PHARMACEUTICALLY ACTIVE AMINO-SUBSTITUTED HETEROARYL AMINES

Abstract: Disclosed are amino-substituted heteroaryl amines of formula (I), which are useful as pharmaceutical agents.

Description: PHARMACEUTICALLY ACTIVE AMINC)-SUBSTπTJTED HETEROARYL AMINES BACKGROUND OF THE INVENTION 1. Field of the Invention The invention relates to complex heteroaryl amines attached to a simple mono- or di-substituted amino portion. These compounds are useful as pharmaceuticals. 2. Description of the Related Art Compounds similar to some of the compounds of the present invention are disclosed in International Publication No. WO 88/08424, pubUshed November 3, 1988 based on International Publication No. PCT/US88/01212. In particular, see the compounds of formula (II). The known compounds of the reference have a "connector portion" [-(CH^-j between the amine portion (M) and the non-amine portion (Xj) of the molecule in which n 2 is 4-14. In the present invention the "connector portion" of the similar compounds is less than 4. SUMMARY OF INVENTION Disclosed are amino-substituted heteroaryl amines of formula (I) (R,)(R 2 )N-Heteroaryl (I) where R t is C r C 3 aikyl, -O-CH 3 , -O-CH 2 CH 3 , where n t is 2 or 3 and R is -H, C C 3 alkyl, -CO-Rι. 2 where Rι. 2 is -H, C r C 3 alkyl or -φ, -CH 2 -CH(OR )-CH 3 where R M is as defined above, where is 1 or 2 and where R is as defined above, -(CH^-CO- ^ where n 3 is 1 thru 3 and R w is -OH, -O-R where R w is C r C 4 alkyl or -CH 2 -φ, C,-C 3 alkyl, -Φ optionally substituted with 1 or 2 -F, -Cl, -Br, -N0 2 , Cj-Cs or -OR 1-7 where R w is - alkyl, -CH 2 -CH=CH-CO-R 1-3 where R 1-3 is as defined above, where n 4 is 2 or 3 and R 1-5 and M are the same or different and are -H and C,-C 3 alkyl, R 2 is -H, C r C 3 alkyl, -(CH 2 . 5 -0-R 2-1 where n 5 is 2 or 3 and R 2-1 is -H, C x -C- alkyl, -CO-R 2-2 where R . 2 is -H, Cr alkyl or -φ, -CH 2 -CH(OR 2- ι)-CH 3 where R 2- ι is as defined above, is 1 or 2 and where R 2 .j is as defined above, -(CH-\--CO-R 2 - 3 where n 7 is 1 thru 3 and R 2 . 3 is -OH, -O-R 2 . 4 where R 2 ^ is -Q alkyl or -CH 2 -ό; - alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NOj, - or -OR 2 - 5 where R 2 . 5 is - alkyl, and where Rj and R 2 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, morpholine, piperazine and piperazine substituted in the 4- position with -(CHz g-O-Rj. ! where n g is 2 or 3 and where R w is -H, C C- alkyl, -CO- R 3 . 2 where Rj. 2 is -H, - alkyl or -φ, -(CR-\--CO-R-_ 3 where n, is 1 thru 3 and R 3 _ 3 is -OH, -0-R where R-^ is C r C 4 alkyl or -CH 2 -φ, Cj- alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO 2 , C x -C- or - OR^ where R w is C r C 3 alkyl, -CH 2 CH 2 -(0-CH 2 CH 2 ) II1 o-0-R 3 -ι where n 10 is 1 or 2 and where R is as defined above, -CH 2 -CH=CH-CO-R 3 _ 3 where R^ is as defined above, -S0 2 R 3 _ 5 where R^ is - alkyl; heteroaryl is pyridin-2-, 3- and 4-yl, pyrimidin-2- and 4-yl, pyrazin-2-yl, SUBSTITUTE SHEET l,3,5-triazin-2-yl, pyridazin-2-yl, substituted with 1 or 2 -NCR + . CR*.^ where R^ and R 4 . 2 are the same or different and are -H, C j - alkyl and where R^ and R^ are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azetidinyl and 4-(C r C 3 alkyl)-piperazinyl -NH-OH -NH-O-CH 2 - , -NH-CH 2 CH 2 -O-R 4 . 3 where _ 3 is -H or C,-C 3 alkyl, -N(CH CH -0-R . 3 ) 2 where R^ is as defined above, and pharmaceutically acceptable salts thereof. DETAILED DESCRIPTION OF THE INVENTION The amino-substituted heteroaryl amines (I) of the present invention are prepared from known compounds by methods well known to those skilled in the art. The present invention involves novel pharmaceutical compounds; the process chemistry used to produce these novel amino-substituted heteroaryl amines (I) is well known to those skilled in the art. There are three general methods to produce the amino-substituted heteroaryl amines (I). One method starts with a substituted halo (preferably chloro) pyrimidine, halo (preferably chloro) pyridazine, halo (preferably chloro)pyra_-_ie or halo (preferably chloro)triazine which is alkylated with a primary or secondary amine. The reaction may be carried out by heating a mixture of the pyrimidine, pyridazine, pyrazine or triazine and excess liquid amine until the starting material is consumed. The temperatures involved range from about 20-25° to the boiling point of the amine, and reaction times of about 1 to about 24 hr are usual. Preferrably equivalent amounts of the halo pyrimidine, pyridazine, pyrazine or triazine and the amine react in solvents such as acetonitrile and THF containing an acid scavenger such as potassium carbonate or an organic base such as pyridine or diisopropylethylamine. Excess pyridine may be used as both solvent and base. Reaction times of one hour to several days at temperatures of about 20-25° to the boiling point of the solvent are operable. The process of EXAMPLES 1-6 are performed by this method. In a second method substituted piperazinopyrimidines, piperazinopyridines or piperazinotriazines are prepared by reaction of the appropriate alkyl halide/mesylate/- tosylate or functionalized alkyl halide/mesylate/tosylate with the piperazino (secondary amine) intermediate. While not necessary, a catalytic amount of iodide may be included in the reaction mixture. Generally the use of a polar, nonhydroxylic solvent such as acetonitrile in the presence of a base such as potassium carbonate, pyridine or diisopropylethylamine is preferred. The process of EXAMPLES 8, 10-12, 14, 20, 21, 24-26 and 28-30 are performed by this method. Other substituted 2,3-diaminopyridines may be prepared in several steps by reaction of 2-chloro-3-nitropyridine with the appropriate primary or secondary amine. Generally use of a solvent such as THF or acetonitrile in the presence of excess base is preferred. The 3-nitropyridine intermediate is conveniently reduced by catalytic hydrogenation, to the corresponding primary amine. The primary amine may be reductively alkylated to give the corresponding mono- and dialkylamine products. In a similar fashion 2,5-diaminopyridines are prepared from 2-chloro-5-nitropyridine and 2,3,6-triaminopyridineare prepared from starting with 2,6-dichloro-3-nitropyridine. The process of EXAMPLES 15-18 were performed by this method. The reaction mixtures described above are purified by standard methods. Briefly, volatile solvents and reagents are removed by distillation under reduced pressure. The residue is partitioned between an organic solvent such as ethyl acetate, methylene chloride, ether, etc and water and/or aqueous bicarbonate. The organic phase is separated, dried and concentrated to a residue which is purified by chromatography. The appropriate fractions are pooled and concentrated to a residue. The residue is crystallized if necessary. The compounds described above can be transformed to other amino-substituted heteroaryl amines (I) by methods known to those skilled in the art (etherification, acylation, hydrolysis, hydrogenolysis, etc). The compounds may be converted to salts of pharmaceutically acceptable acids by known methods. The compounds containing a free carboxyl group can be converted to salts of pharmaceutically acceptable bases by known methods. These include, for example, sodium, potassium, aluminum, calcium, ammonium and tromethamine (TΗAM) salts. R ! and R 2 can either be separate or j and R 2 can be taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, morpholine, piperazine and piperazine substituted in the 4-position. When t and R 2 are not taken together to form a cyclic moiety, it is preferred HEET that R, is C r C 3 alkyl, -0-CH 3 , -(CH 2 ) B ,-0-R w , When R λ and R 2 are not taken together to form a cyclic moiety, it is preferred that R 2 is -H, - alkyl and -(CH 2 ) lS -0-R a .,. When R t and R 2 are taken together to form a cyclic moiety it is preferred that it be morpholine, piperazine substituted in the 4-position, pyrrolidine or piperidine; it is more preferred that R t and R 2 are taken together to form piperazine substituted in the 4- position. It is preferred that heteroaryl is pyrimidin-4-yl or pyridin-2-yl. It is preferred that when heteroaryl is pyrimidin-4-yl that it is substituted with 2,6-di-l-pyrrolidinyl or morpholino, more preferrably with 2,6-di-l-pyrrolidinyl. It is preferred that when heteroaryl is pyridin-2-yl it is substituted with 3-ethylamino. It is preferred that the amino-substituted heteroaryl amine (I) is selected from the compounds of EXAMPLES 1-38. Since the amino-substituted heteroaryl amines (I) of the present invention are amines, they readily form salts when reacted with acids of sufficient strength to produce the corresponding salts. Pharmaceutically acceptable salts include salts of both inorganic and organic acids. The anions of preferred pharmaceutically acceptable salts include acetate, benzoate, bromide, chloride, citrate, fumarate, mesylate, maleate, phosphate, nitrate, succinate, sulfate and tartrate. In humans, the amino-substituted heteroaryl amines (I) are useful in treating spinal trauma, mild and/or moderate to severe head injury, subarachnoid hemorrhage and subsequent cerebral vasospasm, ischemic (thromboembolic) stroke, excess mucous secretion, asthma, muscular dystrophy, adriamycin-induced cardiac toxicity, Parkin- sonism, Alzheimer's disease, other degenerative neurological disorders, multiple scleros¬ is, organ damage during reperfusion after transplant, skin graft rejection, hemorrhagic, traumatic and septic shock, and conditions such as severe burns, ARDS (adult respiratory distress syndrome), inflammatory diseases such as osteo- or rheumatoid arthritis, nephrotic syndrome (immunological), systemic lupus erythematosis, allergic reactions, atherosclerosis, inflammation (for example dermatological, inflammatory and psoriasis conditions), emphysema, stress induced ulcers, cluster headaches, complications from brain tumors (e.g. peritumoral edema), radiation damage (for example during radiation treatment or from accidental exposure to radiation), pre-birth infant strangulation and SUBSTITUTE SHEET infant hypoxia syndrome, such opthalmic disorders as uveitis and optic neuritis, photic retinopathy, age-related macular degeneration, cataracts and glaucoma. In humans, the amino-substituted heteroaryl amines (I) are useful in preventing damage following cardiopulmonary resuscitation, neurological or cardiovascular surgery and from cardiac infarction. The amino-substituted heteroaryl amines (I) are useful in irrigation solutions used in eye surgery. It is to be understood that each of the amino-substituted heteroaryl amines (I) is useful to a different degree for treating each of the conditions above. However, as is known to those skilled in the art, some of the amino-substituted heteroaryl amines (I) are better for treating some conditions and others are better for treating other conditions. In order to determine which compounds are better than others for a particular condition one can utilize known tests that do not require expermentation but only routine analysis. For example, the mouse head injury assay of Hall, J. Neurosurg., 62, 882 (1980) discloses an assay from which one skilled in the art can readily determine which particular amino-substituted heteroaryl amines (I) are useful in the acute treatment of spinal trauma or mild and/or moderate to severe head injury. Additionally, the cat 48 hr motor nerve degeneration model of Hall et al, Exp. Neurol., 79, 488 (1983) discloses a routine assay from which one skilled in the art can readily determine which particular amino-substituted heteroaryl amines (I) are useful in treating chronic degenerative neurological disorders such as Parkinsonism, Alzheimer's disease, etc. H. Johnson in Int. Arch. Allergy Appl. Immunol., 70, 169 (1983) has described the Ascaris suum sensitized rhesus monkey assay for anti-asthma drugs. Further, the arachidonic acid LDso test of Kohler, Thrombosis Res., 9, 67 (1976), identifies compounds which are antioxidants, which inhibit lipid peroxidation, and/or which inhibit the prostaglandin cascade and are useful in treating spinal trauma, mild and or moderate to severe head injury, degenerative neurological disorders, etc. Another method useful for determining which particular compounds inhibit lipid peroxidation and which are therefore useful in treating spinal trauma, mild and/or moderate to severe head injury, degenerative neurological disorders, etc is described by Pryor in Methods of Enzymology 105, 293 (1984). The standard conditions for treatment are to give the amino-substituted heteroaryl amines (I) orally or parenterally, e.g. IV (that is by injection, infusion or continuous drip) or IM, with a standard dose of about 0.05 to about 10 mg/kg/day IV or about 0.5 to about 50 mg/kg/day, one to four times daily by mouth. For treating spinal trauma, mild and moderate to severe head injury, damage following cardiopulmonary resuscitation, cardiac infarction, organ damage during reperfusion after transplant, hemorrhagic, traumatic and septic shock, severe burns, ARDS, and nephrotic syndrome and preventing skin graft rejection, the standard conditions are used. Typical treatment will involve an initial loading dose, e.g. an IV dose of 0.01 mg to 2 mg/kg followed by maintenance dosing e.g. IV infusion for a day to a week depending on the particular condition of the patient and the particular compound used. This may be supplemented with IM or oral dosing for days, weeks or months to prevent delayed neuronal degeneration in neurological applications (eg spinal trauma, head injury). In treating subarachnoid hemorrhage and subsequent cerebral vasospasm or ischemic (thromboembolic) stroke the standard conditions are used and patients at risk are pre-treated orally. In treating excess mucous secretion and asthma, the amino-substituted heteroaryl amines (I) are administered orally, IV and by inhalation in the standard dose. In treating excess mucous secretions the oral dose of the amino-substituted heteroaryl amines (I) used is from about 0.5 to about 50 mg/kg/day. The frequency of administration is one through 4 times daily. The susceptible individuals can be pre-treated a few hours before an expected problem. The IV dose is about 0.05 to about 20 mg/kg/day. The aerosol formulation contains about 0.05 to about 1.0% of the amino-substituted heteroaryl amines (I) and is administered or used about four times daily as needed. In treating muscular dystrophy, Parkinsonism, Alzheimer's disease and other degenerative neurological disorders (amyotrophic lateral sclerosis; multiple sclerosis) amino-substituted heteroaryl amines (I) are administered orally using a dose of about 0.5 to about 50 mg/kg/day, administered or used one to four times a day. The treatment may go on for years. In treating adriamycin-induced cardiac toxicity, the amino-substituted heteroaryl amines (I) are administered orally or IV using a dose of about 0.05 to about 50 mg/kg/day, preferrably about 0.5 to about 10 mg/kg/day. The amino-substituted heteroaryl amines (I) are preferably given concomitantly with IV adriamycin or the individual is pre-treated with the amino-substituted heteroaryl amines (I). For prophylaxis prior to and preventing damage after neurological or cardiovascu¬ lar surgery the amino-substituted heteroaryl amines (I) are used according to the standard conditions. The patient can be pretreated with a single IV or IM dose just prior to surgery and/or orally after surgery. In treating osteo- or rheumatoid arthritis and other inflammatory diseases, the amino-substituted heteroaryl amines (I) are given orally or IM in doses of about 0.5 to about 50 mg kg/day, one to four times daily. Orally the drug will be given alone or with other steroidal or nonsteroidal antiinflammatory agents. The initial dose with some severe rheumatoid patients may be given IV and followed with an IV drip for up to 24 hr or more. In addition, intra-articular administration may be employed. In treating drug allergic reactions, the amino-substituted heteroaryl amines (I) are given in a dose of about 0.5 to 50 mg/kg/day, administered one to four times daily orally and IV. Typical treatment would be an initial IV loading dose followed by oral dosing for a few days or more. In treating atherosclerosis and emphysema, the amino-substituted heteroaryl amines (I) are given orally in a dose of about 0.5 to about 50 mg/kg/day, one to four times daily. In treating dermatological inflammatory conditions including bums and psoriasis, the amino-substituted heteroaryl amines (I) are given orally in a dose of about 0.5 to about 50 mg/kg/day, one to four times daily or applied topically as a cream, ointment or lotion or equivalent dosage form in a concentration of about 0.05 to about 5% as long as needed. In treating these conditions the amino-substituted heteroaryl amines (I) can be used with steroidal agents. For use in eye surgery, an isoosmolar solution containing about 0.001 to about 1% of the amino-substituted heteroaryl amines (I) is used. In treating ophthalmic disorders the amino-substituted heteroaryl amines (I) are given orally in a dose of about 0.5 to about 50 mg/kg/day, one to four times daily or applied topically as a cream, ointment or lotion or equivalent dosage form in a concentration of about 0.001 to about 1 % as long as needed. The amino-substituted heteroaryl amines (I) are useful in the prevention and treat¬ ment of stress ulcers and of gastric intolerance caused by drugs such as nonsteroidal anti- inflammatory compounds (NOS AC) . Stress ulcers are ulcers that develop after exposure to severe conditions such as trauma, burns, sepsis, extensive surgery, acute illnesses, and the like. Patients in intensive care units are particularly prone to develop stress ulcers. Stress ulcers also include lesions that can lead to upper gastrointestinal bleeding; such bleeding is likely to be prevented by these compounds. NOSAC includes drugs such as ibuprofen, aspirin, indomethacin, naproxen, piroxicam and the like that are usually taken for analgesia, and that are often associated with gastrointestinal intolerance characterized by pain and lesions that may lead to bleeding. The amino-substituted heteroaryl amines (I) will be administered preferentially by the oral route either as tablets, capsules or liquids, in doses ranging from about 5 to about 500 g, two to four times a day. The treatment would be either preventive, i.e., starting before ulcers have formed in patients at risk of developing such lesions, or therapeutic, i.e., once the ulcers have formed. In patients whose clinical condition precludes swallowing the oral dosage forms, the amino- substituted heteroaryl amines (I) would be given either through a nasogastric tube, or parenterally, i.e., IV or IM. The parenteral doses would range from about 1 to about 100 mg/kg and be administered one to four times a day. In dogs, the amino-substituted heteroaryl amines CO are useful in treating trauma, intervertebral diseases (slipped disk), traumatic shock, flea bite and other allergies. In horses, the amino-substituted heteroaryl amines (I) are useful in treating endotoxic or septic shock which follows colic, pretreatment before surgery for colic and treatment of Founder (laminitis). In cattle, the amino-substituted heteroaryl amines (I) are useful in treating acute coliform mastitis, bovine mastitis, acute allergic reaction to feed lot vaccination and shipping fever. In pigs, the amino-substituted heteroaryl amines (I) are useful in treating porcine stress syndrome and thermal stress syndrome. The amino-substituted heteroaryl amines (I) can be used with other pharmaceutical agents in treatment of the conditions listed above as is known to those skilled in the art. The exact dosage and frequency of administration depends on the particular amino-substituted heteroaryl amines (I) used, the particular condition being treated, the severity of the condition being treated, the age, weight, general physical condition of the particular patient, other medication the individual may be taking as is well known to those skilled in the art and can be more accurately determined by measuring the blood level or concentration of the amino-substituted heteroaryl amines (I) in the patient's blood and/or the patients response to the particular condition being treated. DEFINΓΠQNS AND CONVENTIONS The definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims. I. CONVENTIONS FOR FORMULAS AND DEFINITIONS OF VARIABLES The chemical formulas representing various compounds or molecular fragments in the specification and claims may contain variable substituents in addition to expressly defined structural features. These variable substituents are identified by a letter or a letter followed by a numerical subscript, for example, "Z x " or "Rj" where "i" is an integer. These variable substituents are either monovalent or bivalent, that is, they represent a group attached to the formula by one or two chemical bonds. For example, a group ∑ι would represent a bivalent variable if attached to the formula CH 3 -C(=Zι)H. Groups i and R j would represent monovalent variable substituents if attached to the formula CH 3 -CH 2 -C(R i )(R j )H 2 . When chemical formulas are drawn in a linear fashion, such as those above, variable substituents contained in parentheses are bonded to the atom immediately to the left of the variable substituent enclosed in parenthesis. When two or more consecutive variable substituents are enclosed in parentheses, each of the consecutive variable substituents is bonded to the immediately preceding atom to the left which is not enclosed in parentheses. Thus, in the formula above, both R* and R j are bonded to the preceding carbon atom. Also, for any molecule with an established system of carbon atom numbering, such as steroids, these carbon atoms are designated as , where "i" is the integer corresponding to the carbon atom number. For example, represents the 6 position or carbon atom number in the steroid nucleus as traditionally designated by those skilled in the art of steroid chemistry. Likewise the term "R^" represents a variable substituent (either monovalent or bivalent) at the C 6 position. Chemical formulas or portions thereof drawn in a linear fashion represent atoms in a linear chain. The symbol "-" in general represents a bond between two atoms in the chain. Thus CH 3 -0-CH 2 -CH(R^-CH 3 represents a 2-substituted-l-methoxypropane compound. In a similar fashion, the symbol "=" represents a double bond, e.g., and the symbol " ■ " represents a triple bond, e.g., HC≡C-CHORi)- CH 2 -CH 3 . Carbonyl groups are represented in either one of two ways: -CO- or - C(=0)-, with the former being preferred for simplicity. When a variable substituent is bivalent, the valences may be taken together or separately or both in the definition of the variable. For example, a variable Rj attached to a carbon atom as might be bivalent and be defined as oxo or keto (thus forming a carbonyl group (-CO-) or as two separately attached monovalent variable substituents ot-R^ and β-Rj- k . When a bivalent variable, Rj, is defined to consist of two monovalent variable substituents, the convention used to define the bivalent variable is of the form "αr-R^B- are attached to the carbon atom to give -C(α-R H )(β-R i _ k )-. For example, when the bivalent variable R-, -C(=R«)- is defined to consist of two monovalent variable substituents, the two monovalent variable substituents are α-R β . 1 : β -R 6 . 2 , .... α-R β-9 :β-R6. 10 , etc, giving -C(Q.-R $ _ i)(B-R«)-, .... -C(a-R 6 . 9 )(&-R 6 . lQ )-, etc. Likewise, for the bivalent variable R n , - C(=R U )-, two monovalent variable substituents are α-R u _ι:β-Ru. 2 . For a ring substituent for which separate α and β orientations do not exist (e.g. due to the presence of a carbon carbon double bond in the ring), and for a substituent bonded to a carbon atom which is not part of a ring the above convention is still used, but the α and β designations are omitted. Just as a bivalent variable may be defined as two separate monovalent variable substituents, two separate monovalent variable substituents may be defined to be taken together to form a bivalent variable. For example, in the formula -C,(R H-C 2 (R j )H- ( and C- define arbitrarily a first and second carbon atom, respectively) Rj and R j may be defined to be taken together to form (1) a second bond between and Cj or (2) a bivalent group such as oxa (-0-) and the formula thereby describes an epoxide. When Rj and R j are taken together to form a more complex entity, such as the group -X-Y-, then the orientation of the entity is such that in the above formula is bonded to X and C 2 is bonded to Y. Thus, by convention the designation "... Rj and R are taken together to form -CH 2 -CH 2 -0-CO- ..." means a lactone in which the carbonyl is bonded to C 2 . However, when designated "... j and Rj are taken together to form -CO-O-CH 2 -CH 2 -the convention means a lactone in which the carbonyl is bonded to C . The carbon atom content of variable substituents is indicated in one of two ways. The first method uses a prefix to the entire name of the variable such as " - ", where both " 1 " and "4" are integers representing the minimum and maximum number of carbon atoms in the variable. The prefix is separated from the variable by a space. For example, " - alkyl -1 represents alkyl of 1 through 4 carbon atoms, (including isomeric forms thereof unless an express indication to the contrary is given). Whenever this single prefix is given, the prefix indicates the entire carbon atom content of the variable being defined. Thus -C 4 alkoxycarbonyl describes a group CH 3 -(CH 2 ) a -0-CO- where n is zero, one or two. By the second method the carbon atom content of only each portion of the definition is indicated separately by enclosing the " -C j " designation in parentheses and placing it immediately (no intervening space) before the portion of the definition being defined. By this optional convention (C,-C 3 )alkoxycarbonyl has the same meaning as -C 4 alkoxycarbonyl because the " - " refers only to the carbon atom content of the alkoxy group. Similarly while both C--C- alkoxyalkyl and ( - C 3 )alkoxy(CrC 3 )alkyl define alkoxyalkyl groups containing from 2 to 6 carbon atoms, the two definitions differ since the former definition allows either the alkoxy or alkyl portion alone to contain 4 or 5 carbon atoms while the latter definition limits either of these groups to 3 carbon atoms. π. DEFINITIONS All temperatures are in degrees Centigrade. TLC refers to thin-layer chromatography. THF refers to tetrahydrofuran. Saline refers to an aqueous saturated sodium chloride solution. NMR refers to nuclear (proton) magnetic resonance spectroscopy, chemical shifts are reported in ppm (δ) downfield from tetramethylsilane and are measured in chloroform-d (CDC1 3 ). CMR refers to C-13 magnetic resonance spectroscopy, chemical shifts are reported in ppm (δ) downfield from tetramethylsilane and are measured in chloroform-d (CDC1 3 ). φ refers to phenyl ( H 5 ). Ether refers to diethyl ether. Pharmaceutically acceptable refers to those properties and/or substances which are acceptable to the patient from a pharmacological toxicological point of view and to the manufacturing pharmaceutical chemist from a physical/chemical point of view regarding composition, formulation, stability, patient acceptance and bioavailability. Treatment or treating refers to and includes both treatment of an existing condition as well as preventing the same condition from occurring where such is possible as is well known to those skilled in the art. For example, the amino-substituted heteroaryl amines (I) can be used to treat existing asthma conditions and to prevent future ones from occurring. For example, the amino-substituted heteroaryl amines (I) treat spinal trauma and prevent rejection of skin grafts. When solvent pairs are used, the ratios of solvents used are volume/volume (v/v). EXAMPLES Without further elaboration, it is believed that one skilled in the art can, using the preceding description, practice the present invention to its fullest extent. The following detailed examples describe how to prepare the various compounds and/or perform the various processes of the invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. Those skilled in the art will promptly recognize appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques. EXAMPLE 1 4-(2-(Hydroxyethyl)memylamino)-2,6-di-l-pyrrollidinylpyrimidine (D A solution of 4-chloro-2,6-di-l-pyrτolidinylpyrimidine (15.5 g) and 2-(methyl- amino)ethanol (30 ml) is heated under reflux for about 20 hours. The mixture is cooled and diluted with ethyl acetate (150 ml) and potassium bicarbonate (IN, 75 ml). The organic extract is washed with water (5 X 50 ml), saline (1 X 100 ml), ethyl acetate backwash (100 ml), then dried (magnesium sulfate) and concentrated. The residue is crystallized from methanol/water (8/5, 130 ml) to give the title compound, mp 108-110°; CMR 163.9, 161.8, 159.5, 71.57, 63.31, 53.47, 46.22, 45.93, 37.28, 25.37 and 25.18 δ. EXAMPLE 2 4-Mθ holino-2,6-di-l-py_τoUdinylpyrimidine (I) A solution of 4-chloro-2,6-di-l-py-Tolidinylpyrimidine (2.53 g) and morpholine (5 ml) is heated under reflux for about 16 hours. The reaction mixture is worked up as in EXAMPLE 1 (the product is sparingly soluble in ethyl acetate). Two crystallizations from methanol gives the title compound, mp 180.3-180.6°; CMR 164.21, 162.33, 160.0, 72.20, 66.70, 46.05, 45.92, 44.83, 25.45 and 25.19 δ. EXAMPLE 3 4-Di(2-Methoxyethyl)amino-2,6-di-l-pyrτolidinylpyrimidine (I) A solution of 4-chloro-2,6-di-l-pyrrolidinylpyrimidine (3.4 g) and di(2-methoxy- ethyl)amine (50 ml) is heated under reflux for about 43 hours. Excess amine is distilled under reduced pressure to give a residue which is partitioned between ethyl acetate/water (both phases dark, separated by volume). The organic extract is dried and concentrated to give a gum. The gum is chromatographed on silica gel eluting with ethyl ace- tate/hexane (50/50), the appropriate fractions are pooled and concentrated to give the title compound, CMR 162.29, 162.1, 160.0, 71.25, 70.66, 58.71, 48.35, 46.01, 45.91, 25.45 and 25.20 δ. EXAMPLE 3A 4-Di(2-Methoxyethyl)amino-2,6-di-l-pyrrolidinylpyrimidine hydrochloride (I) 4-Di(2-Methoxyethyl)arn o-2,6^i-l-pyrτoUdinylpyrimidine (EXAMPLE 3, 1.5 g) is dissolved in dilute hydrochloric acid (0.1 N, 1.0 eq) and the solution is freeze dried to give the title compound. EXAMPLE 4 4-Methoxyamino-2,6-di-l-py-ToIidinylpyrimidine (I) A mixture of methoxylamine hydrochloride (5 g) and 4-chloro- 2,6-di-l-pyr- rolidinylpyrimidine (3.37)in pyridine (10 ml) is sealed in a pressure tube and heated on a steam bath for 2 days (two liquid phases present). The mixture is cooled, diluted with ethyl acetate and aqueous sodium carbonate (20%, 25 ml) is added cautiously. The mixture is filtered through diatomaceous earth (Celite). The organic phase is washed with water and saline and the concentrated to give an oil which is chromatographed on silica gel. The column is eluted with methanol/methylene chloride (10/90), the appropriate fractions are pooled and concentrated and rechromatographed eluting with ethyl acetate/hexane (50%) to give the title compound which is crystallized from hexane, mp 96.5-98°; CMR 166.33, 162.2, 160.2, 73.60, 63,47, 46.13, 45.97, 25.40 and 25.17 δ. EXAMPLE 4A 4-Methoxyamino-2,6-di-l-pyιrolidinylpyrimidine hydrochloride CD Following the general procedure of EXAMPLE 3A and making noncritical variations but starting with 4-methoxyarmno-2,6-di-l-pyrrolidinylpyrimidine(EXAMPLE 4) the title compound is obtained. EXAMPLE 5 4-(Di-(2-hydroxyethyl)amino)-2,6-di-l-pyrrolidinylpyrimidine(I) A solution of 4-chloro-2,6-di-l-pyrrolidinylpyrimidine(5.2 g) and diethanolamine C50 ml) is heated under reflux for 20 hours. The mixture is cooled and worked up as in EXAMPLE 1 to give an oil which is chromatographed on silica gel eluting with methanol/methylene chloride (10/90). The appropriate fractions are pooled and con¬ centrated and the residue crystallized from aqueous acetone to give the title compound, mp 119-120°; CMR 163.03, 161.63, 158.89, 71.89, 61.49, 52.35, 46.27, 46.04, 25.34 and 25.14 δ. EXAMPLE 6 4-Methylamino-2,6-di-l-pyrrolidinylpyrimidine (I) A solution of 4-chloro-2,6-di-l-pyrrolidinylpyrimidine (7.5 g) in pyridine (100 ml) in a steel vessel is cooled in ice water. Methylamine is introduced into the solution for 20 minutes, then the vessel is sealed and heated on a steam bath for about 90 hours. The mixture is then cooled and concentrated under reduced pressure to an oil which is mixed with hydrochloric acid (IN, 50 ml) and ether (100 ml). The aqueous phase is washed with ether, then made basic with potassium hydroxide (45%). Extraction with ether gives a solid which is chromatographed on silica gel, eluting with a metha¬ nol/methylene chloride mixtures. Rechromatography eluting with methanol/methylene chloride (5/95) gives the title compound, mp 93-94.5°; NMR 4.69, 3.53, 3.44, 2.83 and 1.90 δ. EXAMPLE 7 4-(2-(2-Methoxyethoxy)ethylmethylamino)-2,6-di-pyrrolidinyl- pyrimidine (I) A solution of 4-(2-(hydroxyethyl)methylamino)-2,6-di-l-pyrrollidinylpyrimidine (EXAMPLE 1 , 1.16 g) in THF (12 ml) is added to a suspension of sodium hydride (50% mineral oil dispersion, 240 mg) in THF (5 ml). The mixture is stirred for 1 hr then a solution of l-methoxy-2-mesyloxyethane (0.925 g) in THF (2 ml) is added. The mixture is stirred under reflux for 2 days then is partitioned between ethyl acetate and water, the phases are separated and the organic phase concentrated to give an oil. Chromatography on silica gel eluting with methanol/methylene chloride (5/95) gives the title compound; CMR 163.1, 162.3, 160.0, 71.89, 71.28, 70.17, 69.22, 58.94, 48.74, 46.01, 45.88, 36.41, 25.46 and 25.21 δ. EXAMPLE 7A 4-(2-(2-Methoxyethoxy)ethylmethylamino)-2 , 6-di-pyrrolidinyl- pyrimidine hydrochloride (I) 4-C2-C2-Methoxyethoxy)ethylmethylamino)-2,6-di-pyrrolidinylpyrimidine (EXAMPLE 7) is dissolved in dilute hydrochloric acid and freezed dried to give the title compound, mp 120.5-126°. EXAMPLE 8 4-(3-(Ethylamino)-2-pyridinyl)-l-piperazinepropanol (I) A mixture of 4-(3-(ethylamino)-2-pyridinyl)piperazine, (0.58 g) , 3-bromopropanol (0.39 g), potassium carbonate (0.195 g) and a trace of sodium iodide in acetonitrile (40 ml) is heated under reflux for 18 hours and then concentrated under reduced pressure. The residue is partitioned between methylene chloride and water, the phases are separated and the organic phase concentrated to give a solid which is chromatographed on silica gel eluting with methanol/methylene chloride (20/80). The appropriate fractions are pooled and concentrated to give the title compound. A sample is crystallized from acetone, mp 136.5-137°; CMR 150.23, 137.27, 135.06, 119.81, 115.86, 64.22, 61.59, 53.61, 48.56, 37.97, 27.03 and 14.64 δ. EXAMPLE 9 2-C4-Mesyloxy-l-piperazinyl)-3-ethylaminopyridine (I) Methanesulfonyl chloride (0.4 ml) is added slowly to a solution of 4-(3-ethyla- mino)-2-pyridinyl-piperazine (1.11 g) in pyridine (5 ml). The mixture is allowed to warm to 20-25°, then is mixed with ice and allowed to stand overnight. The mixture is diluted with ethyl acetate, the phases are separated, d e organic phase is washed with water and saline, then dried and concentrated to give a yellow oil. Chromatography on silica gel, eluting with ethyl acetate/hexane (50/50), and crystallization of product fractions from acetone/hexane gives the title compound, mp 108-109°; CMR 149.55, 137.14, 135.20, 120.33, 116.37, 48.27, 45.89, 37.95, 34.78 and 14.66 δ. EXAMPLE 10 Methyl 4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l -piperazine ethanoate (I) A mixtureof 4-C2,6-di-l-pyrrolidinyl-4-pyrimidinyl)piperazineCl .51 g), potassium carbonate C0.345 g) and methyl bromoacetate C0.76 g) in acetonitrile C100 ml) is heated under reflux for about 4 hrs and then is concentrated. The residue is partitioned between methylene chloride and aqueous potassium bicarbonate, the phases are separated and the organic phase concentrated to give an oil. The oil is chromatograped on silica gel, eluting with methanol/methylene chloride (5%), the appropriate fractions are pooled and concentrated to give the title compound; CMR 170.57, 163.8, 162.2, 160.0, 72.26, 59.48, 52.76, 51.61, 46.07, 45.94, 44.11, 25.44 and 25.18 δ. EXAMPLE 10A Methyl 4-C2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazine ethanoate dihydrochloride (I) A solution of the free amine containing hydrochloric acid (2 equivalents) is freeze dried to give the title compound. EXAMPLE 11 Methyl 4-(3-(ethylamino)-2-pyridinyl)-l-piperazine ethanoate (I) Following the general procedure of EXAMPLE 10 and making non-critical variations but reacting 4-(3-(ethylamino)-2-pyridinyl)piperazine (1.03 g) with methyl bromoacetate, the title compound is obtained, CMR 170.65, 150.5, 137.17, 135.08, 119.57, 115.76, 59.28, 53.10, 51.52, 48.48, 37.99 and 14.64 δ. EXAMPLE 12 Benzyl 4-C3-(ethylamino)-2-pyridinyl)piperazine ethanoate (I) Following the general procedure of EXAMPLE 10 and making noncritical variations but reacting 4-(3-Cethylamino)-2-pyridinylpiperazine (0.84 g) with benzyl bromoacetate (1.14 g), crude title compound is obtained. Chromatography on silica gel, eluting with methanol/methylene chloride (5/95) gives the title compound, mp 54°; NMR 7.7, 7.47, 6.9, 6.8, 5.19, 4.1, 3.38, 3.15, 2.8 and 1.29 δ. EXAMPLE 13 4-(3-(Ethylamino)-2-pyridinyl)-piperazineethanoic acid hydrochlo¬ A solution of benzyl 4-(3-(ethylamino)-2-pyridinyl)-piperazine ethanoate (EXAMPLE 12, 1.0 mmole) and hydrochloric acid (2N, 0.5 ml) in methanol (50 ml) is hydrogenated (50 psi) in the presence of palladium carbon (5%, 0.1 g) for about 4 hr. The mixture is filtered and concentrated and the residue chromatographed on silica gel. Elution with chloroform/methanol water (65/35/2) gives the title compound, mp 180-188°. EXAMPLE 14 Methyl 4-(2,6-di-l-pyrτolidinyl-4-pyrimidinyl)-l-piperazine propanoate (I) A mixture of 4-(2,6-di-l-pyrτolidinyl-4-pyrimidinyl)-piperazine (1.51 g), potassium carbonate (0.35 g), sodium iodide O.15 g) and methyl 3-bromopropionate (0.84 g) in acetonitrile (100 ml) is heated under reflux for about 18 hours and then concentrated under reduced pressure. The residue is worked up as in EXAMPLE 10 to give an oil which is chromatographed on silica gel eluting with acetone/methylene chloride mixtures. The appropriate fractions are pooled and concentrated to give a solid which is crystallized from acetone to give the title compound, mp 120.5-121°; CMR 173.0, 163.88, 162.33, 160.0, 72.23, 53.54, 52.62, 51.53, 46.04, 45.90, 44.22, 31.90, 25.45 and 25.19 δ. EXAMPLE 15 2-Moτpholino-3-ethylaminopyridine (I) A mixture of 2-chloro-3-nitropyridine (3.17 g), potassium carbonate (2 g), morpholine (5 ml) and acetonitrile (50 ml) is stirred for 2.5 hours and then is allowed to stand overnight. The mixture is concentrated under reduced pressure and the residue partitioned between ethyl acetate and water, the phases separated and the organic extract washed with water and saline, dried and concentrated to give 2-morpholino-3-nitro- pyridine as a solid. A solution of the 2-morpholino-3-nitropyridine in methanol (150 ml) is hydrogenated in the presence of palladium/carbon (5%, 1 g) in a Parr apparatus (45 lb, 2 hr). The mixture is filtered and the filtrate containing 2-morpholino-3-aminopyridine is concentrated to 50 ml and cooled in an ice bath. Acetaldehyde (4 ml) is added followed by the portion-wise addition of sodium cyanoborohydride (1.4 g). The mixture is stirred for 1 hr with continued cooling, is allowed to stand overnight at 20-25° and then is concentrated under reduced pressure. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate, the phases are separated and the organic extract is concentrated to give an oil. The oil is chromatographed on silica gel eluting with ethyl acetate/hexane (50/50) to give the title compound, mp 69.9-71.0°; CMR 150.20, 137.33, 135.13, 119.95, 116.02, 67.24, 49.29, 37.97, 14.65 δ. EXAMPLE 15A 2-Morpholino-3-ethylaminopyridine hydrochloride (I) A solution of 2-morpholino-3-ethylaminopyridine (EXAMPLE 15, 0.207 g) in water (20 ml) containing hydrochloric acid (1 eq) is filtered through hardened filter paper. The filtrate is freeze dried to give the title compound, mp 205-209°. EXAMPLE 16 2-((2-Acetyloxyethyl)ethylamino)-3-ethylaminopyridine (1-1) and 2-CC2-hydroxyethyl)ethylamino)-3-ethylamino-pyridine (1-2) A mixture of 2-chloro-3-nitropyridine (3.17 g), potassium carbonate (2 g) and 2- Cethylamino)ethanol in acetonitrile (50 mi) is allowed to react as in EXAMPLE 15 to give 2-(C2-hydroxyethyl)ethylamino)-3-nitropyridine as an oil. A solution of this compound in acetic anhydride (10 ml) is allowed to stand 20 hr at 20-25°. The mixture is then treated with ice (100 g), made slightly basic with potassium hydroxide (45%) and extracted with ethyl acetate. The extract is washed with water and saline and concentrated to give 2-((2-acetyloxyethyl)ethylamino)-3-nitropyridine. Hydrogenation of 2-((2-acetyloxyethyl)ethylamino)-3-nitropyridine essentially as described in EXAMPLE 15 gives 2-C(2-acetoxyethyl)ethylamino)-3-aminopyridine as an oil. A methanolic solution of this oil is allowed to react with acetaldehyde and sodium cyanoborohydride as described in EXAMPLE 15 to give an oil which is chromato¬ graphed on silica gel eluting with ethyl acetate/hexane mixtures. The appropriate fractions are pooled and concentrated to give 2-((2-acetyloxyethyl)ethylamino)-3-ethyl- amino pyridine (1-1) as an oil, CMR 171.1, 148.9, 139.93, 134.28, 120.70, 116.40, 62.54, 49.41, 46.32, 37.80, 20.80, 14.57 and 12.75 δ and 2-((2-hydroxyethyl)ethyl- amino3-ethylaminopyridine (1-2) as a solid, mp 68-69°. EXAMPLE 16(2)A 2-((2-Hydroxyethyl)ethylamino)-3-ethylaminopyridine hydrochloride (I) Following the general procedure of EXAMPLE 3 A and making noncritical variations but starting with 2-CC2-hydroxyethyl)ethylamino)-3-ethylaminopyridine [EXAMPLE 16C2)], the title compound is obtained, mp 99-102°. EXAMPLE 17 2-CC2-Acetyloxyethyl)methylamino)-3-ethylaminopyridine (I) A solution of 2-chloro-3-nitropyridine (3.17 g) in 2-Cmethylamino)ethanol (10 ml) is heated under reflux for 2 hours. The mixture is then diluted with methylene chloride and washed with aqueous bicarbonate and water. The phases are separated and the organic extract is concentrated to give an oil. The oil is chromatographed on silica gel eluting with methanol/methylene chloride (5/95). The appropriate fractions are pooled and concentrated to gave 2-((2-hydroxyethyl)methylamino)-3-nitropyridine. This inter¬ mediate is acetylated as described in EXAMPLE 16 to give 2-((2acetyloxyethyl)methyl- amino)-3-nitropyridine as an oil. This nitro compound is hydrogenated and the resultant primary amine treated with acetaldehyde sodium cyanoborohydride essentially as described in EXAMPLE 15 to give an oil which is chromatographed on silica gel eluting with acetone/methylene chloride (10/90). The appropriate fractions are pooled and concentrated to give the title compound, NMR 7.7, 6.9, 6.8, 4.42, 4.23, 3.27, 3.13, 2.76, 2.06 and 1.31 δ. EXAMPLE 18 2-DiC2-methoxyethyl)amino-3-ethylaminopyridine (1-1) and 2-di(2-methoxyemyl)ammo-3-diethylaminopyridine (I-2) A mixture of 2-chloro-3-nitropyridine (3.17 g), potassium carbonate (2.0 g) and di(2-methoxyethyl)amine (6.67 g) in acetonitrile (50 ml) is stirred at 20-25° for 25 hr and then is concentrated under reduced pressure. The residue is partitioned between ethyl acetate and water), the phases are separated and the organic phase is concentrated to give 2-di(2-methoxyethyl)amino-3-nitropyridine as an oil. 2-Di(2-methoxyethyl)amino-3-nitropyridine (2.6 g) is hydrogenated as described in EXAMPLE 15 to give 2-di(2-methoxyethyl)amino3-aminopyridine. A methanolic solution (25 ml) of this amine is treated with 2 ml of acetaldehyde (exotherm). The mixture is cooled to 10° and additional acetaldehyde (2 ml) is added (no exotherm) followed by the addition of sodium cyanoborohydride (0.7 g). The mixture is cooled for 1 hr, stirred overnight at 20-25° and then concentrated at reduced pressure. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate, the phases are separated and the organic phases is concentrated to give an oil. The oil is chromato¬ graphed on silica gel eluting with ethyl acetate/hexane (50/50), the appropriate fractions SUBSTITUTE SHEET are pooled and concentrated to give 2-di(2-methoxyethyl)amino-3-ethylaminopyridine (I- 1) CMR 149.o6, 138.96, 133.73, 119.86, 115.29, 70.81, 58.63, 51.23, 37.72 and 14.19 and 2-di(2-methoxyethyl)amino-3-diethylaminopyridine (1-2) CMR 154.23, 140.10, 136.16, 128.17, 115.51, 71.10, 58.47, 49.17, 43.30 and 11.19 δ. EXAMPLE 18(1)A and 18C2)A 2-DiC2-methoxyethyl)amino-3-ethylaminopyridinehydrochloride (I-l) and 2-di(2-meΛoxyethyl)amino-3-diethylarninopyridine hydrochloride (1-2) Following the general procedure of EXAMPLE 3A and making noncritical variations but starting with 2-di(2-methoxyethyl)amino3-ethylaminopyridine [EXAMPLE 18(1-1)] and 2-di(2-meΛoxyethyl)amino-3-diethylamino pyridine [EXAMPLE 18(1-2)], the title compounds are obtained. EXAMPLE 19 4-Di(2-acetyloxyethyl)amino-2,6-di-l-py_Tolidinyl pyrimidine CD A mixture of 4-di(2-hydroxyethyl)amino-2,6-di-l-pyrrolidinyl pyrimidine (EXAMPLE 5, 0.94 g) and acetic anhydride (2 ml) in ethyl acetate (10 ml) is allowed to stand overnight at 20-25°. Ice (25 g) is added, the mixture is stirred and allowed to warm, then is diluted with ethyl acetate and aqueous potassium bicarbonate. The organic phase is separated and concentrated to give an oil which is chromatographed on silica gel. Elution with acetone/methylene chloride (7/93) gives the title compound, mp 90- 92°; CMR 170.91, 162.12, 159.89, 71.34, 62.33, 47.55, 46.00, 45.91, 25.44, 25.21 and 20.86 δ. EXAMPLE 19A 4-DiC2-acetyloxyethyl)amino-2,6-di-l-pyrrolidinyl pyrimidine hydrochloride (I) A solution of 4-diC2-acetyloxyethyl)amino-2,6-di-l-pyrrolidinyl-pyrimidine (EXAMPLE 19, 1.0 mmol) in hydrochloric acid (0.05N, 20 ml) is freeze dried to give the title compound, mp 113-124°. EXAMPLE 20 2-(4-C2-Methoxyethyl)-l-piperazinyl)-3-ethylaminopyridine C Following the general procedure of EXAMPLE 8 and making noncritical variations but reacting 4-C3-ethylamino)-2-pyridinyl- piperazine (1.05 g) with 1-methoxy- -2-mesyloxyethane (1.54 g), the title compound is obtained, CMR 150.56, 137.20, 135.08, 119.47, 115.69, 70.21, 58.80, 57.94, 53.95, 48.48, 38.03 and 14.66 δ. EXAMPLE 20A 2-(4-C2-Methoxyethyl)-l-piperazinyl)-3-ethylaminopyridine hydrochloride (T) An aqueous solution of 2-C4-C2-methoxyethyl)-l-piperazinyl)-3ethylaminopyridine (EXAMPLE 20) containing hydrochloric acid (1.0 eq) is freeze dried. Crystallization of the residue from methanol ethyl acetate gives the title compound, mp 191-191.8°. EXAMPLE 21 2-(4-(2- Acetyloxyethyl)- l-piperazinyl)-3-ethylaminopyridine (D A mixture of 4-(3-Cethylamino)-2-pyridinyl)piperazine(1.54 g), dϋsopropylamine (2 ml) and 2-bromoethyl acetate (1.1 ml) in acetonitrile (40 ml) is stirred at 20-25° for 2 days and then is concentrated. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate, the phases are separated and the organic phase concentrated. The residue is chromatographed on silica gel eluting with metha- nol/methylene chloride (5/95) to give the title compound, CMR 170.92, 150.50, 137.25, 135.06, 119.60, 115.74, 61.68, 56.57, 53.68, 48.60, 38.00, 20.92 and 14.65 δ. EXAMPLE 21A 2-C4-C2- Acetyloxyethyl)- l-piperazinyl)-3-ethylaminopyridine hydrochloride (D Following the general procedure of EXAMPLE 3A and making noncritical variations but starting with 2-C4-(2-acetyloxyethyl)-lpiperazinyl)-3ethylaminopyridine (EXAMPLE 21), the title compound is obtained. EXAMPLE 22 4-((3-Ethylamino)-2-ρyridinyl)-l-piρerazineethanol (I) A mixture of 2-(4-(2-acetyloxyethyl)-l-piperazinyl)-3-ethylaminopyridine (EXAMPLE 21, 0.8 g) and aqueous potassium carbonate (10%, 2 ml) in methanol (20 ml) is stirred at 20-25° for 1 hr and then is treated with acetic acid (0.2 ml) and concentrated. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate. The organic phase is concentrated to give the title compound, CMR 150.44, 137.32, 135.06, 119.75, 115.81, 59.30, 57.60, 53.22, 48.76, 37.98 and 14.65 δ. EXAMPLE 22A 4-((3-Ethylamino)-2-pyridinyl)-l-piperazineethanol hydrochloride (D Following the general procedure of EXAMPLE 3A and making noncritical variations but starting with 4-((3-ethylamino)-2-pyridinyl)-l-piperazineethanol (EXAMPLE 22), the title compound is obtained. EXAMPLE 22B 4-((3-Ethylamino)-2-pyridinyl)-l-piperazineethanol fumarate (I- salt) A solution of the 4-((3-ethylamino)-2-pyridinyl)-l-piperazineethanol (I, EXAMPLE 22, 0.41 g) and fumaric acid (0.19 g) in methanol is concentrated to give the title compound, mp 120-132°. EXAMPLE 23 2-CC2-Hydroxyethyl)meΛylammo)-3-ethylaminopyridine (D Following the procedure of EXAMPLE 22 and making noncritical variations, 2-CC2-acetoxyethyl)memylamino)-3-ethylaminopyridine (EXAMPLE 17) is hydrolyzed. Chromatography on silica gel eluting with acetone/methylene chloride (25/75) gives die titie compound, mp 87-89°; CMR 150.14, 137.78, 133.62, 119.74, 116.10, 58.56, 55.37, 37.96, 36.65 and 14.46 δ. EXAMPLE 23A 2-((2-Hydroxyethyl)memylamino)-3-ethylaminopyridine hydro¬ chloride CD Following the general procedure of EXAMPLE 3A and making non-critical variations but starting with 2-CC2-hydroxyethyl)methylamino)-3-ethylamino pyridine CEXAMPLE 23), the title compound is obtained, mp 158-160°. EXAMPLE 24 4-C4-(2-Methoxyethyl)-l-piperazinyl)-2,6-di-l-pyrrolidinylpyr- imidine CD A mixture of 4-C2,6-di-pyrrolidinyl-4-pyrimidinyl)piperazine (1.51 g), di- isopropylamine (2 ml) and l-methoxy-2-mesyloxyethane (0.97 g) in acetonitrile (50 ml) is stirred at 20-25° for 4 days and then is concentrated. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate. The organic phase is concentrated and the residue chromatographed on silica gel, eluting with metha¬ nol/methylene chloride (5/95). The appropriate fractions are pooled and concentrated to give the title compound as a solid, CMR 163.89, 162.33, 160.08, 72.21, 69.96, 58.80, 58.00, 53.29, 46.04, 45.91, 44.12, 25.46 and 25.19 δ. EXAMPLE 25 4-(4-C2-Acetyloxyethyl)-l-piperazinyl)-2,6-di-pyrrolidinylpyrimi- dine (D Following the general procedure of EXAMPLE 24 and making noncritical variations but replacing l-methoxy-2-mesyloxyethane with 2-bromoethyl acetate, the title compound is obtained as a solid, CMR 170.88, 163.80, 162.23, 72.24, 61.70, 56.67, 53.11, 46.08, 45.94, 44.23, 25.44, 25.19 and 20.93 δ. EXAMPLE 25A 4-(4-(2- Acetyloxyethyl)- l-piperazinyl)-2,6-di-l- pyrrolidinyl- pyrimidine dihydrochloride (D A solution of 4-(4-(2-acetyloxyethyl)-l-piperazinyl)-2,6-di-l-pyrrolidinyl- pyrimidine (EXAMPLE 25, 0.30 g) in water (30 ml) containing hydrochloric acid (2 eq) is freeze dried to give the title compound as a solid, mp 97-104°. EXAMPLE 26 4-(2,6-Di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazinepropanol (I) Following the general procedure of EXAMPLE 24 and making noncritical variations but replacing l-methoxy-2-mesyloxyethane with 3-bromo-l-propanol, crude title compound is obtained. Chromatography on silica gel, eluting with methanol/- methylene chloride (20/80), and crystallization of product fractions from acetone gives the title compound, mp 129-130°; CMR 163.79, 162.29, 160.01, 72.33, 64.33, 58.79, 52.98, 46.06, 45.93, 44.24, 26.90, 25.45 and 25.19 δ. EXAMPLE 26A 4-(2,6-Di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazinepropanol fumarate (I-salt) 4-(2,6-Di-l-py_τolidinyl-4-pyrirnidinyl)-l-piperazinepropanol (EXAMPLE 26) is mixed with an equimolar amount of fumaric acid and crystallized from methanol to give the title compound, mp 199.9-205°. EXAMPLE 27 4-(2, 6-Di-l-pyrτolidinyl-4-pyrimidinyl)-l -piperazine ethanol (D Following the procedure of EXAMPLE 22 and making noncritical variations, 4- (4-(2-acetyloxyethyl)-l-piperazinyl)-2,6-di-l-pyrτolidinylpyrimidine (EXAMPLE 25) is hydrolyzed to give crude title compound. Chromatography on silica gel, eluting with methanol/methylene chloride (15/85) gives the title compound as a solid, CMR 163.86, 162.32, 160.05, 72.29, 59.35, 57.59, 52.59, 46.07, 45.93, 44.33, 25.45 and 25.19 δ. EXAMPLE 27A 4-(2,6-Di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazine ethanol dihydrochloride (D A solution of 4-C2,6-di-l-pyr_oUdinyl-4-pyrimidmyl)-l-piperazineethanol (EXAMPLE 27) in dilute hydrochloric acid (2 eq) is freeze dried to give the title compound, mp 238° dec. EXAMPLE 28 Methyl 4-(3-(ethylamino)-2-pyridinyl)-l-piperazinepropanoate (D Following the general procedure of EXAMPLE 14 and making noncritical variations but reacting 4-(3-ethylamino)-2-pyridinyl- piperazine (1.04 g) with methyl 3-bromopropionate C0.84 g), the title compound is obtained, CMR 173.0, 150.6, 137.25, 135.07, 119.59, 115.72, 53.53, 53.24, 51.52, 48.65, 38.00, 32.06 and 14.65 δ. EXAMPLE 29 Ethyl 4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l piperazine buta- noate (D A mixture of 4-(2,6-di-l-pyrτolidinyl-4-pyrimidinyl)-piperazine (1.51 g), diisopropylamine (2 ml) and ethyl 4-bromobutyrate in acetonitrile (50 ml) is stirred at 20-25° for three days and then is concentrated. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate. The organic phase is separated and concentrated to give an oil. Chromatography on silica gel, eluting with methanol- /methylene chloride C10/90) gives the title compound, CMR 173.4, 164.0, 160.0, 72.23, 60.15, 57.72, 52.85, 46.04, 45.90, 44.29, 32.21, 25.45, 25.19, 22.01 and 14.12 δ. EXAMPLE 30 Ethyl 4-(3-(ethylamino)-2-pyridinyl)-l-piperazine butanoate (D Following the general procedure of EXAMPLE 14 and making noncritical variations but reacting 4-(3-ethylamino)-2-pyridinyl)piperazine (1.04 g) with ethyl 4-bromobutyrate (0.98 g), crude title compound is obtained. Chromatography on silica gel, eluting with methanol methylene chloride (5/95), gives the title compound, CMR 173.6, 150.7, 137.5, 135.06, 119.52, 115.67, 60.15, 57.60, 53.44, 48.68, 38.01, 32.09, 21.99, 14.65 and 14.13 δ. EXAMPLE 31 4-(3-CEthylamino)-2-pyridinyl)- 1 -piperazine butanoic acid CD A mixture of ethyl 4-C3-Cethylamino)-2-pyridinyl)-l-piperazine butanoate (EXAMPLE 30, 0.70 g) and aqueous lithium hydroxide (IN, 2.6 ml) in methanol (25 ml) is heated under reflux for about 1 hour. The mixture is then allowed to cool, treated with hydrochloric acid (IN, 2.6 ml) and concentrated. The residue is mixed with saline (50 ml) and then extracted continuously with ether overnight. The extract is concentrat¬ ed and the residue crystallized from acetone to give the title compound, mp 127-128°. EXAMPLE 32 4-Py_τo_idinyl-2,6-di-l-morpho_inopyrinιidine (D A m_ tture of4-cWo__τ 2,6^i-l-morpholinopyrimidine [Rocz. chem. 41, 1047-52 (1967), CA 68:114539s, 2.84 g) and pyrrolidine (25 ml) is heated under reflux for 3 hr and then is concentrated. The residue is partitioned between ethyl acetate and aqueous potassium bicarbonate. The organic phase is separated and concentrated and the residue crystallized from methylene chloride/ethyl acetate to give the title compound, mp 210-210.8°; CMR 164.12, 162.17, 73.22, 66.96, 66.62, 46.00, 44.77, 44.35 and 25.16 δ. EXAMPLE 33 4-Piperidinyl-2,6-di-l-morpholinopyrimidine (D Following the general procedure of EXAMPLE 32 and making noncritical variations but reacting 4-chloro-2,6-di-l-morpholinopyrimidine with piperidine, the title compound is obtained, mp 217-218°; CMR 164.83, 164.24, 161.3, 73.03, 66.93, 66.61, 45.31, 44.76, 44.36, 25.39 and 24.74 δ. EXAMPLE 34 4-C2,6-Di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazinebutanoic acid (D A mixture of ethyl 4-(2,6-di-pyrrolidinyl-4-pyrimidinyl)-l-piperazine butanoate CEXAMPLE 29, 1.5 g) and methanol C40 ml) containing lithium hydroxide (IN, 4 ml) is heated under reflux overnight and then concentrated. The residue is partitioned between ethyl acetate and water. The aqueous phase is mixed with hydrochloric acid (IN, 4 ml), the precipitate collected and dried to give the title compound, m.p. 186- 188°. EXAMPLE 35 4-C2,6-Di- l-pyrrolidinyl-4-pyrimidinyl)- 1 -piperazine ethanoic acid (D Following the general procedure of EXAMPLE 34 and making noncritical variations but starting with methyl 4-C2,6-di-l-pyrro_idinyl-4-pyrimidinyl)-l-piperazine ethanoate (EXAMPLE 10) the title compound is obtained, m.p. 226-229° dec. EXAMPLE 36 4-(2,6-Di-l-pyr-Olidinyl-4-pyrirnidinyl)-l-piperazinφropanoicιcid CD Following the general procedure of EXAMPLE 34 and making noncritical variations but starting with methyl 4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazine propanoate CEXAMPLE 14), the titie compound is obtained. EXAMPLE 37 Benzyl 4-C3-ethylamino-2-pyridinyl)-l-piperazine propanoate CD Following the general procedure of EXAMPLE 12 and making noncritical variations but reacting 4-(3-ethylamino-2-pyridinyl)-piperazine with benzyl 3-bromo- propionate, the title compound is obtained. EXAMPLE 38 4-(3-Ethylamino-2-pyridinyl)-l-piperazine propanoic acid hydro¬ chloride CD Following the procedure of EXAMPLE 13 and making noncritical variations but starting with benzyl 4-(3-ethylamino-2-pyridinyl)-l-piperazine propanoate (EXAMPLE 37), the title compound is obtained.

Claims: C AIMS 1. A amino-substituted heteroaryl amine of formula CD Rj-N-Heteroaryl (I) i where Ri is - alkyl, -0-CH 3 , -0-CH 2 CH 3 , -(CH^ O-Rn where ^ is 2 or 3 and R M is -H, C,-C 3 alkyl, -CO-R^ where R,. 2 is -H, C,-C 3 alkyl or -φ, -CH 2 -CHCOR,.,)-CH 3 where R M is as defined above, where > ~ - is 1 or 2 and where R w is as defined above, -CCH^-CO-R^ where n 3 is 1 thru 3 and R L3 is -OH, -O-R M where R M is C r C 4 alkyl or -CH 2 - , Cj- alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NOj, - or -ORj. 7 where R M is - alkyl, -CH 2 -CH=CH-CO-Rι. 3 where R,. 3 is as defined above, -CCH 2 ) B4 -N(R 1 . 5 )(R 1 ^) where 11 4 is 2 or 3 and R^ and R w are the same or different and are -H and - alkyl, R 2 is -H, Cj- alkyl, -CCH^-O-R M where n 5 is 2 or 3 and R 2 .ι is -H, C r C 3 alkyl, -CO-R 2 . 2 where 2 . 2 is -H, - alkyl or -φ, -CH 2 -CHCOR 2 -ι)-CH 3 where R^ is as defined above, where n- is 1 or 2 and where 2 .ι is as defined above, -CCH 2 ) n7 -CO-R 2 , 3 where n 7 is 1 thru 3 and R 2 . 3 is -OH, -0-R M where R 2 is C,-C 4 alkyl or -CH 2 -φ; - alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO j , - or -OR 2 . 5 where R 2 - 5 is C t - alkyl, and where R, and R 2 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, morpholine, piperazine and piperazine substituted in the 4- position with where n, is 2 or 3 and where Rj., is -H, -C 3 alkyl, -CO- R 3 - 2 where R^ is -H, Ci-C 3 alkyl or -φ, -CCH^-CO-R^ where α, is 1 thru 3 and R^ is -OH, -O-R^ where - 4 is C r C 4 alkyl or -CH 2 -ø, Cj- alkyl, -φ optionally substituted with 1 or 2 -F, -Cl, -Br, -NO . , C r C 3 or -OR„ where R^ is -C, alkyl, -CH 2 CH 2 -CO-CH 2 CH 2 ) βl o-0-R 3 -, where n 10 is 1 or 2 and where R-_ t is as defined above, -CH 2 -CH=CH-CO-R 3 . 3 where R M is as defined above, -SU 2 R 3 . 5 where R^ is -C 3 alkyl; heteroaryl is pyridin-2-, 3- and 4-yl, pyrimidin-2- and 4-yl, pyrazin-2-yl, l,3,5-triazin-2-yl, pyridazin-2-yl, substituted with 1 or 2 -NCR^ CRw) where R^ and I 2 are the same or different and are -H, C r Cj alkyl and where R 4 . 1 and R 4 . 2 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azetidinyl and 4-C - alkyl)-piperazinyl -NH-OH -NH-O-CH 2 -Φ, -NH-CHzCHj-O-Rw where R 4 _ 3 is -H or Cj- alkyl, -N(CH 2 CH 2 -0-R 4 - 3 ) 2 where R^ is as defined above, and pharmaceutically acceptable salts thereof. 2. A amino-substituted heteroaryl amine (D according to claim 1 where R t is selected from the group consisting of C r C 3 alkyl, -0-CH 3 , -(CH-) Λl -0- lA , -(CH^^-CO-R^ and -CH 2 -CH=CH-CO-R,. 3 . 3. A amino-substituted heteroaryl amine CD according to claim 1 where R 2 is selected from the group consisting of -H, - alkyl and -(CH^O-R^. 4. A amino-substituted heteroaryl amine (D according to claim 1 which is 4-(2-Chydroxyethyl)methylamino)-2,6-di-l-pyrrollidinylpyrimidine, 4-di(2-Methoxyethyl)amino-2,6-di-l-pyrrolidinylpyrimidine, 4-methoxyammo-2,6-di-l-pyrrolidinylpyrirnidine, 4-Cdi-C2-hydroxyethyl)amino)-2,6-di-l-pyrrolidinylpyrimidine, 4-methylamino-2,6-di-l-py_τolidinylpyrimidine, 4-(2-(2-memoxyethoxy)ethylmethylammo)-2,6-di-pyrτolidinylpyrimidine, 2-CC2-acetyloxyethyl)ethylamino)-3-ethylaminopyridine, 2-CC2-hydroxyethyl)ethylamino)-3-ethylamino-pyridine, 2-C(2-acetyloxyethyl)methylamino)-3-ethylaminopyridine, 2-di(2-methoxyethyl)amino-3-ethylaminopyridine, 2-di(2-methoxyethyl)amino-3-diethylaminopyridine, 4-di(2-ace-yloxyethyl)amino-2,6-di-l-pyrrolidinylpyrimidine, 2-C(2-hydroxyethyl)methylamino)-3-ethylaminopyridine. 5. A amino-substituted heteroaryl amine (D according to claim 1 where Rj and R 2 are taken together with the attached nitrogen atom to from a heterocyclic ring which is morpholine. 6. A amino-substituted heteroaryl amine CD according to claim 5 which is 4-morpholino-2 , -di- 1 -pyrrolidinylpyrimidine, 2-morpholino-3-ethylaminopyridine. 7. A amino-substituted heteroaryl amine CD according to claim 1 where Rj and R 2 are taken together with the attached nitrogen atom to form a heterocyclic ring which is piperazine substituted in the 4-position. 8. A amino-substituted heteroaryl amine CD according to claim 7 which is 4-C3-Cethylamino)-2-pyridinyl)-l-piperazinepropanol, 2-C4-mesyloxy- 1 -piperazinyl)-3-ethylaminopyridine, methyl 4-C2,6-di-l-pyrτolidinyl-4-pyrimidinyl)-l-piperazineethanoate, methyl 4-(3-(emylamino)-2-pyridinyl)-l-piperazine ethanoate, benzyl 4-C3-Cethylamino)-2-pyridinyl)piperazine ethanoate, 4-C3-Cethylamino)-2-pyridinyl)-piperazine ethanoic, methyl 4-C2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazine propanoate, 2-C4-C2-methoxyethyl)- l-piperaz_nyl)-3-ethylaminopyridine, 2-C4-C2-acetyloxyethyl)- l-piperazinyl)-3-ethylaminopyridine, 4-CC3-ethylamino)-2-pyridinyl)-l-piperazineethanol, 4-C4-C2-methoxyethyl)-l-piperazinyl)-2,6-di-l-pyrrolidinylpyrimidine, 4-C4-C2-acetyloxyethyl)-l-piperazinyl)-2,6-di-pyrτolidinylpyrimidine, 4-C2,6-di-l-pyrτolidinyl-4-pyrimidinyl)-l-piperazinepropanol, 4-C2 , 6-di- 1 -pyrrolidinyl-4-pyrimidinyl)- 1-piperazineethanol, methyl 4-C3-Cethylamino)-2-pyridinyl)-l-piperazinepropanoate, ethyl 4-C2 , 6-di- 1 -pyrτolidinyl-4-pyrimidinyl)- 1-piperazinebutanoate, ethyl 4-C3-Cethylamino)-2-pyridinyl)-l-piperazine butanoate, 4-C3-Cethylamino)-2-pyridinyl)-l-piperazine butanoic acid, 4-(2,6-di-l-py_TOUdinyl-4-pyrirnidinyl)-l-pipera_dne butanoic acid, 4-(2,6^i-l-py-Tθlidinyl-4-pyrimidinyl)-l-piperazine ethanoic acid, 4-C2,6-di- l-pyrτolidinyl-4-pyrimidinyl)- 1-piperazine propanoic acid, benzyl 4-C3-ethylamino-2-pyridinyl)- 1-piperazine propanoate, 4-C3-ethylamino-2-pyridinyl)-l-piperazine propanoic acid. 9. A amino-substituted heteroaryl amine CD according to claim 1 where R, and R 2 are taken together with the attached nitrogen atom to form a heterocyclic ring which is pyrrolidine. 10. A amino-substituted heteroaryl amine (D according to claim 9 which is 4-pyrτolidin- yl-2 , 6-di- 1 -morpholinopyrimidine. 11. A amino-substituted heteroaryl amine CD according to claim 1 where Ri and R 2 are SUBSTITUTE SHEET taken togedier with the attached nitrogen atom to form a heterocyclic ring which is piperidine. 12. A amino-substituted heteroaryl amine CD according to claim 11 which is 4-piperidin- yl-2,6-di-l-morpholinopyrimidine. 13. A amino-substituted heteroaryl amine (D according to claim 1 where heteroaryl is pyrimidin-4-yl. 14. A amino-substituted heteroaryl amine CD according to claim 13 which is 4-C2-Chydroxyethyl)methylamino)-2,6-di-l-pyrrolidinylpyrimidine, 4-moφholino-2,6-di-l-pyrrolidinylpyrimidine, 4-di(2-Methoxyedιyl)amino-2,6-di-l-pyrτolidinylpyrimidine, 4-methoxyamino-2,6-di-l-pyrτolidinylpyrimidine, 4-Cdi-C2-hydroxyethyl)amino)-2,6-di-l-pyrτolidinylpyrimidine, 4-methylammo-2,6-di-l-py-Tθlidinylpyrirnidine, 4-C2-(2-methoxyethoxy)ethylmethylamino)-2,6-di-pyrrolidinylpyrin_idine, methyl 4-P,6-di-l-pyrτoUdinyl-4-pyrimidinyl)-l-piperazineethanoate, methyl 4-C2,6-di-l-pyrrolidinyl-4-pyrimidinyl)- 1-piperazine propanoate, 2-morpholino-3-ethylaminopyridine, 4-diC2-acetyloxyethyl)ammo-2,6^i-l-pyrτoUdinylpyrimidine, 4-C4-C2-methoxyethyl)-l-piperazinyl)-2,6-di-l-py-_Olidinylpyrimidine, 4-C4-C2-acetyloxyethyl)- l-piperazinyl)-2, 6-di-pyrrolidinylpyrimidine, 4-(2,6-di-l-pyττolidinyl-4-pyrimidinyl)-l-piperazinepropanol, 4-(2,6-di-l-py-Tθlidinyl-4-pyrimidinyl)-l-piperazineethanol, ethyl 4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazine butanoate, 4-pyrrolidinyl-2,6-di-l-moφholinopyrimidine, 4-piperidinyl-2,6-di-l-moφholinopyrimidine, 4-(2,6-di- l-py__τolidinyl-4-pyrimidinyl)-l-piperazine butanoic acid, 4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazineethanoic acid, 4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazine propanoic acid. 15. A amino-substituted heteroaryl amine (D according to claim 1 where heteroaryl is SUBSTITUTE SHEET pyridin-2-yl. 16. A amino-substituted heteroaryl amine (D according to claim 15 which is 4-(3-(ethylamino)-2-pyridinyl)-l-piperazinepropanol, 2-C4-mesyloxy- l-piperazinyl)-3-ethylaminopyridine, methyl 4-C3-CeΛylamino)-2-pyridinyl)-l-piperazine ethanoate, benzyl 4-(3-Cethy_amino)-2-pyridinyl)piperazine ethanoate, 4-C3-(ethylamino)-2-pyridinyl)-piperazineethanoic, 2-CC2-acetyloxyethyl)ethylamino)-3-emylaminopyridine, 2-C(2-hydroxyethyl)ethylamino)-3-ethylaminopyridine, 2-C(2-acetyloxyethyl)memylammo)-3-ethylaminopyridine, 2-di(2-methoxyethyl)amino-3-ethylaminopyridine, 2-diC2-medioxyethyl)amino-3-diethylaminopyridine, 2-C4-C2-methoxyethyl)-l-piperazinyl)-3-ethylan inopyridine, 2-C4-C2-acetyloxyethyl)-l-piperazinyl)-3-ethylaminopyridine, 4-C(3-ethylamino)-2-pyridinyl)-l-piperazineethanol, 2-CC2-hydroxyediyl)methylamino)-3-ethylaminopyridine, methyl 4-C3-(edιylamino)-2-pyridinyl)- 1-piperazinepropanoate, ethyl 4-(3-(ethylamino)-2-pyridinyl)- 1-piperazine butanoate, 4-C3-Cethylamino)-2-pyridinyl)- 1-piperazine butanoic acid, benzyl 4-(3-ethylamino-2-pyridinyl)- 1-piperazine propanoate, 4-(3-ethylamino-2-pyridinyl)- 1-piperazine propanoic acid. SUBSTITUTE SHEET

Inventors: AYER DONALD E, AYER, DONALD, E.
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1990
Main classification: C07D213
IPC codes: A61K31, A61P9, A61P11, A61P17, A61P25, C07D213, C07D239