Provided herein are intermediates and processes useful for facile synthesis of compounds of formula (I): ##STR00001##
or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Q, P.sup.1 and P.sup.2 are as defined in this disclosure.

The present invention relates to compounds of formula I ##STR00001##
or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein R.sub.1 is C.sub.1-C.sub.3alkyl optionally substituted with F, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3alkoxy; X represents a bond or C.sub.1-C.sub.3alkylene optionally substituted with OH, ONO, ONO.sub.2; R.sub.2 is H, OH, ONO, ONO.sub.2, C(O)OH, C(O)OC.sub.1-C.sub.3alkyl, CHO, CN, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)—C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl, CR.sub.8═N—OR.sub.9, CR.sub.8═N—NR.sub.10R.sub.11, CR.sub.8═NR.sub.12 or CR.sub.8═N—ONO.sub.2; R.sub.3 is C.sub.1-C.sub.6alkyl optionally substituted with F, OH, ONO, ONO.sub.2, C.sub.1-C.sub.3alkoxy, C.sub.3-C.sub.6cycloalkyl; C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl; R.sub.4 is C.sub.1-C.sub.6alkyl optionally substituted with C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6alkoxy, F, ONO, ONO.sub.2; C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl; R.sub.5 is H, SO.sub.2NR.sub.13R.sub.14, NHSO.sub.2NR.sub.13R.sub.14; R.sub.6 is H or C.sub.1-C.sub.3alkyl; R.sub.7 is H, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C.sub.1-C.sub.3alkyl, F; R.sub.8 is H, CH.sub.3 or C.sub.2H.sub.5; R.sub.9: H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)—C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl; R.sub.10 and R.sub.11 are each independently H, C.sub.1-C.sub.3alkyl optionally substituted with OH, ONO, ONO.sub.2, CN, COOH, COOC.sub.1-C.sub.3, C.sub.1-C.sub.3alkoxy, OC(O)H, OC(O)—C.sub.1-C.sub.3alkyl, C(O)N(R.sub.6)OR.sub.7, OC.sub.1-C.sub.3alkylene-C(O)OH, OC.sub.1-C.sub.3alkylene-C(O)OC.sub.1-C.sub.3alkyl, OC.sub.1-C.sub.3alkylene-C(O)N(R.sub.6)OR.sub.7, S(O.sub.0-2)C.sub.1-C.sub.3alkyl, or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C.sub.1-C.sub.3 alky

New pharmaceutical uses of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof are provided.

In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of a tissue, such as bone, cartilage, muscle, fat, brown fat and/or neuronal tissue and for treating metabolic disorders such as diabetes and obesity, as well as disorders associated with any of the foregoing tissue.

Disclosed herein are compositions and methods for acutely raising nitric oxide levels in a subject. In one example, the composition can include, an effective amount of a NOS dependent source of nitric oxide; an effective amount of a NOS independent source of nitric oxide; and an effective amount of a myeloperoxidase inhibitor; wherein the composition acutely raises nitric oxide levels in a subject above a level provided by the available sources of nitric oxide in the subject prior to administration of the composition. Further presented is a method of treating a subject for a condition or disorder that is response to nitric oxide therapy, including: acutely raising nitric oxide levels in a subject by simultaneously increasing biosynthesis of nitric oxide, increasing nitrate/nitrite levels, and inhibiting myeloperoxidase activity.

Novel methods for prevention, reduction or elimination of the incidence of male androgen deficiency symptoms or diseases including male hypogonadism-associated symptoms and diseases associated with low serum testosterone and/or low DHEA or low total androgens in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and a selective estrogen receptor modulator (SERM) (particularly acolbifene), an antiestrogen or a prodrug of the two. The symptoms or diseases are loss of libido, erectile dysfunction, tiredness, loss of energy, depression, bone loss, muscle loss, muscle weakness, fat accumulation, memory loss, cognition loss, Alzheimer's disease, dementia, loss of body hair, fertility problems, insomnia, gynecomastia, anemia, hot flushes, sweats, decreased sense of well-being, obesity, osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, cardiovascular disease and type 2 diabetes. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

A class of fluorine-substituted indazole compounds and uses thereof having the general formula depicted below ##STR00001##
in which C1 is ##STR00002##
where ##STR00003##
is the bond through which C1 is attached to L, and C2 is ##STR00004##
where ##STR00005##
is the bond through which C2 is attached to indazole, and pharmaceutical compositions containing these compounds. The compounds and pharmaceutical compositions of the invention can be used as soluble guanylate cyclase simulators.

The present invention is directed to compounds according to formula,

(R.sup.2R.sup.3)-A.sup.1-c(A.sup.2-A.sup.3-A.sup.4-A.sup.5-A.sup.6-A.sup.7-A.sup.8-A.sup.9)-A.sup.10-R.sup.1,

and pharmaceutically-acceptable salts thereof that act as ligands for one or more of the melanocortin receptors, to methods of using such compounds to treat mammals and to pharmaceutical compositions comprising said compounds.

The present application relates to novel amino-substituted fused pyrimidines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

The present invention provides 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid choline salt having excellent solubility and storage stability.