Abstract: The present specification discloses tetrahydroindolone derivatives or analogues and methods for treating cognitive/attention deficit disorders using such tetrahydroindolone derivatives and analogues.

Abstract: The present specification discloses tetrahydroindolone derivatives or analogues and methods for treating cognitive/attention deficit disorders using such tetrahydroindolone derivatives and analogues.

Abstract: The present specification discloses tetrahydroindolone derivatives or analogues and methods for treating cognitive/attention deficit disorders using such tetrahydroindolone derivatives and analogues.

Abstract: Methods for treating cognitive/attention deficit disorders in general using tetrahydroindolone derivatives and analogues, particularly tetrahydroindolone derivatives or analogues in which the tetrahydroindolone derivative or analogue is covalently linked to another moiety to form a bifunctional conjugate are disclosed. More specifically, methods and compositions for treating attention deficit disorder and attention deficit hyperactivity disorders in adults and children as well as mild cognitive impairment and dementia are provided.

Abstract: Methods for treating cognitive/attention deficit disorders in general using tetrahydroindolone derivatives and analogues, particularly tetrahydroindolone derivatives or analogues in which the tetrahydroindolone derivative or analogue is covalently linked to another moiety to form a bifunctional conjugate are disclosed. More specifically, methods and compositions for treating attention deficit disorder and attention deficit hyperactivity disorders in adults and children as well as mild cognitive impairment and dementia are provided.

Abstract: Methods for treating cognitive/attention deficit disorders in general using tetrahydroindolone derivatives and analogues, particularly tetrahydroindolone derivatives or analogues in which the tetrahydroindolone derivative or analogue is covalently linked to another moiety to form a bifunctional conjugate are disclosed. More specifically, methods and compositions for treating attention deficit disorder and attention deficit hyperactivity disorders in adults and children as well as mild cognitive impairment and dementia are provided.

Abstract: An improved method of synthesis of a 9-substituted hypoxanthine derivative comprises the steps of: (1) reacting aminocyanacetamide with triethyl orthoformate to form an imidoester derivative of aminocyanacetamide; (2) forming a compound having a reactive amino group on a hydrocarbyl moiety, the hydrocarbyl moiety being linked through an amide group to a physiologically active moiety or an esterified derivative of a physiologically active moiety including therein an esterified benzoyl group; (3) reacting the imidoester with the compound having the reactive amino group on the hydrocarbyl moiety to form a derivative of aminoimidazole-4-carboxamide substituted at the 1-position with a hydrocarbyl moiety linked through an amide group to a physiologically active moiety including therein an optionally esterified benzoyl group; (4) forming the six-membered heterocyclic ring of the purine moiety of the hypoxanthine by reacting the derivative of 5-aminoimidazole-4-carboxamide formed in step (3) with triethyl orthoforma

Abstract: Pharmaceutical composite compositions comprising tetrahydroindolones linked to arylpiperazines and derivatives thereof are disclosed. Specifically, composite compositions useful in treating anti-psychotic disorders are disclosed. The composite compositions disclosed herein can effectively ameliorate symptoms and treat psychotic disorders without causing a decrease in cognitive function. Generally, the composite compounds consist of two moieties, moiety A and B in which a tetrahydroindolone comprises a moiety A linked through a linker L to a moiety B, where B is an arylpiperazinyl moiety. The composite compound provides anti-psychotic actively by interaction with GABA, seratoninne and dopamine receptors. The composite molecules with the combined activities will provide treat psychiatric and neurological diseases without cognitive impairment.

Abstract: A tetrahydroindolone derivative or analogue comprises a 9-atom bicyclic moiety, moiety A, linked through a linker L to a moiety B, where B is a carboxylic acid, a carboxylic acid ester, or a moiety of the structure N(Y1)-D, where Y1 can be one of a variety of substituents, including hydrogen or alkyl, and D is a moiety that enhances the pharmacological effects, promotes absorption or blood-brain barrier penetration of the derivative or analogue. The moiety A has a six-membered ring fused to a five-membered ring. The moiety A can have one, two, or three nitrogen atoms in the five membered ring. The moiety A can be a tetrahydroindolone moiety. The moiety B can be one of a variety of moieties, including moieties having nootropic activity or other biological or physiological activity.

Abstract: A pyrimidine derivative or analogue comprises an amino-substituted six-membered heterocyclic moiety, moiety A, linked through a linker L to a moiety B, where B is a carboxylic acid, a carboxylic acid ester, or a moiety of the structure N(Y1)-D, where Y1 can be one of a variety of substituents, including hydrogen or alkyl, and D is a moiety that enhances the pharmacological effects, promotes absorption, or promotes blood-brain barrier penetration of the derivative or analogue. The moiety A can have two or three nitrogen atoms in the ring; typically, the moiety A is a pyrimidine moiety, with two nitrogen atoms in the ring. The moiety B can be one of a variety of moieties, including moieties having nootropic activity or other biological or physiological activity.

Abstract: A method of treating disease-induced peripheral neuropathy comprises administering to a patient with disease-induced peripheral neuropathy an effective quantity of a purine derivative or analogue, a tetrahydroindolone derivative or analogue, or a pyrimidine derivative or analogue. If the compound is a purine derivative, the purine moiety can be guanine or hypoxanthine. The compound can induce peripheral nerve sprouting through the action of a neurotrophic factor such as nerve growth factor (NGF) without the occurrence of hyperalgesia. The peripheral nerve sprouting can be nociceptive nerve sprouting. The disease-induced peripheral neuropathy can be diabetic neuropathy or disease-induced peripheral neuropathy with another basis.

Abstract: A method of treating drug-induced peripheral neuropathy comprising administering to a patient with drug-induced peripheral neuropathy an effective quantity of N-4-carboxaphenyl-3-(6-oxohydropurin-9-yl)propananide AIT-082, is disclosed. Peripheral nerve sprouting can be induced through the action of a neurotrophic factor such as nerve growth factor (NGF) without the occurrence of hyperalgesia. The peripheral nerve sprouting can be nociceptive nerve sprouting. The drug-induced peripheral neuropathy is associated with the administration of oncolytic drugs, such as a vinca alkaloid, cisplatin, paclitaxel, suramin, altretamine, carboplatin, chlorambucil, cytarabine, dacarbazine, docetaxel, etoposide, fludarabine, ifosfamide with mesna, tamoxifen, teniposide, or thioguanine.

Abstract: Pharmaceutical composite compositions comprising tetrahydroindolones linked to arylpiperazines and derivatives thereof are disclosed. Specifically, composite compositions useful in treating anti-psychotic disorders are disclosed. The composite compositions disclosed herein can effectively ameliorate symptoms and treat psychotic disorders without causing a decrease in cognitive function. Generally, the composite compounds consist of two moieties, moiety A and B in which a tetrahydroindolone comprises a moiety A linked through a linker L to a moiety B, where B is an arylpiperazinyl moiety. The composite compound provides anti-psychotic actively by interaction with GABA, seratoninne and dopamine receptors. The composite molecules with the combined activities will provide treat psychiatric and neurological diseases without cognitive impairment.

Abstract: A pyrimidine derivative or analogue comprises an amino-substituted six-membered heterocyclic moiety, moiety A, linked through a linker L to a moiety B, where B is a carboxylic acid, a carboxylic acid ester, or a moiety of the structure N(Y1)-D, where Y1 can be one of a variety of substituents, including hydrogen or alkyl, and D is a moiety that enhances the pharmacological effects, promotes absorption, or promotes blood-brain barrier penetration of the derivative or analogue. The moiety A can have two or three nitrogen atoms in the ring; typically, the moiety A is a pyrimidine moiety, with two nitrogen atoms in the ring. The moiety B can be one of a variety of moieties, including moieties having nootropic activity or other biological or physiological activity.

Abstract: Methods for treating cognitive/attention deficit disorders in general using tetrahydroindolone derivatives and analogues, particularly tetrahydroindolone derivatives or analogues in which the tetrahydroindolone derivative or analogue is covalently linked to another moiety to form a bifunctional conjugate are disclosed. More specifically, methods and compositions for treating attention deficit disorder and attention deficit hyperactivity disorders in adults and children as well as mild cognitive impairment and dementia are provided.

Abstract: A tetrahydroindolone derivative or analogue comprises a 9-atom bicyclic moiety, moiety A, linked through a linker L to a moiety B, where B is a carboxylic acid, a carboxylic acid ester, or a moiety of the structure N(Y1)-D, where Y1 can be one of a variety of substituents, including hydrogen or alkyl, and D is a moiety that enhances the pharmacological effects, promotes absorption or blood-brain barrier penetration of the derivative or analogue. The moiety A has a six-membered ring fused to a five-membered ring. The moiety A can have one, two, or three nitrogen atoms in the five membered ring. The moiety A can be a tetrahydroindolone moiety. The moiety B can be one of a variety of moieties, including moieties having nootropic activity or other biological or physiological activity.

Abstract: Disclosed herein are methods and associated compositions and medicaments directed generally to the control of cellular and neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as proteins or neurotrophic factors and induces the endogenous production of such naturally occurring compounds through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological functions and activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, cellular, and physiological disorders.

Abstract: A purine derivative or analogue comprises a 9-atom bicyclic moiety, moiety A, linked through a linker L to a moiety B, where B is a carboxylic acid, a carboxylic acid ester, or a moiety of the structure N(Y1)—D, where Y1 can be one of a variety of substituents, including hydrogen or alkyl, and D is a moiety that enhances the pharmacological effects, promotes absorption or blood-brain barrier penetration of the derivative or analogue. The moiety A has a six-membered ring fused to a five-membered ring. The moiety A can have one, two, or three nitrogen atoms in the five membered ring and has two nitrogen atoms in the six-membered ring. The moiety A can be a purine moiety. The moiety B can be one of a variety of moieties, including moieties having nootropic activity or other biological or physiological activity.

Abstract: The bifunctional compound N-4-carboxyphenyl-3-(6-oxohydropurin-9-yl) propanamide monopotassium salt occurs in a number of crystal forms which differ in their stability. Of these forms, the most stable is designated Type I, which is a monopotassium salt monohydrate in which the water is held as water of crystallization. Other crystalline forms, designated Type II and Type III, convert to Type I. Methods are disclosed for the synthesis of Type I and for the conversion of Type II or Type III to Type I.

Abstract: A method of treating drug-induced peripheral neuropathy comprises administering to a patient with drug-induced peripheral neuropathy an effective quantity of a purine derivative or analogue, a tetrahydroindolone derivative or analogue, or a pyrimidine derivative or analogue. If the compound is a purine derivative, the purine moiety can be guanine or hypoxanthine. The compound can induce peripheral nerve sprouting through the action of a neurotrophic factor such as nerve growth factor (NGF) without the occurrence of hyperalgesia. The peripheral nerve sprouting can be nociceptive nerve sprouting. The drug-induced peripheral neuropathy can be drug-induced peripheral neuropathy associated with the administration of oncolytic drugs, such as a vinca alkaloid, cisplatin, paclitaxel, suramin, altretamine, carboplatin, chlorambucil, cytarabine, dacarbazine, docetaxel, etoposide, fludarabine, ifosfamide with mesna, tamoxifen, teniposide, or thioguanine.