amino-4-hydroxy- Oxepan, trans-3-amino-4-hydroxy-azocaine, cis-3-amino-4-hydride There is roxy-azocaine.         The fragment D-C (= O) of the formula I is obviously a kettle derived from aromatic carboxylic acids. Or a derivative thereof. Therefore, a number of (and commercially available) ) It is believed that available starting materials are available. Furthermore, the chemistry of aromatic compounds Are very well developed and the group of available compounds is further increasing. Preparation of compounds of general formula I         The synthesis of compound I is illustrated in the following method, FIG. With reference to general formula I The two-terminal radicals A are 2,6-naphthalene and 1,2-phenylene, respectively, in the scheme. As shown. The two-terminal radical B is an aliphatic or non-aromatic carbocyclic or It may be a heterocyclic group or an aromatic or heteroaromatic group. The terminal group K is OH, L¹Is -O-, L^TwoIs -NR^Five-, And D are phenyl. In addition, the solid phase material is Although it is represented by the symbol of [Method diagram 2]         Method The example shown in FIG. 2 is two embodiments of the method of the present invention. therefore In each of the steps (A) to (D), deformation is possible. The following describes each step of the method of the present invention. Here are some general indicators:         Process (A): Arbitrarily protected functional group molecule -C (= O ) -A-C (= O) -M¹[Wherein, -C (= O) -M¹Means a carboxy group or a derivative thereof] I will provide a.         Method As shown in FIG. 2, various possibilities for immobilization are within the scope of the invention. is there. Lack of monoselectivity in the reaction between the activated solid phase material and diacid And the use of dicarboxylic acids can cause by-products, , Using monoester diacid preferable. Therefore, if a dicarboxylic acid in the form of the free acid is used, Raw material, that is, the yield is low enough to make up for the monoester And also shown.         Another example is the intramolecular anhydride of a dicarboxylic acid. Dicarbon If the acid is mono-protected, the protecting group is C (= O) -M¹Provides carboxy functionality in the form of In step (B), it is preferred to deprotect the coupling in a ready state No. Hence the group M¹Is OH or O^-Preferably. Dicarboxylic acid as solid phase material The conditions for coupling to the material are closely related to the choice of solid phase material and linker. Are described further below.         Process (B): Arbitrarily protected bifunctional group moiety L '¹-B-L '^Two Fixed molecule -C (= O) -A-C (= O) -M¹-C (= O) -M at the end of¹Fixed, optionally protected Functional group fragment -C (= O) -A-C (= O) -L¹-B-L '^TwoTo form         First, the group -C (= O) -M¹Is L '¹-B-L '^TwoExist in a form that can react with the As mentioned, -C (= O) -M¹Is a carboxy group or a carboxylate group, or It is instead preferably present in a reactive form, for example in the active ester form. M¹Is OH Or O^-Is preferred. L '¹-B-L '^TwoL 'of the part¹The group is L of compound I¹Ends with it is obvious. Therefore, L '¹Is L¹Represents -O-, a hydroxyl group or Derivatives thereof, preferably hydroxyl groups. L¹Is -NR^Five-Means , Group L '¹Is a derivative that releases a free amino group or a free amino group under the reaction conditions Is preferred. L '¹Is a primary amine [ie, R^FiveIs hydrogen] or a secondary amine R^FiveIs C_1-4-Alkyl group], or It is preferred to mean an additional bond to B.         Group L '^TwoShould remain unaffected by the reaction conditions, Preferably refers to a protected hydroxy group or a protected primary or secondary amine. New Group L '^TwoIs an example of -O-P (L^TwoIs -O-) [where P is dimet Xytrityl (DMT), monomethoxytrityl (MMT), trityl, 9- (9-phenyl) Santhenyl (pixil), tetrahydropyranyl (thp), methoxytetrahydride Lopiranil (mthp), trimethylsilyl (TMS), triisopropylsilyl (TIPS) , Tert-butyldimethylsilyl (TBDMS), triethylsilyl, phenyldimethylsilyl Such as ril, benzyloxycarbonyl, 2-bromobenzyloxycarbonyl Substituted benzyloxycarbonyl ether, tert-butyl ether, methyl Halogen substitution such as ether, acetyl, chloroacetyl and fluoroacetyl Acetyl, isobuteryl, pivaloyl, benzoyl, substituted benzoyl Methoxymethyl (MOM), benzyl ether, and 2,6-dichlorobenzyl (2 , 6-Cl_TwoHydroxy protecting groups selected from substituted benzyl ethers such as Bzl) Means] and -NR^Five-P (L¹Is -NR^Five-) [Where P is Fmoc (fluorenylmeth Xoxycarbonyl), BOC (tert-butyloxycarbonyl), trifluoroacetyl , Allyloxycarbonyl (alloc, AOC), benzyloxycarbonyl (Z, C bz), substituted such as 2-chlorobenzyloxycarbonyl (such as 2-ClZ) Benzyloxycarbonyl, DDE (Bloomberg, G.B., et.al., Tetrahedron Lett 1993, 34, 4709-4712), monomethoxytrityl (MMT), dimethoxytrityl ( Amino protection selected from DMT) and 9- (9-phenyl) xanthenyl (pixil) Means a group].         The coupling reaction of step (B) is performed by a coupling reagent such as a group -C (= O) -M¹ To an active derivative, such as an active ester or acid halide. Including for a while. A number of very effective coupling reagents and active forms of carboxylic acids are It is known to those skilled in the art of amide bond formation (peptide chemistry). As a specific example, Py BrOP (Coste, J; Frerot, E .; Jouin, P. and Castro, B. Tetrahedron Lett. 1 991, 32, 1967-1970), Acid fluorides (Carpino, L.A .; Sadat-Aalaee, D .; Chao, H.G. and De. Selms, R. H. J. Am. Chem. Soc.) And HATU (Carpino, L. A. J. Am. Chem. Soc.) , 1993, 115, 4397-4398; Angell, Y.M .; Gracia-Echeverria, C. and Rich, D. H. Tetrahedron Lett. 1994, 35, 5981-5984 and Angell, Y.M .; Thomas, T. L .; Flenkte, G. R. and Rich, D. R. J. Tetrahedron, 1991, 47 (2), pp 259-270), and CF_Three-NO_Two-PyBOP (Wijkmans, J. C. H.M., et.al., Tetrahedron Lett., 1995, 36 (26), pp 4643-4646) You. Coupling reagents are equal in forming amide bonds as well as in forming ester bonds. Applicable.         Step (c)： Arbitrarily protected functional group D-C (= O) -M^Two[Where C (= O) -M^Two Is a carboxy group or a derivative thereof] -immobilized fragment -C (= O) -A-C (= O) -L¹-B-L '^Two L '^TwoTerminally attached, fixed and optionally protected compound-C (= O) -A-C (= O) -L¹ -B-L^Two-C (= O) -D is formed. The process is optional L '^TwoAny protecting group contained in Including deprotection of         As described in step (B), the group L ′^TwoTypically contain protecting groups and are therefore In such a case, such a group would have the moiety D-C (= O) -M^TwoTo the fixed fragment It is preferably removed before. Group -C (= O) -M^TwoWith respect to the carboxy group or its It may be a derivative. In one variation, the group -C (= O) -M^TwoIs a reactive derivative of carboxylic acid E.g. active esters or acid halides, e.g. acid chlorides or fluoro Ride. Another variation is the group -C (= O) -M^TwoIs the free acid or its carboxy Rate. In the latter case, the reaction typically involves the use of a coupling reagent. I have. Hence, M^TwoIs OH, O^-, Halogens such as fluorine or chlorine, or active It may mean the remainder of the stell.         Process (D)： Compound K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D is a solid support Disconnect from the fee. The process involves one or more functional groups attached to A, B and / or D Deprotection.         The conditions for cleaving the compound from the solid phase material are described below along with examples of the solid phase material. I do. The cleavage step may include deprotection of one or more protected functional groups, if applicable. Good. Deprotection may be performed before cleavage or after cleaving the compound from the solid phase material. I think it is. Furthermore, as an interesting example, deprotection can be used to excise compounds from solid phase materials. There is something to do at the same time as refusing. The latter is applicable when using Won resin It is. In this example, trifluoroacetic acid (TFA) is used to cleave the compound and Used for deprotection of a protecting group.         In the text, the term "optionally protected functional group" and similar terms refer to the problem Any of the radicals, i.e., any or all of A, B and D One chemical functionality (or Some chemical functionalities) or because of lack of regioselectivity of reagents Means that such chemical functionality may be protected. Starting materials are protected Protection may be provided prior to potentially harmful reactions in a separate reaction step. Protection may be provided and protection may be included in the reaction step. Unprotected compound in question Is difficult to transform or virtually impossible to purify, protection of the chemical functionality is appropriate. Sometimes it runs out. In such cases, protection-purification-deprotection schemes may be used. Is also good. Protecting groups are described in Greene, T.W. and Wuts, P.G.M. (Protecting Groups in Organic Synthesis). Preferred protecting groups are solid phase synthesis, peptide synthesis (e.g., Steward, J.M & Young, J.D. , Solid Phase Peptide Synthesis, Pierce Chemical Company (1984) or Rob ert C. Sheppard E. Atherton, Solid-Phase Peptide Synthesis, IRL Press, 1 989), oligonucleotide (See, eg, M. J. Gait, Oligonucleotide Synthesis, IRL Press, 1984) , A protecting group frequently used during oligosaccharide synthesis, organic synthesis and natural product synthesis It is. Protecting groups can directly interfere with the reactions performed in steps (B) and (C), and Suitable for mino, hydroxy and mercapto and carboxy groups You. Thus, among the many protecting groups known to those skilled in the art, protecting groups may be used to suppress by-product formation. It is essential as well as favorable.         Possible protecting groups include, but are not limited to, Fmoc (fluorenylmethoxy) Carbonyl), BOC (tert-butyloxycarbonyl), trifluoroacetyl , Allyloxycarbonyl (alloc, AOC), benzyloxycarbonyl (Z, Cbz ) Or substituted such as 2-chlorobenzyloxycarbonyl (such as 2-ClZ) Benzyloxycarbonyl, DDE (Bloomberg, GB, et.al., Tetrahedron  Lett. 1993, 34, 4709-4712), monomethoxytrityl (MMT), dimethoxytriti (DMT) and amino protection such as 9- (9-phenyl) xanthenyl (pixyl) Groups: dimethoxytrityl (DMT), monomethoxytrityl (MMT), trityl, 9- (9- Phenyl) xanthenyl (pixil), tetrahydropyranyl (thp), methoxy Tetrahydropyranyl (mthp), trimethylsilyl (TMS), triisopropylsilyl Ryl (TIPS), tert-butyldimethylsilyl (TBDMS), triethylsilyl, phenyl Dimethylsilyl, benzyloxycarbonyl or 2-bromobenzyloxycal Substituted benzyloxycarbonyl ethers such as bonyl, tert-butyl ether Of methyl, ether, acetyl or chloroacetyl or fluoroacetyl Halogen-substituted acetyl, isobutyryl, pivaloyl, benzoyl and the like And substituted benzoyl, methoxymethyl (MOM), benzyl ether or 2,6 -Dichlorobenzyl (2,6-Cl_TwoLike substituted benzyl ethers such as Bzl) Hydroxy C-protecting group; allyl ester, methyl ester, ethyl ester, 2-cyanoethyl Ester, trimethylsilylethyl ester, benzyl ester (Obzl), 2-ada Mantyl ester (O-2-Ada), cyclohexyl ester (OcHex), 1,3-oxa Zoline, oxazole, 1,3-oxazolidine, amide or hydrazide Or activated esters such as N-hydroxysuccinimide or symmetric Or a carboxy protecting group, such as in the form of an asymmetric anhydride; and trityl (Trt), Cetamide methyl (acm), trimethylacetamidomethyl (Tacm), 2,4,6-trimethoxy Cibenzyl (Tmob), tert-butylsulfenyl (StBu), 9-fluorenylmethyl (Fm ), 3-nitro-2-pyridinesulfenyl (Npys) and 4-methylbenzyl (Meb) Such mercapto protecting groups are included.         Deprotection of "optionally protected functional groups" is described by Greene, T.W. and Wuts, P. G. M. (Protecting Groups in Organic Synthesis) This is performed according to a method known to a trader.         The compounds of the invention can be prepared by known methods or for the production of amide or ester bonds. It may be produced by a coupling reaction. Like an ester bond, Such a method for establishing an amide bond between the combined fragment compound and the second species Coupling reactions are known to those skilled in the art of solid phase synthesis. One example is the established Me rrifield solid phase synthesis techniques (eg, Barany, G., and Merrifield, R.B., The Pep tides, Vol. 2, Academic Press, New York, 1979, pp. 1-284).         As used herein, the term "solid phase material" includes solid state materials in the art. In particular, Suitable solid phase materials (polymers) are cross-linked with 0.2-2% divinylbenzene and Loose "Won-type" resin (Wang, S.-S., J. Am. Chem. Soc., 1973, 94, 1328-1333) [Treatment with trifluoroacetic acid / dichloromethane (1: 1, v / v) for 30 minutes at room temperature and Para-alcohol which, when cleaved, produces free acid Xybenzyl alcohol resin] or “link-type” resin (Rink, H. Tetrahedron)  Lett., 1987. 28, 3787-3790) [trifluoroacetic acid / dichloromethane (3: 7, v / Trialkoxy to form acid amide when treated and cleaved in v) for 60 minutes at room temperature -Diphenyl-methyl ester resin] as described in the literature. Polystyrene based. Similarly, more polar solvents than polystyrene resin "Tentagel (TentaGel) tree with the property of expanding more and more uniformly The resin is grafted with polyethylene glycol (PEG) to produce a "fat" , Based on polystyrene cross-linked with 0.2-2% divinylbenzene (Ba yer, E. Angew. Chem. Int. Ed. Engl., 1991, 30, 113-129). PEG-modified Resins of similar properties obtained from are commercially available with a variety of functionalities Various trade names (eg, ArgGel, ArgoGel, PEGA resin or PEG-PS) onaut Inc., Peptide Laboratories, Novabiochem, etc.).         In a further embodiment of the method of the invention, the formation of other compounds of general formula I For this purpose, compound I may be subjected to a further step (E) after cleavage from the solid phase material. No. In this reaction step, the modification of the group K-C (= O)-and the diversity of the group K-C (= O)- When desired by the fact that it is determined in an applicable way to cut things, Especially appropriate. Synthesis of monoester of dicarboxylic acid         As an initial step in the preparation of compound I containing the molecule -C (= O) -A-(= O)- Molecule -C (= O) -A-C (= O) -M¹When providing, for example, free acid, monoester, or May clearly use diacid HOOC-A-CO0H in the form of an intramolecular anhydride. is there.         A wide range of bifunctional aromatic and heterocyclic compounds in the preparation of compound I In order to be able to utilize aromatic molecules, for example, aromatic dicarboxylic monocarboxylic acids It would be advantageous to have access to synthetic routes to esters. Three different A new synthesis is described in Tong, G. and Nielsen, J. Bioorg. Med. Chem. 1996, 4, 693-698. Has been described. The first method involves esterification of a mono-cesium salt of a dicarboxylic acid, In particular, it is based on allylation, where naphthalene-2,6-dicarboxylic acid This is exemplified as esterification with rubromide (Example 3). The second way is Anion exchange to block one of the carboxylic acid groups while the other is esterified Based on the use of exchange resins (Blankemeyer-Menge, B .; Nimtz, M. And Frank, R. Tetrahedron Lett. 1990, 31, 1701-1704). The third method is Selective deesterification of dicarboxylic diesters. Further possibilities , Phase transfer chemistry (Friedrich-Bochnitschek S., J. Org. Chem. 54, 1989, 751-7 56). Monoester production with minimum diester yield Advantageous conditions for production are that small portions are added over a long period of time, such as 16 hours. 1 equivalent of Cs_TwoO_ThreeAnd 2 equivalents of allyl bromide. Of purified monoester The yield obtained is at least 30%. Anion exchange for naphthalene diacid Adsorbed on resin, then mesitylenesulfonyl nitrotriazolide (MSNT), According to another method of reacting N-methylimidazole and allyl alcohol, The desired monoester is formed. The third method is to convert a certain aromatic dimethyl ester It is based on the possibility of deesterification. Mixed methyl-allyl-dieste And subsequent selective demethylation (NaCN / HMPA (hexamethylphosphoramide) ) Gives the corresponding monoallyl ester. Preparation of libraries of compounds of general formula I         The production of a library of balanol analogs is Follow the same principles as described for manufacturing. Appropriate amounts of each theoretically available compound Split-mix to ensure that it occurs in the appropriate amount Peptide Protein Res. 1991, 37, 487-493) was used. Other methods may be used in accordance with the present invention. Applicable within the context.         Therefore, the present invention provides a compound of the general formula I               K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D I -Dimensional array of compounds consisting of at least four compounds each having the formula {A}-{B }-{D}, ie, a method for producing a combinatorial library. So Is an array of compounds corresponding to the two-terminal radical C (= O) -A-C (= O)- A} is a two-terminal free radical L¹-B-L^Two{B} consisting of compounds corresponding to-and free radical C (= O)- It is constructed by combining with the array {C} corresponding to D. Compound sum The number depends on the number of fragments, m, n and o. These numbers m, n and o Are all positive integers and for a multidimensional array of at least four compounds, m The product of * n * o must be at least 4. one of m, n and o is A combination of 4 and the other two each being 1 is possible within the method of the invention. However, in order to obtain a highly diverse combinatorial library, at least two One, and preferably all three, are at least two. Therefore, The binatorial library preferably has a range of 6-200 different compounds, more Preferably different compounds in the range 6-100, especially different compounds in the range 8-64 It is preferred to include         As mentioned above, the production of multi-dimensional arrays / libraries of compounds is unified The synthesis was carried out according to the same principle as the production of the compound, and thus the synthesis plan consisted of the following steps -Described for when using a mixed synthesis):         Process (A): M arbitrarily protected fixed to solid support material Functional group molecule -C (= O) -A-C (= O) -M¹[Wherein, -C (= O) -M¹Is a carboxy group or its derivative Array {A} is obtained. According to split-mixed synthesis, various fixed Each of the moieties is individually synthesized, so each solid phase particle or moiety is one type of moiety. Consists only of minutes. After this step, the solid phase material is pooled and n ready for step (B) (See below). A lot of fixed parts are manufactured, It is believed that the material can be retained for later experiments.         Process (B): N optionally protected bifunctional moieties L '¹-B-L '^TwoArray {B} , Immobilized molecule -C (= O) -A-C (= O) -M¹Terminal -C (= O) -M¹And optionally a functional group Protected m * n fragments -C (= O) -A-C (= O) -L¹-B-L '^TwoArray of {A}- Form {B}. Also, in this step, the coupling is performed by pooling the reacted materials. In the next coupling step, i.e. n different batches divided for step (C) It is preferable to carry out at.         Process (C): Optionally protected o functional group moieties DC (= O) -M^Two[Wherein, -C (= O) -M^TwoMeans a carboxy group or a derivative thereof]]. Piece-C (= O) -A-C (= O) -L¹-B-L '^TwoTerminal L 'of^TwoAnd optionally protected functional groups, Defined m * n * o compounds -C (= O) -A-C (= O) -L¹-B-L^TwoArray of -C (= O) -D {A}-{B}-{ D}. The process is L '^TwoDeprotection of any protecting groups contained in It may be. Also, in this process the coupling takes place in o different batches. Preferably. Reacted materials do not need to be pooled before cutting in step (D) .         Process (D): Compound K-C (= O) -A-C (= O) -L from solid support material¹-B-L^Two-C (= O) -D Array {A}-{B}-{D}. This process is performed on individual A, B and / or D Optionally includes deprotection of one or more attached functional groups. O different batches from step (C) Chis may be cut individually or pooled prior to cutting. Before cutting Pooling is economical and It is convenient from the point of view. However, analysis of manufactured libraries is performed In that case, it is (of course) advantageous to work with a relatively small number of compounds. Therefore In addition, an array of m * n * o compounds actually contains o * Present in batch. These compounds are then used, for example, in actual screening. It may be pooled before performing. Alternatively, screen each batch individually May be used. The third and most interesting alternative is to reach m * n * o ( Library consisting of a batch (or a large number of these) containing Screened, and if biological activity is observed, o batches are individually To screen, thereby biologically interested in one particular part Return to D. The principle of screening is described below. Screening method         Screening of combinatorial libraries can be done by scientists in the field. And any of the methods commonly used by technicians. This These include, but are not limited to, deconvoluting libraries containing mixtures. By deconvolution, or by locating a library of mixtures Scan sub-libraries by scanning or indexed library Screening involves the screening of individual compounds. Therefore The size of the library is limited to a single compound, one vial to one compound. And enantiomers, diastereomers, geometric or positional isomers The active substance as a small mixture of isomeric compounds containing stereoisomers in the form Typically 10-100 compounds per vial for fast deconvolution Quickly script large mixtures or large combinatorial libraries Per vial so that It may exist as a large mixture of compounds greater than 100. Screening is As with neutral and negative antagonists (reverse agonists), enzyme inhibitors and receptors A high-throughput method that can be used for automated drug and partial agonist search Frequently used, typically 96-well, 384-well, or other microplates Perform the assay format using the format.         According to such a screening method, it is produced by the method according to the invention. It is expected that the biological activity of Compound I will be apparent. Therefore, the following areas One biological activity can be shown: (a) Interesting biological effects in treating mammals such as humans: anesthetics, [sedative sleeping pills Central nervous system depressants, such as anticonvulsants, neuroleptics and anxiolytics] Drugs to treat neuromuscular disorders or skeletal muscle relaxants, analgesics, like Kinson's CNS stimulants, local anesthetics, cholinergic drugs, acetylcholinesterase inhibition Drugs or cholinergic antagonists, adrenergic drugs, [cardiac glycoside analogs, Like antianginal drugs, antiarrhythmic drugs] cardiovascular agents, anticoagulants, coagulants and plasma augmentation Drugs, diuretics, antiallergic and antiulcer drugs, antilipidemic drugs, nonsteroidal anti-inflammatory Drugs, drugs that affect glucose metabolism, antimycobacterials, antibiotics or antibacterials, Cancer chemotherapy or light, such as antifungals, preservatives or disinfectants, hormone antagonists Antineoplastic, antiviral for chemotherapy, or possible for HIV-infection or AIDS Like sex drugs. (b) Biological effects of interest in the field of crop protection: compounds affecting sugar metabolism, Antifungals such as antibiotics or antibacterials, insecticides, disinfectants and hormone antagonists .         Thus, a further aspect of the present invention is to provide novel compounds for use as pharmaceuticals. By providing and using the novel compounds for the manufacture of one or more medicaments as described above. is there. As a further aspect of the present invention, It is to provide a new compound which can be used by using. Figure description         1 and 2 illustrate various examples of a two-terminal free radical A. Sign Taste is defined above.         FIG. 3 illustrates various examples of a two-terminal free radical B. The meaning of the symbol is Is defined. Example Example 1 Synthesis method of N-Fmoc-amino alcohol         N-Fmoc-1-amino-2-propanol. The synthesis method is 1-amino-2-prop        N-Fmoc-2-amino-1-butanol. Synthetic method is 2-amino-1-butanol         N-Fmoc-3-amino-1-propanol. Synthetic method is 3-amino-1-prop         trans-N-Fmoc-4-amino-cyclohexanol. The synthesis method is trans-4-amino -Starting from cyclohexanol, as described above. White solid (37%). Example 2 Synthetic method of aromatic dicarboxylic acid (a) Methylation of phenolic alcohol         2-nitro-5-methyl-anisole. 4.6 g (30 mmol) of 2-nitro-5-methyl- Phenol and 20.7 g (150 mmol) of dry K_TwoCO_Three In a 150 ml acetone suspension, add 42. 6 g (300 mmol) of MeI were added. The reaction mixture was stirred at reflux for 16 hours. , Filtered and concentrated in vacuo. The residue was redissolved in EtOAc, filtered and filtered. 4.9 g (98%) of a pale yellow solid when concentrated in the sky        2-methyl-3-nitro-anisole. Synthetic method is 2-methyl-3-nitrophenol Departure from Le, as described above. Yellow solid (91%).         2-nitro-3-methyl-anisole. Synthetic method is 2-nitro-3-methyl-pheno Departures as described above. Yellow solid (98%). (b) Nitrogen hydrogenation         2-methoxy-4-methyl-aniline. 4.9 g (29.3 mmol) of 2-nitro-5-methyl To a solution of le-anisole in 100 ml of EtOH and 5 ml of concentrated HCl was added N_Two250mg under atmosphere 5% Pd on charcoal was added. The solution was hydrogenated at room temperature and 200 psi. 16 After hours, the reaction mixture was filtered using celite and concentrated in vacuo. Hex residue Chromatography / EtOAc 1: 1 to give 2.8 g (70%) of a red oil.         2-methyl-3-methoxy-aniline. The synthesis method is 3-nitro-2-methyl-aniso Departures as described above. Red oil (60%). (c) Diazotization of amino group to nitrile group (Sandmeier)         2-methyl-3-methoxy-benzonitrile. 2.5 g (18 mmol) of 2-methyl-3- A solution of methoxy-aniline in 55 ml of 2N HCl was cooled to −5 ° C. in an ice / salt bath for 30 minutes. Stirred. 1.37 g (19.8 mmol) of NaNO_TwoOf 28ml of H_TwoO 2 solution was added dropwise at -5 ° C. The reaction mixture was stirred for 30 minutes and about 3.7 g of Na_TwoCO_ThreeNeutralize carefully, then 1.8g (19.8 mmol) CuCN and 1.9 g (39.6 mmol) NaCN in 28 ml of H_TwoAdd O solution all at once Was. After 18 hours, the reaction mixture is 3 * 100 ml CHCl_ThreeExtracted with The collected organic layer is H_Two Extracted with O, Na_TwoSO_FourDried in (d) Synthesis of benzophenone         3,3'-dimethyl-benzophenone. 3.6 g (110 mmol) M in 10 ml THF To the g-shavings was added crystalline iodine and 17.1 g (100 mmol) of 1/4 of 3-bromotoluene . The mixture was heated to 40 ° C. and after a while the Grignard reaction started. In THF The remainder (3/4) of the 3-bromotoluene was added at such a rate as to maintain reflux. Addition After that, the reaction mixture is refluxed for 1 hour, cooled to room temperature and 7.3 g (63 mmol) of 3-methyl -Benzonitrile in 40 ml of toluene at room temperature, then at 70 ° C for 16 hours Held. The reaction mixture was cooled on a water bath and 33 ml of concentrated HCl was added, followed by 170 ml of Me. OH was added dropwise and refluxed for 7 hours. The reaction mixture was cooled and 100 ml of H_TwoAdd O and add EtOAc Extracted with c. The collected organic layer is MgSO_Four, Filtered and concentrated in vacuo. Residue Is purified by chromatography (hexane / EtOAc 19: 1) to give a colorless oil 10.5 g (80%) I got         2,4'-dimethyl-benzophenone. The synthesis method is 2-bromotoluene and 4-methyl Starting from benzonitrile, as described above. Colorless oil (77%).         2-methoxy-2 ', 5-dimethyl-benzophenone. Synthetic method is 2-bromo-4-methyl Starting from le-anisole and 2-methylbenzonitrile, as described above. toluene Was used instead of THF. Colorless oil (36%).         2-methoxy-4 ', 5-dimethyl-benzophenone. Synthetic method is 2-bromo Starting from -4-methyl-anisole and 4-methylbenzonitrile, as described above. ( Chromatography was performed with hexane / EtOAc 9: 1). Colorless oil (56%). (e) Synthesis of benzophenone via benzhydrol         4,4'-dimethylbenzhydrol. 3.6 g (150 mmol) Mg in 10 ml THF -To the shavings was added crystalline iodine and 17.1 g (100 mmol) of 1/4 of 4-bromotoluene. The mixture was heated to 40 ° C. and after a while the Grignard reaction started. 4- in THF The remainder (3/4) of the bromotoluene was added at such a rate that reflux could be maintained. Additive Afterwards, the reaction mixture is refluxed for 1 hour, cooled to 0 ° C. and the remaining Mg-swarf is removed. did. A solution of 12.3 g (103 mmol) of 4-methyl-benzaldehyde in 20 ml of THF was added to 0 ml. It was added dropwise at ° C. After 2 hours, cool the reaction mixture with 200 ml of ice and raise the temperature to room temperature. Raised to 25% H_TwoS0_FourWas added until the solution became clear. The reaction mixture is extracted with DCM. Issued. The collected organic layer was dried over MgSO_Four, Filtered and concentrated in vacuo. Hep the residue Recrystallization from tan gave 10.6 g (50%) of a white solid.       4,4'-dimethyl-benzophenone. 12.96 g (60 mmol) of pyridinium chroma 6.36 g (30 mmol) of 4,4'-dimethylbenzhi were added to a 60 ml DCM suspension of rochromate. Droll was added. The mixture was stirred for 24 hours and 240 ml of diethyl ether was added. I got it. The reaction mixture is filtered through 3X silica gel and concentrated in vacuo to a white solid 3.7 g (59%) were obtained. (f) Synthesis of methyl-methylphenyl-benzene         2-methyl- (4-methylphenyl) -benzene. 5.2 g (24 mmol) of 2-iodo N is added to a solution of toluene in 12 ml of diethyl ether._TwoAt -78 ° C under atmosphere, 32ml of 1.5M (48m mol) A hexane solution of tert-BuLi was added dropwise. The reaction mixture is kept at -78 ° C for 1 hour and Stirred at room temperature for 1 hour then concentrated in vacuo. 16 ml of THF was added to the residue at 0 ° C. The reaction mixture was combined with 3.3 g (24 mmol) of dry ZnCl_TwoN in 12 ml of THF_TwoAtmosphere 0 It was added dropwise at ° C. The reaction mixture was stirred at room temperature for 1 hour, then 3.4 g (20 mmol) of 4- Bromo-toluene, 0.23 g (0.2 mmol) of Pd (PPh_Three)_FourTo a 20 ml THF solution of N_TwoAtmosphere sewage Cooled in the bath and added. The reaction mixture was stirred at 50 ° C. for 16 hours, cooled and 20 ml Poured into diethyl ether and 60 ml of 4N HCl solution. The mixture is 2 * 40ml ether Extracted. The collected organic layer is NaHCO_Three(Sat.) And washed with MgSO_FourDry in vacuum Concentration gave 2.0 g (47%) of a colorless oil. (g) Aromatic side chain oxidation of methyl group         Biphenyl-2,4'-dicarboxylic acid. 5.2 g (33 mmol) of KMnO_FourOf 48mml 50% In a pyridine solution (aq.) At 100 ° C., 0.6 ml of concentrated NaOH and 2.0 g (11 mmol) of 2-methyl- (4- Methylphenyl) -benzene in 15 ml pyridine, then 15 ml H_TwoAdd O I got it. The reaction mixture was stirred for 1 hour and 5.2 g (33 mmol) of KMnO_FourWas added. This place 41.6 g (264 mmol) of KMnO_FourWas continued until was added. Hot reaction mixture Filter and filter cake 4 * 30ml H_TwoWashed with O and 10 ml of pyridine. The filtrate is ice Cool in bath, pH = 1 with concentrated HCl Until acidified. Brine was added and the reaction mixture was extracted with 4 * 150 ml EtOAc. Issued. The collected organic layers were concentrated in vacuo to give 0.9 g (33%) of a white solid.         Benzophenone-2,2'-dicarboxylic acid. The synthesis method is 2,2'-dimethylbenzophen Starting from Nong, as described above. White solid (69%).         Benzophenone-3,3'-dicarboxylic acid. The synthesis method is 3,3'-dimethylbenzophen Starting from Nong, as described above. White solid (56%).         Benzophenone-4,4'-dicarboxylic acid. The synthesis method is 4,4'-dimethylbenzophen Starting from Nong, as described above. White solid (66%).         Benzophenone-2,4'-dicarboxylic acid. Synthetic method is 2,4'-dimethylben       2-methoxy-benzophenone-2 ', 5-dicarboxylic acid. Synthetic method is 2-methoxy-2 ' Starting from, 5-dimethyl-benzophenone, as described above. WhiteExample 3 Method for synthesizing mono-alkylated aromatic diacids         Benzophenone-2,2'-dicarboxylic acid monoallyl ester. 1.08g (4mmol ) Of benzophenone-2,2'-dicarboxylic acid in 90 ml of DMF was added to 0.16 g (0.5 mmol) of Cs_TwoCO_ThreeWas added. After 30 minutes, 0.34 ml (0.484 g, 4 mmol) of allyl bromide was added. The reaction mixture was stirred for 24 hours and 0.16 g (0.5 mmol) of Cs_TwoCO_ThreeWas added. This process 0.64 g (2 mmol) of Cs_TwoCO_ThreeWas continued until was added. After another 24 hours, The reaction mixture was filtered and chromatographed (CHCl_Three/ AcOH 99: 1) 0.52g (42%). Mp 205-207 ° C. Unreacted benzophenone-2,2'-dicarboxylic acid 0. 312g (29%)         Benzophenone-3,3'-dicarboxylic acid monoallyl ester. The synthesis method is Ben Starting from zophenone-3,3'-dicarboxylic acid, as described above. White solid         Benzophenone-4,4'-dicarboxylic acid monoallyl ester. The synthesis method is Ben Starting from zophenone-4,4'-dicarboxylic acid, as described above. White solid         Benzophenone-2,4'-dicarboxylic acid monoallyl ester. The synthesis method is Ben Starting from zophenone-2,4'-dicarboxylic acid, as described above. Two differences with a ratio of 7: 1 White solid (64%) of the active substance (2-allyl ester / 4'-allyl ester). Chromatography Fee (CHCl_Three/ MeOH / triethylamine 8: 1: 1) to give 2-allyl as a pure white solid. Ester (39%) (Mp 125-127 ° C) and 4'-allyl ester (6%) of pure white solid (mp 119-12 0 ° C). 2-allyl esthetic         Biphenyl-2,2'-dicarboxylic acid monoallyl ester. Synthetic method is biphenyl Starting from a 2,2'-dicarboxylic acid as described above. Colorless oil (35%). Biphenyl-2, The 2'-dicarboxylic acid (40%) was isolated for reuse.         Naphthoic-2,6-dicarboxylic acid monoallyl ester. Cs_TwoCO_Three(1.60g, 5.00 mmol) with naphthoic-2,6-dicarboxylic acid (2.16 g, 10 mmol) in anhydrous DMF (97 m L) The solution was added twice in equal amounts over 0.5 hour. Allyl bromide (17.3 mL, 200 mmol) was then added and the reaction mixture was stirred vigorously for 24 hours. Same amount of Cs_Two CO_ThreeIs then added in two equal portions over 8 hours and the reaction allowed to proceed for a further 17 hours Was. The precipitate was filtered and washed with DMF (3x20mL). The collected filtrate is then concentrated in vacuo. And extracted with hot 50% MeOH / acetone (2 × 100 mL). After evaporation of the solution Silica gel chromatography (acetone / hexane / HOAc, 50/48 / Removed in 2). The resulting filter containing a mixture of monoester and diester Concentrate the fractions and redissolve in 10% MeOH / dichloromethane to remove A-26 (hydroxide form) resin (24.0 g, 96 meq) was treated for 17 hours. The resin is behind And diester was found in the eluate by TLC (CHCl_Three/ MeOH, HOAc, 94/4/2) Washed with fresh solvent (about 3 L) until dry. The monoallyl ester is then MeOH / Elution was carried out with dichloromethane / acetic acid (10:80:10). After removing the solvent, Recrystallization from 3 gave a fine colorless solid (0.77 g, 30%). Example 4 Solid-phase synthesis of balanol analogues         The Balanol Library uses a split-synthesis method And synthesized. After each step, the resin is mixed in equal density with 1,2-dichloroethane and DMF. Mixed in the material (2: 1) and expanded, then the resin was split for the next step in the synthesis . A 50% solution of TFA in dichloromethane to analyze the content bound to the resin Was used to cut from the resin.         Two dicarboxylic acids are used in step (A) (m = 2) and four amino alcohols In step (B) (n = 4), four aromatic carboxylic acids are used in step (C) (o = 4) Used in. Therefore, a library having 2 * 4 * 4 = 32 compounds was produced. (A) Coupling of aromatic acid to Won resin (corresponds to step (A) in the general method diagram)         Phthalic acid and naphthalene-2,6- as intramolecular anhydride and monoallyl ester The dicarboxylic acid was bound to the resin using two different methods.         Coupling of phthalic acid to Won resin. 1.6g (0.87meq / g) won 10 m of resin (polystyrene cross-linked with 1% divinylbenzene, from NovaBiochem) of phthalic anhydride, 1.95 ml (1.425 g (1.425 g) 14.1 mmol) Et_ThreeN and 0.2346 g (1.92 mmol) of DMAP were added. Reaction mixing The material was shaken for 4 days, then 2 * 10 ml 30% MeOH in dichloromethane and 4 * 10 ml dichloromethane Washed with dichloromethane. The resin was dried and analyzed by HPLC. Loading L = 0.66meq / g.         Naphthalene-2,6-dicarboxylic acid monoallyl ester Pulling. 0.8g (0.87meq / g) of Won resin in 8ml of dry DMF Swell with 0.321 g (1.25 mmol) of monoallyl naphthalene-2,6-dicarboxylate Stele, 0.412 g (1.39 mmol) of MSNT and 0.443 ml (5.7 mmol) of 1-methylimida Zole (NMI) was added. The reaction mixture is shaken for 4 days and 2 * 10 ml Washed with 30% MeOH in tan and 4 * 10 ml of dichloromethane. The resin is dried and HPLC  Was analyzed. Loading L = 0.87meq / g.         Deallylation of immobilized allyl ester of naphthalene-2,6-dicarboxylic acid . 15ml CHCl with 5% HOAc and 2.5% NMM_Three2.4 g (2.09 mmol) of Pd (PPh_Three)_FourA Added under Lugon. The mixture was shaken for 10 minutes and 0.8 g (0.87 meq / g, 0.696 mmol) The mono-allylated resin was added under argon. Shake the reaction mixture for 18 hours 6 * 15 ml of 0.5% DIPEA, 0.5 sodium-diethyl-dithio-carbamate in DM Washed with F solution for 10 minutes each and with 3 * 15 ml dichloromethane. Dry the resin, Analyzed by HPLC. Loading L = 0.83 · eq / g. -N-Fmoc amino alcohol coupling to -COOH functionalized resin (Step (B) Corresponding to)         Four different N-Fmoc-amino alcohols were used.         trans-N-Fmoc-4-amino-1-cyclohexanol. 0.4g (0.87-0.66meq / g ) Is swollen in 5 ml of dry dichloromethane and 0.27 g ( 0.8 mmol) of trans-N-Fmoc-4-amino-1-cyclohexanol in 5 ml of dry dichloro A methane solution was added. The reaction mixture was shaken for 2 minutes and 0.237 g (0.8 mmol) of MSNT And 0.254 ml (3.2 mmol) of NMI were added. After 4 days, the reaction mixture is diluted with 10 ml Washed with dichloromethane, 10 ml 30% MeOH in DCM, 10 ml DMF and 2 * 10 ml DCM . The resin dries and Analysis by HPLC identified two products.       N-Fmoc-1-amino-2-propanol. The synthesis method was 0.238 g (0.8 mmol) of N-Fmoc- Use 1-amino-2-propanol and as described above. HPLC identifies two products did.       N-Fmoc-2-amino-1-propanol. The synthesis method was 0.249 g (0.8 mmol) of N-Fmoc- Using 2-amino-1-propanol, as described above. HPLC identifies two products did.       N-Fmoc-3-amino-1-propanol. The synthesis method was 0.238 g (0.8 mmol) of N-Fmoc- Using 3-amino-1-propanol as described above. HPLC identifies two products did. -NH_TwoCoupling of benzoic acid derivative to functionalized resin (corresponding to step (C))         Four different benzoic acids were used.         Diisopropyl ether of 4,4'-dimethoxytrityl-oxymethyl-benzoic acid Tyl ammonium salt. 0.4 g (about 0.6 meq / g) of -NH-Fmoc functionalized resin is 2 * 10m Washed with 1 * 20% piperidine in DMF for 2 * 40 min and 3 * 10 ml DMF. Resin is Swell in 7 ml of dry DMF and add 0.584 g (1.0 mmol) of 4,4'-dimethoxytrityl-o Add diisopropylethylammonium salt of xymethyl-benzoic acid, then add 0 .520 g (1.0 mmol) PyBOP, 0.135 g (1.0 mmol) HOBT and 0.33 ml (2.0 mmol) Of DIPEA was added. After 4 days, the resin was washed with 2 * 10 ml DMF, 2 * 10 ml 30% MeOH in DCM and 2 * 10ml Washed with DCM for 10 minutes each.         4-nitro-benzoic acid. 0.4g (about 0.6meq / g) of -NH-Fmoc functionalized tree Wash the fat with 2 * 10 ml 20% piperidine in DMF for 2 * 40 min and 3 * 10 ml DMF Was. The resin was swollen in 7 ml of dry DMF and 0.167 g (1.0 mmol) of 4-nitro-benzoic acid Is added, then 0.520 g (1.0 mmol) of PyBOP, 0.135 g (1.0 mmol) of HOBT and 0.3 3 ml (2.0 mmol) of DIPEA was added. After 4 days, the resin was mixed with 2 * 10 ml DMF, 2 * 10 ml D Washed with 30% MeOH in CM and 2 * 10 ml DCM for 10 minutes each.         4-methoxy-benzoic acid. The synthesis method is 0.152 g (1.0 mmol) of 4-methoxy-benzo Use perfume acid, as described above.       3-fluoro-benzoic acid. The synthesis method is 0.140g (1.0mmol) of 3-fluoro-benzoic Using an acid, as described above. Cleavage combinatorial library from WON resin (corresponds to step (D))         To perform this synthesis on a solid phase, the results of important coupling reactions Optimization was performed according to the cleave-&-analyse technique. This cutting- & According to the analytical method, weigh about 5 mg of the resin with an analytical balance and use trifluoroacetic acid (TFA) / Cut with dichloromethane (DCM) (1: 1, v / v) and evaporate (Speedvac, Spe ed-Vac^TM), Re-dissolved and pre-calibrated reverse phase using a minimum of three standard concentrations Weighed by HPLC. The product is a combination of Won-type resin with a combinatorial library. Cut with TFA / DCM (1: 1, v / v) when used for diode-array HPLC -UV (Hitachi) and Analyzed by HPLC-MS (Perkin-Elmer, Sciex), the composition of each of the four sub-libraries Minutes were identified.         Batch of 4,4'-dimethoxytrityl-oxomethyl-benzoic acid. DMT protecting group Was removed by washing with 4 * 10 ml of 3% dichloroacetic acid in DCM and then 4 * 10 ml of Washed with DCM. The resin is dried, analyzed by HPLC (LC-MS), and Six out of eight rule analogs were identified.         Batch of 4-nitro-benzoic acid. The resin was dried, analyzed by HPLC (LC-MS), Seven out of eight theoretically obtained balanol analogs were identified.         Batch of 4-methoxy-benzoic acid. The resin was dried and analyzed by HPLC (LC-MS). Seven out of eight theoretically obtained balanol analogs were identified.         Batch of 3-fluoro-benzoic acid. The resin was dried and analyzed by HPLC (LC-MS), Seven out of eight theoretically obtained balanol analogs were identified.         The above sub-library, 4,4'-dimethoxytrityl-oxomethyl -Benzoic acid batch, 4-nitro-benzoic acid batch, 4-methoxy-benzoic acid batch 6, 7, 7 and 7, respectively, in batches of thiocyanate and 3-fluoro-benzoic acid. The lanol structure was identified as a distinct peak in the LC-UV / MS analysis. Bildin Gblock of 1-amino-propan-2-ol or 3-amino-propan-1-ol The remaining five bars, including any one No lanol analog was observed in the library analysis. For this observation Several explanations, including partial precipitation of individual libraries or co-elution by HPLC But very likely.

────────────────────────────────────────────────── ─── Continuation of front page    (81) Designated countries EP (AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, L U, MC, NL, PT, SE), OA (BF, BJ, CF) , CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (KE, LS, MW, SD, S Z, UG), UA (AM, AZ, BY, KG, KZ, MD , RU, TJ, TM), AL, AM, AT, AT, AU , AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, CZ, DE, DE, DK, DK, E E, EE, ES, FI, FI, GB, GE, HU, IL , IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, M K, MN, MW, MX, NO, NZ, PL, PT, RO , RU, SD, SE, SG, SI, SK, SK, TJ, TM, TR, TT, UA, UG, US, UZ, VN, Y U

Claims (1)

[Claims] 1. The following steps: (A) A molecule with an optionally protected functional group immobilized on a solid support material -C (= O) -A-C (= O) -M¹[Wherein, -C (= O) -M¹Means a carboxy group or a derivative thereof] , (B) Bifunctional moiety L 'optionally protected with a functional group¹-B-L '^Two With the immobilized molecule -C (= O) -A-C (= O) -M¹Terminal of -C (= O) -M¹Immobilized with functional groups protected Fragment -C (= O) -A-C (= O) -L¹-B-L '^TwoTo form (C) Arbitrarily protected functional group D-C (= O) -M^Two[Where C (= O) -M^TwoIs carboxy Represents a group or a derivative thereof] -C (= O) -A-C (= O) -L¹-B-L '^TwoL '^Two Compound -C (= O) -A-C (= O) -L bound to the terminal and optionally protected with a functional group¹- B-L^Two-C (= O) -D [this step is L '^TwoDeprotection of any protecting groups contained in Include), and (D) Compound K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D can be cleaved from the solid support material. And [The step optionally deprotects one or more functional groups attached to A, B and / or D. Included in The following general formula I consisting of:         K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D I Wherein K—C (= O) — represents a carboxy group or a derivative thereof; Each of A and B means an organic biterminal radical; L¹And L^TwoAre each independently -NR^Five-Or -O- [wherein each R^FiveIs hydrogen, optionally Transformed C_1-20-Alkyl, optionally substituted C_1-20-Alkenyl, optionally substituted Done C_1-20-Alkadienyl, optionally substituted C_1-20-Alkatrienyl, Independent of optionally substituted aryl, and optionally substituted heteroaryl Or R^ThreeMeans an additional bond to B Taste (whereby B becomes a truncated radical)]; and D is optionally Means substituted aryl or optionally substituted heteroaryl] A method for producing a compound of the formula: 2. Organic two-terminal radical -C (= O) -A-C (= O)-has the formula                       -C (= O)-(CO^ThreeR^Four)_n-C (= O)- Wherein n is 1-20, preferably 1-12, especially 2-8, and each R^ThreeAnd R^FourBut hydrogen, Optionally substituted C_1-6-Alkyl, optionally substituted C_2-6-Alkenyl, optionally Commutated C_4-8-Alkadienyl, optionally substituted C_6-8-Alkatrienyl, ar Droxy, oxo (thus forming keto or aldehyde functionality), -O-R⁶ , Formyl, -C (= O) -R⁶, -O-C (= O) -R⁶, Carboxy, -C (= O) -0O-R⁶Arbitrarily Substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted Aryl, optionally substituted aryloxy, fluorine, chlorine, bromine and Halogen such as iodine, nitro, cyano-N (R^Five)_Two, -N (R⁷) -CO-R⁶, Carbamoy , Mono- or di (C_1-6-Alkyl) aminocarbonyl, sulfanyl, optionally Exchanged C_1-6-Alkylthio, optionally substituted C_1-6-Alkylthio-C_1-6-Al Kill, (optionally substituted aryl) thio, guanidino, sulfono (-SO_ThreeH), Sulfino (-SO_TwoH), halosulfonyl, -OS (O)_m-R⁶[M is 2 or 3], -N (R⁷) S (O)_m-R⁶[M is 2 or 3], -S (O)_m-N (R⁷)_Two[M is 2 or 3], -S (O)_m-NH (R⁷ ) [M is 2 or 3], -S (O)_m-NH_Two[M is 2 or 3], isocyano, isothiosi Ano, thiocyano, -OP (O)_p(R⁶)_q[P is 1, 2 or 3, q is 1 or 2, and And p + q are 3, 4 or 5] and -N (R⁷) P (O)_p(R⁶)_q[P is 1, 2 or 3, q is 1 Or 2, and p + q are independently selected from 3, 4 or 5] [each R^FiveAnd each R⁶ Is hydrogen, optionally Exchanged C_1-20-Alkyl, optionally substituted C_2-20-Alkenyl, optionally substituted C_4-20-Alkadienyl, optionally substituted C_6-20-Alkatrienyl, optional Independently selected from substituted aryl and optionally substituted heteroaryl. , Each R⁷Is hydrogen and C_1-4-Alkyl], at most 5, preferably at most At most three substituents R^ThreeAnd R^FourIs different from hydrogen], or 1 and 2, wherein X is> NR^Five,> NH, -O-, -S-, -Se-, -Te -, -CR¹R^Two-,> C = O,> C = S¹, Y^Two, R¹And R^TwoEach Independently defined as optional substituents on aryl and heteroaryl (described above) Or substituted Y; or Y¹Is Y^TwoTogether with these substituents With atoms, a 4-, 5-, 6-, 7- or 8-membered ring (optionally substituted non-aromatic carbocycle With a formula or heteroaromatic ring or an optionally substituted aromatic or heteroaromatic ring May be present) to form a two-terminal free radical; each Z¹And Z^TwoIs independently = N -, = N⁺R^Five-Means]. 3. Organic two-terminal free radical -L¹-B-L^Two-Is the formula                           -L¹-(CR^ThreeR^Four)_n-L^Two- [Where L¹, L^Two, R^Three, R^FourAnd n is as defined in claim 1 or 2] Group two-terminal radical or The aliphatic or aromatic amino alcohol shown in FIG. [Where X is> NR⁶,> NH, -O-, -S-, -Se-, -Te-, -CR¹R^Two-,> C = O,> C = S Selected from the group, Y¹, Y^Two, R¹And R^TwoEach independently represents an optional substituent Or Y¹Is Y^TwoWith, along with the primitives present between these substituents, 4-, 5-, 6-, 7- or 8-membered rings (optionally substituted non-aromatic carbocyclic or heteroaromatic Ring or optionally substituted aromatic or A heteroaromatic ring) to form a two-terminal radical; each Z¹ And Z^TwoAre independently = N-, = N⁺R^FiveThe method according to claim 1 or 2, wherein 4. L¹And L^TwoOne means -O- and the other is -NR^Five-[Where R^FiveIs hydrogen, C_1-4-Arki Or further binding to B or B). Law. 5. K is OH, O^-, OR ", NH_Two, NHR or NRR 'where R and R' are C_1-6-Alkyl and Selected from benzyl, R "is C_1-6-Alkyl, C_2-6-Alkenyl, phenyl and Selected from benzyl], especially OH, methoxy or NH_TwoMeans the destination bill Any of the methods in the section. 6. Step (E) comprises converting a compound of general formula I to another compound of general formula I The method of any of the preceding claims, further comprising a step (E) performed after step (D) . 7. (A) m molecules immobilized on a solid support material and optionally protected with functional groups -C (= O) -A-C (= O) -M¹[Wherein, -C (= O) -M¹Represents a carboxy group or a derivative thereof. Ray {A}, (B) n bifunctional group moieties L 'optionally protected with functional groups¹-B-L '^Two The fixed minutes Child -C (= O) -A-C (= O) -M¹Terminal of -C (= O) -M¹And optionally protected functional groups Defined m * n fragments -C (= O) -A-C (= O) -L¹-B-L '^TwoForm an array {A}-{B} (C) o-parts optionally protected with a functional group D-C (= O) -M^TwoArray of {D} [where C (= O) -M^TwoRepresents a carboxy group or a derivative thereof. Piece -C (= O) -A-C (= O) -L¹-B-L '^TwoL '^TwoAttached to the terminus and optionally protected with a functional group * n * o immobilized compounds -C (= O) -A-C (= O) -L¹-B-L^TwoArray of -C (= O) -D {A}-{B}-{ D} and the process is L '^TwoOptionally includes deprotection of any protecting group contained in ,and (D) Compound K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D array {A}-{B}-{D} Cleaving from the substrate (the process involves binding individual A, B and / or D Optionally including the deprotection of the above functional groups] Having the general formula I               K-C (= O) -A-C (= O) -L¹-B-L^Two-C (= O) -D I Wherein K—C (= O) — denotes a carboxy group or a derivative thereof; Each of A and B means an organic biterminal radical; L¹And L^TwoAre each independently -NR^Five-Or -O- [wherein each R^FiveIs hydrogen, optionally Exchanged C_1-20-Alkyl, optionally substituted C_1-20Alkenyl, optionally substituted C_1-20-Alkadienyl, optionally substituted C_1-20-Alkatrienyl, optional Independently selected from aryl substituted with, and optionally substituted heteroaryl. Or R^ThreeMeans an additional bond to B (whereby B is a three-terminal radical )]; And D represents an optionally substituted aryl or an optionally substituted heteroaryl R] Consisting of at least four compounds each having And 4, preferably in the range of 6-200, more preferably in the range of 6-100. Method for producing a multidimensional array of compounds {A}-{B}-{D}. 8. Wherein the organic biterminal radical -C (= O) -A-C (= O)-is as defined in claim 2 The method of claim 7. 9. Organic two-terminal free radical -L¹-B-L^Two-Is as defined in claim 3, claim 7 or Is the method of 8. 10. L¹And L^TwoOne means -O- and the other is -NR^Five-[Where R^FiveIs hydrogen, C_1-4-Al A further bond to B or B). Method. 11. K is OH, O^-, OR ", NH_Two, NHR or NRR 'where R and R' are C_1-6-Alkyl and And benzyl, where R "is C_1-6-Alkyl, C_2-6-Alkenyl, phenyl and And benzyl], especially OH, methoxy or NH_TwoClaim 7 which means -10 any way. 12. If step (E) is at least some compound of the array of compounds of general formula I A step performed after step (D) comprising the conversion to another compound of general formula I ( The method of any of claims 7-11, further comprising E). 13. Use of an array of compounds according to any of claims 7-13 for screening purposes. 14． Manufactured by the method defined in any of claims 1-6 or 7-13 as a drug Use of the compound made.